Relatório Científico Final 2011-13 – UMIB

Transcrição

Relatório Científico Final 2011-13 – UMIB
Relatório Científico Final 2011-13 – UMIB
Research Group Title: (RG-Norte-215-2560) - Pharmacology and Neurosciences
Principal Investigator: Paulo Jorge Silva Correia Sa
Research Area: Health Sciences
Home Institution: Instituto de Ciências Biomédicas Abel Salazar
Relatório Científico Final 2011-13 – UMIB
Research Group Title: (RG-Norte-215-2560) - Pharmacology and Neurosciences
Principal Investigator: Paulo Jorge Silva Correia Sa
Research Area: Health Sciences
Home Institution: Instituto de Ciências Biomédicas Abel Salazar
Section – Objectives and Achievements
1. Objectives:
The main objective of the Pharmacology and Neurosciences group is to investigate the pathophysiological role of
purines (ATP and its metabolites) in human cells signaling and in animal models of human diseases, searching for new
targets for therapeutic intervention. Considering the group previous findings on basic physiological mechanisms,
ongoing collaborative work with clinical departments of the HGSA-CHPorto, CHVNGaia and the Forensics Institute
(INML Porto) and abroad, has opened new avenues towards translational research projects covering the following
topics:
- The origin and fate of extracellular purines regulating bone formation and neuron-fibroblast interaction using
human cells in culture (Collab. Depart. Orthopedics and Maxillofacial Surgery – HGSA-CHPorto and CHVNGaia) Integrative activities with GCR/UMIB) + 3 PhD students (JBNM, ARP, MC) + 2 FCT Projects (PTDC/SAUOSM/73576/2006, 85,324 € and PTDC/SAU-FCF/108263/2008, 121,764 €).
- The pharmacological aspects of purinergic signaling of overactive human bladders in situ, in vitro and in the
rat in vivo (Collab. Depart. Urology - HGSA-CHPorto) - Integrative activities with GCR/UMIB) + 1 PhD student
(MSR) + 1 FCT Project (PTDC/SAU-OSM/104369/2008, 113,424 €).
- The purinergic modulation of cavernosal vessel tonus in men with vasculogenic erectile dysfunction (Collab.
Depart. Urology – HGSA-CHPorto; Inst. Andrologia (Madrid, Spain); Hosp. Ramon y Cajal (Madrid, Spain) Integrative activities with GCR/UMIB) + 2 PhD students (MF, NL) + 2 Projects (supported by UP / Santander Totta
(3,800 €) and Soc. Port. Andrologia / Lilly (10,000 €).
- - The functional status of the purinergic system and the neuron-glial interaction in patients with pharmacoresistant Mesial Temporal Lobe Epilepsy (Depart. Neurosciences - HGSA, INML and INSA Dr Ricardo Jorge; Fac.
Pharmacy UP) - Integrative activities with IGIA/UMIB + 2 PhD students (ABB, BGL) + 2 FCT Projects
(PIC/IC/83297/2007, 100,000 € and PTDC/SAU-TOX/115597/2009, 109,823€); FCT also funded the Eur. Sci.
Foundation’s EuroEPINOMICS consortium (200,000 €) + 2 projects (supported by Liga Port. Epilepsia (7,500 €) and
by UP / Santander Totta (3,500 €).
- Pathophysiological role of subtype-specific ecto-NTPDases in human diseases (Collab. Centre de Recherche en
Rhumatologie et Immunologie (Jean Sévigny, Laval, Quebec, Canada) + Tasks in 3 FCT Projects (PTDC/SAUOSM/73576/2006, 85,324 €; PTDC/SAU-FCF/108263/2008, 121,764 €; and PTDC/SAU-OSM/104369/2008, 113,424
€).
- Animal-based research studies on the role of purines as potential targets for therapeutic intervention:
- Myasthenic syndromes (Collab. Depart. Neurosciences – HGSA; Univ. Estadual de Maringá (Paraná,
Brasil); UT Southwestern Med. Center (Steven Vernino, Dallas, USA); Weatheral Inst. Mol. Med., John
Radcliffe Hosp. (M. Isabel Leite, Oxford, UK). - Integrative activities with GCR/UMIB) + 2 FCT Projects
(PTDC/SAU-FCF/108462/2008, 103,995 €, and PTDC/NEU-NMC/0237/2012, 143,983€ in collaboration
with ICETA-Porto/UP, UCL-London and REQUIMTE) + 1 Project (supported by UP / Santander Totta
(3,500 €).
- Inflammatory instestinal diseases (Collab. Depart. of General Surgery – HGSA); Nestlé Research Centre
(Lausanne, Switzerland). 2 PhD students (MDA, CV) + 1 FCT Project (PTDC/CVT/74462/2006, 85,894 €) +
1 Project (supported by Univ. Porto / Santander Totta (3,500 €).
- Involvement of purines in heart failure and pulmonary hypertension (Depart. of Physiology – FMUP
(Porto, Portugal) + 1 FCT Project (PTDC/DTP-FTO/0802/2012, 121,792 €).
The group provides an attractive environment, grounded in cutting-edge pieces of equipment, for molecular biology
(e.g. real-time PCR, laser-microdissection system, flow cytometry), life-cell and tissue imaging (e.g. spectral laserscanning confocal microscope), and functional studies (e.g. liquid scintillation counter, electrophysiology equipment,
in vivo experimental setups). Metabolite identification potential was recently upgraded from HPLC to UPLC in
tandem with mass spectrometry. Research capability of the group attracted scientists (e.g. medicinal chemistry and
toxicology from FFUP, biosensors development from FCUP, biomaterials from IST) seeking for collaborative
projects. Such an example is the ongoing collaboration with Professor Augusto Matos (Veterinary Clinics, ICBAS)
regarding the immunocytochemical analysis of putative prognostic factors (e.g. MMP-2, TIMP-2, VEGF, urokinase
plasminogen activation factor) in canine mammary tumors. Two post-docs and one MSc students coming from Brasil
(funded by CAPES and CNPQ) worked at the Pharmacology and Neurosciences group during 2012 and 2013.
2. Main Achievements during 2011-13:
Data using neurochemistry, electrophysiology and real-time videomicroscopy techniques, indicate that retrograde
adenosine release from myasthenic skeletal muscle causes profound changes in the control of neuromuscular
transmission (see e.g. Noronha-Matos et al., 2011). We also gathered information indicating that A2A receptors play a
significant role in train-of-four fade and tetanic failure produced by antinicotinic muscular relaxants (Bornia et al.,
2011; Pereira et al., 2011; 2012; Paula-Ramos et al., 2013). In 2013, we demonstrated for the first time in collaboration
with Brazilian colleagues from UNESP (Botucatu, S. Paulo) that the venom from the snake Bothrops jararacussu
(Bothropstoxin-I) produce neuromuscular blockade due to the reduction of evoked acetylcholine release from
stimulated motor nerve terminals prior to the establishment of the characteristic myonecrosis. This finding may have
significant impact on the therapeutic procedure and fatality of snakebite accidents.
ATP regulates gastrointestinal transit. The relative contribution of ecto-ATPase (forming ADP) and of ecto-NTPDase
(bypassing ADP formation) pathways was tested to probe their role in controlling [3H]ACh release from the myenteric
plexus of the rat ileum (Duarte-Araújo, 2011, PhD Thesis). A model of inflammatory disease in the rat ileum was
successfully implemented in the lab. Using confocal microscopy we demonstrated that inhibitory A1 and excitatory
A2A adenosine receptors are located in different sub-regions of myenteric neurons (Vieira et al., 2011). This must be
taken into consideration for data interpretation regarding the pathophysiological implications of the nucleoside on
intestinal motility/inflammatory disorders.
We provided information showing that cholinergic nerve hyperactivity in patients with outflow bladder obstruction is
associated with decreased hydrolysis of ATP released from urothelium, channeling to the activation of excitatory P2X3
receptors (Silva et al., 2011; Correia, 2011, MSc Thesis). In addition, we demonstrated that urinary ATP may be a
sensitive dynamic biomarker for the diagnosis and follow-up of detrusor overactivity in women with hyperactive
bladder (Silva-Ramos et al., 2013; Silva-Ramos & Correia-de-Sá, 2013). Data from in vivo studies in the anaesthetized
rat showed for the first time that uracil nucleotides (UTP and UDP) cause bladder hyperactivity by indirectly releasing
ATP from the urothelium, via pannexin-1 hemichannels (Timóteo et al., 2013), and subsequent activation of P2X3
receptors on suburothelial nerve afferents. Using in vivo studies, in vitro myographic recordings, neurochemical and
histoenzymatic experiments, and immunofluorescnece confocal microscopy, we demonstrated that bladder overactivity
may be partially counteracted by ATP hydrolysis into ADP by ecto-NTPDases, thereby restraining acetylcholine
release from cholinergic nerve efferents expressing P2Y1 receptors (Timóteo et al., 2014, in press).
ATP is a potent relaxant agent in the human corpus cavernosum (HCC) acting either directly, through P2Y12 receptors
located on endothelium and smooth muscle fibres, or indirectly, via adenosine generated by ecto-nucleotidases.
Relaxation of the HCC by P2 purinoceptor agonists is severely attenuated in erectile dysfunction (ED) patients (Faria,
2011, PhD Thesis). Involvement of the NO/cyclic GMP pathway has also been investigated (e.g. Angulo et al., 2012)
Using single-cell Ca2+ imaging, immunofluorescence confocal microscopy and enzymatic assays, together with
methods to evaluate proliferation and osteogenic differentiation, we demonstrated that uracil nucleotides are important
regulators of osteogenic differentiation of primary bone marrow stromal cells from postmenopausal women (NoronhaMatos et al., 2012). Endogenous actions of uracil nucleotides, via UDP-sensitive P2Y6 receptors, are balanced through
specific ecto-NTPDases determining whether osteoblast progenitors are driven into proliferation or differentiation
(Noronha-Matos et al., 2012). Our findings also indicate that adenosine derived from ATP hydrolysis is an important
regulator of osteogenic cell differentiation predominantly through the activation of A2B receptors (Costa et al., 2011).
Recently, we showed that human and rodent fibroblasts act as inflammatory sensors (e.g. to bradikinin and histamine)
and mechano-sensory intermediates between epithelia and primary afferent neurons by releasing purines in a Ca2+dependent manner (Certal, 2011, MSc Thesis). We, therefore, hypothesized that fibroblasts may amplify purinergic
signaling between neighboring cells (e.g. sensory neurons) under painful situations (Pinheiro et al, 2013a and 2013b).
Adenosine is considered an endogenous anti-convulsing agent, because of its neuromodulation effect regulating brain
excitability via widespread inhibitory A1 receptor. At restricted synapses (e.g. hippocampus) adenosine may act on colocalized facilitatory A2A receptors. Data from our group demonstrate that increased adenosine A2A and decreased A1
receptors expression in the hippocampus and adjacent neocortex from patients with mesial temporal lobe epilepsy
(MTLE) shifts adenosine modulation towards excitability. The mechanism by which adenosine promotes neuronal
excitability may involve Ca2+ influx via VOCC and/or changes in the control of high-affinity GABA and glutamate
transport assignment dedicated to terminate neurotransmission and control synaptic excitability (Barros-Barbosa, 2011,
MSc Thesis).
Concomitantly, a series of high-significant clinical research papers have been produced by members of the research
team in collaboration with other groups, working namely in Urology and Neuropathology fields.
Section – Activities
1. Integrative/multidisciplinary activities in 2011-13. Special activities that aim to carry out research
across disciplines.
Ongoing collaborative work with clinical departments of the HGSA-CHPorto, CHVNGaia and the Forensics Institute
(INML Porto) and abroad, has opened new avenues towards translational research projects. In addition, efforts have
been made to integrate multidisciplinary activities from various groups of UMIB (e.g. Clinical Research Group - CRG,
ImmunoGenetics, Inflammation and Auto-immunity Group - IGIA) within the translational framework created by the
Pharmacology and Neurosciences Group. Examples of these interactions are as follows (see also Objectives):
- The origin and fate of extracellular purines regulating bone formation and neuron-fibroblast interaction using human
cells in culture - Integrative activities with CRG/UMIB).
- The pharmacological aspects of purinergic signaling of overactive human bladders in situ, in vitro and in the rat in
vivo - Integrative activities with CRG/UMIB).
- The purinergic modulation of cavernosal vessel tonus in men with vasculogenic erectile dysfunction - Integrative
activities with CRG/UMIB).
- The functional status of the purinergic system and the neuron-glial interaction in patients with pharmaco-resistant
Mesial Temporal Lobe Epilepsy - Integrative activities with IGIA/UMIB.
- Animal-based research studies on the role of purines as potential targets for therapeutic intervention: a) Myasthenic
syndromes - Integrative activities with CRG/UMIB.
2. Outreach activities during 2011-13. Science and Society/general public/schools, etc.
Undergraduates and students from high schools around Porto city visit the Group of Pharmacology and Neurosciences
at UMIB/ICBAS/UP on a regular basis. During these visits, students and their tutors are offered simple explanations
about the scientific projects undergoing in the lab and how can these be clinically relevant. Concerning the students’
interests, they can follow complete experiments upon appointment. The PI often participates in radio and TV
broadcasting debates on the topic of his research. In addition, the University of Porto and affiliated research centres
dedicates an open week to public at large; the PI of this group took on his own the responsibility of organizing last
year´s show on Biomedical Research and the activities of the International Brain Awareness Week (Portuguese
Society for Neuroscience, on behalf of the Dana Farber Foundation) taking place at UMIB/ICBAS/UP.
Section – Funding
3. In this section include funding details during the reporting period.
Units FCT:
Apresentar o total do financiamento recebido pela FCT (ex: projetos de ICDT, Redes Temáticas,
etc.), excluindo o financiamento apresentado no ponto anterior.
- Eur. Sci. Foundation – EuroEPINOMICS, aiming at identifying novel epilepsy genes and genetic variants predisposing
to epilepsy and drug response (FCT, 200,000 €)
Projects FCT:
Apresentar o total do financiamento recebido directamente pelos projectos financiados pela FCT, a
funcionar no âmbito do Laboratório/Unidade
- P. Correia-de-Sá et al. (2007-10) Enteric purines as potential therapeutic targets for inflammatory bowel diseases. FCT,
PTDC/CVT/74462/2006 (85,894 €).
- P. Correia-de-Sá et al. (2007-10) Origin and fate of extacellular purines regulating human bone formation. FCT,
PTDC/SAU-OSM/73576/2006 (85,324 €).
- C. Pereira & P. Correia-de-Sá (2007-10) Biosensors for endogenous catecholamines. FCT, PTDC/QUI/69685/2006
(93,300 €).
- M. Berta Silva & M.G.B. Lobo (2008-11) The relevance of HHV-6B in patients with Mesial Temporal Lobe
Epilepsy...... FCT, PIC/IC/83297/2007 (100,000 €).
- P. Correia-de-Sá et al. (2010-12) Pathophysiological role of purines (ATP and adenosine) in the human bladder
hyperactivity. FCT, PTDC/SAU-OSM/104369/2008 (113,424 €).
- P. Correia-de-Sá et al. (2010-12) Fibroblasts as mechano-sensory signalling intermediates between epithelia and primary
afferent neurons…FCT, PTDC/SAU-FCF/108263/2008 (121,764 €).
- Laura Oliveira & P. Correia-de-Sá (2010-12) Is there a place for adenosine mediating impairment of both neuromuscular
and immunological synapses in myasthenics? FCT, PTDC/SAU-FCF/108462/2008 (103,995 €).
- Glória Queiroz & P. Correia-de-Sá (2010-12) Astrocyte-microglia crosstalk in astrogliosis: modulation by P2 receptors.
FCT, PTDC/SAU-TOX/115597/2009 (109,823€).
- Ana Patrícia Fontes Sousa & P. Correia-de-Sá (2013-15) On the role of adenosine signalling in the progression of
pulmonary hypertension to heart failure. FCT, PTDC/DTP-FTO/0802/2012 (121,792€).
- Jorge Oliveira & P. Correia-de-Sá (2013-15) KDAC inhibition and intracellular dynamics: impact on neuronal
development, survival and transmission. FCT, PTDC/NEU-NMC/0237/2012 (143,983€).
Other (National):
Apresentar o total dos financiamentos recebidos de fontes nacionais que não provenham da FCT
- R. Rangel, M. Berta Silva, P. Correia-de-Sá & M.G.B. Lobo (2009-10) Actividade da ADK, ADA e NTPDases sobre os
níveis de adenosina endógena no hipocampo e córtex temporal de doentes com MTLE. Supported by Liga Port. Epilepsia
(7,500 €).
- P. Correia-de-Sá et al. (2009-10) Papel dos receptors da adenosina no crescimento e remodelação dos vasos cavernosos
humanos: Repercussão na fisiopatologia da disfunção eréctil vasculogénica. Supported by Univ. Porto / Santander Totta
(3,800 €).
- P. Correia-de-Sá et al. (2010-11) Toxin-induced myasthenia gravis and in vitro assays to characterize neuromuscular
impairment…. Supported by Univ. Porto / Santander Totta (3,500 €).
- Fátima Ferreirinha et al. (2010-11) Sinalização purinérgica numa nova sinapse mioentérica tripartida: relevância
funcional. Supported by Univ. Porto / Santander Totta (3,500 €).
- João Miguel Cordeiro et al. (2010-11) A adenosina na modulação do transporte de GABA e de glutamato em doentes
com MTLE. Supported by Univ. Porto / Santander Totta (3,500 €).
Other (International):
Apresentar o total dos financiamentos recebidos de outras fontes internacionais
N/a
National Industry:
Apresentar o total dos financiamentos diretamente provenientes da industria nacional
- N Louro & P. Correia-de-Sá et al. (2008-10) Purinergic signaling in the human corpus cavernosum as a therapeutic
target for vasculogenic erectile dysfunction. Supported by Soc. Port. Andrologia / Lilly (10,000 €).
International Industry:
Apresentar a soma dos financiamentos diretamente provenientes da industria internacional
N/a
Section – General Indicators
This section is designed to provide information regarding the researchers and the technical
personnel hired, and the total number of completed PhDs thesis during the reported period.
Composition and Training
In this section indicate the number of researchers hired through the Ciência Programme,
during the reporting period. Include also the total number of integrated Researchers with PhD
and the PhD thesis completed in the period.
No. of Researchers Hired (Ciência Programme):
(Apresentar o número total de doutorados contratados no âmbito do Programa Ciência durante
o ano a que respeita o Relatório):
0
No. of Researchers integrated with PhD(Apresentar o número total de membros da equipa
doutorados integrados):
17
Training PhDs (PhD thesis completed) (Apresentar o número total de teses de
doutoramento concluídas, com a orientação de membros integrados na equipa do respectivo
Laboratório/Unidade): 3
Researchers Hired
In this section indicate the individual researchers hired in the period by introducing the
association key (previously named as public key), their starting date and if applicable their
finishing date. In case the researchers also hold a part-time position at another institution
(teaching at University or Polytechnic) also indicate this in Other Institution.
Chave de
Associação*
Data de início do contrato
(dd-mm-aaaa)
Data de fim do contrato
(dd-mm-aaaa)
Outra
Instituição**
* Introduzir a chave de associação do investigador contratado pelo Programa Plurianual, pelo Projeto Estratégico ou
ainda pelo Programa Ciência. Após inserção da mesma aparece o seu nome para confirmação. Os contratos de bolsas
não devem ser considerados neste ponto.
** Caso o contrato seja celebrado com outra instituição que não seja a FCT, apresentar a sua designação
Technical Personnel Hired
In this section indicate individual technical personal hired. To do so all personal must be registered at
the FCT and have an association key.
Chave de
Associação*
Data de início do contrato
(dd-mm-aaaa)
Data de fim do contrato
(dd-mm-aaaa)
Outra
Instituição**
* Introduzir a chave de associação do investigador contratado pelo Programa Plurianual, pelo Projeto Estratégico ou
ainda pelo Programa Ciência. Após inserção da mesma aparece o seu nome para confirmação. Os contratos de bolsas
não devem ser considerados neste ponto.
** Caso o contrato seja celebrado com outra instituição que não seja a FCT, apresentar a sua designação
Additional Comments:
In this space you can provide any additional information regarding the
Section General Indicators.
Section – Group Productivity
PRODUCTIVITY (Adicionar items)
1. Publications in peer review Journals
1.
2.
3.
4.
5.
6.
7.
8.
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11.
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13.
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15.
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17.
18.
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20.
Costa MA, Barbosa A, Neto E, Sá-e-Sousa A, Freitas R, Neves JM, Magalhães-Cardoso T,
Ferreirinha F, Correia-de-Sá P. On the role of subtype selective adenosine receptor agonists during proliferation
and osteogenic differentiation of human primary bone marrow stromal cells. J. Cell. Physiol. (2011) 226, 13531366.
Noronha-Matos JB, Morais T, Trigo D, Timóteo MA, Magalhães-Cardoso MT, Oliveira L, Correiade-Sá P. Tetanic failure due to decreased endogenous adenosine A2A tonus operating neuronal Cav1 (L-type) influx
in Myasthenia gravis. J. Neurochem. (2011) 117, 797-811.
Bornia EC, Correia-de-Sá P, Alves-Do-Prado W. Presynaptic facilitatory A2A receptors mediate fade
induced by neuromuscular relaxants that exhibit anticholinesterase activity.Clin. Exp. Pharmacol. Physiol. (2011)
38, 164-169.
Pereira MW, Bornia ECS, Correia-de-Sá P, Alves-Do-Prado, W. Presynaptic muscarinic and
adenosine receptors involved in 2 Hz-induced train-of-four fade caused by antinicotinic neuromuscular relaxants in
the rat. Clin. Exp. Pharmacol. Physiol. (2011) 38, 764-770.
Cordeiro JM, Gonçalves PP, Dunant Y. Synaptic vesicles control the time course of neurotransmitter
secretion via a Ca²+/H+ antiport. J. Physiol. (London) (2011) 589, 149-167.
Vieira C, Ferreirinha F, Silva I, Duarte-Araújo M, Correia-de-Sá P. Localization and function of
adenosine receptor subtypes at the longitudinal muscle – myenteric plexus of the rat ileum. Neurochem. Int. (2011)
59, 1043-1055.
Falcao-Pires I, Fontes-Sousa AP, Lopes-Conceiçao L, Brás-Silva C, Leite-Moreira AF. Modulation of
myocardial stiffness by beta-adrenergic stimulation - its role in normal and failing heart. Physiol Res. (2011) 60,
599-609.
Lopes-Conceição L, Dias-Neto M, Fontes-Sousa AP, Mendes-Ferreira P, Maia-Rocha C, HenriquesCoelho T, de Keulenaer G, Leite Moreira AF, Brás-Silva C. Neuregulin1/ErbB system: importance in the control of
cardiovascular function. Acta Med Port (2011) 24 Suppl 4:1009-20.
Munz MR, Faria MA, Monteiro JR, Aguas AP, Amorim MJ. Surgical porcine myocardial infarction
model through permanent coronary occlusion. Comp Med. (2011) 61, 445-452.
Taipa R, Martins da Silva A, Santos E, Pinto PS, Melo-Pires M. Gliomatosis cerebri diagnostic
challenge: two case reports. Neurologist (2011) 17, 269-272.
Pinto PS, Taipa R, Moreira B, Correia C, Melo-Pires M. Acute hemorrhagic leukoencephalitis with
severe brainstem and spinal cord involvement: MRI features with neuropathological confirmation. J Magn Reson
Imaging. (2011) 33, 957-961.
Cavadas V, Branco F, Carvalho FL, Osório L, Gomes MJ, Silva-Ramos M. The quality of reporting of randomized
controlled trials in pelvic organ prolapse. Int Urogynecol J. (2011) 22, 1117-1125.
Osório L, Carvalho FL, Branco F, Cavadas V, Autorino R, Soares J. Endoscopic removal of an intravesical
calcified sling using pneumatic lithotripsy and cystoscopic resection. Urol Int. (2011) 87, 489-491.
Branco F, Cavadas V, Osório L, Carvalho F, Martins L, Dias L, Castro-Henriques A, Lima E. The incidence of
cancer and potential role of sirolimus immunosuppression conversion on mortality among a single-center renal
transplantation cohort of 1,816 patients. Transplant Proc. (2011) 43, 137-141.
Branco F, Pini G, Osório L, Cavadas V, Versos R, Gomes M, Autorino R, Correia-Pinto J, Lima E. Transvesical
peritoneoscopy with rigid scope: feasibility study in human male cadaver. Surg Endosc. (2011) 25, 2015-2019.
Perdonà S, Cavadas V, Di Lorenzo G, Damiano R, Chiappetta G, Del Prete P, Franco R, Azzarito G, Scala S, Arra
C, De Sio M, Autorino R. Prostate cancer detection in the "grey area" of prostate-specific antigen below 10 ng/ml:
head-to-head comparison of the updated PCPT calculator and Chun's nomogram, two risk estimators incorporating
prostate cancer antigen 3. Eur Urol. (2011) 59, 81-87.
de Oliveira JT, de Matos AJ, Santos AL, Pinto R, Gomes J, Hespanhol V, Chammas R, Manninen A, Bernardes
ES, Albuquerque Reis C, Rutteman G, Gärtner F. Sialylation regulates galectin-3/ligand interplay during
mammary tumour progression--a case of targeted uncloaking. Int J Dev Biol. (2011) 55, 823-834.
Ferreira RR, Gopegui RR, Matos AJ. Frequency of dog erythrocyte antigen 1.1 expression in dogs from Portugal.
Vet Clin Pathol.(2011) 40, 198-201.
Santos A, Lopes C, Marques RM, Amorim I, Ribeiro J, Frias C, Vicente C, Gärtner F, de Matos A.
Immunohistochemical analysis of urokinase plasminogen activator and its prognostic value in canine mammary
tumours. Vet J. (2011) 189, 43-48.
Santos A, Lopes C, Frias C, Amorim I, Vicente C, Gärtner F, Matos A. Immunohistochemical evaluation of
MMP-2 and TIMP-2 in canine mammary tumours: a survival study. Vet J. (2011) 190, 396-402.
21. Noronha-Matos JB, Costa MA, Magalhães-Cardoso MT, Ferreirinha F, Freitas R, Neves JM, Sévigny J, Correiade-Sá P. Role of ecto-NTPDases on UDP-sensitive P2Y6 receptor activation during osteogenic differentiation of
primary bone marrow stromal cells from postmenopausal women. J. Cell. Physiol. (2012) 227:2694-2709.
22. Fernandes C§, Oliveira L§, Tiritan ME, Leitao L, Pozzi A, Noronha-Matos JB, Correia-de-Sá P, Pinto M.
Synthesis of new chiral xanthone derivatives acting as nerve conduction blockers in the rat sciatic nerve. Eur. J.
Med. Chem. (2012) 55:1-11.
23. Pereira MW, Correia-de-Sá P, Alves-Do-Prado W. Adenosine A2A receptor antagonists are broad facilitators of
antinicotinic neuromuscular blockade monitored either with 2-Hz train-of-four or 50-Hz tetanic stimuli. Clin. Exp.
Pharmacol. Physiol. (2012) 39:869-877.
24. Correia-de-Sá P, Noronha-Matos JB, Timóteo MA, Ferreirinha F, Marques P, Soares AM, Carvalho C, Cavalcante
WLG, Gallacci M. Bothropstoxin-I reduces evoked acetylcholine release from rat motor nerve terminals:
radiochemical
and
real-time
video-microscopy
studies.
Toxicon
(2013)
61:16-25,
http://dx.doi.org/10.1016/j.toxicon.2012.10.014.
25. Silva R, Carmo H, Vilas-Boas V, Guedes de Pinho P, Dinis-Oliveira R, Carvalho F, Silva I, Correia-de-Sá P,
Bastos ML, Remião F. Doxorubicin decreases paraquat accumulation and toxicity in Caco-2 cells. Toxicol. Lett.
(2013) 217:34-41, http://dx.doi.org/10.1016/j.toxlet2012.11.028.
26. Matos AJ, Baptista CS, Gärtner MF, Rutteman GR. Prognostic studies of canine and feline mammary tumours:
The need for standardized procedures. Vet J.(2012) [Epub ahead of print].
27. Angulo J, Cuevas P, Fernández A, La Fuente JM, Allona A, Moncada I, Sáenz de Tejada I. Tadalafil enhances the
inhibitory effects of tamsulosin on neurogenic contractions of human prostate and bladder neck. J Sex Med. (2012)
9:2293-306. doi: 10.1111/j.1743-6109.2012.02821.x.
28. Munz M, Amorim MJ, Faria M, Vicente C, Pinto A, Monteiro J, Leite-Moreira AF, Aguas AP. Cardiac venous
arterialization in acute myocardial infarction: how great is the benefit? Interact Cardiovasc Thorac Surg. (2012)
30 [Epub ahead of print].
29. Bettencourt A, Martins da Silva A, Pinho E Costa P, Martins Silva B. Molecular genetic studies of multiple
sclerosis in the portuguese population. Acta Med Port. (2012) 25:224-30.
30. Coelho T, Maia LF, Martins da Silva A, Waddington Cruz M, Planté-Bordeneuve V, Lozeron P, Suhr OB,
Campistol JM, Conceição IM, Schmidt HH, Trigo P, Kelly JW, Labaudinière R, Chan J, Packman J, Wilson A,
Grogan DR. Tafamidis for transthyretin familial amyloid polyneuropathy: a randomized, controlled trial.
Neurology. (2012) 79:785-92. doi: 10.1212/WNL.0b013e3182661eb1.
31. Gomes MJ, Martins da Silva A, Salinas J, Silva MC, Figueiredo A, Cavadas V, Coelho T. Female sexual and
pelvic floor muscles dysfunctions in familial amyloidotic polyneuropathy (FAP-Portuguese type). Arch Esp Urol.
(2012) 65:476-88.
32. Cavaco S, Martins da Silva A, Santos E, Coutinho E, Marinho A, Moreira I, Gonçalves A, Pinto C, Teixeira-Pinto
A, Vasconcelos C. Are cognitive and olfactory dysfunctions in neuropsychiatric lupus erythematosus dependent
on anxiety or depression? J Rheumatol. (2012) 39:770-6. doi: 10.3899/jrheum.110574.
33. Da Silva AM, Willmore LJ. Posttraumatic epilepsy. Handb Clin Neurol. (2012) 108:585-99. doi: 10.1016/B978-0444-52899-5.00017-4.
34. Leite MI, Coutinho E, Lana-Peixoto M, Apostolos S, Waters P, Sato D, Melamud L, Marta M, Graham A,
Spillane J, Villa AM, Callegaro D, Santos E, da Silva AM, Jarius S, Howard R, Nakashima I, Giovannoni G,
Buckley C, Hilton-Jones D, Vincent A, Palace J. Myasthenia gravis and neuromyelitis optica spectrum disorder: a
multicenter study of 16 patients. Neurology. (2012) 78:1601-7. doi: 10.1212/WNL.0b013e31825644ff.
35. Da Silva AM, Willmore LJ. Posttraumatic epilepsy. Handb Clin Neurol. (2012) 108:585-99. doi: 10.1016/B978-0444-52899-5.00017-4.
36. Kasteleijn-Nolst Trenité D, Rubboli G, Hirsch E, Martins da Silva A, Seri S, Wilkins A, Parra J, Covanis A, Elia
M, Capovilla G, Stephani U, Harding G. Methodology of photic stimulation revisited: updated European algorithm
for visual stimulation in the EEG laboratory. Epilepsia. (2012) 53:16-24. doi: 10.1111/j.1528-1167.2011.03319.x.
37. Cruto C, Taipa R, Monteiro C, Moreira I, Melo-Pires M, Correia M. Multiple cerebral infarcts and intravascular
central nervous system lymphoma: A rare but potentially treatable association. J Neurol Sci. (2013) 325:183-5.
doi: 10.1016/j.jns.2012.10.012.
38. Taipa R, Pinho J, Melo-Pires M. Clinico-pathological correlations of the most common neurodegenerative
dementias. Front Neurol. (2012) 3:68. doi: 10.3389/fneur.2012.00068.
39. Taipa R, Tuna A, Damásio J, Pinto PS, Cavaco S, Pereira S, Milterberger-Miltenyi G, Galimberti D, Melo-Pires
M. Clinical, neuropathological, and genetic characteristics of the novel IVS9+1delG GRN mutation in a patient
with frontotemporal dementia. J Alzheimers Dis. (2012) 30:83-90. doi: 10.3233/JAD-2012-112084.
40. Silva-Ramos M, Louro N, Versos R, Cavadas V, Marcelo F. Does 3D Ultrasound Enhance the Diagnosis of
Bladder Tumours in Patients with Haematuria? ISRN Urol. (2012) 2012:158437. doi: 10.5402/2012/158437.
41. Oliveira A, Neto A, Almeida C, Silva-Ramos M, Versos R, Barros A, Sousa M, Carvalho F. Comparative study of
gene expression in patients with varicocele by microarray technology. Andrologia (2012) 44 Suppl 1:260-5. doi:
10.1111/j.1439-0272.2011.01173.x.
42. Figueira AC, Teodósio AS, Carvalheira J, Lacerda M, de Matos A, Gärtner F. P-cadherin expression in feline
mammary tissues. Vet Med Int. (2012) 2012:687424. doi: 10.1155/2012/687424.
43. Santos AA, Lopes CC, Marques RM, Amorim IF, Gärtner MF, de Matos AJ. Matrix metalloproteinase-9
expression in mammary gland tumors in dogs and its relationship with prognostic factors and patient outcome. Am
J Vet Res. (2012) 73:689-97. doi: 10.2460/ajvr.73.5.689.
44. Silva-Ramos M, SilvaI, Oliveira O, Ferreira S, Reis MJ, Oliveira JC, Correia-de-Sá P. Urinary ATP may be a
dynamic biomarker of detrusor overactivity in women with overactive bladder syndrome. PLoS ONE (2013) 8,
e64696. doi:10.1371/journal.pone.0064696.
45. Pinheiro AR, Paramos-de-Carvalho D, Certal M, Costa MA, Costa AC, Magalhães-Cardoso MT, Ferreirinha F,
Sévigny J, Correia-de-Sá P. Histamine induces ATP release from human subcutaneous fibroblasts, via pannexin-1
hemichannels, leading to Ca2+ mobilization and cell proliferation. J. Biol. Chem. (2013) 288, 27571–27583. doi:
10.1074/jbc.M113.460865.
46. Pinheiro AR, Paramos-de-Carvalho D, Certal M, Costa AC, Magalhães-Cardoso MT, Costa MA, Correia-de-Sá P.
Bradykinin Ca2+ signaling in human subcutaneous fibroblasts involves ATP release via hemichannels and P2Y12
receptors activation. Cell Commun. Signal. (2013) 11, 70. doi:10.1186/1478-811X-11-70.
47. Paula-Ramos E, Antônio MB, Ambiel CR, Correia-de-Sá P, Alves-do-Prado W. Paradoxical neostigmine-induced
TOFfade: on the role of presynaptic cholinergic and adenosine receptors. Eur. J. Pharmacol. (2013, in press).
doi:pii: S0014-2999(13)00845-5. 10.1016/j.ejphar.2013.11.001.
48. Silva-Ramos M, Correia-de-Sá P. For women with overactive bladder syndrome, urinary ATP may be a dynamic
biomarker of detrusor overactivity. UroToday "Beyond the Abstract" (2013) Commentary published on 08
November 2013 in UroToday.com.
49. Timóteo MA, Carneiro I, Silva I, Noronha-Matos JB, Ferreirinha F, Silva-Ramos M, Correia-de-Sá P. ATP
released via pannexin-1 hemichannels mediates bladder overactivity triggered by urothelial P2Y6 receptors.
Biochem. Pharmacol. (2013, in press). doi:pii: S0006-2952(13)00738-7. 10.1016/j.bcp.2013.11.007.
50. Carneiro I, Timóteo MA, Silva I, Vieira C, Baldaia C, Ferreirinha F, Silva-Ramos M, Correia-de-Sá P. Activation
of P2Y6 receptors causes bladder overactivity in the anaesthetized rat by releasing ATP from the urothelium. Br. J.
Pharmacol. (2013, submitted 2013-BJP-0849-RP)
51. Oliveira-Monteiro N, Bragança B, Ferreirinha F, Faria M, Fontes-Sousa AP, Correia-de-Sá P. Rationale for
understanding chronoselectivity of adenosine A1 receptor in the rat spontaneously beating atria: enrolment of KCa2
(SK) and Cav1 (L-type) ion channels. Am. J. Physiol. (Heart Circ. Physiol.) (2012, submitted H-00711-2012)
2. Other publications
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
M.J. Valente, R. Amorim, R. Viais, M. Faria, J.-M. LaFuente-de-Carvalho & P. Correia-de-Sá.
Comparação dos efeitos da adenosine e de outros agents relaxantes dependentes do endotélio no tecido
cavernoso humano e de rato. Acta Urológica (2011) 28 (Suppl 1), C179, 26.
S. Ferreira, I. Silva, O. Oliveira, M. Duarte-Araújo, J.C. Oliveira, F. Bravo, M. Silva-Ramos & P.
Correia-de-Sá. Poderá o ATP urinário desempenhar um papel como biomarcador da bexiga hiperactiva? Acta
Urológica (2011) 28 (Suppl 1), C194, 33.
L. Oliveira, D. Trigo, T. Morais, A. Sá-e-Sousa, C. Costa, M.T. Magalhães-Cardoso, M.A. Timóteo & P.
Correia-de-Sá. Retrograde signalling by adenosine is impaired in toxin-induced Myasthenia gravis: cross-talk
with excitatory nicotinic α3β2 and muscarinic M1 autoreceptors. J. Neurochemistry (2011).
P. Marques, I. Silva, C. Vieira, F. Ferreirinha, T. Magalhães-Cardoso, M. Duarte-Araújo & P. Correia-deSá. Interstitial Cells of Cajal control cholinergic neurotransmission in the tripartite myenteric synapse by
releasing adenosine. J. Neurochemistry (2011).
A. Alves, F. Nascimento, P. Correia-de-Sá & J.M. Cordeiro. Presynaptic nicotinic autoreceptors outlying
release sites facilitate cholinergic neurotransmission in the Torpedo electric organ. J. Neurochemistry (2011).
I. Silva, J. Correia, F. Ferreirrinha, M.T. Magalhães-Cardoso, M. Silva-Ramos, J. Sévigny & P. Correiade-Sá. Bladder overactivity due to global impairment of ecto-NTPDases in humans with lower urifnary tract
disorders exhibiting unbalanced ATP / adenosine formation. Autonomic Neuroscience: Basic & Clinical
(2011) 163:1-2, P.023, 49-50 & Clinical Autonomic Research (2011) 21:4, P.023, 227.
I. Silva, P. Marques, C. Vieira, F. Ferreirrinha, M.T. Magalhães-Cardoso, M. Duarte-Araújo & P.
Correia-de-Sá. Amplification of cholinergic neurotransmission by adenosine released from interstitial Cells of
Cajal at a tripartite myenteric synapse of the rat ileum Autonomic Neuroscience: Basic & Clinical (2011)
163:1-2, P.063, 64-65 & Clinical Autonomic Research (2011) 21:4, P.063, 242.
A.R. Pinheiro, C. Costa, C. Soares, M.T. Magalhães-Cardoso, M.A. Costa & P. Correia-de-Sá. Kinetics
of the extracellular catabolism of adenine nucleotides by fibroblasts of the human subcutaneous connective
tissue. Purinergic Signalling (2012) 8, PS4.2, p. 160.
C. Costa, D. Meireles, M. Viegas, D. Paramos, M.A. Timóteo, M.T. Magalhães-Cardoso, L. Oliveira &
P. Correia-de-Sá. Inhibition of adenosine deaminase (ADA) overactivity failed to restore neuromuscular
transmission failure in rats with toxin-induced Myasthenia gravis. Purinergic Signalling (2012) 8, PS4.11, p.
165.
N. Oliveira-Monteiro, A.P. Fontes-Sousa, B. Bragança, S. Marques, M. Faria & P. Correia-de-Sá. Cav1
(L) channel blockade uncovers adenosine negative inotropism leading to a loss of A1 “chronoselectivity” in
the spontaneously beating rat atria. Purinergic Signalling (2012) 8, PS6.3, p. 171.
P. Marques, I. Silva, C. Vieira, M. Duarte-Araújo, F. Ferreirinha, T. Magalhães-Cardoso & P. Correia-deSá. M3- and NK1-receptor facilitation of [3H]-acetylcholine release from myenteric motoneurons depends on
extracellular adenosine accumulation acting on prejunctional A2A receptors. Neurogastroenterol. Motil. (2012)
24 (Suppl. 2) P006, 44.
C. Vieira, J. Oliveira, P. Marques, T. Magalhães-Cardoso, M. Duarte-Araújo & P. Correia-de-Sá.
Impairement of the adenosine fine-tuning control of acetylcholine release from myenteric motoneurons in the
inflamed rat ileum. Neurogastroenterol. Motil. (2012) 24 (Suppl. 2) P087, 67.
M. Duarte-Araújo, P. Marques, C. Vieira, I. Silva, T. Magalhães-Cardoso & P. Correia-de-Sá. Adenosine
modulates its own release throught activation of A2A receptors on myenteric cholinergic nerve terminals of the
rat ileum. Neurogastroenterol. Motil. (2012) 24 (Suppl. 2): P375, 152.
C Rocha-Pereira, JB Sousa, P Fresco, J Gonçalves, SM Arribas, MC González, F Ferreirinha, P Correiade-Sá & C Diniz. Less efficient prejunctional adenosine receptor-mediated inhibitory effects in mesenteric
vessels of spontaneously hypertensive rats (SHR). Proceedings of the British Pharmacological Society (2012)
10 (Issue 3): P092, 282 (http://www.pA2online.org/abstracts/Vol10Issue3abst282P.pdf).
D Paramos, AR Pinheiro, F Ferreirinha, MA Costa & P Correia-de-Sá. Interplay between P2X7 and
P2Y1 receptors controls intracellular [Ca2+] signals in fibroblasts of the human subcutaneous connective
tissue. Proceedings of the British Pharmacological Society (2012) 10 (Issue 3): P426, 327
(http://www.pA2online.org/abstracts/Vol10Issue3abst327P.pdf).
JB Noronha-Matos, A Sá-e-Sousa, J Coimbra, S Gomes, R Rocha, J Marinhas, R Freitas, J MoraisNeves, MA Costa & P Correia-de-Sá. The P2X7 receptor may be a novel therapeutic target to promote
osteogenic differentiation and mineralization of postmenopausal bone marrow stromal cells. Proceedings of the
British
Pharmacological
Society
(2012)
10
(Issue
3):
P418,
242
(http://www.pA2online.org/abstracts/Vol10Issue3abst242P.pdf).
M. Faria, J.-M. LaFuente-de-Carvalho & P. Correia-de-Sá. Thromboxane A2 release from the endothelium
mediates transient P2 purinoceptor-induced contractions of the human corpus cavernosum. Proceedings of the
British
Pharmacological
Society
(2012)
10
(Issue
3):
P511,
563
(http://www.pA2online.org/abstracts/Vol10Issue3abst563P.pdf).
18. AR Pinheiro, M Certal, D Paramos, MA Costa & P Correia-de-Sá. Bradykinin activation of fibroblasts of the
rat subcutaneous tissue triggers the release of ATP and P2 purinoceptors activation. Journal of Bodywork and
Movement Therapies (Fascia Science and Clinical Applications) (2012) 16 (Issue 2): 155-156
[DOI:10.1016/j.jbmt.2012.01.069].
19. M.G. Lobo, C. Teixeira, M. Mendes, S. Guerra-Gomes, F. Ferreirinha, A. Santos, R. Rangel, J.M. Cordeiro &
P. Correia-de-Sá. A alteração do tonus entre receptors inibitórios A1 e excitatórios A2A da adenosina explica a
acumulação de Ca2+ pelos terminais nervosos isolados de deontes com epilepsia do lobo mesial temporal
(MTLE). Sinapse (2013) 13 in press.
20. A. Barros-barbosa, S. Guerra-Gomes, F. Ferreirinha, M.T. Magalhães-Cardoso, M.G. Lobo, A. Santos, R.
Rangel & P. Correia-de-Sá. Papel dos purinoceptores na modulação do transporte de GABA e de glutamato em
doentes com epilepsia do lobo mesial temporal (MTLE) resistente a fármacos. Sinapse (2013) 13 in press.
21. P. Correia-de-Sá, A. Barros-Barbosa, S. Guerra-Gomes, M. Mendes, F. Ferreirinha, M.T. Magalhães-Cardoso,
M.G. Lobo & J.M. Cordeiro. Fine-tuning modulation of GABA and glutamate uptake by purinoceptors in the
human epileptic neocortex. J. Neurochem. (2013), 125 (Suppl. 1), 259.
22. I. Silva, J. Correia, F. Ferreirinha, M. Silva-Ramos, J. Sévigny & P. Correia-de-Sá. P2Y6-induced release of
ATP from the urothelium exerts a dual role in the human urinary bladder. FEBS Journal (2013) 280 (Suppl. 1),
1742-464.
23. M. Silva-Ramos*, I. Silva1*, O. Oliveira, S. Ferreira, M.J. Reis, J.C. Oliveira & P. Correia-de-Sá. Overactive
bladder syndrome: Evidence that urinary ATP is a dynamic biomarker of detrusor overactivity. Autonomic
Neuroscience: Basic & Clinical (2013) 177 (Issue 1), 21-22.
24. I. Silva, M.A. Timóteo, J. Correia, F. Ferreirinha, M. Silva-Ramos, J. Sévigny & P. Correia-de-Sá. Dual role of
P2Y6 receptors in the human urinary bladder: on the role of ATP released from the urothelium. Autonomic
Neuroscience: Basic & Clinical (2013) 177 (Issue 1), 21-22.
25. C. Vieira, F. Ferreirinha, M.T. Magalhães-Cardoso, J. Oliveira, P. Marques, M. Duarte-Araújo & P. Correiade-Sá. Changes in the fine-tuning adenosine control of acetylcholine release from myenteric motoneurons in
TNBS-inflamed rat ileum. Autonomic Neuroscience: Basic & Clinical (2013) 177 (Issue 1), 21-22.
3. Other national publications
1. J.M. Cordeiro & P. Correia-de-Sá. Acetilcolina. In Neurociências (2011). Eds. C. Rego, C. Duarte &
C. Oliveira, LIDEL - Edições Técnicas, Lda – Lisboa.
2. J-M LaFuente de Carvalho & N. Louro. Disfunção eréctil na Diabetes mellitus 2 (2012). LIDEL Edições Técnicas, Lda – Lisboa.
3. P. Correia-de-Sá. Sistema colinérgico. In Terapêutica Medicamentosa e suas Bases Farmacológicas
(2013). Eds. S. Guimarães, D. Moura & P. Soares da Silva, 6ª Edição, Porto Editora – Porto (in
press).
4. Master and Ph.D. thesis completed
PhD Thesis completed:
1.
2.
3.
Margarida Duarte Cerqueira Martins de Araújo (2011). Endogenous purines as potential pharmacological targets
to control myenteric neurotransmission. PhD in Biomedical Sciences (supervised by P. Correia-de-Sá). Instituto de
Ciências Biomédicas de Abel Salazar – Universidade do Porto. Supported by FCT (SFRH/BD/29044/2006).
Miguel Augusto Soucasaux Marques Faria (2011). Purinergic regulation of human corpus cavernosum tonus in
patients with vasculogenic erectile dysfunction. PhD in Biomedical Sciences (supervised by P. Correia-de-Sá).
Instituto de Ciências Biomédicas de Abel Salazar – Universidade do Porto. Supported by FCT
(SFRH/BD/25470/2005).
Ana Rita Vieira Pinheiro (2013). The purinome in fibroblasts of the human subcutaneous tissue – a contribution to
elucidate the pathogenesis of myofascial pain. PhD in Biomedical Sciences (supervised by P. Correia-de-Sá).
Instituto de Ciências Biomédicas de Abel Salazar – Universidade do Porto. Supported by FCT
(SFRH/BD/47373/2008).
Master Thesis completed:
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
Sónia Andreia Mimoso Lopes de Oliveira Ferreira (2010-11). O ATP como biomarcador da bexiga hiperactiva e o
benefício clínico da toxina botulínica. Master Thesis in Medicine (supervised by M. Silva-Ramos & P. Correia-deSá) (20/20). Instituto de Ciências Biomédicas de Abel Salazar – Universidade do Porto.
Cátia Andreia Rodrigues Vieira (2010-11). Distribuição dos receptores da adenosina no plexo mioentérico –
músculo longitudinal do íleo de rato: Implicações funcionais. Master Thesis in Chemical Sciences and
Biomolecules (supervised by P. Correia-de-Sá) (19/20). Escola Superior de Tecnologia da Saúde do Porto
(ESTSP), Instituto Politecnico do Porto.
Mariana de Sousa Certal (2010-11). Fibroblastos como intermediáris na sinalização mecano-sensitiva entre o
epitélio e os neurónios aferentes primários: o papel do ATP extracelular e das ondas de [Ca2+]i. Master Thesis in
Biochemistry (supervised by M.A. Costa, A.R. Pinheiro & P. Correia-de-Sá) (19/20). Faculdade de Ciências /
Instituto de Ciências Biomédicas de Abel Salazar – Universidade do Porto.
Aurora Raquel Barros Barbosa (2010-11). Modulação purinérgica do transporte de GABA e glutamato na
epilepsia. Master Thesis in Biochemistry (supervised by J.M. Cordeiro, M.G.B. Lobo & P. Correia-de-Sá) (19/20).
Faculdade de Ciências / Instituto de Ciências Biomédicas de Abel Salazar – Universidade do Porto.
Patrícia Alexandra Rocha Marques (2010-11). Contribution of interstitial cells of Cajal to the regulation of
cholinergic neurotransmission at the rat ileum tripartite myenteric synapse: does endogenous adenosine play a
role. Master Thesis in Health Sciences (supervised by P. Correia-de-Sá) (19/20). Escola de Ciências da Saúde –
Universidade do Minho.
Carla Alexandra Araújo Leite (2010-11). Isolamento e cultura de células do tecido cavernoso humano:
Caracterização fenotípica e identificação de purinoceptores por imunofluorescência. Master Thesis in Chemical
Sciences and Biomolecules (supervised by P. Correia-de-Sá) (18/20). Escola Superior de Tecnologia da Saúde do
Porto (ESTSP), Instituto Politecnico do Porto.
Carla Patrícia da Silva e Sousa Reis (2010-11). P2 purinoceptors signaling in fibroblasts of the rat subcutaneous
tissue. Master Thesis in Molecular Biology (supervised by M.A. Costa, A.R. Pinheiro & P. Correia-de-Sá) (17/20).
Universidade de Aveiro.
Catarina Raquel Marques Baldaia Moreira (2010-12). Ectonucleotidases – Relevância fisiopatológica e terapêutica
num modelo de bexiga hiperactiva na ratazana. Master Thesis in Molecular Therapy (supervised by T. Magalhães
Cardoso & P. Correia-de-Sá) (18/20). Instituto Superior de Ciências da Saúde – Norte (ISCS-N / CESPU).
Célia Cristina Moreira Soares (2010-12). Papel da adenosina na proliferação e diferenciação dos fibroblastos do
tecido conjuntivo subcutâneo. Master Thesis in Medicine (supervised by A.R. Pinheiro & P. Correia-de-Sá)
(20/20). Instituto de Ciências Biomédicas de Abel Salazar - Universidade do Porto.
Bruno Miguel Martins Bragança (2011-12). Papel da adenosina na insuficiência cardíaca num modelo animal de
hipertensão pulmonar. Master Thesis in Biochemistry (supervised by A.P. Fontes de Sousa & P. Correia-de-Sá)
(20/20). Faculdade de Ciências / Instituto de Ciências Biomédicas de Abel Salazar – Universidade do Porto.
Marina Raquel Henriques Mendes (2011-12). Alterações da expressão dos receptores A1 e A2A da adenosina no
hipocampo e no neocórtex de doentres com epilepsia mesial temporal (MTLE). Master Thesis in Biochemistry
(supervised by F. Ferreirinha & P. Correia-de-Sá). Faculdade de Ciências / Instituto de Ciências Biomédicas de
Abel Salazar – Universidade do Porto.
Cristina Eusébio Mendes (2012-13). Papel dos receptores P2X7 na transmissão sináptica mioentérica após
isquémia e reperfusão do íleo de rato. Master Thesis in Morphofunctional Sciences (supervised by P. Castelucci &
P. Correia-de-Sá). Departamento de Anatomia, ICB – Universidade de São Paulo (USP, Brasil).
Marisa Rosalina Gonçalves da Cunha (2011-13). Disfunção imunológica na Miastenia Gravis: Papel da via
CD39/CD73/A2AR. Master Thesis in Medicine (supervised by L. Oliveira, E. Santos & P. Correia-de-Sá)
(19.4/20.0). Instituto de Ciências Biomédicas de Abel Salazar - Universidade do Porto.
14. Elsa Marina Cerqueira Meireles (2011-13). Papel dos recetores P2X7 na diferenciação osteogénica das células
mesenquimatosas do estroma da medula óssea - Análise comparativa entre mulheres em idade fértil e
pós‐menopáusicas com osteoporose. Master Thesis in Medicine (supervised by J.B. Noronha-Matos & P. Correiade-Sá) (19/20). Instituto de Ciências Biomédicas de Abel Salazar - Universidade do Porto.
15. Mónica Isa Moreira Rodrigues (2012-13). Role of adrenaline on the maturation of adrenoceptors. Master Thesis in
Medicine (supervised by D. Moura & P. Correia-de-Sá) (20/20). Instituto de Ciências Biomédicas de Abel Salazar
- Universidade do Porto.
16. Sílvia Manuela Nogueira Marques (2012-13). Regulação diferencial do cronotropismo e inotropismo em aurículas
isoladas de ratazana a contrair espontaneamente por purinorecetores P1 e P2. Master Thesis in Biochemistry
(supervised by A.P. Fontes de Sousa & P. Correia-de-Sá) (19/20). Faculdade de Ciências / Instituto de Ciências
Biomédicas de Abel Salazar – Universidade do Porto.
17. Sónia Isabel Nunes Guerra Gomes (2012-13). The role of adenosine A2A receptors in the regulation of neuronal
and immunological responses in rats with Experimental Autoimmune Myasthenia gravis (EAMG). Master Thesis
in Biochemistry (supervised by F. Ferreirinha, L. Oliveira & P. Correia-de-Sá) (19/20). Faculdade de Ciências /
Instituto de Ciências Biomédicas de Abel Salazar – Universidade do Porto.
18. Ricardo Silva dos Santos Viais (2012-13, ERASMUS Program, Universitat Autònoma de Barcelona). Dynamics
of purinergic and nitrergic neuromuscular transmission in the mouse colon. Master Thesis in Biochemistry
(supervised by Marcel Jiménez & P. Correia-de-Sá) (20/20). Faculdade de Ciências / Instituto de Ciências
Biomédicas de Abel Salazar – Universidade do Porto.
19. Carla Daniela da Silva Pereira (2012-13). Papel dos receptores purinérgicos no crescimento e remodelação do
tecido cavernoso. Master Thesis Biochemical Technology in Health (supervised by M.A. Costa, M. Faria & P.
Correia-de-Sá) (18/20). Escola Superior de Tecnologia da Saúde do Porto (ESTSP), Instituto Politecnico do Porto.
Degree Thesis completed:
1.
Diana Manuela Ferreira de Meireles (2010-11). Predomínio da actividade dos receptores inibitórios A1 da
adenosina no controlo da transmissão neuromuscular num modelo animal de Miastenia Gravis. Degree in
Biochemistry (supervised by L. Oliveira & P. Correia-de-Sá) (17/20). Faculdade de Ciências / Instituto de
Ciências Biomédicas de Abel Salazar - Universidade do Porto.
2. Joana Sofia Silva Correia (2009-11). Alterações da expressão da ecto-5’-nucleotidase (CD73) e dos receptores P1
da adenosina na bexiga de doentes com obstrução infravesical: avaliação imunohistoquímica por microscopia
confocal. Degree in Biochemistry (supervised by F. Ferreirinha & P. Correia-de-Sá) (17/20). Faculdade de
Ciências / Instituto de Ciências Biomédicas de Abel Salazar - Universidade do Porto.
3. Matilde de Freitas Ribeiro Viegas (2010-11). Immunohistochemical localization of adenosine A1 and A2A
receptors at the rat motor endplate: pathophysiological implications in Myasthenia gravis. Degree in Biochemistry
(supervised by L. Oliveira & P. Correia-de-Sá) (15/20). Faculdade de Ciências / Instituto de Ciências Biomédicas
de Abel Salazar - Universidade do Porto.
4. Sara Gomes Moreira (2010-11). Ionotropic P2X7 receptor favours osteogenic differentiation and membrane cell
dynamics of human bone stromal cells. Degree in Biochemistry (supervised by M.A. Costa, J.B. Noronha-Matos
& P. Correia-de-Sá) (17/20). Faculdade de Ciências / Instituto de Ciências Biomédicas de Abel Salazar Universidade do Porto.
5. Ricardo Silva Santos Viais (2010-11). Comparação dos efeitos da adenosina e de outros agentes relaxantes
dependentes do endotélio no tecido cavernoso de rato e de humano. Degree in Biochemistry (supervised by M.
Faria, J.M. LaFuente-de-Carvalho & P. Correia-de-Sá) (19/20). Faculdade de Ciências / Instituto de Ciências
Biomédicas de Abel Salazar - Universidade do Porto.
6. Sílvia Manuela Nogueira Marques (2010-11). Contribuição dos receptores A2A e β1 para o efeito “cronoselectivo” da adenosina na contracção espontânea das aurículas isoladas de ratazana. Degree in Biochemistry
(supervised by A.P. Fontes-de-Sousa & P. Correia-de-Sá) (19/20). Faculdade de Ciências / Instituto de Ciências
Biomédicas de Abel Salazar - Universidade do Porto.
7. Filipe Jorge do Nascimento Fernandes (2010-11). Modulação da transmissão colinérgica no órgão eléctrico de
Torpedo marmorata. Degree in Biochemistry (supervised by J.M. Cordeiro & P. Correia-de-Sá) (18/20). Faculdade
de Ciências / Instituto de Ciências Biomédicas de Abel Salazar - Universidade do Porto.
8. Diana Isabel Pinto de Almeida (2011-12). On the role of adenosine A2A receptors expressed on motor nerve
terminals of rats with Experimental Autoimmune Myasthenia Gravis (EAMG). Degree in Biology (supervised by
L. Oliveira & P. Correia-de-Sá) (18/20). Faculdade de Ciências da Universidade do Porto.
9. Pedro Miguel Coelho Paiva (2011-12). Caracterização morfológica e funcional das células endoteliais e
musculares lisas do tecido cavernoso de ratazana em cultura por microsccopia confocal. Degrre in Biochemistry
(supervised by P. Correia-de-Sá, A. Leite, M. Faria - Dept. Clínicas Veterinárias, and J.-M. LaFuente de Carvalho
- Serviço de Urologia, CHP/HGSA) (19/20). Faculdade de Ciências / Instituto de Ciências Biomédicas de Abel
Salazar - Universidade do Porto.
10. Bruna Isabel Nunes Oliveira (2011-12). Caracterização dos receptores nicotínicos pré-sinápticos facilitatórios no
órgão eléctrico de Torpedo marmorata. Degree in Biochemistry (supervised by J.M. Cordeiro & P. Correia-de-Sá)
(16/20). Faculdade de Ciências / Instituto de Ciências Biomédicas de Abel Salazar - Universidade do Porto.
11. José Miguel Sousa de Matos (2011-12). Comparative hydrolysis of adenine and uracil nucleotides by NTPDases in
rat and human derived mesenchymal cells. Degree in Biochemistry (supervised by M.A. Costa, M.T. MagalhãesCardoso, J.B. Noronha-Matos, A.R. Pinheiro & P. Correia-de-Sá) (16/20). Faculdade de Ciências / Instituto de
Ciências Biomédicas de Abel Salazar - Universidade do Porto.
12. Ana Catarina Costa Pereira (2011-12). Modulação diferencial do cronotropismo e do inotropismo pelos
nucleótidos de adenina e uracilo em aurículas isoladas de Rattus norvegicus. Degree in Biology (supervised by
A.P. Fontes de Sousa & P. Correia-de-Sá; co-supervised by A. Silva - UTAD) (19/20). Universidade de Trás-osMontes e Alto Douro (UTAD).
13. Carla Anita Gomes Tavares (2011-12). Atividade histoenzimática das ecto-NTPDases no plexo mioentérico do
íleo de ratazanas. Degree in Biotechnology (supervised by M. Duarte-Araújo, F. Ferreirinha and P. Correia-de-Sá;
co-supervision by A. Queiroz) (19/20). Escola Superior Agrária de Ponte de Lima, Instituto Politécnico de Viana
do Castelo.
14. Carla Adriana Araújo Vinhas (2012-13). Papel dos nucleótidos de adenina e uracilo na proliferação e
diferenciação de fibroblastos cardíacos de ratazana. Degree in Biotechnology (supervised by M. Certal, A.R.
Pinheiro and P. Correia-de-Sá; co-supervision by A. Queiroz) (18/20). Escola Superior Agrária de Ponte de Lima,
Instituto Politécnico de Viana do Castelo.
15. Ana Salomé Monteiro (2012-13). Expressão, localização e actividade das ecto-nucleotidases no intestino de
ratazana. Degree in Biotechnology (supervised by M. Duarte-Araújo, M.T. Magalhães-Cardoso, F. Ferreirinha
and P. Correia-de-Sá; co-supervision by A. Queiroz) (20/20). Escola Superior Agrária de Ponte de Lima, Instituto
Politécnico de Viana do Castelo.
5. Patents/propotypes
None.
6. Organization of conferences and scientific meetings
PHARMACOLOGICAL STRATEGIES TO ENHANCE PDE5 EFFICACY IN THE TREATMENT OF ERECTILE
DYSFUNCTION: PRECLINICAL STUDIES
Porto, 15 December 2011
Javier Angulo
Servicio de Histologia, Departamento de Investigacion, Hospital Ramon y Cajal, Madrid, Espanha
Organizer: P. Correia-de-Sá.
PURINERGIC NEUROTRANSMISSION IN THE GI TRACT
Porto, 6 December 2011
Marcel Jimenez
Dept. of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona, Spain
Organizer: P. Correia-de-Sá.
EPHAR 2012 MEETING
Granada (Espanha), 17-20 de Julho de 2012
Federation of European Pharmacological Societies (EPHAR) e Sociedade Espanhola de Farmacologia (SEF)
Antonio Zarzuelo (President, University of Granada); Julio Gálvez (Deputy President, Department of
Pharmacology, School of Pharmacy, University of Granada), Teresa Tejerina (President of the Spanish
Society of Pharmacology Spanish representative in EPHAR, University Complutense of Madrid), Fermín
Sánchez-Medina (Treasurer, University of Granada), Rosario Jiménez (Secretary, University of Granada),
Juan Tamargo (Spanish representative in EPHAR, University Complutense of Madrid), Ulrich
Förstemann (Mainz University, Germany), Daniel McQuenn (University of Edinburgh, UK) and Michael
Mulvany (University of Aarhus, Denmark) (Comité Executivo)
Marija Carman-Krzan (University of Ljubljana, Slovenia), Paulo Correia-de-Sá (University of Porto, Portugal),
Jukka Hakkola (University of Oulu, Finland), Robin Hiley (University of Cambridge, England), Janet
Mifsud (University of Malta, Malta) (Comité de Aconselhamento Científico).
XLIII REUNIÃO ANUAL DA SOCIEDADE PORTUGUESA DE FARMACOLOGIA, XXXI REUNIÃO DE
FARMACOLOGIA CLÍNICA E XII REUNIÃO DE TOXICOLOGIA
Porto, 6-8 de Fevereiro de 2013
Sociedade Portuguesa de Farmacologia
Organizer: P. Correia de Sá (President Scientific and Organizing Committees)
7. Industry contract research
None.
8. Internationalization
(Collaborative publication, Research, Graduate Training Networks or other forms of participation of the Research Group at the
international level)
- European Research Network for investigating adenosine (ADEURO)
In collaboration with: Dept. Chem. (Camerino), Rega Instituut (Leuven), Dept. Med. Chem. (Leiden), Dept.
Org. Pharmac. Chem. (Uppsala), Lab. Mol. Biol. (München), Inst. Pharmacol. (Vienna), Dept. Pharmacol.
(Heidelberg), Dept. Pharmacol. (Milan), Dept. Pharmacol. (Florence), Dept. Pharmacol. (Leiden), Inst.
Histol. Neurobiol. (Stockholm), Dept. Pharmacol. (Stockholm), Dept. Pharmacol. (IGC-Oeiras/ICBASPorto). Supported by EC, ADEURO Project.
- Harvard Medical School – Portugal Collaboration in Biomedicine and Health Sciences
An international collaboration to advance biomedical graduate education and research.
Member of the steering group for creating the National Consortium for Biomedicine and Health Sciences.
- Collaborative research at the International level
Lab. Farmacologia, Univ. Maringá - Paraná (Brazil) - Prof. Alves-do-Prado (modulation of neuromuscular
transmission)
Inst. Biociências, UNESP, Botucatu, São Paulo (Brazil) - Prof. Márcia Gallacci (mechanisms underlying
neuromuscular blockade of BthTX-I – the major myotoxin from Bothrops jararacussu snake venom)
Lab. Disfunções Neurogastrointestinais, Instituto de Ciências Biomédicas (ICB), USP (Brazil) - Prof.
Patrícia Castelucci (on the role of purinoceptors on synaptic transmission after ischemia/reperfusion
of the rat ileum)
Inst. Andrology, Hospital Ramon y Cajal, Madrid (Spain) - Prof. J. Angulo (vasculogenic erectile
dysfunction)
Dept. of Cell Biology, Physiology and Immunology, Universitat Autònoma de Barcelona, Barcelona (Spain)
– Prof. Marcel Jimenez (purinergic signaling in the gut)
Brain Res. Institute - Amsterdam (The Netherlands) - Prof. F. Lopes-da-Silva (scientific advisor on
mesotemporal lobe epilepsy)
Nestlé Res. Centre - Lausanne (Switzerland) - Dr. Christine Cherbut, Dr. Gabriela Bergonzelli and Prof.
Luisa Lopes (maturation of the intestinal neuromuscular function)
UT Southwestern Medical Center, Depart. Neurology - Dallas (USA) – Prof. Steven Vernino (autonomic
dysautonomia and myasthenia)
Weatheral Inst. Mol. Med., John Radcliffe Hospital - Oxford (UK) – Prof. M. Isabel Leite (translational
research on myasthenic syndromes).
Centre de Recherche en Rhumatologie et Immunologie, Depart. Anatomy & Physiol., Fac. Medicine, Univ.
Laval – Quebec (Canada) – Prof. Jean Sevigny (role of the ectonucleotidase pathway in cell
signalling)
-Protocol for research collaboration with OLYMPUS Confocal Microscopy International Division
UMIB signed with OLYMPUS Portugal a protocol considering the Laboratory of Electrophysiology and Cell
Signalling (Pharmacology and Neurobiology Group, UMIB) a centre of reference for developing and testing
hardware and software applications for Life-Cell Confocal Microscopy
Indicadores de Realização Física
Neste quadro deve indicar os valores referentes ao período a que corresponde o Relatório de Progresso.
Neste quadro deve apenas indicar concretizações efectivas. Não indique publicações submetidas para publicação, nem
teses que ainda não tenham sido discutidas.
Indicadores
Quantidade
realizada
A - Publicações
Livros
3
Artigos em revistas internacionais
76
Artigos em revistas nacionais
0
B - Comunicações
Comunicações em encontros científicos internacionais
54
Comunicações em encontros científicos nacionais
67
C - Relatórios
0
D - Organização de seminários e conferências
4
E - Formação avançada
Teses de Doutoramento
3
Teses de Mestrado
19
Outras (e.g. Licenciatura)
15
F - Modelos
0
G - Aplicações computacionais
0
H - Instalações piloto
0
I - Protótipos laboratoriais
0
J - Patentes
0
L - Outros (Prémios)
4
Relatório Científico Final 2011-13 – UMIB
Research Group Title: Anatomy: Experimental Medicine
Principal Investigator: Artur Perez Águas
Research Area: Health Sciences
Home Institution: Instituto de Ciências Biomédicas Abel Salazar
Relatório de Progresso
Informação: Qualquer dúvida relacionada com o preenchimento do Formulário de Relatório de Progresso, por favor contacte-nos.
Atenção: - O formato da data a utilizar é dd-mm-yyyy
Formulário Relatório de Progresso - Componente Científica
Relatório Final
Período a que o relatório diz respeito:
Data de início: 01-01-2011
Data de fim: 31-12-2013
1. Identificação do Projecto
Referência do Projecto: PEst-OE/SAU/UI0215/2011
Investigador Responsável: Paulo Jorge Silva Correia Sa
Instituição Proponente: Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP)
Data de Início: 01-01-2011
Data de Fim: 31-12-2012
1. Identificação do grupo
Nome: Anatomy: Experimental Medicine
Investigador Responsável: Professor Ártur Águas
Instituição Proponente: Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP)
Data de Início: 01-01-2011
Data de Fim: 31-12-2013
2.
Resumo dos Trabalhos Desenvolvidos e Desvios à Proposta aprovada
EXPERIMENTAL CALICIVIRUS INFECTION
Our study on the pathogenesis of rabbit haemorrhagic disease (RHD) has been focused on two major pathogenic
mechanisms that could be responsible for the resistance/susceptibility of young and adult rabbits to RHD, namely: the
expression of the viral receptor on the membrane of hepatocytes (cell-target of RHDV) and the interaction between
RHDV and the immune response of the host. Our findings revealed that the viral hepatic cellular receptor is a
macroglycolipid. Additionally, the ELISA assays showed that there seems to be no differences in the expression of the
receptor between young and adult rabbits. Alternatively, the flow cytometry analysis indicated that, in RHDV-infected
adult rabbits, the infection induces a local and systemic acute lymphocytic depletion as a result of cellular apoptosis that
precedes and attends liver damage. RHDV-infected young rabbits, however, developed a rapid and effective
inflammatory response by the liver, with few damage hepatocytes, and with a sustained elevation of local and systemic B
and T cells. The results also showed that the RHDV infection of adult rabbits is capable of inducing an exacerbated
inflammatory response, characterized by a substantial increase of cytokines, especially, TNF-α. The following work
+
+
showed that regulatory T cells (CD4 Foxp3 ), which have an important role in the regulation of inflammation, were
significantly decreased in the spleen of infected adult rabbits. In the next study was evaluated the effect of
immunosuppression in the response of young rabbits to RHDV infection. The results showed that immunosuppressed
and infected young rabbits die within 3 days with a fulminant hepatitis, presenting a large number of damaged
hepatocytes that were also RHDV-positive, similarly to infected adult rabbits. This result weakens the hypothesis that the
resistance of young rabbits to RHD derives from a different expression of the viral receptor in the liver and also reaffirms
the importance of the immune response in the resistance/susceptibility to infection.
CLINICAL AND EXPERIMENTAL ENDOCRINOLOGY
The research efforts of the Clinical and Experimental Endocrinology field have been dedicated to (i) Study the role of the
vagus nerve in the mechanism of action of gastro-intestinal hormones, in particular of GLP-1, in energy and glucose
homeostasis, which has been characterized. (ii) Development of innovative medical and surgical treatments for obesity
and type 2 diabetes, through the optimization of the surgical techniques used in the clinical setting towards improved
outcomes, use of surgical animal models of bariatric surgery and implementation of novel pharmacological approaches
for obesity with an anti-ghrelin vaccine. Clinical prospective studies of obese type 2 diabetic patients and patients with
metabolic syndrome submitted to long limb metabolic gastric bypass were performed and the surgical modification has
shown to improve the diabetes remission rate and metabolic syndrome parameters. Rodent models of experimental
bariatric surgery have been successfully established and the alterations induced in the energy regulatory pathways have
been described. Since the suppression of ghrelin rise, a gastro-intestinal hormone that increases appetite and decreases
energy expenditure, after food deprivation, has been one of the most promising findings after bariatric surgery, an antighrelin therapeutic vaccine has been developed being a promising target for obesity treatment. (iii) Study the role of
obesity and metabolic syndrome in prostate cancer progression and the pathways leading to adrenal cancer, since
obesity and metabolic syndrome have also been recently linked to the increased risk of endocrine related cancer.
Obesity has been shown to modulate cell proliferation and angiogenesis in prostate cancer and p27 has been
demonstrated to be a potential novel molecular marker for the diagnosis of adrenal cancer.
Desvios à Proposta Aprovada
Se tiver havido desvios à proposta aprovada, quer do ponto de vista científico como financeiro, aponte os desvios e justifique-os. Se teve dificuldades na execução do plano de trabalhos aprovado, identifique-os e indique
de que modo pretende ultrapassá-los. Se no período em apreço tiver informado a FCT sobre alteração orçamental inter-rubricas (necessitem ou não de autorização por parte da FCT), indique aqui o motivo. (4000
caracteres sem espaços)
The research in the Endocrinology field has expanded in to related fields in order to optimize the availability of human and technical resources and the
collaborations with other national and international institutions has been enlarged. The research in gastrointestinal hormones been performed in
collaboration with the Department of Metabolic Medicine at Imperial College, UK; the clinical research was performed in patients recruited from the Obesity
Surgery Outpatient Clinic of Hospital de São Sebastião, CHEDV, under medical follow-up by Mariana P. Monteiro; the rodent models and experimental
bariatric surgery, has been performed at Centro de Cirurgia Experimental Avançada (CCEA) by the same group of surgeons that operate human patients;
the development of an anti-ghrelin vaccine has been developed with the collaboration of Professor Polly Roy, Department of Pathogen Molecular Biology,
London School of Hygiene and Tropical Medicine, UK and Professor Felipe Casanueva from Molecular Endocrinology Department of University Santiago
de Compostela, Spain; and the research in endocrine related cancer is being developed in collaboration with Professor Pignatelli from IPATIMUP.
Equipa de Investigação
d
a
t
a
data
Nome
Cargo
Tarefas
%Te
de
mpo
entra
da
d
e
s
a
Desistiu
(marcar
com
Gru
uma X
po
se for o
caso)
í
d
a
1.Study the role of the vagus nerve in the mechanism of action of gastro-intestinal
hormones, in particular of GLP-1, in energy and glucose homeostasis.
Ana Raquel Dias Pinto
Investig
ador
AN
2.Study the role of obesity and metabolic syndrome in prostate cancer
progression and the pathways leading to adrenal cancer,
50
AT
1. What is the molecule responsible for the binding of the virus to the surface of
rabbit hepatocytes?
2. Does CV infection interfere with the innate immune response in adult rabbits,
António Duarte Costa e Silva
Investig
António Manuel de Sousa Pereira
Investig
AN
namely with the early production of cytokines?
50
ador
ador
AT
AN
A exercer cargo público de direção.
20
AT
1. What is the molecule responsible for the binding of the virus to the surface of
rabbit hepatocytes?
2. Does CV infection interfere with the innate immune response in adult rabbits,
Artur Manuel Perez Neves Aguas
Investig
AN
namely with the early production of cytokines?
ador
50
AT
2. Does CV infection interfere with the innate immune response in adult rabbits,
Carlos Manuel Zagalo Fernandes Ribeiro
Investig
Cristiana Jorge Silva Praça Vasconcelos
Investig
ador
AN
namely with the early production of cytokines?
ador
20
hormones, in particular of GLP-1, in energy and glucose homeostasis
AT
AN
Study the role of the vagus nerve in the mechanism of action of gastro-intestinal
20
AT
1.Study the role of the vagus nerve in the mechanism of action of gastro-intestinal
hormones, in particular of GLP-1, in energy and glucose homeostasis.
Joaquim Duarte Monteiro
Investig
ador
Joaquim Luís Ramos Torres Couto Reis
Investig
ador
AN
2.Study the role of obesity and metabolic syndrome in prostate cancer
progression and the pathways leading to adrenal cancer.
50
Study the role of the vagus nerve in the mechanism of action of gastro-intestinal
hormones, in particular of GLP-1, in energy and glucose homeostasis
AT
AN
20
AT
2. Does CV infection interfere with the innate immune response in adult rabbits,
Jorge Celso Dias Correia da Fonseca
Investig
AN
namely with the early production of cytokines?
20
ador
AT
2. Does CV infection interfere with the innate immune response in adult rabbits,
José António Mesquita Martins dos Santos
Investig
AN
namely with the early production of cytokines?
ador
20
AT
1-Study the role of the vagus nerve in the mechanism of action of gastro-intestinal
hormones, in particular of GLP-1, in energy and glucose homeostasis.
2-Development of innovative medical and surgical treatments for obesity and type
2 diabetes.
3-Study the role of obesity and metabolic syndrome in prostate cancer
Lídia Mariana Rodrigues Pereira Monteiro
Investig
AN
progression and the pathways leading to adrenal cancer.
ador
50
AT
1. What is the molecule responsible for the binding of the virus to the surface of
rabbit hepatocytes?
2. Does CV infection interfere with the innate immune response in adult rabbits,
Luzia Manuela Lima Teixeira
Madalena Cristina Marques da Costa Santos
Investig
AN
namely with the early production of cytokines?
ador
100
AT
Investig
50
AN
Development of innovative medical and surgical treatments for obesity and type 2
ador
AT
diabetes,
Study the role of obesity and metabolic syndrome in prostate cancer progression
and the pathways leading to adrenal cancer,
Maria Ermelinda Antunes Soares Rodrigues
Munz
Investig
ador
Maria Helena Cardoso Pereira da Silva
Investig
ador
Maria João Feytor Pinto Rodrigues de Oliveira
de Meireles Moreira
AN
Deixou de pertencer à Unidade por mudança de instituição de trabalho.
50
AT
AN
Development of innovative medical and surgical treatments for obesity and type 2
diabetes.
X
20
AT
1. What is the molecule responsible for the binding of the virus to the surface of
Investig
AN
rabbit hepatocytes?
ador
50
AT
1. What is the molecule responsible for the binding of the virus to the surface of
rabbit hepatocytes?
2. Does CV infection interfere with the innate immune response in adult rabbits,
Maria Manuela Morais da Silva
Investig
AN
namely with the early production of cytokines?
ador
50
AT
1. What is the molecule responsible for the binding of the virus to the surface of
rabbit hepatocytes?
2. Does CV infection interfere with the innate immune response in adult rabbits,
Paula Cristina Gomes Ferreira Proença
Investig
AN
namely with the early production of cytokines?
ador
50
AT
1. What is the molecule responsible for the binding of the virus to the surface of
rabbit hepatocytes?
2. Does CV infection interfere with the innate immune response in adult rabbits,
Raquel Alexandra Machado Marques
AN
namely with the early production of cytokines?
Bolseiro
100
AT
1.
Publicações
•
Publicações em revistas internacionais com peer review (n=14)
Ano
Publicações
URL
Nora M, Guimarães M, Almeida R, Martins P, Gonçalves G, Santos
M, Morais T,Freitas C, Monteiro MP. Excess body mass index loss http://www.ncbi.nlm.nih.gov/pmc/articl
predicts metabolic syndrome remission after gastric bypass.
2014
es/PMC3881494/
Diabetol Metab Syndr. 2014 Jan 2;6(1):1. (epub em 2013)
Moreira A, Pereira SS, Machado CL, Morais T, Costa M, Monteiro
MP. Obesity inhibits lymphangiogenesis in prostate tumors. Int J Clin
2013
2013
Exp Pathol. 2013;7(1):348-52.
http://www.ncbi.nlm.nih.gov/pmc/articl
es/PMC3885490/
Monteiro MP. Obesity vaccines. Hum Vaccin Immunother. 2013 Dec https://www.landesbioscience.com/art
23;10(4).
icle/27537/full_text/#load/info/all
Guimarães M, Rodrigues P, Gonçalves G, Nora M, Monteiro MP.
Heterotopic pancreas in excluded stomach diagnosed after gastric
bypass surgery. BMC Surg. 2013 Nov 23;13:56
http://www.biomedcentral.com/14712482/13/56
2013
Pereira SS, Morais T, Costa MM, Monteiro MP, Pignatelli D. The
emerging role of the molecular marker p27 in the differential
2013
diagnosis of adrenocortical tumors. Endocr Connect. 2013 Aug
http://www.endocrineconnections.co
m/content/early/2013/08/07/EC-130025.full.pdf+html
28;2(3):137-45.
Andrade S, Pinho F, Ribeiro AM, Carreira M, Casanueva FF, Roy P,
2013
Monteiro MP. Immunization against active ghrelin using virus-like http://www.ncbi.nlm.nih.gov/pmc/articl
particles for obesity treatment. Curr Pharm Des. 2013;19(36):6551-
es/PMC3850261/
8.
Guimarães M, Nora M, Ferreira T, Andrade S, Ribeiro AM, Oliveira V,
2013
Carreira MC, Casanueva FF, Monteiro MP. Sleeve gastrectomy and
http://link.springer.com/article/10.100
gastric plication in the rat result in weight loss with different
7%2Fs11695-013-0886-2/fulltext.html
endocrine profiles. Obes Surg. 2013 ;23(5):710-7.
Marques, RM, Costa-e-Silva, A, Águas, AP, Teixeira, L, Ferreira, PG.
2012
“Early Inflammatory Response of Young Rabbits Attending Natural
http://www.sciencedirect.com/science
Resistance to Calicivirus (RHDV) Infection”. Veterinary Immunology
/article/pii/S0165242712003686
and Immunopathology. 2012; 150 (3-4):181-8.
Marques RM, Costa-E-Silva A, Águas AP, Teixeira L, Ferreira PG. Early
inflammatory response of young rabbits attending natural resistance
2012
to calicivirus (RHDV) infection. Vet Immunol Immunopathol.
2012;150(3-4):181-8.
http://www.sciencedirect.com/science
/article/pii/S0165242712003686
Teixeira, L, Marques, RM, Águas, AP, Ferreira, PG. “Regulatory T cells
2012
are decreased in acute RHDV lethal infection of adult rabbits”
http://www.sciencedirect.com/science
Veterinary Immunology and Immunopathology. 2012; 148(3-4):343-
/article/pii/S0165242712001419
7.
Ribeiro AM, Pereira S, Andrade S, Costa M, Lopes C, Aguas AP,
Monteiro MP. Insulin prevents leptin inhibition of RM1 prostate
2012
cancer cell growth. Pathol Oncol Res. 2012;18(2):499-507.
Monteiro MP. Anti-ghrelin vaccine for obesity: a feasible alternative
to dieting? Expert Rev Vaccines. 2011 Oct;10(10):1363-5.
2011
http://link.springer.com/article/10.100
7%2Fs12253-011-9473-9/fulltext.html
http://informahealthcare.com/doi/abs/
10.1586/erv.11.115
Nora M, Guimarães M, Almeida R, Martins P, Gonçalves G, Freire MJ,
2011
Ferreira T, Freitas C, Monteiro MP. Metabolic laparoscopic gastric
http://link.springer.com/article/10.100
bypass for obese patients with type 2 diabetes. Obes Surg. 2011
7%2Fs11695-011-0418-x/fulltext.html
Nov;21(11):1643-9.
Teixeira L, Marques RM, Águas AP, Ferreira PG. A simple and rapid
method for isolation of caliciviruses from liver of infected rabbits.
Res Vet Sci. 2011 Aug;91(1):164-6.
http://www.sciencedirect.com/science
/article/pii/S0034528810002699
2011
•
Capítulos de livros com distribuição international (n=2)
Ano
Publicações
URL
Andrade, S., Carreira M, Casanueva FF, Roy P, Monteiro MP.
Anti-ghrelin Therapeutic Vaccine: A Novel Approach for
2014
Obesity Treatment, in Molecular Vaccines, M. Giese, Editor.
2014, Springer International Publishing. p. 463-476. (epub em
http://link.springer.com/chapter/10.1007
%2F978-3-319-00978-0_2
2013)
Carreira MC, Crujeiras AB, Andrade S, Monteiro MP,
Casanueva FF. Ghrelin as a GH-releasing factor. Endocr Dev.
2013
2013;25:49-58. (Karger)
http://www.karger.com/Article/FullText/3
46052
•
Comunicações orais (n=6)
1-
NORA, M.; GUIMARAES, M.; SANTOS, M.; ALMEIDA, R.;MARTINS, P.; MONTEIRO, M. LAPAROCOPIC
GASTRIC BYPASS AND METABOLIC SYNDROME REMISSION -STUDY WITH 153 PATIENTS. V Congress of the
International Federation for the Surgery of Obesity and Metabolic Disorders, European Chapter (IFSO-EC).
Barcelona, April 26 – 28, 2012
2-
Morais. T., Pereira. S.S., Andrade. S., Costa. M., Monteiro. D., Monteiro. M.P. The effects of truncal
vagotomy in energy homeostasis and acute response to glp-1. World Diabetes Congress, Melbourne –
2013.
3-
Pereira. S.S., Morais,T., Costa, M., Monteiro, M.P., Pignatelli, D., The use of a morphometric
computerized analysis tool in the differential diagnosis of adrenocortical tumors. European Joint Congress
of Clinical Anatomy, Lisbon – 2013.
4-
Morais. T., Pereira. S.S., Andrade. S., Monteiro. D., Costa. M., Monteiro. M.P., Phenotypical
characterization of vagotomized rat and their feeding response to acute glp-1 administration. European
Joint Congress of Clinical Anatomy, Lisbon – 2013.
5-
Moreira. A., Pereira. S.S., Morais. T., Machado. C., Costa. M., Monteiro. M.P. Evaluation
lymphangiogenesis in prostate tumours induced in different obese mice models. European Joint Congress
of Clinical Anatomy, Lisbon – 2013.
6-
Costa. M., Guedes. T., Martins. S., Pereira. S.S., Morais. T., Santos. A., Monteiro. M.P., Tissue
microarray technology and immunohistochemistry for characterization of the relative distribution of
neuroendocrine cells in the human small intestine. European Joint Congress of Clinical Anatomy, Lisbon –
2013.
•
Comunicações em poster (n=11)
1-
Marques, RM, Águas, AP, Teixeira, L, Ferreira, PG., 2012. Is the expression of calicivirus (RHDV)
receptor in the membrane of hepatocytes different in young and adult rabbits that are, respectively,
resistant and susceptible to the infection? XXXVIII Annual Meeting of the Portuguese Society for
Immunology (SPI). Porto, 25-27 November, 2012
2-
Raquel M. Marques, Luzia Teixeira, António Costa e Silva, Artur P. Águas, Paula G. Ferreira. “Rabbit
haemorrhagic disease fulminant hepatitis: citology of liver damage”. 12th European Joint Congress of
Clinical Anatomy. Lisboa, 26-29 de Junho, 2013.
3-
Pereira. S., Morais, T., Costa, M., Monteiro, M.P., Pignatelli, D. “Adrenocortical tumors: Evaluation
of the role of immunohistochemistry markers in the differential diagnosis of adrenocortical tumors”, One
Day Symposium sponsored by European Association for Cancer Research, Porto – 2012
4-
Ribeiro, A. M., Pereira, S., Andrade, S., Costa, M., Lopes, C., Aguas, A. P., Monteiro, M. P. “Insulin
prevents leptin inhibition of RM1 prostate cancer cell growth” no 2º Congresso da Associação Luso Galaica
da Endocrinologia, Diabetes e Metabolismo – 2012 Vencedor do Prémio de Melhor Comunicação.
5-
Marta Guimarães, Mário Nora, Tiago Ferreira, Sara Andrade, Andreia M Ribeiro, Vera Oliveira,
Marcos C Carreira, Felipe F. Casanueva, Mariana P Monteiro. Sleeve gastrectomy and gastric plication in the
rat result in similar weight loss but in different endocrine profiles. 19th European Congress of Obesity.
Lyon, 9 a 12 de Maio, 2012.
6-
Andrade. S., Casanueva. F., Monteiro. M., Carreira. M., Desarrollo de una vacuna anti-ghrelina para
el tratamiento de la obesidade, Sociedad Gallega de Endocrinologia, Nutrición y Metabolismo - 2012
7-
Nora. M., Guimarães. M., Almeida. R., Martins. P., Gonçalves. G., Santos. M., Morais. T., Freitas. C.,
Monteiro. M.P., The excess body mass index loss is the best predictor of metabolic syndrome criteria
remission after laparoscopic metabolic gastric bypass, World Diabetes Congress, Melbourne – 2013
8-
Moreira. A., Pereira. S.S., Santos. M., Morais. T., Monteiro.M.P., Adipocyte secretome enhances
metabolic activity and migration of prostate carcinoma, 17º Congresso Português de Obesidade, Porto 2013
9-
Andrade. S., Carreira. M., Fernandéz. B., Diz. D., Crujeiras. M., Monteiro. M.P., Casanueva. F., Effect
of alcohol consumption on pre-adipocyte proliferation and adipogenic capacity,17º Congresso Português
de Obesidade, Porto - 2013
10-
Pereira. S.S.,
Morais,T., Costa, M.,
Monteiro, M.P.,
Pignatelli,
D. Possible
Use of
Immunohistochemistry Markers in the Differential Diagnosis of Adrenocortical Tumors, The Endocrine
Society's 95th Annual Meeting & Expo, San Francisco - 2013
11-
Pereira. S.S., Morais,T., Costa, M., Monteiro, M.P., Pignatelli, D. “Immunohistochemistry markers in
the differential diagnosis of adrenocortical tumors”, XIX Curso Pós Graduado de Endocrinologia, Diabetes e
Metabolismo, Porto – 2013
•
Teses de Mestrado (n=3)
1-
Sofia Daniela da Silva Pereira, Mestrado em Oncologia, com a tese “Tumores do córtex da supra-
renal: Avaliação do papel dos marcadores imunocitoquímicos em tumores do córtex da supra-renal”,
Outubro de 2012. Orientador: Prof. Mariana P. Monteiro ICBAS/UP e co-orientador Prof. Duarte Pignatelli,
IPATIMUP.
2-
Tiago André Pereira Guedes, Mestrado Integrado em Medicina do ICBAS/UP, com a tese
“Caraterização da distribuição relativa de células neuroendócrinas no jejuno-íleo”, Julho de 2013.
Orientador: Prof. Doutora Mariana P. Monteiro ICBAS/UP.
3-
Ângela Marisa Almeida Moreira, Mestrado Tecnologia Bioquímica em Saúde, com a tese
“Obesidade e cancro da Próstata: Avaliação do efeito dos adipócitos nas células RM1 de carcinoma da
próstata, Outubro de 2013. Orientador: Prof. Mariana P. Monteiro ICBAS/UP e co-orientada pelo Prof. Ruben
Fernandes, ESTESP/IPP.
•
Organização de atividades de disseminação científica (n=5)
1-
1st Joint Meeting on Adrenal Cancer, 28th of May 2013, ICBAS-UP, Porto, Portugal. With the special
participation of Prof. Gavin Vinson, from Queen Mary, University of London, UK
2-
1ª Reuniao Luso - Galaica de Endocrinologia Experimental, 26 de Outubro 2012, ICBAS-UP, Porto,
Portugal. An Exchange meeting between researchers of UMIB and University of Santiago de Compostela,
Spain.
3-
17º CONGRESSO PORTUGUÊS DE OBESIDADE, 22 a 24 de Novembro de 2013, Hotel Porto Palácio,
Porto, Portugal. Monteiro MP has organized the congress as Vice-President of the Portuguese Obesity
Society.
4-
16º CONGRESSO PORTUGUÊS DE OBESIDADE, 9 a 11 de Novembro de 2012, Hotel Olissippo
Oriente, Lisboa, Portugal. Monteiro MP has organized the congress as Vice-President of the Portuguese
Obesity Society.
5-
15º CONGRESSO PORTUGUÊS DE OBESIDADE, 11 a 13 de Novembro 2011, Hotel Vila Galé, Coimbra,
Portugal. Monteiro MP has organized the congress as Vice-President of the Portuguese Obesity Society
4.
Indicadores de Realização Física
Neste quadro deve indicar os valores referentes ao período a que corresponde o Relatório de Progresso.
Neste quadro deve apenas indicar concretizações efectivas. Não indique publicações submetidas para publicação, nem teses que
ainda não tenham sido discutidas.
Indicadores
Quantidade
realizada
A - Publicações
Livros
2
Artigos em revistas internacionais
14
Artigos em revistas nacionais
0
B - Comunicações
Comunicações em encontros científicos internacionais
12
Comunicações em encontros científicos nacionais
5
C - Relatórios
1
D - Organização de seminários e conferências
5
E - Formação avançada
Teses de Doutoramento
0
Teses de Mestrado
3
Outras
0
F - Modelos
0
G - Aplicações computacionais
0
H - Instalações piloto
0
I - Protótipos laboratoriais
0
J - Patentes
0
L - Outros
5.
Ficheiros Anexos (opcional)
Poderá enviar, apenas se entender como estritamente necessário, ficheiros com formato PDF, que tenham sido referidos no relatório, por
exemplo, gráficos, esquemas, fotografias.
O conjunto dos ficheiros (em número máximo de cinco) ou o arquivo comprimido a enviar não poderão ultrapassar 10MB.
Nome do ficheiro
Agradecemos a sua colaboração.
Ponto do Relatório de Progresso
Descrição
Relatório Científico Final 2011-13 – UMIB
Research Group Title: Biology and Genetics of Reproduction
Principal Investigator: Mario Leite de Sousa
Research Area: Health Sciences
Home Institution: Instituto de Ciências Biomédicas Abel Salazar
Relatório de Progresso
Informação: Qualquer dúvida relacionada com o preenchimento do Formulário de Relatório de Progresso, por favor contacte-nos.
Atenção: - O formato da data a utilizar é dd-mm-yyyy
Formulário Relatório de Progresso - Componente Científica
Relatório Final
Período a que o relatório diz respeito:
Data de início: 01-01-2011
Data de fim: 31-12-2013
1. Identificação do Projecto
Referência do Projecto: PEst-OE/SAU/UI0215/2011
Investigador Responsável: Paulo Jorge Silva Correia Sa
Instituição Proponente: Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP)
Data de Início: 01-01-2011 Data de Fim: 31-12-2012
1. Identificação do grupo
Nome: Biology and Genetics of Reproduction
Investigador Responsável: Professor Mário Sousa
Instituição Proponente: Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP)
Data de Início: 01-01-2011 Data de Fim: 31-12-2013
3.
Resumo dos Trabalhos Desenvolvidos e Desvios à Proposta aprovada
Resumo dos trabalhos
Descreva de forma breve as actividades desenvolvidas no período em apreço e os resultados alcançados. Refira-se em concreto às tarefas
que tiveram execução no período a que o relatório respeita. (6000 caracteres sem espaços)
1-Divulgação:
Divulgou-se a nossa área de investigação básica e aplicada à clínica através de Palestras (Liceus; Universidades), e na formação com orientação de Projectos de Licenciatura, Mestrados
e Doutoramentos.
2-Parte científica:
Obteve-se um excelente número de publicações internacionais, com várias colaborações (Univ. Beira Interior-UBI; Univ. Trás os Montes e Alto Douro-UTAD; Fac. Medicina da Univ
Porto-FMUP; IPATIMUP; Univ. Lisboa-FFUL; Instituto de genética Médica –IGM; Centro Hospitalar do Porto-CHP; Univ. Aveiro-UA; Germany), tendo-se contribuído para um
melhor conhecimento da regulação da espermatogénese humana, normal e patológica, bem como para uma melhor tomada de decisões em termos clínicos na área da infertilidade:
2.1-RAT AND HUMAN SPERMATOGENESIS
-Rat and Human Sertoli Cell Metabolism
-The effect of sex steroid hormones on human Sertoli cell metabolism provided the first assessment of androgens and estrogens as metabolic modulators of human Sertoli cells. (UBI)
Int J Androl (2011) 34: e612–e620. Curr Med Chem (2013) 2: 4037-4049.
-We first report the effect of insulin-deprivation on human Sertoli cell metabolism. (UBI)
Biochim Biophys Acta (2012) 1820: 84–89; Mol Hum Reprod (2012) 18: 161–170; Biochim Biophys Acta (2012) 1823: 1389–1394.
-Rat and Human Androgen and Estrogen Actions
-Deregulation of the expression of Aven (apoptosis inhibitor) was shown to be related with male infertility.
Expression of Regucalcin (calcium binding protein: regulates intracellular calcium homeostasis and is a sex steroid-regulated gene) was shown to be age dependent and upregulated by
the non-aromatizable androgen DHT. (UBI)
Reproduction (2011) 142: 447-456; Fertil Steril (2011) 96: 745-750. Mol Hum Reprod (2012) 18: 161–170.
-This is the first report revealing the existence of Androgen Receptor variants in the testis of evolutionarily distant vertebrate species and in non-pathological tissues. (UBI)
Andrologia (2013) 45: 187-194;
-Apoptosis in Human Azoospermia
-Results suggest that apotosis is induced by nuclear lesions in tubular obstruction and by mitochondrial lesions in hypospermatogenesis. (FMUP)
Int J Androl (2011) 34: e407-4014. J Assist Reprod Genet (2013) 30:487–495.
-Effects of Hormones in Human Spermatogenesis
-Using organ culture, a gradual loss of germ cells, no decrease in Sertoli cell numbers, and maintenance of the general architecture were observed. Both FSH and testosterone increased
germ cell survival, spermatogonia proliferation, and germ cell differentiation.
Reprod Sci (2012) 19: 1063-1074.
-Expression of Stem Cell Markers in the Male Germinal Epithelium
-We determined the specific markers of testicular stem cells.
Syst Biol Reprod Med (2013) 59: 233–243.
2.2-BOVINE OOCYTES
-We could demonstrate the presence of three distinct follicular cell populations in cumulus cells. (UTAD)
Anim Reprod Sci (2011) 123: 23–31.
2.3-ANIMAL TOXICOLOGY
-We determined the effects of sublethal and lethal copper concentrations on the gill epithelium. (UTAD)
Zool Studies (2012) 51: 977-987.
2.4-HUMAN CORD BLOOD
-We established the best culture medium to induce de differentiation and proliferation of natural killer cells. (FMUP-Germany).
Cell Comm Adhes (2011) 18: 45-55. J Recep Signal Transd (2012) 32: 238-249.
2.5-HUMAN ENDOMETRIUM
-We characterized the epithelium cell types during the implantation window.
Reprod Sci (2011) 18: 525-539.
2.6-HUMAN OOCYTE DIMORPHISMS
-The clinical use of human oocytes with large tubular smooth endoplasmic reticulum aggregates should not be implemented as they are associated with newborn malformations.
Fertil Steril (2011) 96: 143–149.
2.7-HUMAN SPERM
-Protein phosphorilation
-We report for the first time the identification of three new serine/threonine-protein PPs, and two tyrosine-PPs in human sperm. (UA)
OMICS: J Integ Biol (2013) 17: 1-13.
2.8-HUMAN GENETICS
-Prenatal Diagnosis
-Microsatellite markers can accurately assess zygosity with the same STRs applied in aneuploidy screening with a high power of discrimination and a matching probability of over
99.999999%. (IGM)
Twin Res Hum Genet (2011) 14: 221-227.
-Imprinting in Human Spermatogenesis
-Methylation imprints are established in spermatogonia A and are maintained in subsequent stages and DNA methyltransferases are expressed throughout human spermatogenesis.
(FMUP)
Epigenetics (2011) 6: 1354-1361.
-Pyruvate Dehydrogenase Complex
We determined which type of germ cells express the PDHA2 gene. The switch from the X-linked to autosomic gene expression (PDHA1) occurred in spermatocytes. (FFUL)
Gene (2012) 506: 173–178.
-Y Chromosome Microdeletions
-Three new deletion patterns were identified in oligozoospermic patients presenting AZFb and AZFc microdeletions. (FMUP)
Fertil Steril (2012) 97: 858–863.
-DNA Mismatch Repair
-MLH3 mutation analysis in patients with maturation arrest showed two missence and one intronic mutation. One missence mutation predicted to affect MLH3 function. Two patients
overexpressed MLH3 and one also overexpressed MLH1. (FMUP)
Reprod Sci (2012) 19: 587-596.
-Varicocele
-Microarrays analysis in patients with varicocele showed decreased expression levels of genes involved in stress situations and increased expression levels of genes involved in normal
function of spermatogenesis after surgery. (CHP)
Andrologia (2012) 44: 260–265.
-Cystic Fibrosis Transmembrane Receptor
-We demonstrated the localization of CFTR in normal and disrupted human spermatogenesis. (FMUP)
Syst Biol Reprod Med (2013) 59:53-59.
-Rare Deleterious Mutations
-DMRT1 loss-of-function mutations are a risk factor and potential genetic cause of human spermatogenic failure and that other recurrent CNVs are potential causes of idiopathic
azoospermia. (FMUP-IPATIMUP)
PLOS Genetics (2013) 9: 1-16.
2.9-ASSISTED REPRODUCTION TECHNOLOGIES:
-Embryo Culture and Cryopreservation
-Extended culture to the blastocyst stage and the efficient freeze–thaw procedure for blastocysts are associated with high clinical success rates.
Arch Gynecol Obstet (2012) 285: 1473-1478.
-Preservation of Fertility in Males
-An efficient method for cryopreservation of enriched fractions in diploid germ cells isolated from human testicular biopsies was developed. The open pulled straw vitrification was
found to be the protocol that best preserved cell viability.
Andrologia (2012) 44: 366–372.
Desvios à Proposta Aprovada
Se tiver havido desvios à proposta aprovada, quer do ponto de vista científico como financeiro, aponte os desvios e justifique-os. Se teve
dificuldades na execução do plano de trabalhos aprovado, identifique-os e indique de que modo pretende ultrapassá-los.
Se no período em apreço tiver informado a FCT sobre alteração orçamental inter-rubricas (necessitem ou não de autorização por parte da
FCT), indique aqui o motivo. (4000 caracteres sem espaços)
Nenhum.
Equipa de Investigação
desistiu
Nome
Cargo
(marcar com
Tarefas
% Tempo
Ângela Raquel Pinto Rocha Alves
data de
data de
entrada
saída
uma X se for
o caso)
Gr
Técnica
Investigador
Elsa Maria de Deus Gonçalves de Oliveira
40
BGR
50
BGR
50
BGR
50
BGR
Técnica
Investigador
Mário Manuel Silva Leite Sousa
IR
Investigador
Rosália Maria Pereira de Oliveira e Sá
Investigador
Investigador
4.
Publicações
•
Peer reviewed paper published in international journals: 34
1.
Calado AM, Oliveira E, Colaço A, Sousa M (2011) Ultrastructural and Cytochemical Characterization of Follicular Cell Types in Bovine (Bos taurus) Cumulus-Oocyte Complexes Aspirated
from Small and Medium Antral Follicles during the Estrus Cycle. Animal Reproduction and Science, 123 (1) 23-31.
2.
Bartosch C, Lopes JM, Beires J, Sousa M (2011) Human endometrium during the implantation window: a new perspective of the epithelium cell types. Reproductive Sciences, 18 (6): 525539.
3.
S. Pires, A.J.A. Nogueira, O. Pinho, T. Delgado, M. Sousa, R. Santos, P. Jorge (2011) Statistical approach to prenatal zygosity assessment following a decade of molecular aneuploidy
screening. Twin Research and Human Genetics, 14 (3): 221-227.
4.
Sá R, Cunha M, Silva J, Luís A, Oliveira C, Teixeira da Silva J, Barros A, Sousa M (2011) Ultrastructure of tubular smooth endoplasmic reticulum aggregates in human MII oocytes and
clinical implications. Fertil Steril 96 (1): 143-149, 149.e1-149.e7.
5.
Almeida C, Cunha M, Ferraz L, Barros, Sousa M (2011) Caspase-3 detection in human testicular spermatozoa from azoospermic and non-azoospermic patients. International Journal of
Andrology, 34: E407-e414.
6.
Sandra Laurentino, Sara Correia, José Eduardo Cavaco, Pedro Fontes Oliveira, Luís Rato, Mário Sousa, Alberto Barros, Sílvia Socorro (2011). Regucalcin is broadly expressed in
reproductive tissues and a new androgen target gene in mammalian testis. Reproduction, 142 (3) 447-456.
7.
Pinho MJ, Barros A, Sousa M (2011) Ex vivo differentiation of natural killer cells from human umbilical cord blood CD34+ progenitor cells. Cell Communication and Adhesion, 18(3) 45-55.
8.
Laurentino S, Gonçalves J, Cavaco JEB, Oliveira PF, Alves M, Sousa M, Barros A, Socorro S (2011) Apoptosis-inhibitor Aven is down regulated in defective spermatogenesis and a novel
estrogen target gene in mammalian testis. Fertil Steril., 96 (3): 745-750
9.
Marques CJ, Pinho MJ, Marques P, Carvalho F, Bieche I, Barros A, Sousa M (2011) DNA methylation imprinting marks and DNA methyltransferases expression in human spermatogenic
cell stages. Epigenetics. 6 (11): 1354-1361.
10.
Oliveira PF, Alves MG, Rato L, Sá R, Barros A, Sousa M, Carvalho RA, Cavaco JE, Socorro S (2011) Influence of 5a-Dihydrotestosterone and 17b-Estradiol on Human Sertoli Cells
Metabolism. Int J Androl., 34: e612-e620.
11.
Oliveira PF, Alves MG, Rato L, Laurentino S, Silva J, Sá R, Barros A, Sousa M, Carvalho RA, Cavaco JE, Socorro S (2012) Effect of insulin deprivation on metabolism and metabolismassociated gene transcript levels on in vitro cultured human Sertoli cells. Biochimica et Biophysica Acta (BBA)- General Subjetcs, 1820 (2): 84-89. DOI: 10.1016/j.bbagen.2011.11.006
12.
Sandra Laurentino, Sara Correia, José Eduardo Cavaco, Pedro Fontes Oliveira, Luís Rato, Mário Sousa, Alberto Barros, Sílvia Socorro (2011). Regucalcin, a calcium-binding protein with a
role in male reproduction?. Molecular Human Reproduction. 18 (4) 161-170. DOI: 10.1093/MOLEHR/GAR075
13.
Ana Soares, Paula Costa, Joaquina Silva, Mário Sousa, Alberto Barros, Susana Fernandes (2012) AZFb microdeletions and oligozoospemia-Which mechanisms? Fertil Steril, 97 (4) 858863. DOI: 10.1016/j.fertnstert.2012.099
14.
Oliveira A, Neto A, Almeida C, Silva-Ramos M, Versos R, Barros A, Sousa M, Carvalho F (2012) Comparative study of gene expression in patients with varicocelo by microarrays
technology. Andrologia, 44 (5) (suppl s1): 260-265. DOI: 10.1111/j.1439-0272.2011.01173.x
15.
Sousa M, Cunha M, Viana P, Silva J, Teixeira da Silva J, Oliveira C, Barros A (2012) Outcomes of human blastocyst transfer after slow-freezing using sequential culture: a clinical report.
Arch Gynecol Obstet, 285 (5): 1473-1478. DOI 10.1007/s00404-011-2174-5
16.
Ferrás C, Fernades S, Silva J, Barros A, Sousa M. (2012) Expression analysis of MLH3, MLH1 and MSH4 in maturation arrest. Reprod Sc 19 (6): 587-596. DOI:
10.1177/1933719111428521
17.
Alves MG, Socorro S, Silva J, Barros A, Sousa M, Cavaco JE, Oliveira PF (2012) In vitro cultured human Sertoli cells secrete high amounts of acetate that is stimulated by 17<beta>
estradiol and suppressed by insulin deprivation. Biochimica et Biophysica Acta (BBA) - Mol Cell Res 1823 (8): 1389-1394. DOI: 10.1016/j.bbamcr.2012.06.002
18.
Pinheiro A, Silva MJ, Graça I, Silva J, Sá R, Sousa M, Barros A, Almeida IT, Rivera I. (2012) Pyruvate dehydrogenase complex: transcriptional and translational patterns of PDHalfa subunit
genes in human spermatogenesis. Gene 506 (1): 173-178. DOI: 10.1016/j.gene.2012.06.068
19.
Sá R, Inês Graça, Joaquina Silva, Isabel Malheiro, Filipa Carvalho, Alberto Barros, Mário Sousa (2012) Quantitative analysis of cellular proliferation and differentiation of the human
seminiferous epithelium in vitro. Reprod Sciences, 19 (10) 1063-1074. DOI: 10.1177/1933719112440746
20.
MJ Pinho, CJ Marques, F Carvalho, M Punzel, M Sousa and A Barros (2012) Genetic regulation on ex-vivo differentiated natural killer cells from human umbilical cord blood CD34+ cells. J
Receptor and Signal Transduction, 32 (5): 238-249. DOI: 10.3109/10799893.2012.700716
21.
Sá R, Miranda C, Leite C, Malheiro I, Carvalho F, Silva J, Barros A, Sousa M. (2012). Biomarkers Expression in Human Seminiferous Epithelium. Microsc Microanal, 18 (Suppl 5): 15-16.
DOI: 10.1017/S1431927612012731
22.
Sá R, Nieves Cremades, Isabel Malheiro, Mário Sousa (2012) Cryopreservation of human testicular diploid germ cell suspensions. Andrologia, 44 (6): 366-372. DOI: 10.1111/j.14390272.2012.01290.x
23.
Lima M; Sousa M, Oliveira C, Teixeira da Silva J, Cunha M, Viana, P, Barros A (2013) Ovarian Hyperstimulation Syndrome. Experience of a Reproductive Medicine Center from 2005-2011.
Proceedings of the 17th World Congress on Controversies in Obstetrics, Gynaecology & Infertility (COGI). Ben-Rafael Z (Ed.). Nonduzzi Editoriale / Proceedings : 97-100.
24.
Lima P, Monteiro M, Machado J, Sousa M (2013) A histological study of the oogenesis of the freshwater mussel Anodonta cygnea (Linnaeus, 1771) in Mira lagoon, Portugal. Malacologia
55(2): 251-261
25.
Sílvia Teixeira, Rosália Sá, Ana Grangeia, Joaquina Silva, Cristiano Oliveira, Luís Ferráz, Ângela Alves, Sandra Paiva, Alberto Barros, Mário Sousa (2013) Immunohystochemical analysis
of CFTR in normal and disrupted spermatogenesis. Syst Biol Reprod Med. 59 (1): 53-59. DOI: 10.3109/19396368.2012718851
26.
Almeida C, Correia S, Rocha E, Alves A, Ferraz L, Silva J, Sousa M, Barros A (2013) Caspase signalling pathways in human testicular disorders. J Ass Reprod Genet. 30 (4): 487-493.
DOI: DOI 10.1007/s10815-013-9938-8
27.
Lopes AM, Aston KI, Carvalho F, Gonçalves J, Matthiesen R, Huang N, Ramu A, Downie JM, Fernandes S, Amorim A, Barros A, Hurles M, Moskovtsev S, Ober C, Schiffman JD, Schelegel
PN, Sousa M, Carrell DT, Conrad DF (2013) Human spermatogenic failure purges deleterious mutation load from the autosomes and both sex chromosomes, including the gene DMRT1.
PLOS Genetics 9 (3): 1-16. DOI: 10.1371/journal.pgen.1003349
28.
Monteiro SM, Oliveira E, Fontaínhas-Fernandes A, Sousa M (2013) Effects of sublethal and lethal copper concentrations on the ultrastructural organization on the gill epithelium
ultrastructure in tilapia Oreochromis niloticus. Zoological Studies. 51 (7): 977-987.
29.
Cabral M, Pires I, Figueiredo H, Oliveira E, Sousa M, Ferraz L (2013) Ultraestrutura de um caso de astenozoospermia. Rev Int Androl 10 (4): 156-159. DOI: 1698-031X/$
30.
Sandra Laurentino, Patrícia Pinto, Joana Tomas, José Eduardo Cavaco, Mário Sousa, Alberto Barros, Deborah Power, Adelino Canário, Sílvia Socorro (2013). Identification of androgen
receptor variants in testis from humans and other vertebrates. Andrologia 45 (3) 187-194. DOI: 10.1111/j.1439-0272.2012.01333.x
31.
Bernardino RL, Jesus TT, Martins AD, Sousa M, Barros A, Cavaco EJ, Socorro S, Alves MG, Oliveira PF (2013) Molecular Basis of bicarbonate membrane transport in th emale
reproductive tract. Current Medicinal Chemistry, 20 (32): 4037-4049. DOI: 0929-8673/13$58.00+.00
32.
Fardilha M, Ferreira M, Pelech S, Vieira S, Rebelo S, Korrodi-Gregorio L, Sousa M, Barros A, Silva V, da Cruz e Silva OAB, da Cruz e Silva EF (2013) “OMICS” of human sperm: Profiling
Protein Phosphatases. OMICS: A Journal of Integrative Biology 17 (9): 460-472. DOI: 10.1089/omi.2012.0119
33.
Sá R, C Miranda, F Carvalho, A Barros, M Sousa (2013) Expression of stem cell markers, OCT4, KIT, ITGA6 and ITGB1 in the male germinal epithelium. Syst Biol Repro Med. 59 (5): 233243. DOI: 10.3109/19396368.2013.804964
34.
Mário Sousa, José Teixeira da Silva, Joaquina Silva, Mariana Cunha, Paulo Viana, Elsa Oliveira, Rosália Sá, Célia Soares, Cristiano Oliveira, Alberto Barros (2013) Embryological, clinical
and ultrastructural study of human oocytes presenting indented zona pellucida. Zygote, 2 (): 1-13. DOI: 10.1017/SO967199413000403
•
Other International Publications (6000 ca.): 11
Book Chapters: 4
1.
Marques CJ, Barros A, Sousa M (2011) Sperm Epigenetic Profile. In: Sperm Chromatin: Biological and Clinical Application in Male Infertility and Assisted Reproduction. Armand Zini and
Ashok Agarwal, Editors. Human Press, Springer. Part 2, Chapter 17, 243-257.
2.
Merkan M, Sousa M (2011) Ultrastructural studies of vitellogenesis in Asellus aquaticus (Crustacea, Isopoda). In: Perspectives in Animal Ecology and Reproduction. Volume VII. ViJay K
Gupta, Editor. Anil Mittal, Daya Publishing House, New Delhi, India. Chapter 20, 294-315.
3.
Marques CJ, Sousa M (2013) Inprinted Gene Anomalies in Sperm In: Paternal Influences in Human Reproductive Success. Carrell DT (ed). Cambridge University Press, USA. Chapter 4,
pp.: 27-37.
4.
Sá R, Sousa M (2013) Androgens and the ovary. In: Protein Biochemistry, Synthesis, Structure and Cellular Functions. Androgen Receptors. Structural Biology, Genetics and Molecular
Defects, Chapter VII. Socorro S (ed.). Nova Biomedical, Nova Science Publishers Inc., NY, USA. pp: 165-190.
Indexed Abstracts: 7
5.
Almeida C, Correia S, Rocha E, Alves A, Cunha M, Ferraz L, Silva S, Sousa M, Barros A (2011) Caspase signalling pathways in human testicular disorders. Hum Reprod 26 (suppl 1): i144.
6.
Carvalho B, Silva J, Cunha M, Viana P, Leite R, Stevenson D, Carvalho A, Oliveira C, Teixeira da Silva J, Póvoa AM, Soares S, Calejo L, Sousa S, Xavier P, Sousa M, Barros A, Carvalho F
(2012). Preimplantation genetic diagnosis for portuguese familial amyloidotic polyneuropathy- 12 year’s experience. RBMOnline, 24 (suppl 2): S59. DOI:
7.
A Cunha, M.; Viana, P.; Gonçalves, A.; Silva, J.; Oliveira, C.; Teixeira da Silva, J.; Ferráz, L.; Madureia, C., Dória, S., Sousa, M.; and Barros, A. (2012) Evaluation of 140 patients with
Klinefelter syndrome – clinical outcomes after intracytoplasmic sperm injection. Hum Reprod, 27 (suppl 2): 30-31. DOI: 10.1093/humrep/27.s2.74.
8.
Alves M, Socorro S, Silva J, Barros A, Sousa M, Cavaco J, Oliveira PF (2012) Human Sertoli cells Produce High Amounts of Acetate that is Under Strict Hormonal Control. J.
Reproduktionsmed. Endokrinol. 9 (5): 370. DOI:
9.
Teixeira da Silva J, Cunha M, Silva J, Viana P, Gonçalves A, Barros N, Oliveira C, Sousa M, Barros A (2013) Low-dose human Chorionic Gonadotropin at oocyte retrieval after
Gonadotropin-releasing hormone agonist triggering: retrospective study. 29th ESHRE Annual Meeting, London, UK, 7-10 July. Hum Reprod 28 (suppl 1): i 319 (P-486)
10.
Gomes M, Gonçalves A, Rocha E, Silva J, Barros A, Sousa M (2013) In vitro effect of lead chloride on sperm parameters and sperm DNA damage. ASEBIR 18 (2): 220.
11.
Mário Sousa, José Teixeira da Silva, Joaquina Silva, Mariana Cunha, Paulo Viana, Elsa Oliveira, Rosália Sá, Célia Soares, Cristiano Oliveira, Alberto Barros (2013) Embryological, clinical
and ultrastructural study of human oocytes presenting indented zona pellucida. ASEBIR. 18 (2): 242-243.
•
National Publications: 5
Book chapters: 2
1-
Azevedo C, Sousa M (2012) Especializações da Membrana. In: Biologia Celular e Molecular. Azevedo C, Sunkel C (eds), Edições Técnicas Lidel, Porto, Cap. 4, pp 58-77.
2-
Sousa M (2012) Fertilização Animal. In: Biologia Celular e Molecular. Azevedo C, Sunkel C (eds), Edições Técnicas Lidel, Porto, Cap. 26, pp 436-454.
Artigos científicos: 3
3-
Mariana Lima, Mário Sousa, Cristiano Oliveira, Joaquina Silva, José Teixeira da Silva, Mariana Cunha, Paulo Viana, Alberto Barros (2013) Síndrome de Hiperestimulação ovárica.
Experiência de um Centro de Medicina da Reprodução: 2005-2011. Acta Médica Portuguesa 26 (1): 24-32.
4-
Cunha M, Sousa M, Silva J, Xavier P, Viana P, Teixeira da Silva J, Oliveira C, Gonçalves A, Osório C, Barros N, Barros A (2013) Impacto da acupunctura na Medicina da Reprodução:
revisão do estado da arte e considerações a propósito de um caso clínico. Arquivos de Medicina. 26 (1): 17-25.
5-
Oliveira A, Sousa M, Granja B (2013) A Percepção de Si Enquanto Mulher Infértil. Saúde Reprodutiva, Sexualidade e Sociedade 3 (): 5-19.
PhD Thesis Completed: 5
•
1-
Carolina Neves de Sousa e Almeida (2011). Regulação da Apoptose no Epitélio Germinal Masculino.
Doutoramento em Biomedicina.
Departamento de Genética, Faculdade de Medicina, Universidade do Porto (FMUP).
Co-orientador. Prof. Doutor Mário Sousa
2-
Sandra Filipa Tomás Sequeira Laurentino (2011). Sexual steroid regulation of spermatogenesis: new actors enter the stage.
Doutoramento em Biomedicina.
Faculdade de Ciências da Saúde, Universidade da Beira Interior (UBI).
Co-orientador. Prof. Doutor Mário Sousa
3-
Ana Sofia Costa Pinheiro (2011). Somatic expression of the testis-specific PDHA2 gene: mechanisms of activation/silencing.
Doutoramento em Biomedicina.
Reitoria da Universidade de Lisboa. Acompanhamento: Prof. Doutor Mário Sousa
4-
Maria João Nascimento de Pinho (2012) In vitro determination and functional maturation of natural killer cells from umbilical cord blood progenitor cells.
Doutoramento em Biomedicina.
Faculdade de Medicina do Porto, Universidade do Porto.
Co-orientador. Prof. Doutor Mário Sousa
5-
Rosália Maria Pereira de Oliveira e Sá (2012) Molecular Cell Biology Characterization Of Human Male Testicular Adult Stem Cells.
Doutoramento em Ciências Biomédicas.
Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto.
Acompanhamento: Prof. Doutor Mário Sousa
MSc Thesis Completed: 3
•
1-
Liliana Alexandra Marques de Castro (2012)
Mestrado em Biologia Clínica Laboratorial
Universidade de Trás-os-Montes e Alto Douro, Vila Real.
Correcção da Tese: Prof. Dr. Mário Sousa
2-
Eurico Costa (2012) Caracterização molecular de crianças com Síndrome de Cornélia Lange (CdLS).
Mestrado em Biologia,
Instituto de Genética Médica Jacinto Magalhães, Porto.
Orientador: Prof. Dr. Mário Sousa
3-
Diana Raquel Veloso Cardona (2013) Epidemiologia da infertilidade.
Mestrado em Medicina Legal.
Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto.
Orientador: Prof. Dr. Mário Sousa
Indicadores de Realização Física
Neste quadro deve indicar os valores referentes ao período a que corresponde o Relatório de Progresso.
Neste quadro deve apenas indicar concretizações efectivas. Não indique publicações submetidas para publicação, nem teses que ainda não
tenham sido discutidas.
Indicadores
A - Publicações
Livros : Book chapters Internacionais
Capítulos de Livro Nacionais
Artigos em revistas internacionais
Abstracts Internacionais indexados
Artigos em revistas nacionais
B - Comunicações
Quantidade
realizada
45 / 5
4/2
34 / 7
3
17 /31
Comunicações em encontros científicos internacionais
17
Comunicações em encontros científicos nacionais
31
C - Relatórios
7
D - Organização de seminários e conferências
0
E - Formação avançada
Teses de Doutoramento
5
Teses de Mestrado
3
Outras
Teses de Licenciatura
3
F - Modelos
0
G - Aplicações computacionais
0
H - Instalações piloto
0
I - Protótipos laboratoriais
0
J - Patentes
0
L - Outros
6.
Ficheiros Anexos (opcional)
Poderá enviar, apenas se entender como estritamente necessário, ficheiros com formato PDF, que tenham sido referidos no relatório, por
exemplo, gráficos, esquemas, fotografias.
O conjunto dos ficheiros (em número máximo de cinco) ou o arquivo comprimido a enviar não poderão ultrapassar 10MB.
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Agradecemos a sua colaboração.
Ponto do Relatório de Progresso
Descrição
Relatório Científico Final 2011-13 – UMIB
Research Group Title: ImmunoGenetics, Inflammation and Autoimmunity (IGIA)
Principal Investigator: Berta Silva
Research Area: Health Sciences
Home Institution: Instituto de Ciências Biomédicas Abel Salazar
Relatório de Progresso
Informação: Qualquer dúvida relacionada com o preenchimento do Formulário de Relatório de Progresso, por favor contacte-nos.
Atenção: - O formato da data a utilizar é dd-mm-yyyy
Formulário Relatório de Progresso - Componente Científica
Relatório Final
Período a que o relatório diz respeito:
Data de início: 01-01-2011
Data de fim: 31-12-2013
1. Identificação do Projecto
Referência do Projecto: PEst-OE/SAU/UI0215/2011
Investigador Responsável: Paulo Jorge Silva Correia Sa
Instituição Proponente: Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP)
Data de Início: 01-01-2011
Data de Fim: 31-12-2013
1. Identificação do grupo
Nome: ImmunoGenetics, Inflammation and Autoimmunity (IGIA)
Investigador Responsável: Professora Berta Silva
Instituição Proponente: Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP)
Data de Início: 01-01-2011
Data de Fim: 31-12-2013
5.
Resumo dos Trabalhos Desenvolvidos e Desvios à Proposta aprovada
Resumo dos trabalhos
Descreva de forma breve as actividades desenvolvidas no período em apreço e os resultados alcançados. Refira-se em concreto às tarefas
que tiveram execução no período a que o relatório respeita. (6000 caracteres sem espaços)
1.
Epilepsy
1.1. MTLE-HS
We were able to show that the IL-1B -511T allele is associated with MTLE-HS susceptibility, as previously reported for other populations.
Separately, the role of Human HerpesVirus-6B (HHV-6B) in epileptogenic lesion in MTLE patients was assessed. We concluded that this viral
infection is not an important etiopathogenic factor for MTLE-HS in the Portuguese population. Regarding the role of the glutamatergic pathways
in this disease, we observed that Glutamate transporter EAAT1 was over-expressed in the adjoining cortex indicates that this area may also be
involved in disease evolution.
Evidences from animal models have implicated the serotonergic system in epileptogenesis. HTR2A expression levels may be modulated by a
102 T>C polymorphism. We did not find differences in allelic or genotype frequencies between MTLE-patients and healthy controls. HTR2A
function may be influenced by the rs6314 polymorphism that but no association with disease development was found in our population.
Serotonin receptors HTR1A could have an anti-convulsant effect. HTR1A expression may be modulated by the polymorphism rs6295. The
frequency of rs6295CC genotype was higher in MTLE-HS patients when compared to controls. Serotonin transporter (5-HTT) plays a key role
in the regulation of serotonin levels. The expression of the 5-HTT gene could be modulated by a 17bp variable number of tandem repeats in
the second intron (5-HTTVNTR). In our population the genotype 12/9 was overrepresented in MTLE patients compared to controls. Variations
in the 5-HTT gene expression may lead to changes in serotonergic neurotransmission and consequently in brain homeostasis, lowering the
threshold for seizure development.
During 2011 we established a collaboration with the group of Prof. Sanjay Sisodiya from University College London (UCL). In February 2012
our PhD student Bárbara Leal spent two weeks in UCL participating in a Genome Wide Association Study. The results of this study suggest SCN1A
involvement in a common epilepsy syndrome and give new direction to biological understanding of mesial temporal lobe epilepsy with hippocampal sclerosis with
febrile seizures opening new avenues for investigation of prognostic factors and possible prevention of epilepsy in some children with febrile seizures
(Brain.
2013 Oct;136(Pt 10):3140-50).
1.2. Progressive Mioclonic Epilepsy
We described a patient with Unverricht-Lundborg disease with a new splicing alteration in the cystatin B gene (CSTB). Mutation Gln22Gln
leads to abnormal splicing and partial inclusion of the intronic sequence. This is a rare case of homozygosity for a non-classic mutation and
adds to mutational heterogeneity of CSTB. Separately, two siblings with PME and a rare new lysossomopathy due to 2-LIMP-2 (SCARB2)
mutation were identified. Substrate-reduction therapy, to correct the storage of glucocerebroside in the cells was instituted in one of the
siblings, and a significant improvement was observed (Seizure 2011, 20(9)).
2.
Systemic Lupus Erythematosus
In the context of the European BioLupus project, further refinement of the ongoing association studies took place. New publications explore the
IL2/IL21, PP2CA, TRAF6, and complement factor-H genes. More recently, a role for the microRNA gene miRNA-146a and for the AID
susceptibility gene BLK was uncovered. Genetic factors relevant in gender and ethnic differences were also explored (Ann Rheum Dis 2012;
Genes Immun 2012). Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a negative regulator of T-cell activation associated with
several autoimmune diseases, including systemic lupus erythematosus (SLE). Missense rs2476601 is associated with SLE in individuals with
European ancestry and may influence auto-antibody production ( PLoS One. 2013;8(8):e69404). It has been previously described an
association between rs3853839G allele (gene of Toll-like receptor 7 (TLR7)) and SLE development. This polymorphism is a binding site for the
epigenetic factor miR-3148. The rs3853839G allele has lower affinity to miR-3148 than rs3853839C. So, these data establish rs3853839 of
TLR7 as a shared risk variant of SLE (PLoS Genet. 2013;9(2):e1003336).
It has been showed that SLE and Systemic sclerosis (SSc) share multiple genetic susceptibility loci. In order to gain insight into the genetic
basis of these diseases, it was performed a pan-meta-analysis of two genome-wide association studies (GWASs) together with a replication
stage including additional SSc and SLE cohorts. In this study, we add KIAA0319L, PXK, JAZF1 and KIAA0319L new susceptibility loci for SSc
and SLE, respectively, increasing significantly the knowledge of the genetic basis of autoimmunity (Hum Mol Genet. 2013 Oct 1;22(19):40219).
3.
Multiple Sclerosis
3.1. Iron and Vitamin D
We found that the HFE C282Y polymorphism may be implicated in MS aggressiveness, being a marker of worse prognosis.
A high prevalence of vitamin D insufficiency was found in MS patients. Patients with higher disability seemed especially prone to vitamin D
deficiency (lower levels of sun exposure?). These results suggest that vitamin D may be a disease modifier in genetically susceptible
individuals. Tailoring vitamin D supplementation to genetic profile (i.e. selecting for the presence of HLA-DRB1*15) may be an efficient method
for providing benefits. Vitamin D acts via its receptor (VDR), a nuclear receptor that is expressed in multiple immune cell types. Various singlenucleotide polymorphisms in the VDR gene have been described, but only for FokI polymorphism a functional impact on the immune response
has been demonstrated. In our population the ff genotype frequency was significantly higher in the patient’s group compared to controls.
3.2. KIR
We have observed that the presence of activating KIR2DS1 gene decreased the risk of MS independently from the presence of HLA-DRB1*15. No
significant associations were found for age at onset or disease course (results accepted for publication in Journal of Neuroimmunology ).
3.3. ApoE
We have not found a negative impact of the APOE-epsilon4 allele on the physical and cognitive manifestations of MS disease, in agreement
with recent reports.
3.4. NF-kB pathway
A collaborative study with Miguel Soares from the IGC in Oeiras began recently, that aims to translate to the human disease the results from
animal studies establishing the importance of the transcription factor Nfr2 in neuroinflammation.
4.
Behçet’s Disease
Association studies were extended to a larger cohort of patients, with negative results. We confirmed that APoE polymorphism does not
contribute to pathogenesis in BD. We have pursued nevertheless, as this cohort is one of the largest studied in European populations
(accepted for publication in Journal of Rheumatology).
5.
Systemic Sclerosis (SSc)
We sought to determine whether the innate immunity-related KIR genotypes are associated with SSc. We confirmed the protective role of the
KIR2DS2 phenotype, in the presence of KIR2DL2, as previously described.
The role of the HLA system was also explored. We found that autoantibody production in SSc is associated with the presence of certain HLADRB1 alleles. Overall these results confirm previous reports in larger cohorts.
6.
Psoriasis
A study to evaluate cardiovascular disease risk in psoriatic patients and associated genetic determinants is underway. Both classical
immunogenetic markers and a panel of 30 SNP(s) already described as associated with CVD risk or other known comorbidities were already
assayed in 200 patients. Statistical evaluation is underway (J Dermatol. 2013; accepted for publication in American Journal of Clinical
Dermatology)
7.
Amyloidosis
In Familial Amyloidotic Polyneuropathy, type I, a genetic disease relatively common in the north of Portugal, activation of signaling cascades,
such as ERK, mediated by engagement of RAGE receptors by pre-amyloid protein aggregates, leads to up regulation of the NF-kB parthway,
oxidative stress and apoptosis. We have underway a project to elucidate the role of these functional disturbances in the dysregulation of the
erythropoietin (EPO) gene, that is known to be under expressed both in patients and pre-symptomatic carriers, resulting in a high incidence of
severe anemia, but also possibly implicated in neurodegeneration, since EPO has been recently reported as a potent neuroprotective
hormone.
8.
HLA-NET
The HLA-NET Action (COST BM0803) involves 21 European countries, and aims at networking researchers working in bone marrow
transplantation, epidemiology and population genetics to improve the molecular characterization of the HLA genetic diversity of human
populations. Culminating several rounds of workgroup meetings and biocomputational developmental work, new guidelines and methodological
recommendations were published (Int J Immunogenet 2012, 39(6)).
Desvios à Proposta Aprovada
Se tiver havido desvios à proposta aprovada, quer do ponto de vista científico como financeiro, aponte os desvios e justifique-os. Se teve
dificuldades na execução do plano de trabalhos aprovado, identifique-os e indique de que modo pretende ultrapassá-los.
Se no período em apreço tiver informado a FCT sobre alteração orçamental inter-rubricas (necessitem ou não de autorização por parte da
FCT), indique aqui o motivo. (4000 caracteres sem espaços)
Não se verificaram desvios assinaláveis à proposta aprovada.
Equipa de Investigação
desistiu
Nome
Cargo
Tarefas
%Tempo
data de
data de
(marcar com
entrada
saída
uma X se for o
Gr
caso)
Ana Alexandra Duarte Martins da Silva
Investigador
25
IGIA
Andreia Alexandra Ferreira dos Santos
Investigador
100
IGIA
Andreia Manuela Teixeira Bettencourt
Investigador
100
IGIA
Augusto Manuel Rodrigues Faustino
Investigador
50
IGIA
Bárbara Alexandra Padrão Guerra Leal
Investigador
100
IGIA
Carlos Alberto da Silva e Vasconcelos
Investigador
20
IGIA
Cláudia Alexandra Moreira de Carvalho
Investigador
80
IGIA
Helena Maria Sousa Barreiros Martins
Investigador
15
IGIA
Henrique Luis Lopes Ferreira Reguengo da Luz
Investigador
15
IGIA
Isabel Maria Pereira Alves de Almeida
Investigador
20
IGIA
João Manuel Monteiro Chaves
Investigador
15
IGIA
José Carlos Azevedo Oliveira
Investigador
15
IGIA
Maria Berta de Jesus Duarte Silva
Investigador
50
IGIA
Maria Fátima Graça Farinha
Investigador
20
IGIA
Maria Fernanda Ramos Bravo
Investigador
15
IGIA
Maria Júlia da Silva Reis
Investigador
15
IGIA
Paulo Jorge Barbosa Carvalho
Investigador
20
IGIA
Paulo Manuel de Castro Pinho e Costa
Investigador
20
IGIA
6.
Publicações
1.
T, Torres, R Sales, C Vasconcelos, B Martins da Silva, M Selores. “Framingham Risk Score underestimates cardiovascular disease risk
in severe psoriatic patients: Implications in cardiovascular risk factors management and primary prevention of cardiovascular disease.” J
Dermatol. 2013 Oct 16. doi: 10.1111/1346-8138.12267
http://www.ncbi.nlm.nih.gov/pubmed/24128349
2.
C. Carvalho, S. L. Calvisi, B. Leal, A. Bettencourt, A. Marinho, I. Almeida, F. Farinha, P. P.Costa, B. M.Silva, C. Vasconcelos. ”CCR5Delta32: implications in SLE development” Int J Immunogenet. 2013 Oct 29. doi: 10.1111/iji.12094
http://www.ncbi.nlm.nih.gov/pubmed/24164722
3.
D. Kasperavičiūtė, C. B. Catarino, M. Matarin, C. Leu, J. Novy, A. Tostevin, B. Leal,et al. “Epilepsy, hippocampal sclerosis and febrile
seizures linked by common genetic variation around SCN1A” Brain. 2013 Oct;136(Pt 10):3140-50. doi: 10.1093/brain/awt233
http://www.ncbi.nlm.nih.gov/pubmed/24014518
4.
Amato N, Riva N, Cursi M, Martins-Silva A, Martinelli V, Comola M, Fazio R, Comi G, Leocani L. “Different Frontal Involvement in ALS and PLS
Revealed by Stroop Event-Related Potentials and Reaction Times.” Front Aging Neurosci. 2013 Dec 12;5:82. doi: 10.3389/fnagi.2013.00082.
http://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+24376417
5.
da Silva AM, Santos ME; On behalf of the Portuguese JEMS Study Investigators.” JCV epidemiology in MS (JEMS)-Epidemiology of anti-JCV
antibody prevalence in multiple sclerosis patients-Portuguese data.” Neurol Sci. 2013 Dec 1. pii: S0022-510X(13)03060-8. doi: 10.1016/j.jns.2013.11.031
http://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+24369270
6.
Teixeira F, Moreira I, Silva AM, Vasconcelos C, Farinha F, Santos E “Neurological involvement in Primary Sjögren Syndrome.” Acta Reumatol
Port. 2013 Jan-Mar;38(1):29-36.
http://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+24131909
7.
Coelho T, Maia LF, da Silva AM, Cruz MW, Planté-Bordeneuve V, Suhr OB, Conceiçao I, Schmidt HH, Trigo P, Kelly JW, Labaudinière R, Chan
J, Packman J, Grogan DR. “Long-term effects of tafamidis for the treatment of transthyretin familial amyloid polyneuropathy.” J Neurol. 2013
Nov;260(11):2802-14. doi: 10.1007/s00415-013-7051-7.
http://www.ncbi.nlm.nih.gov/pubmed/?term=PMID%3A+23974642
8.
Martin JE, Assassi S, Diaz-Gallo LM, Broen JC, Simeon CP, Castellvi I, Vicente-Rabaneda E, Fonollosa V, Ortego-Centeno N,
González-Gay MA, Espinosa G, Carreira P; Spanish Scleroderma Group; SLEGEN consortium; U.S. Scleroderma GWAS group;
BIOLUPUS, Camps M, Sabio JM, D'alfonso S, Vonk MC, Voskuyl AE, Schuerwegh AJ, Kreuter A, Witte T, Riemekasten G, Hunzelmann
N, Airo P, Beretta L, Scorza R, Lunardi C, Van Laar J, Chee MM, Worthington J, Herrick A, Denton C, Fonseca C, Tan FK, Arnett F,
Zhou X, Reveille JD, Gorlova O, Koeleman BP, Radstake TR, Vyse T, Mayes MD, Alarcón-Riquelme ME, Martin J. “A systemic sclerosis
and systemic lupus erythematosus pan-meta-GWAS reveals new shared susceptibility loci”. Hum Mol Genet. 2013 Oct 1;22(19):4021-9.
doi: 10.1093/hmg/ddt248.
http://www.ncbi.nlm.nih.gov/pubmed/23740937
9.
Deng Y, Zhao J, Sakurai D, Kaufman KM, Edberg JC, Kimberly RP, Kamen DL, Gilkeson GS, Jacob CO, Scofield RH, Langefeld CD,
Kelly JA, Ramsey-Goldman R, Petri MA, Reveille JD, Vilá LM, Alarcón GS, Vyse TJ, Pons-Estel BA; Argentine Collaborative Group,
Freedman BI, Gaffney PM, Sivils KM, James JA, Gregersen PK, Anaya JM, Niewold TB, Merrill JT, Criswell LA, Stevens AM, Boackle
SA, Cantor RM, Chen W, Grossman JM, Hahn BH, Harley JB, Alarcόn-Riquelme ME; BIOLUPUS and GENLES networks, Brown EE,
Tsao BP. “MicroRNA-3148 modulates allelic expression of toll-like receptor 7 variant associated with systemic lupus erythematosus.”
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11. Löfgren SE, Frostegård J, Truedsson L, Pons-Estel BA, D'Alfonso S, Witte T, Lauwerys BR, Endreffy E, Kovács L, Vasconcelos C,
Martins da Silva B, Kozyrev SV, Alarcón-Riquelme ME. “Genetic association of miRNA-146a with systemic lupus erythematosus in
Europeans through decreased expression of the gene”. Genes Immun. 2012 Apr;13(3): PMID:22218224
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%20gene
12. Fesel C, Barreto M, Ferreira RC, Costa N, Venda LL, Pereira C, Carvalho C, Morães-Fontes MF, Ferreira CM, Vasconcelos C, Viana
JF, Santos E, Martins B, Demengeot J, Vicente AM. “Compensatory T-cell regulation in unaffected relatives of SLE patients, and
opposite IL-2/CD25-mediated effects suggested by coreferentiality modeling.”. PLoS One. 2012;7(3).
PubMed PMID: 22479496
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of highly conserved major histocompatibility complex (MHC) extended haplotypes on iron and low CD8+ T lymphocyte
phenotypes in HFE C282Y homozygous hemochromatosis patients from three geographically distant areas.” PLoS One.
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Brown EE, Alarcón GS, Edberg JC, Kim JH, Choi J, Ramsey-Goldman R, Petri MA, Reveille JD, Vilá LM, Boackle SA, Freedman BI,
Tsao BP, Langefeld CD, Vyse TJ, Jacob CO, Pons-Estel B; Argentine Collaborative Group, Niewold TB, Moser Sivils KL, Merrill JT,
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Liz Lightstone, Stephen D. Marks, Alberto Martini, Gabriela Moroni, Irmgard Neumann, Manuel Praga, Martin Schneider, Vladimir Tesar,
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36. Stoenoiu MS, Aydin S, Tektonidou M, Ravelingien I, le Guern V, Fiehn C, Remy P, Delahousse M, Petera P, Quémeneur T,
Vasconcelos C, D'Cruz D, Gilboe IM, Jadoul M, Karras A, Depresseux G, Guillevin L, Cervera R, Cosyns JP, Houssiau FA; MAINTAIN
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37. Salvador F, Ribeiro S, Macedo C, Neves J, Teixeira S, Farinha F, Almeida I, Vasconcelos C. Vacinação para gripe A (H1N1) em
doentes com Lupus Eritematoso Sistémico Influenza A (H1N1) vaccination in Systemic Lupus Erythematosus patients. Medicina INterna
2012, 19, 140-44
38. Andreia Bettencourt, Ana Martins da Silva, Paulo Pinho e Costa, Berta Martins Silva. “Molecular genetic studies of multiple sclerosis in
the Portuguese population.” Acta Med Port 2012 Jul-Aug;25(4):224-230.
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patients with familial amyloidosis ATTR V30M. Retina. 2011 Jul-Aug;31(7):1373-7. PubMed PMID: 21358362.
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41. Nery F, Franca M, Almeida I, Vasconcelos C. From Clinical Presentation to the Outcome: the Natural History of PML in a Portuguese
Population of HIV Infected Patients. J Clin Med Res. 2011 Feb 12;3(1):17-22. PMID: 22043267
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Adler A, Glenn SB, Alarcón-Riquelme ME; BIOLUPUS Network; GENLES Network, Pons-Estel BA, Harley JB, Bae SC, Bang SY, Cho
SK, Jacob CO, Vyse TJ, Niewold TB, Gaffney PM, Moser KL, Kimberly RP, Edberg JC, Brown EE, Alarcon GS, Petri MA, RamseyGoldman R, Vilá LM, Reveille JD, James JA, Gilkeson GS, Kamen DL, Freedman BI, Anaya JM, Merrill JT, Criswell LA, Scofield RH,
Stevens AM, Guthridge JM, Chang DM, Song YW, Park JA, Lee EY, Boackle SA, Grossman JM, Hahn BH, Goodship TH, Cantor RM,
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43. Vasconcelos C, Kallenberg C, Shoenfeld Y. Refractory disease in autoimmune diseases. Autoimmun Rev. 2011 Sep;10(11):653-4. 2
PMID: 21601657
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44. Campar A, Farinha F, Vasconcelos C. Refractory disease in systemic lupus erythematosus. Autoimmun Rev. 2011 Sep;10(11):685-92.
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45. Almeida I, Faria R, Vita P, Vasconcelos C. Systemic sclerosis refractory disease: from the skin to the heart. Almeida I, Faria R, Vita P,
Vasconcelos C. Autoimmun Rev. 2011 PMID: 21575745
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46. Tan W, Sunahori K, Zhao J, Deng Y, Kaufman KM, Kelly JA, Langefeld CD, Williams AH, Comeau ME, Ziegler JT, Marion MC, Bae SC,
Lee JH, Lee JS, Chang DM, Song YW, Yu CY, Kimberly RP, Edberg JC, Brown EE, Petri MA, Ramsey-Goldman R, Vilá LM, Reveille
JD, Alarcón-Riquelme ME, Harley JB, Boackle SA, Stevens AM, Scofield RH, Merrill JT, Freedman BI, Anaya JM, Criswell LA, Jacob
CO, Vyse TJ, Niewold TB, Gaffney PM, Moser KL, Gilkeson GS, Kamen DL, James JA, Grossman JM, Hahn BH, Tsokos GC, Tsao BP,
Alarcón GS; BIOLUPUS Network; GENLES Network. Association of PPP2CA polymorphisms with systemic lupus erythematosus
susceptibility in multiple ethnic groups. Arthritis Rheum. 2011 Sep;63(9):2755-63. PMID: 21590681
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47. Hughes T, Kim-Howard X, Kelly JA, Kaufman KM, Langefeld CD, Ziegler J, Sanchez E, Kimberly RP, Edberg JC, Ramsey-Goldman R,
Petri M, Reveille JD, Martín J, Brown EE, Vilá LM, Alarcón GS, James JA, Gilkeson GS, Moser KL, Gaffney PM, Merrill JT, Vyse TJ,
Alarcón-Riquelme ME; BIOLUPUS Network, Nath SK, Harley JB, Sawalha AH. Fine-mapping and transethnic genotyping establish
IL2/IL21 genetic association with lupus and localize this genetic effect to IL21. Arthritis Rheum. 2011: PMID: 21425124
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48. Abecasis AB, Martins A, Costa I, Carvalho AP, Diogo I, Gomes P, Camacho RJ. Portuguese Hiv-1 Resistance Study Group Molecular
epidemiological analysis of paired pol/env sequences from Portuguese HIV type 1 patients. AIDS Res Hum Retroviruses. 2011
Jul;27(7):803-5.
49. Sarmento-Castro R, Vasconcelos C, Aguas MJ, Marques R, Oliveira J. Virologic suppression in treatment-experienced patients after
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50. Valadares D, Neves J, Almeida A, Lopes C, Vasconcelos C. Iron Lady: A Case of Eosinophilic Fasciitis. J Med Cases 2011;2(1):34-36
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Participação /agradecimento
Christopher J. Lessard,1,2 Indra Adrianto,1 John A. Ice,1 Graham B. Wiley,1 Jennifer A. Kelly,1 Stuart B. Glenn,1 Adam J. Adler,1 He
Li,1,2 Astrid Rasmussen,1 Adrienne H. Williams,3 Julie Ziegler,3 Mary E. Comeau,3 Miranda Marion,3 Benjamin E. Wakeland,4
Chaoying Liang,4 Paula S. Ramos,5 Kiely M. Grundahl,1 Caroline J. Gallant,6 Marta E. Alarcón-Riquelme for the BIOLUPUS and
GENLES Networks. Identification of IRF8, TMEM39A, and IKZF3-ZPBP2 as Susceptibility Loci for Systemic Lupus Erythematosus in
a Large-Scale Multiracial Replication Studys. Am J Hum Genet. 2012 April 6; 90(4): 648–660. PMID: 22464253
http://www.ncbi.nlm.nih.gov/pubmed?term=PMID%3A%2022464253
Indicadores de Realização Física
Neste quadro deve indicar os valores referentes ao período a que corresponde o Relatório de Progresso.
Neste quadro deve apenas indicar concretizações efectivas. Não indique publicações submetidas para publicação, nem teses que ainda não
tenham sido discutidas.
Indicadores
Quantidade
realizada
A - Publicações
Livros
0
Artigos em revistas internacionais
50
Artigos em revistas nacionais
4
B - Comunicações
Comunicações em encontros científicos internacionais
51
Comunicações em encontros científicos nacionais
28
C - Relatórios
0
D - Organização de seminários e conferências
0
E - Formação avançada
Teses de Doutoramento
0
Teses de Mestrado
6
Outras
0
F - Modelos
0
G - Aplicações computacionais
0
H - Instalações piloto
0
I - Protótipos laboratoriais
0
J - Patentes
0
L - Outros
7.
Ficheiros Anexos (opcional)
Poderá enviar, apenas se entender como estritamente necessário, ficheiros com formato PDF, que tenham sido referidos no relatório, por
exemplo, gráficos, esquemas, fotografias.
O conjunto dos ficheiros (em número máximo de cinco) ou o arquivo comprimido a enviar não poderão ultrapassar 10MB.
Nome do ficheiro
Agradecemos a sua colaboração.
Ponto do Relatório de Progresso
Descrição
Relatório Científico Final 2011-13 – UMIB
Research Group Title: Parkinson Disease Study Group
Principal Investigator: António Bastos Lima / Sara Cavaco
Research Area: Health Sciences
Home Institution: Instituto de Ciências Biomédicas Abel Salazar
Relatório de Progresso
Informação: Qualquer dúvida relacionada com o preenchimento do Formulário de Relatório de Progresso, por favor contacte-nos.
Atenção: - O formato da data a utilizar é dd-mm-yyyy
Formulário Relatório de Progresso - Componente Científica
Relatório Final
Período a que o relatório diz respeito:
Data de início: 01-01-2011
Data de fim: 31-12-2013
1. Identificação do Projecto
Referência do Projecto: PEst-OE/SAU/UI0215/2011
Investigador Responsável: Paulo Jorge Silva Correia Sa
Instituição Proponente: Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP)
Data de Início: 01-01-2011
Data de Fim: 31-12-2013
1. Identificação do grupo
Nome: Parkinson Disease Study Group
Investigador Responsável: Professor António Bastos Lima/Professora Sara Cavaco
Instituição Proponente: Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP)
Data de Início: 01-01-2011
Data de Fim: 31-12-2013
7.
Resumo dos Trabalhos Desenvolvidos e Desvios à Proposta aprovada
Resumo dos trabalhos
Descreva de forma breve as actividades desenvolvidas no período em apreço e os resultados alcançados. Refira-se em concreto às tarefas
que tiveram execução no período a que o relatório respeita. (6000 caracteres sem espaços)
De acordo com o planeado, em 2011, 2012 e 2013, o grupo de estudos da doença de Parkinson focalizou-se:
1) na caracterização dos sintomas não motores da doença de Parkinson;
No âmbito das teses de doutoramento da Dra. Alexandra Gonçalves (FMP), do Dr. Alexandre Mendes (ICBAS) e do Dr. Nuno Vila-Chã (FMP),
estão a ser estudados transversalmente todos os doentes de Parkinson da consulta de doenças do movimento do Centro Hospitalar do Porto para
os sintomas motores e não motores (cognitivos, olfactivos, da dor, do sono, neuropsiquiátricos e disautonómicos) e para a qualidade de vida.
Foram estudados 200 doentes de Parkinson até ao final de 2013. Dados preliminares dos estudos foram apresentados em comunicações (orais ou
pósteres). Estão também a ser estudados sujeitos saudáveis da comunidade como amostra de controlo. Encontra-se em fase avançada de
preparação um artigo científico que ilustra pela primeira vez o efeito da reserva cerebral nas manifestações motoras da doença de Parkinson.
Em colaboração com o Grupo de Imunogenética, Inflamação e Autoimunidade está a ser recolhido e estudado material genético de todos os
doentes que integram o estudo transversal, de forma a melhor compreender os sintomas não motores da doença de Parkinson. Em colaboração
com o grupo IGIA e com o laboratório Lysosome & Peroxisome Biology do IBMC, uma aluna de mestrado de Ciências Forenses do ICBAS sob
a orientação da Prof. Dra. Sara Cavaco e Prof. Dra. Berta Martins (grupo IGIA) explorou a mutação de Gaucher (mutação do gene da
glucocerebrosidase - N370S) numa amostra de 100 doentes de Parkinson. Esta mutação foi encontrada em dois doentes (esta frequência não é
superior à da população portuguesa). Nesta amostra de doentes foram também exploradas associações entre polimorfismos do sistema
dopaminérgico, do sistema glutamatérgico e do sistema serotoninérgico e a Perturbação no Controlo de Impulsos na doença de Parkinson. Foi
encontrada uma associação significativa entre o polimorfismo do sistema glutamatérgico e a ocorrência da Perturbação no Controlo de Impulsos.
Está prevista a divulgação destes resultados em reuniões científicas nacionais e internacionais.
2) na avaliação custo-eficiência da opção pela estimulação cerebral profunda sub-talámica (STN-DBS) vs. a melhor terapêutica médica no
tratamento da doença de Parkinson em fases avançadas ou com complicações motoras incapacitantes;
O estudo custo-eficiência da STN-DBS foi explorado por uma aluna de medicina do ICBAS sob a orientação do Dr. Alexandre Mendes. A STNDBS apresentou claro beneficio motor e relativa segurança cognitiva (dados apresentados em comunicações orais ou pósteres). Nos primeiros
dois anos após a cirurgia, a STN-DBS apresentou-se relativamente mais dispendiosa do que a melhor terapêutica médica. No entanto, verificouse uma marcada redução dos custos da opção STN-DBS com o tempo. A componente económica do estudo foi divulgada em reuniões científicas
nacionais.
3) na aferição e validação de instrumentos de avaliação cognitiva e psicopatológica para a população Portuguesa
Foram aferidos para a população portuguesa, usando técnicas de co-normalização, a Dementia Rating Scale – 2 (Cavaco & Teixeira-Pinto, 2011),
o Trail Making Test (Cavaco et al., 2013), a fluência verbal categorial (Cavaco et al., 2013), a fluência verbal literal (Cavaco et al., 2013), e o
Brief smell identification test (Martins da Silva et al 2012; Cavaco et al 2012; comunicações orais e pósteres). Foi desenvolvida em colaboração
com o grupo CINTESIS uma aplicação online (neuropsi.up.pt) para uso mais fácil das fórmulas de aferição baseadas na regressão do Trail
Making Test, da fluência verbal categorial e da fluência verbal literal, por parte de clínicos e investigadores portugueses. Os dados normativos
recolhidos na aferição do Trail Making Test, da fluência verbal categorial, da fluência verbal literal e do Auditory Verbal Learning Test
integraram o estudo multicêntrico liderado pela Johns Hopkins University School of Medicine, chamado International Neuropsychological
Normative Database Initiative (http://inndi.org/), que procura desenvolver a aferição mundial de um conjunto de testes neuropsicológicos,
através de técnicas de regressão que tenham em conta não só as variáveis demográficas como também as característics culturais e linguísticas dos
sujeitos. Foram desenvolvidos trabalhos de validação clínica destes instrumentos para a doença de Parkinson sem demência, para a doença de
Huntington, para a doença de Alzheimer, para a demência frontotemporal e para doenças auto-imunes (Cavaco & Teixeira-Pinto, 2011; Martins
da Silva et al, 2011a, 2011b, 2012; Cavaco et al 2012; Taipa et al., 2012; comunicações orais e pósteres).
Desvios à Proposta Aprovada
Se tiver havido desvios à proposta aprovada, quer do ponto de vista científico como financeiro, aponte os desvios e justifique-os. Se teve
dificuldades na execução do plano de trabalhos aprovado, identifique-os e indique de que modo pretende ultrapassá-los.
Se no período em apreço tiver informado a FCT sobre alteração orçamental inter-rubricas (necessitem ou não de autorização por parte da FCT),
indique aqui o motivo. (4000 caracteres sem espaços)
O reconhecimento de emoções em expressões faciais continuou a ser explorado em doentes de Parkinson. Começou também a ser explorado noutras
populações neurológicas (esclerose múltipla, esclerose mesial e doença de Huntington). Os resultados preliminares para doentes de Parkinson e para
doentes com esclerose mesial foram apresentados em comunicações (orais ou pósteres). O estudo do reconhecimento de emoções em expressões
faciais foi completado em doentes com esclerose múltipla (Pinto et al., 2012) e doença de Huntington (Van Asselen et al., 2012).
O Professor Dr. Bastos Lima integrou o estudo epidemiológico de avaliação da prevalência da Doença de Parkinson em Portugal, chamado Estudo
PrevPark.
A Prof. Dra. Sara Cavaco integrou o grupo multicêntrico de estudo da doença de Huntington, chamado Euro-Huntington’s Disease Network
(http://www.euro-hd.net) (Orth et al., 2011; Quarrell et al., 2012) e o grupo multicêntrico de aferição de testes neuropsicológicos, chamado
International Neuropsychological Normative Database Initiative (http://inndi.org/)
O Grupo de Estudos da Doença de Parkinson organizou em colaboração com a Reitoria da Universidade do Porto e com o Centro Hospitalar do Porto
“O Curso em Neurociências Clínicas: da patologia a avaliação diagnóstica”, que se realizou a 18 e 19 de Novembro de 2011. Este curso de educação
contínua destinou-se a profissionais das áreas de medicina, neurociências e psicologia.
Continuou a colaboração com o Grupo de Imunogenética, Inflamação e Autoimunidade e o com o Laboratório de Neurobiologia do Comportamento
Humano para os estudos “Funcionamento cognitivo em doenças autoimunes multi-sistémicas” e “Funcionamento cognitivo numa população de
doentes portugueses com Esclerose Múltipla”.
Continuou a colaboração com a University of Iowa Carver College of Medicine Division of Behavioral Neurology and Cognitive Neuroscience e com
o Laboratório de Neurobiologia do Comportamento Humano para o estudo “Envolvimento do cortex parietal posterior na aprendizagem de skills”.
Equipa de Investigação
desistiu
(marcar
com
Nome
Cargo
Tarefas
%Tempo
data
uma X
data de
de
se for o
entrada
saída
caso)
Gr
X
PDSG
Ana Paula Andrade Correia de
Mesquita Guimarães
Investigador
20
- Investigador principal em diversos estudos
António Fernando Bastos Lima
Investigador de investigação;
20
PDSG
20
PDSG
20
PDSG
25
PDSG
25
PDSG
- Colaborou em estudos de investigação
relacionados com a cirurgia STN-DBS em
António José Verdelho Vieira
Investigador doentes de Parkinson;
- Colaborou em diversos estudos de
investigação: aferição e validação de provas
neuropsicológicas; estudos relacionados
com a cirurgia STN-DBS em doentes de
Cláudia Sofia Teles de Meneses
Malheiro Pinto
Parkinson; estudos em doenças autoimunes
Investigador (esclerose múltipla, lúpus)
- Colaborou em diversos estudos de
investigação relacionados com a doença de
Parkinson;
- Orientação do “Estudo económico da
estimulação bilateral dos núcleos
subtalâmicos na doença de Parkinson”
realizado pela aluna do ICBAS Sofia Daniela
Martins Carvalho
- Iniciou o Programa Doutoral em Ciências
Médicas, do ICBAS – Universidade do Porto;
Tema da tese: Evolução da doença de
Parkinson – operacionalização da decisão
cirúrgica; Orientadores: Professor Doutor
Fernando Alexandre Pereira
Mendes
Bastos Lima, Professora Dra. Sara Cavaco e
Investigador Professor Doutor Paul Krack
- Colaborou em diversos estudos de
investigação: aferição e validação de provas
neuropsicológicas; estudos relacionados
com a cirurgia STN-DBS em doentes de
Parkinson; estudos em doenças autoimunes
(esclerose múltipla, lúpus);
Filomena Maria Correia Gomes
Investigador - Iniciou o Programa Doutoral em
Neurociências, da Faculdade de Medicina –
Universidade do Porto; Tema da tese: Test
of Memory Malingering: Utility of
Neuropsychophysiological measures for
detecting malingering; Orientadores:
Professora Dra. Sara Cavaco e Professora
Dra. Carolina Garrett
- Colaborou em estudos de investigação
Luis Filipe Botelho Casal dos
Santos
relacionados com a cirurgia STN-DBS em
Investigador doentes de Parkinson;
15
PDSG
50
PDSG
- Colaborou em diversos estudos de
investigação: aferição e validação de provas
neuropsicológicas; estudos em doenças
autoimunes (esclerose múltipla, lúpus);
- Iniciou o Programa Doutoral em
Neurociências, da Faculdade de Medicina –
Universidade do Porto; Tema da tese: Nonmotor symptoms in Parkinson's disease: a
comprehensive and integrated approach;
Orientadores:
Maria Alexandra Ribeiro
Gonçalves
Prof. Doutora Sara Cavaco e Prof. Doutor
Investigador Marques-Teixeira
- Colaborou em diversos estudos de
investigação: aferição e validação de provas
neuropsicológicas; estudos relacionados
com a cirurgia STN-DBS em doentes de
Parkinson; estudos em doenças autoimunes
(esclerose múltipla, lúpus);
- Em 2012, registou-se uma mudança de
Maria Inês Dias Moreira
Investigador estatuto, passou de investigadora a bolseira
50
x
PDSG
Investigador
25
X
PDSG
Marina Justino Matias de
Magalhaes Castelo Branco
- Colaborou em diversos estudos de
investigação relacionados com a doença de
Parkinson;
- Iniciou o Programa Doutoral em
Investigação Clínica e em Serviços de
Saúde, da Faculdade de Medicina –
Universidade do Porto
Tema da tese: Dor na doença de Parkinson;
Orientador: Professor Doutor José Manuel
Castro Lopes, Professor Catedrático da
Faculdade de Medicina – Universidade do
Nuno Miguel dos Santos Vila-Chã
Investigador Porto
15
PDSG
- Investigadora principal e colaboradora em
Sara Marta Pereira dos Santos
Cavaco
diversos estudos de investigação;
Investigador - Orientação de teses de doutoramento
50
PDSG
3.
Publicações
Apenas para o período a que respeita o Relatório de Progresso, indique trabalhos apresentadas ou aceites para publicação ou apresentação, e
trabalhos submetidos no período a que o relatório respeita.
A informação pretendida neste campo é inserida em formato livre. Para cada publicação deve ser indicada a seguinte informação:
1.
Descrição, contendo os seguintes elementos:
•
Em livros ou monografias: autor(es), título, número e/ou identificação da edição, número do volume, lugar da publicação,
número de páginas;
•
Em revistas científicas: autor(es), título, título da revista, lugar da publicação, número do volume, número da primeira e última
página;
•
Em artigos ou abstracts de comunicações científicas ou outras participações de índole científica em congressos internacionais
ou nacionais: autor(es), título do artigo
•
ou comunicação, nome da publicação, volume, número de páginas;
2.
Estado, indicando a situação:
•
Publicado/Apresentado;
•
Aceite para publicação/apresentação;
•
Submetido.
Nos trabalhos aceites para apresentação ou publicação, a data de aceitação deve ser indicada no campo descrição.
Nota em 22-11-2011: Para os trabalhos que tenham sido publicados ou apresentados deve ser indicado o URL onde o mesmo possa ser
consultado, devendo este URL ser mantido pelo mesmo período do dossier de projecto.
Exemplos:
•
Aceite - I. Santos, J. Rodrigues, "Non linear control design of a team of autonomous vehicles", aceite (Dezembro de 2008) para
apresentação na IEEE Conference on Control Systems, Madrid, Espanha, Maio de 2009. URL: http://www.xpto.xpto.pt
•
Publicado - A. Silva, P. Oliveira, "Social behaviour of a dog colony in extreme conditions", Journal of Animal Behaviour, Elsevier, Vol. 2,
Nº3, pp.373-395, September 2009. URL: http://www.xpto.xpto.pt
•
Apresentado - V. Santos, J. Rodrigues, "Medical image segmentation for endoscopy applications", Proc. of the International Conference
on Medical Imaging, Pittsburgh, USA, March 2009, pp. 304-312. URL: http://www.xpto.xpto.pt
•
Submetido - M. Santos, P. Oliveira, "Comparative Analysis of Elephant Populations", submetido (Fevereiro de 2009) para apresentação
na International Conference on Veterinary Studies, S. Paulo, Brasil, Novembro de 2009.
Nota em 22-11-2011: Chama-se a atenção para a necessidade absoluta do cumprimento das Normas de Informação e Publicidade
disponíveis para consulta em http://www.fct.pt/apoios/projectos/regulamentos
Nessas normas são indicadas frases tipo de publicitação para o caso de artigos científicos e teses. (até 6000 caracteres sem espaços)
Ferramenta online: http://neuropsi.up.pt/
Livro:
Publicado - Cavaco S. & Teixeira-Pinto A. (2011). Dementia Rating Scale-2: Manual Técnico (Versão Portuguesa). Lisboa: Cegoc-Tea.
http://www.cegoc.pt/teste/escala-de-avaliacao-da-demencia-2/ ISBN: 978-972-8817-62-6
Artigos originais:
Publicado - Cavaco S, Anderson, SW, Correia M, Magalhães M, Pereira C, Tuna A, Taipa R, Pinto P, Pinto C, Cruz R, Bastos Lima A, Castro-Caldas
A, Martins da Silva A, Damásio H. Task specific contribution of the human striatum to perceptual-motor skill learning. Journal of Clinical and
Experimental Neuropsychology. 2011; 33(1): 51-62. http://www.ncbi.nlm.nih.gov/pubmed/20603739
Publicado - Martins da Silva Ana, Cavaco S, Taipa R, Pinto P, Melo Pires M. Medulloblastoma and gliomatosis cerebri: rare brain tumors in Multiple
Sclerosis patients. Neurological Sciences. 2011. 32(5):893-7. http://www.ncbi.nlm.nih.gov/pubmed/21234776
Publicado - Martins da Silva Ana, Vilhena E, Lopes A, Santos E, Gonçalves MA, Pinto C, Moreira I, Mendonça D, Cavaco S. Depression and anxiety
in a Portuguese MS population: associations with physical disability and severity of disease. Journal of the Neurological Sciences. 2011; 306: 66–70.
http://www.ncbi.nlm.nih.gov/pubmed/21497358
Publicado - Martins Silva A, Santos E, Moreira I, Coutinho E, Bettencourt A, Gonçalves A, Pinto C, Montalban X, Cavaco S. Olfactory
dysfunction
in
multiple
sclerosis:
association
with
secondary
progression.
Multiple
Sclerosis.
2012;
18(5):616-21.
http://www.ncbi.nlm.nih.gov/pubmed/22020420
Publicado - Cavaco S, Martins da Silva Ana, Santos E, Coutinho E, Marinho A, Moreira I, Gonçalves A, Pinto C, Teixeira-Pinto A, Vasconcelos C.
Are Cognitive And Olfactory Dysfunctions In Neuropsychiatric Lupus Erythematosus Dependent on Anxiety or Depression? J Rheumatol. 2012;
39(4):770-6. http://www.ncbi.nlm.nih.gov/pubmed/22382338
Publicado - Pinto C, Gomes F, Moreira I, Rosa B, Santos E, Martins Silva A, Cavaco S. Emotion recognition in Multiple Sclerosis. Journal of
Eyetracking, Visual Cognition and Emotion. 2012, 2(1): 76-81.
Publicado - Taipa R, Tuna A, Damásio J, Pinto PS, Cavaco S, Pereira S, Milterberger-Miltenyi G, Galimberti D, Melo Pires M. Clinical,
neuropathological and genetic characteristics of the novel IVS9+1delG GRN mutation in a patient with frontotemporal dementia. J Alzheimers Dis.
2012, 30(1):83-90. http://www.ncbi.nlm.nih.gov/pubmed/22366770
Publicado - Van Asselen M, Júlio F, Januário C, Bobrowicz Campos E, Almeida I, Cavaco S, Castelo Branco M. Scanning patterns of faces do not
explain impaired emotion recognition in Huntington Disease: Evidence for a high level mechanism. Frontiers in Psychology 2012, 3, 31.
http://www.ncbi.nlm.nih.gov/pubmed/22355293
Publicado - Cavaco S, Feinstein JS, van Twillert H, Tranel D. Musical memory in a patient with severe anterograde amnesia. Journal of Clinical and
Experimental Neuropsychology. 2012, 34 (10), 1089-1100. http://www.ncbi.nlm.nih.gov/pubmed/23036073
Publicado - Barros J, Mendes A, Matos I, Pereira-Monteiro J. Psychotic aura symptoms in familial hemiplegic migraine type 2 (ATP1A2). The Journal
of Headache and Pain 2012, 13 (7): 581-585. http://www.ncbi.nlm.nih.gov/pubmed/22661290
Publicado - Cavaco S; Gonçalves A, Pinto C, Almeida E, Gomes F, Moreira I, Fernandes J, Teixeira-Pinto A. Trail Making Test: regression-based norms
for the Portuguese population. Archives of Clinical Neuropsychology. 2013, 28(2):189-98. http://www.ncbi.nlm.nih.gov/pubmed/23299183
Publicado - Cavaco S; Gonçalves A, Pinto C, Almeida E, Gomes F, Moreira I, Fernandes J, Teixeira-Pinto A. Semantic Fluency and Phonemic
Fluency:
regression-based
norms
for
the
Portuguese
population.
Archives
of
Clinical
Neuropsychology.
2013,
28(3):262-271.
http://www.ncbi.nlm.nih.gov/pubmed/23341434
Artigos listados como colaborador:
Publicado - Orth M; European Huntington's Disease Network, Handley OJ, Schwenke C, Dunnett S, Wild EJ, Tabrizi SJ, Landwehrmeyer GB.
Observing Huntington's disease: the European Huntington's Disease Network's REGISTRY. Journal Of Neurology Neurosurgery And Psychiatry
2011; 82(12):1409-12. http://www.ncbi.nlm.nih.gov/pubmed/21097549
Publicado - Quarrell OW, Handley O, O'Donovan K, Dumoulin C, Ramos-Arroyo M, Biunno I, Bauer P, Kline M, Landwehrmeyer GB; European
Huntington’s Disease Network. Discrepancies in reporting the CAG repeat lengths for Huntington's disease. European Journal of Human Genetics.
2012; 20(1):20-6. http://www.ncbi.nlm.nih.gov/pubmed/21811303
Publicado - Hubers AA, van Duijn E, Roos RA, Craufurd D, Rickards H, Bernhard Landwehrmeyer G, van der Mast RC, Giltay EJ; REGISTRY
investigators of the European Huntington's Disease Network. Suicidal ideation in a European Huntington's disease population. J Affect Disord. 2013
Oct;151(1):248-58. http://www.ncbi.nlm.nih.gov/pubmed/23876196
Resumos Publicados em reuniões nacionais e internacionais com arbitragem:
Publicado - Cavaco S, Martins Silva Ana, Santos E, Coutinho E, Moreira I, Gonçalves A, Pinto C, Teixeira-Pinto A, Marinho A, Vasconcelos C.
Olfactory dysfunction in systemic lupus erythemathosus with neuropsychiatric manifestations. Lupus 2011; 20(4): 381.
Publicado - Cruto C, Freitas J, Carvalheiras G, Mendes A, Bastos Lima A. HIV infection and Parkinson’s Disease: is there a causal relationship?
Journal of Neurology 2011; 258 (supplement 1): S86.
Publicado - Cruto C, Martins da Silva A, Lopes J, Vila-Chã J. Movimentos periódicos das pernas como manifestação paraneoplásica. Sinapse 2011;
11(2): 89.
Publicado - Rua A, Cruto C, Monteiro C, Damásio J, Vila-Chã, N. Duas etiologias tratáveis para uma síndrome demencial e tremor. Sinapse 2011;
11(2): 66.
Publicado - Martins da Silva Ana, Cavaco S, Santos E, Coutinho E, Moreira I, Gonçalves A, Pinto C, Vasconcelos C. Quality Of Life In Systemic
Lupus Erythematosus With Neuropsychiatric Manifestations. Lupus 2011; 20(4): 400.
Publicado - Cavaco S, Martins da Silva Ana, Santos E, Coutinho E, Moreira I, Gonçalves A, Pinto C, Vasconcelos C. Are neuropsychological
impairments in systemic lupus erythematosus independent of psychopathology? Lupus 2011; 20(4): 349.
Publicado - Bettencourt A, Martins da Silva Ana, Tavares A, Carvalho C, Leal B, Santos E, Gonçalves A, Moreira I, Vasconcelos C, Costa PP,
Cavaco S, Silva BM. No association between apoE polymorphisms and neurolupus in Portuguese patients. Lupus 2011; 20(4): 362.
Publicado - Leal B, Bettencourt A, Martins da Silva Ana, Carvalho C, Maia S, Santos E, Pinto C, Moreira I, Costa PP, Vasconcelos C, Cavaco S,
Silva BM. The serotonin HTR2A receptor 102 T>C gene polymorphism is associated with depression in Portuguese patients with systemic lupus
erythematosus. Lupus 2011; 20(4): 362
Publicado - Martins Silva Ana, Bettencourt A, Ribeiro A, Gonçalves A, Pinto C, Moreira I, Santos E, Coutinho E, Tavares A, Costa P, Martins Silva
B, Cavaco S. Dementia in Multiple Sclerosis: demographic, clinical and genetic features. Journal of Neurology 2011; 258 (supplement 1): S91.
Publicado - Martins Silva Ana, Bettencourt A, Gonçalves A, Pinto C, Santos E, Moreira I, Tavares A, Coutinho E, Gomes F, Costa P, Martins Silva
B, Cavaco S. Does APOE-epsilon4 have a detrimental effect in Multiple Sclerosis? Journal of Neurology 2011; 258 (supplement 1): S148.
Publicado - Cavaco S, Vila-Chã N, Moreira I, Mendes A, Bastos Lima A. Validação do Brief-Smell Identification Test para a doença de Parkinson.
Sinapse 2011; 11(2): 85.
Publicado - Correia FD, Domingos J, Ferreira J, Roque R, Taipa R, Cavaco S, Correia J, Martins da Silva Ana. Meningoencefalite recorrente como
apresentação sistémica de artrite reumatoide. Sinapse 2011; 11(2): 80.
Publicado - Domingos J, Santos E, Coutinho E, Pinho C, Gonçalves A, Cavaco S, Martins da Silva Ana. Afasias agudas em doentes com Esclerose
Múltipla. Sinapse 2011; 11(2): 42.
Publicado - Taipa R, Tuna A, Damásio J, Pinto PS, Cavaco S, Miltenberger G, Galimberti D, Manuel Melo-Pires. Características clínicas, genéticas e
neuropatológicas de uma nova mutação da progranulina na DFT. Sinapse 2011; 11(2): 44-45.
Publicado - Martins da Silva Ana, Vilhena E, Cavaco S, Santos E, Pinto C, Gonçalves A, Moreira I, Mendonça D, Pais-Ribeiro J. Predictor factors of
quality of life in MS Portuguese patients. European Journal Of Neurology, 18 (Supplement 2): 585.
Publicado - Vila-Chã N, Mendes A, Cavaco S, Bastos Lima A. Avaliação da qualidade dos registos clínicos na Doença de Parkinson. Sinapse 2011;
11(2): 49-50.
Publicado - Costa A, Rocha S, Mendes A, Ramalheira J. A importância dos distúrbios do sono na abordagem da Sindrome da Deficiência de
Desidrogenase Semialdeído Succínica. Sinapse 2011; 12(2): 116.
Publicado - Verdelho A, Silva C, Mendes A, Vila Chã N, Felgueiras R, Temudo T, Botelho L, Bastos Lima A. Report of GPi-DBS in two patients
with Pantothenate Kinase-Associated Neurodegeneratation: long term follow-up and video illustration. Stereotact Funct Neurosurg, 2012, 90(S1): 55.
Publicado - Almeida E, Gomes F, Gonçalves A, Pinto C, Moreira I, Lopes Lima J, Chaves J, Cavaco S. Qualidade de vida na Epilepsia: Relação com
características clínicas, demográficas e psicopatológicas. Sinapse 2012; 12(1): 141.
Publicado - Moreira I, Cavaco S, Pinto C, Gonçalves A, Almeida E, Marinho A, Santos E, Martins da Silva Ana, Vasconcelos C. Psicopatologia no
Lúpus Eritematoso Sistémico e na doença de Behçet. Sinapse 2012; 12(1): 150.
Publicado - Gomes F, Pinto C, Moreira I, Verdelho A, Silva C, Botelho L, Vila-Chã N, Mendes A, Bastos Lima A, Cavaco S. Identificação de
Emoções na doença de Parkinson antes e após STN-DBS. Sinapse 2012; 12(1): 170.
Publicado - Gonçalves A, Moreira I, Pinto C, Cavaco S, Mendes A, Vila-Chã N, Bastos Lima A. Dementia Rating Scale-2 e Doença de Parkinson.
Sinapse 2012; 12(1): 130.
Publicado - Fernandes J, Moreira I, Cavaco S, Damásio J, Loureiro R, Magalhães M, Quality of life in Huntington disease and its association with
psychopathology. European Journal of Neurology 2012, 19 (Supplement 1): 330.
Publicado - Taipa R, Pinto PS, Monteiro C, Santos E, Cavaco S, Correia AP. Presenting symptoms and structural MRI analysis of early onset
Alzheimer’s disease and frontotemporal lobar degeneration. Dementia and Geriatric Cognitive Disorders 2012, 33 (Supplement 1): 244-245.
Publicado - Taipa, R, Santos, E, Pinto, PS, Cavaco, S, Galimberti, D, Correia, AP. Demencia frontotemporal e doença de neurónio motor: descrição
de 3 casos com expansão do gene C9orf72. Sinapse 2013; 13(1): 68.
Publicado - Moreira I, Cavaco S, Gomes F, Moreira I, Chaves J. Efeitos da lateralidade da esclerose mesial na identificação de emoções. Sinapse
2013; 13(1): 185.
Publicado - Domingos J, Rodrigues T, Pinto P, Taipa R, Melo Pires M, Cavaco S, Mendes A, Magalhães M, Damásio J. Síndrome cortico-basal:
caracterização clínica e imagiológica de uma série de doentes. Sinapse 2013; 13(1): 206.
Publicado - Gomes F, Gonçalves A, Pinto C, Almeida E, Moreira I, Verdelho A, Silva C, Botelho L, Vila-Chã N, Mendes A, Bastos Lima A, Cavaco
S. STN-DBS na Doença de Parkinson: Importância da Fluência Verbal na Selecção dos Candidatos. Sinapse 2013; 13(1): 208.
Publicado - Gonçalves A, Mendes A, Moreira I, Vila-Chã N, Bastos Lima A, Cavaco S. Apatia na Doença de Parkinson. Sinapse 2013; 13(1): 210.
.
Publicado - Fernandes J, Moreira I, Gonçalves A, Pinto C, Almeida E, Gomes F, Damásio J, Loureiro R, Magalhães M, Cavaco S Fluência verbal na
doença de Huntington. Sinapse 2013; 13(1): 212.
Publicado - Pinto C, Pinto P, Cavaco S, Taipa R. Variante direita da Demência Semântica: descrição de dois casos. Sinapse 2013; 13(2): 173.
Publicado - Gomes F, Pinto C, Pinto, Correia AP, Santos E, Taipa R, Cavaco S. Funcionamento cognitivo, características clínicas e imagiológicas na
Demência de Alzheimer e Degenerescência Lobar Frontotemporal. Sinapse 2013; 13(2): 172.
Publicado - Varanda S, Rangel R, Chaves J, Moreira B, Cavaco S, Martins da Silva A, Lopes J, Ramalheira J. Cirurgia da epilepsia com
monitorização invasiva. Sinapse 2013; 13(2): 99.
.
Publicado - Moreira I, Vila-Chã N, Gonçalves A, Moreira Inês, Cavaco S, Bastos Lima A, Alexandre Mendes Flutuações motoras nos primeiros 5
anos da doença de Parkinson. Sinapse 2013; 13(2): 77.
Publicado - Domingos J, Alves JE, Correia F, Cavaco S, Damásio J, Pessegueiro Miranda H, Magalhães M. Degenerescência hepato-cerebral
adquirida: caracterização de um coorte de 26 doentes. Sinapse 2013; 13(2): 77.
Publicado - Martins Silva Ana, Moreira I, Pinto C, Santos E, Samões R, Gonçalves A, Bettencourt A, Montalban X, Cavaco S. The influence of
education on cognition in Multiple Sclerosis. Multiple Sclerosis 2013, 19(11 suppl): 203.
Publicado - Samões R, Lopes D, Moreira I, Santos E, Fernandes J, Bettencourt A, Cavaco S, Martins Silva Ana. Smoking and age of onset in
Multiple Sclerosis patients. Multiple Sclerosis 2013, 19(11 suppl): 106.
Publicado - Mendes A, Gonçalves A, Vila-Chã N, Moreira I, Cavaco S, Bastos Lima. Association between gait and cognitive functioning in
Parkinson’s Disease. Journal of Neurology 2013, 260 (1 supplement): S140-141.
Publicado - Gonçalves A, Mendes A, Vila-Chã N, Moreira I, Moreira I, Bastos Lima A, Cavaco S. Axial symptoms and cognitive functioning in
Parkinson's disease. Journal of the Neurological Sciences 2013, 333: e76.
Publicado - Domingos J, Correia F, Cavaco S, Almeida A, Damasio J, Miranda HP, Magalhães M. Acquired hepatocerebral degeneration:
characterization of a cohort of 17 patients. Journal of Neurology 2013, 260 (1 supplement): S62
Publicado - Domingos JP, Alves JE, Cavaco S, Ferreira S, Lopes V, Pereira JP, Moreira B, Miranda HP, Magalhães M. The role of liver transplant in
the treatment of acquired hepatocerebral degeneration and hepatic encephalopathy. Journal of the Neurological Sciences 2013, 333: e78.
Outras comunicações (orais ou pósteres) em reuniões internacionais:
Apresentado - Domingos, R Loureiro, J Damásio, M Magalhães, P Krack, A Mendes. Symptoms
Progression in a DYT1 Positive Patient with Gpi-DBS – failure of a second lead implant. 5th
International Dystonia Symposium, Barcelona, October 2011.
http://www.internationaldystoniasymposium.org/programa.pdf
Apresentado - Sá J, Mendes A, Quelhas D, Salomons GS, Jakobs C, Soares G. Succinic Semialdehyde Dehydrogenase Deficiency: a rare disease
affecting two sisters. VIII International Symposium SPDM, Porto, November 2011.
Indicadores de Realização Física
Neste quadro deve indicar os valores referentes ao período a que corresponde o Relatório de Progresso.
Neste quadro deve apenas indicar concretizações efectivas. Não indique publicações submetidas para publicação, nem teses que ainda não
tenham sido discutidas.
Indicadores
Quantidade
realizada
A - Publicações
Livros
1
12 artigos
originais
Artigos em revistas internacionais
3 artigos
listados como
colaboradores
Artigos em revistas nacionais
0 artigos
B - Comunicações
18 resumos
publicados
Comunicações em encontros científicos internacionais
+2
comunicações
sem resumo
Comunicações em encontros científicos nacionais
23 resumos
publicados
C - Relatórios
D - Organização de seminários e conferências
1
E - Formação avançada
Teses de Doutoramento
4 doutorandos
Teses de Mestrado
0
Outras
0
F - Modelos
0
G - Aplicações computacionais
1
H - Instalações piloto
0
I - Protótipos laboratoriais
0
J - Patentes
0
L - Outros
8.
Ficheiros Anexos (opcional)
Poderá enviar, apenas se entender como estritamente necessário, ficheiros com formato PDF, que tenham sido referidos no relatório, por
exemplo, gráficos, esquemas, fotografias.
O conjunto dos ficheiros (em número máximo de cinco) ou o arquivo comprimido a enviar não poderão ultrapassar 10MB.
Nome do ficheiro
Agradecemos a sua colaboração.
Ponto do Relatório de Progresso
Descrição
Relatório Científico Final 2011-13 – UMIB
Research Group Title: Blood, lymphopoietic and haematopoietic disorders
Principal Investigator: Margarida Lima
Research Area: Health Sciences
Home Institution: Instituto de Ciências Biomédicas Abel Salazar
UMIB - FORMULÁRIO RELATÓRIO FINAL - COMPONENTE CIENTÍFICA 2011 – 2012 - 2013
Nota Informativa:
Relatório de Execução Científica
O Relatório de Execução Científica (pontos 2 a 9) tem de ser obrigatoriamente lacrado pelo IR no prazo de 1 mês após o envio da comunicação da FCT a solicitar o seu
preenchimento, a fim de ser disponibilizado ao painel de avaliação final.
O ponto 8 deve conter uma descrição pormenorizada (incluindo tabelas, quadros ou mapas) da execução dos trabalhos do projecto ao longo do período considerado,
de acordo com a programação e calendarização constante na proposta aprovada, bem como análise dos desvios verificados face ao programado, a fim de permitir a avaliação
dos trabalhos de investigação desenvolvidos. Deve ser feito upload de um ficheiro PDF contendo esta informação.
Ficheiros anexos podem ser incluídos no ponto 9.
Relatório de Execução Financeira
Após conclusão da análise da execução financeira por parte da FCT, o Investigador Responsável será contactado para, no prazo de 10 dias úteis:
Lacrar a Componente Financeira do Relatório Final (RF)
Imprimir o Termo de Responsabilidade que, devidamente assinado e autenticado pelos subscritores e rubricado pelo Investigador Responsável em todas as páginas, deverá
ser enviado por correio para a FCT, I.P. ao cuidado de: Departamento de Suporte à Rede de Instituições Científicas e Tecnológicas.
Atenção
- A sessão expira ao fim de 20 minutos de inactividade;
- O formato da data a utilizar é dd-mm-yyyy;
- No Ponto 8, o tamanho máximo do ficheiro em PDF é de 5MB;
- No Ponto 9, a soma do tamanho dos ficheiros PDF não pode exceder 10MB!
Caso não consiga fazer o Upload dos ficheiros é favor contactar [email protected]
Componente Financeira do Relatório Final (RF)
Nota: Os dados que surgem nos quadros da Componente Financeira do Relatório Final são provisórios, até à conclusão da análise da execução por
parte da FCT.
1. Identificação do Projecto
Referência do Projecto: PEst-OE/SAU/UI0215/2011
Investigador Responsável: Paulo Jorge Silva Correia Sa
Instituição Proponente: Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP)
Data de Início: 01-01-2011 Data de Fim: 31-12-2013
2. Caracterização Sumária do Projecto
Objectivos do Projecto (indicar endereço electrónico do(s) site(s) criado(s), quando aplicável)
Breve descrição das actividades desenvolvidas bem como dos desvios ocorridos durante a execução do
projecto
Objectivos atingidos
Realização Financeira (justificação sumária dos desvios ocorridos durante a execução do projecto)
3. Instituições que Participam no Projecto
Designação
Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP)
Centro Hospitalar do Porto, EPE (CHP/MS)
Nº Pessoas Mês
14289
0
14290
0
Lista de membros da equipa (preenchido automaticamente)
PhD = 4
1.
Ana Paula Guimarães da Mota, graduated in Clinical Analysis, PhD in Biomedical Sciences
2.
Magdalena Ann Leander, graduated in Pharmaceutical Sciences, PhD in Biomedical Sciences
3.
Margarida Maria de Carvalho Lima, MD, PhD in Medical Sciences
4.
Maria Beatriz Beça Gonçalves Porto e Vasconcelos, graduated in Biology, PhD in Human Genetics
MhD = 9 + 1 = 10
Desistiu
1.
Ana Helena Ribeiro Santos, graduated in Clinical Analysis, graduated in History of Art, MsD in Health Organization Management.
2.
Cláudia Angelina Borges Torres, graduated in Biochemistry, MsD in Biochemistry, PhD student (ICBAS/UP)
3.
Ivette Conceição Filipe Fernandes de Lima, graduated in Pharmaceutical Sciences, MsD in Pharmaceutical Sciences
4.
João Bernardo Coelho Pinho Sousa Rodrigues, graduated in Microbiology, MsD in Microbiology
5.
Maria Esmeralda de Azevedo Rodrigues Neves, MD (Clinical Pathology), MsD in Clinical Pathology and Chemistry, PhD student (ICBAS/UP)
6.
Maria Luís Araújo Queirós, graduated in Pharmaceutical Sciences, MsD in Pharmaceutical Sciences, PhD student (FF/UP)
7.
Marlene Araújo dos Santos, graduated in Clinical Analysis, MsD in Clinical Analysis
8.
Marta Marina Melo Gomes, graduated in Clinical Analysis, MsD in Clinical Analysis
9.
Mónica Cristina Teixeira Pereira, graduated in Biochemistry, MsD in Molecular Genetics, PhD student (ICBAS/UP)
10. Paula Cristina dos Santos Lino Carneiro, graduated in Pharmaceutical Sciences, MsD in Clinical Analysis
GRADUATED = 15 + 5 = 20
1.
Fernanda José Teixeira Leite, MD (Immunohemotherapy), PhD student (FM/UP)
2.
José Alberto Barcelos de Morais Barbot MD (Clinical Hematology) (*)
3.
Júlia Maria Andrade Mendes de Vasconcelos, MD (Clinical Pathology)
4.
Laura Elvira Gonçalves Novo da Hora Marques, MD (Pediatrics)
5.
Manuel César Santos Araújo de Campos, MD (Clinical Hematology)
6.
Margarida Maria dos Santos Guedes Carolino, MD (Pediatrics)
7.
Margarida Sara Mendes Moreira MD (Psichiatry) (*)
8.
Maria Catarina Panelas Nunes Lau, MD (Immunohemotherapy)
9.
Maria da Conceição Ramos de Morais Cerveira, MD (Clinical Pathology) (*)
10. Maria de Lurdes Baptista de Oliveira Marques Fino, graduated in Clinical Analysis, graduated in Pharmacia
11. Maria del Rosário Alves dos Santos, MD (Dermatology, Dermatopathology)
12. Maria dos Anjos Coutinho Teixeira, MD (Immunohemotherapy)
13. Maria Fernanda Soares Teixeira, MD (Pediatrics)
14. Maria Inês Oliveira Azevedo Freitas, MD (Clinical Pathology) (*)
15. Maria Judite Varela de Almeida Guimarães, graduated in Pharmaceutical Sciences
16. Maria Luciana Gomes de Pinho, MD (Clinical Pathology) (*)
17. Marika Mónica Bini Antunes, MD (Immunohemotherapy)
18. Marta Sofia da Cunha Gonçalves, graduated in Biochemistry
19. Sara Maria Teixeira Simões Morais, MD (Immunohemotherapy)
20. Sónia Cristina Pinho da Fonseca, graduated in Clinical Analysis
(*) Estiveram integrados no período 2011-2013, mas deixaram de estar em 2014
5. Indicadores de Realização Física
Indicadores
A - Publicações
2011
2012
2013
Quantidade
realizada
25
38
18
81
Livros
1
1
0
2
Artigos em revistas internacionais
22
33
13
68
Artigos em revistas nacionais
2
4
5
11
B - Comunicações
78
70
13
161
Comunicações em encontros científicos
26
24
6
52
46
7
1
1
1
11
10
8
internacionais
Comunicações em encontros científicos
nacionais
C - Relatórios
D - Organização de seminários e
conferências
56
105
3
29
E - Formação avançada
1
1
1
3
Teses de Doutoramento
1
0
0
1
Teses de Mestrado
0
1
1
2
Outras
0
0
0
0
F - Modelos
0
0
0
0
G - Aplicações computacionais
0
0
0
0
H - Instalações piloto
0
0
0
0
I - Protótipos laboratoriais
0
0
0
0
J - Patentes
0
0
0
0
L - Outros
0
0
0
0
6. Publicações
Ano
Publicações
2013 A CASE OF HEPATOPULMONARY
SYNDROME SOLVED BY
MYCOPHENOLATE MOFETIL (AN
INHIBITOR OF ANGIOGENESIS
AND NITRIC OXIDE PRODUCTION).
Moreira Silva H, Reis G, Guedes M,
Cleto E, Vizcaíno JR, Kelly D,
Gennery AR, Santos Silva E. J
Hepatol. 2013 Mar;58(3):630-3. doi:
10.1016/j.jhep.2012.10.021. Epub
2012 Oct 24. No abstract available.
URL
http://www.ncbi.nlm.nih.gov/pubmed/?term=23104163
PMID: 23104163
2013 A DRAMATIC CASE OF BEHÇET
http://www.ncbi.nlm.nih.gov/pubmed/?term=24021377
DISEASE SUCCESSFULLY
TREATED WITH INFLIXIMAB. PintoAlmeida T, Amorim I, Alves R,
Selores M. Dermatol Online J. 2013
Apr 15;19(4):18187. PMID: 24021377.
2013 A NOVEL SYNDROME OF
http://www.ncbi.nlm.nih.gov/pubmed/?term=23553769
CONGENITAL SIDEROBLASTIC
ANEMIA, B-CELL
IMMUNODEFICIENCY, PERIODIC
FEVERS, AND DEVELOPMENTAL
DELAY (SIFD). Wiseman DH, May A,
Jolles S, Connor P, Powell C, Heeney
MM, Giardina PJ, Klaassen RJ,
Chakraborty P, Geraghty MT, MajorCook N, Kannengiesser C, Thuret I,
Thompson AA, Marques L, Hughes
S, Bonney DK, Bottomley SS,
Fleming MD, Wynn RF. Blood. 2013
Jul 4;122(1):112-23. doi:
10.1182/blood-2012-08-439083. Epub
2013 Apr 3. PMID: 23553769
2013 AGGRESSIVE MATURE NATURAL
http://www.ncbi.nlm.nih.gov/pubmed/?term=23816348
KILLER CELL NEOPLASMS: FROM
EPIDEMIOLOGY TO DIAGNOSIS.
Lima M. Orphanet J Rare Dis. 2013
Jul 1;8:95. doi: 10.1186/1750-1172-895. PMID: 23816348
2013 BONE MARROW CELL
TRANSCRIPTS FROM FANCONI
ANAEMIA PATIENTS REVEAL IN
VIVO ALTERATIONS IN
MITOCHONDRIAL, REDOX AND
DNA REPAIR PATHWAYS.Pagano
G, Talamanca AA, Castello G,
http://www.ncbi.nlm.nih.gov/pubmed/?term=23646927
d'Ischia M, Pallardó FV, Petrović S,
Porto B, Tiano L, Zatterale A. Eur J
Haematol. 2013 Aug;91(2):141-51.
doi: 10.1111/ejh.12131. Epub 2013
Jun 15. PMID: 23646927
2013 BROADENED T-CELL REPERTOIRE http://www.ncbi.nlm.nih.gov/pubmed/?term=23064977
DIVERSITY IN IVIG-TREATED SLE
PATIENTS IS ALSO RELATED TO
THE INDIVIDUAL STATUS OF
REGULATORY T-CELLS. Costa N,
Pires AE, Gabriel AM, Goulart LF,
Pereira C, Leal B, Queiros AC,
Chaara W, Moraes-Fontes MF,
Vasconcelos C, Ferreira C, Martins J,
Bastos M, Santos MJ, Pereira MA,
Martins B, Lima M, João C, Six A,
Demengeot J, Fesel C. J Clin
Immunol. 2013 Feb;33(2):349-60. doi:
10.1007/s10875-012-9816-7. Epub
2012 Oct 14. PMID: 23064977
2013 CYTOGENETIC AND
http://www.ncbi.nlm.nih.gov/pubmed/?term=23514064
IMMUNOLOGICAL EFFECTS
ASSOCIATED WITH
OCCUPATIONAL FORMALDEHYDE
EXPOSURE. Costa S, García-Lestón
J, Coelho M, Coelho P, Costa C,
Silva S, Porto B, Laffon B, Teixeira
JP. J Toxicol Environ Health A.
2013;76(4-5):217-29. doi:
10.1080/15287394.2013.757212.
PMID: 23514064
2013 FOSFOMYCIN INCREASES
http://www.ncbi.nlm.nih.gov/pubmed/?term=23624100
CHROMOSOME INSTABILITY IN
LYMPHOCYTES FROM FANCONI
ANEMIA PATIENTS. Sousa R, Ponte
F, Teixeira S, Andrade L, Gonçalves
C, Barbot J, Coutinho J, Carvalho F,
Porto B. Mutat Res. 2013 Jun
14;754(1-2):58-62. doi:
10.1016/j.mrgentox.2013.04.005.
Epub 2013 Apr 25. PMID: 23624100
2013 FROM CLINICAL DESCRIPTION, TO http://www.ncbi.nlm.nih.gov/pubmed/?term=23376230
IN VITRO AND ANIMAL STUDIES,
AND BACKWARD TO PATIENTS:
OXIDATIVE STRESS AND
MITOCHONDRIAL DYSFUNCTION
IN FANCONI ANEMIA. Pagano G,
Talamanca AA, Castello G, d'Ischia
M, Pallardó FV, Petrović S, Porto B,
Tiano L, Zatterale A. Free Radic Biol
Med. 2013 May;58:118-25. doi:
10.1016/j.freeradbiomed.2013.01.015.
Epub 2013 Jan 29. PMID: 23376230
2013 GROUP B STREPTOCOCCUS
http://www.ncbi.nlm.nih.gov/pubmed/?term=23658816
HIJACKS THE HOST
PLASMINOGEN SYSTEM TO
PROMOTE BRAIN ENDOTHELIAL
CELL INVASION. Magalhães V,
Andrade EB, Alves J, Ribeiro A, Kim
KS, Lima M, Trieu-Cuot P, Ferreira P.
PLoS One. 2013 May 2;8(5):e63244.
doi: 10.1371/journal.pone.0063244.
PMID: 23658816
2013 IMMUNOGLOBULIN DEFICIENCIES: http://www.ncbi.nlm.nih.gov/pubmed/?term=22809661
THE B-LYMPHOCYTE SIDE OF
DiGEORGE SYNDROME. Patel K,
Akhter J, Kobrynski L, Benjamin
Gathmann MA, Davis O, Sullivan KE;
International DiGeorge Syndrome
Immunodeficiency Consortium.
(Marques L). J Pediatr. 2012
Nov;161(5):950-3. doi:
10.1016/j.jpeds.2012.06.018. Epub
2012 Jul 17. Erratum in: J Pediatr.
2013 Mar;162(3):658. Gathman,
Benjamin [corrected to Benjamin
Gathmann, M A]. PMID: 22809661
2013 IRON DEFICIENCY ANEMIA DUE
TO LYMPHOCYTIC GASTRITIS
WITH HELICOBACTER PYLORI
INFECTION IN CHILDHOOD: CASE
REPORT. Santalha MF Jr, Costa E,
Miguel N, Vizcaíno R, Barbot J,
Pereira F. J Pediatr Hematol Oncol.
http://www.ncbi.nlm.nih.gov/pubmed/?term=23528908
2013 May;35(4):321-2. doi:
10.1097/MPH.0b013e318286d129.
PMID: 23528908
2013 CARACTERIZAÇÃO DAS INFEÇÕES
http://www.scielo.gpeari.mctes.pt/scielo.php?script=sci_arttext&pid=S0872-07542013000100002&lng=en&nrm=iso
EM DOENTES COM SÍNDROME DE
DELECÇÃO 22q11. Oliveira M,
Teixeira C, Vasconcelos J, Neves E,
Álvares S, Guedes M, Marques L.
Nascer e Crescer 2013; 22(1): 8-11.
ISSN 0872-0754.
2013 MASTOIDITE AGUDA: AUMENTO
http://revistas.rcaap.pt/app/article/view/498/2388
DA INCIDÊNCIA E DAS
COMPLICAÇÕES? Silva HM, Zilhão
C, Soares T, Coutinho M, Senra V,
Guedes M. Acta Pediatr Port 2013;
44: 25-9.
2013 NEUTROPENIA IN A PATIENT WITH
http://www.journalmc.org/index.php/JMC/article/view/1176/726
RHEUMATOID ARTHRITIS
ASSOCIATED WITH ab/gd T-CELL
LARGE GRANULAR LYMPHOCYTE
LYMPHOPROLIFERATIVE
DISORDER MANIFESTING AS
FELTY’S SYNDROME: FROM
DIAGNOSIS TO THERAPY. Cabral
R, Lau C, Rodrigues J, Lima M. J
Med Cases • 2013;4(6):450-457. doi:
http://dx.doi.org/10.4021/jmc1176w
2013 O IMPACTO DO RISCO SOCIAL
http://revistas.rcaap.pt/app/article/view/2941/2386
NUM INTERNAMENTO
PEDIÁTRICO. Nascimento J, Ferreira
I, Zilhão C, Pinto S, Ferreira C,
Caldas L, Guedes M, Senra V. Acta
Pediatr Port 2013; 44(1):15-9.
2013 REMÉDIO SEM RECEITA. Guedes
M. Nascer e Crescer 2013; 22(2):130130. ISSN 0872-0754.
http://www.scielo.gpeari.mctes.pt/scielo.php?script=sci_arttext&pid=S0872-07542013000200016&lng=en&nrm=iso
2012 [ANTICOAGULATION CLINICS,
http://www.ncbi.nlm.nih.gov/pubmed/?term=22541036
PRESENT SITUATION AND
FUTURE PERSPECTIVES]. Cruz E,
Campos M. Rev Port Cardiol. 2012
Apr;31 Suppl 1:51-7. Portuguese.
PMID: 22541036
2012 A CASE OF BLASTIC
http://www.ncbi.nlm.nih.gov/pubmed/?term=22577284
PLASMACYTOID DENDRITIC CELL
NEOPLASM. Pinto-Almeida T,
Fernandes I, Sanches M, Lau C,
Lima M, Alves R, Selores M. Ann
Dermatol. 2012 May;24(2):235-7. doi:
10.5021/ad.2012.24.2.235. Epub
2012 Apr 26. No abstract available.
PMID: 22577284
2012 ADAMS-OLIVER SYNDROME AND
http://www.ncbi.nlm.nih.gov/pubmed/?term=22307742
PORTAL HYPERTENSION:
FORTUITOUS ASSOCIATION OR
COMMON MECHANISM? Silva G,
Braga A, Leitão B, Mesquita A, Reis
A, Duarte C, Barbot J, Silva ES. Am
J Med Genet A. 2012
Mar;158A(3):648-51. doi:
10.1002/ajmg.a.34435. Epub 2012
Feb 3. PMID: 22307742
2012 APREPITANT: EVIDENCE OF ITS
http://www.ncbi.nlm.nih.gov/pubmed/?term=22177649
EFFECTIVENESS IN PATIENTS
WITH REFRACTORY PRURITUS
CONTINUES. Torres T, Fernandes I,
Selores M, Alves R, Lima M. J Am
Acad Dermatol. 2012 Jan;66(1):e145. doi: 10.1016/j.jaad.2011.01.016. No
abstract available. PMID: 22177649
2012 CAN THE LEVEL OF CD52
EXPRESSION ON SÉZARY CELLS
BE USED TO PREDICT THE
RESPONSE OF SÉZARY
SYNDROME TO ALEMTUZUMAB?
Fernandes IC, Gonçalves M, dos
Anjos Teixeira M, Gonçalves C,
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2012 CASE FOR DIAGNOSIS. Fernandes
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2012 CD8-POSITIVE PRIMARY
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CUTANEOUS PERIPHERAL T-CELL
LYMPHOMA, UNSPECIFIED.
Rosmaninho A, Sanches M, Alves R,
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2012 Jan-Feb;22(1):131-2. doi:
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2012 COMPLETE RESOLUTION OF
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ZOON BALANITIS WITH
PHOTODYNAMIC THERAPY--A
NEW THERAPEUTIC OPTION?
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2012 DEMOGRAPHIC AND CLINICAL
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DATA IN ACQUIRED HEMOPHILIA
A: RESULTS FROM THE
EUROPEAN ACQUIRED
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2012 ERYTHROPHAGOCYTOSIS BY
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COLD HAEMOGLOBINURIA. Santos
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2012 EUROFLOW ANTIBODY PANELS
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FOR STANDARDIZED NDIMENSIONAL FLOW CYTOMETRIC
IMMUNOPHENOTYPING OF
NORMAL, REACTIVE AND
MALIGNANT LEUKOCYTES. van
Dongen JJ, Lhermitte L, Böttcher S,
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2012 EXUBERANT CUTANEOUS
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ULCERS ON THE BUTTOCKS
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2012 HB IBERIA [Α104(G11)CYS →
ARG,TGC>CGC (Α2)
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VARIANT FOUND IN THE IBERIAN
PENINSULA: REPORT OF SIX
CASES. Bento C, Oliveira AC, Neves
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2012 HAEMOPHILIA CARE IN EUROPE:
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THE ESCHQoL STUDY. Schramm W,
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2012 IgM+IgD+CD27+ B CELLS ARE
http://www.ncbi.nlm.nih.gov/pubmed/?term=23002119
MARKEDLY REDUCED IN IRAK-4-,
MYD88-, AND TIRAP- BUT NOT
UNC-93B-DEFICIENT PATIENTS.
Weller S, Bonnet M, Delagreverie H,
Israel L, Chrabieh M, Maródi L,
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2012 IMMUNOSUPPRESSION FOR
ACQUIRED HEMOPHILIA A:
RESULTS FROM THE EUROPEAN
ACQUIRED HAEMOPHILIA
REGISTRY (EACH2). Collins P,
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Blood. 2012 Jul 5;120(1):47-55. doi:
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2012 IMPROVEMENT OF GENETIC
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STABILITY IN LYMPHOCYTES
FROM FANCONI ANEMIA
PATIENTS THROUGH THE
COMBINED EFFECT OF Α-LIPOIC
ACID AND N-ACETYLCYSTEINE.
Ponte F, Sousa R, Fernandes AP,
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2012 INFANTILE PYKNOCYTOSIS: AN
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UNDER-RECOGNIZED FORM OF
NEONATAL HEMOLYTIC ANEMIA?
Coutinho M, Costa E, Monteiro T,
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I, Barbot J. Lab Hematol. 2012
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2012 JUVENILE GANGRENOUS
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VASCULITIS OF THE SCROTUM:
AN EXCEPTIONAL CAUSE OF
SCROTAL ULCERS. Pinto-Almeida
T, Rosmaninho A, Lobo I, Alves R,
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2012 KAWASAKI DISEASE AND
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2012 LETTER: PRIMARY CUTANEOUS
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MARGINAL ZONE B CELL
LYMPHOMA OF THE FACE: A
CHALLENGING DIAGNOSIS. Oliveira
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2012 LICHEN PLANUS PEMPHIGOIDES
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IN A CHILD. Conde Fernandes I,
Pinto Almeida T, Mendes I, Cunha
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2012 MANAGEMENT OF BLEEDING IN
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ACQUIRED HEMOPHILIA A:
RESULTS FROM THE EUROPEAN
ACQUIRED HAEMOPHILIA (EACH2)
REGISTRY. Baudo F, Collins P, HuthKühne A, Lévesque H, Marco P,
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OF PTAQUILOSIDE IN HUMAN
LYMPHOCYTES: ANEUGENESIS,
CLASTOGENESIS AND INDUCTION
OF SISTER CHROMATID
EXCHANGE. Gil da Costa RM,
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2012 NEONATAL ALLOIMMUNE
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NEUTROPENIA: STILL A
DIAGNOSTIC AND
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Águeda S, Rocha G, Ferreira F, Vítor
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2012 PREGNANCY-ASSOCIATED
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ACQUIRED HAEMOPHILIA A:
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ACQUIRED HAEMOPHILIA (EACH2)
REGISTRY. Tengborn L, Baudo F,
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2012 PROLIFERATING TRICHILEMMAL
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TUMOR OF THE NOSE. Rosmaninho
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2012 SYSTEMIC LUPUS
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ERYTHEMATOSUS, PROGRESSIVE
MULTIFOCAL
LEUKOENCEPHALOPATHY, AND TCD4+ LYMPHOPENIA. Brandão M,
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2012 THE CIRCULATING PLATELET
COUNT IS NOT DICTATED BY THE
LIVER, BUT MAY BE DETERMINED
IN PART BY THE BONE MARROW –
ANALYSES FROM HUMAN LIVER
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AND STEM CELL
TRANSPLANTATIONS. Lisman T,
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2012 TWO NOVEL MUTATIONS IN THE
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TMPRSS6 GENE ASSOCIATED
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PARTIAL EXPRESSION IN THE
HETEROZYGOUS FORM. Pellegrino
RM, Coutinho M, D'Ascola D, Lopes
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2012 USE OF HYBRID CHITOSAN
MEMBRANES AND HUMAN
MESENCHYMAL STEM CELLS
FROM THE WHARTON JELLY OF
UMBILICAL CORD FOR
PROMOTING NERVE
REGENERATION IN AN
AXONOTMESIS RAT MODEL.
Gärtner A, Pereira T, Simões,
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2012 USE OF POLY(DL-LACTIDE-Ε-
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CAPROLACTONE) MEMBRANES
AND MESENCHYMAL STEM CELLS
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THE UMBILICAL CORD FOR
PROMOTING NERVE
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VIVO ANALYSIS. Gärtner A, Pereira
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2012 VESICO-BULLOUS SUBACUTE
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CUTANEOUS LUPUS
ERYTHEMATOSUS--AN
UNCOMMON ENTITY
SUCCESSFULLY TREATED WITH
DAPSONE AND
HYDROXYCHLOROQUINE. PintoAlmeida T, Sanches M, Alves R,
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2012 CONTRACEÇÃO PARA
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ERITEMATOSO SISTÉMICO. Couto
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2012 FEBRE DE ETIOLOGIA
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ENCRUZILHADA DE
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2012 INFECÇÃO POR H1N1 NUM
SERVIÇO DE PEDIATRIA.
http://www.scielo.gpeari.mctes.pt/scielo.php?script=sci_arttext&pid=S087207542012000100002&lng=en&nrm=iso
Magalhães J, Pinho L, Mendes C,
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2011 ACINETOBACTER COMMUNITY-
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ACQUIRED PNEUMONIA IN A
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2011 AUTOIMMUNE
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LYMPHOPROLIFERATIVE
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2011 CHRONIC LIVER DISEASE AND
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CIRRHOSIS AMONG PATIENTS
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2011 ERYTHROPOIESIS VERSUS
INFLAMMATION IN HEREDITARY
SPHEROCYTOSIS CLINICAL
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2011 FANCONI ANEMIA: CYTOGENETIC
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DIAGNOSIS OF 40 CASES. Porto B,
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2011 GIANT CUTANEOUS HORN ON THE http://www.ncbi.nlm.nih.gov/pubmed/?term=22233746
LOWER LIP. Pinto-Almeida T,
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2011 GIANT MERKEL CELL CARCINOMA. http://www.ncbi.nlm.nih.gov/pubmed/?term=21622090
Pinto-Almeida T, Oliveira A, Sanches
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2011 GRANULOMA ANNULARE OF THE
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PENIS - SUBCUTANEOUS
PRESENTATION. Pinto-Almeida T,
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2011 HEPATITIS B GENOTYPE
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DISTRIBUTION IN PORTUGAL AND
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2011 IMUNODEFICIÊNCIA COMBINADA
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GRAVE: A IMPORTÂNCIA DO
DIAGNÓSTICO PRECOCE. Teixeira
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2011 LETTER: PENILE KAPOSI
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SARCOMA: A CASE OF COMPLETE
RESOLUTION WITH HIGHLY
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THERAPY ALONE. Pinto-Almeida T,
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2011 LICHEN PLANUS PEMPHIGOIDES
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INDUCED BY A WEIGHT
REDUCTION DRUG. Rosmaninho A,
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2011 MANIFESTAÇÃO ATÍPICA DE
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INFECÇÃO POR BARTONELLA
HENSELAE? Dias A, Pinto D, Borges
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2011 MIXED NEUROTHEKEOMA OF THE
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UPPER LIMB. Rosmaninho A,
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2011 NODULAR SECONDARY SYPHILIS.
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2011 OCCUPATIONAL EXPOSURE TO
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RISK EVALUATION BY COMET
ASSAY AND MICRONUCLEUS TEST
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2011 ORIGIN, FUNCTIONAL ROLE, AND
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CLINICAL IMPACT OF FANCONI
ANEMIA FANCA MUTATIONS.
Castella M, Pujol R, Callén E, Trujillo
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2011 PRIMARY CUTANEOUS CD30
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POSITIVE ANAPLASTIC LARGE
CELL LYMPHOMA--REPORT OF A
CASE TREATED WITH
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L-CARNITINE AND Α-LIPOIC ACID
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28;289(1):52-8. doi:
10.1016/j.tox.2011.07.009. Epub 2011
Jul 22. PMID: 21807063
2011 SCLEROMYXEDEMA VS
SCLEREDEMA: A DIAGNOSTIC
CHALLENGE. Conde Fernandes I,
http://www.ncbi.nlm.nih.gov/pubmed/?term=21771713
Sanches M, Velho G, Lobo I, Alves
R, Selores M. Eur J Dermatol. 2011
Sep-Oct;21(5):822-3. doi:
10.1684/ejd.2011.1493. No abstract
available. PMID: 21771713
2011 SEZARY SYNDROME PRESENTING http://www.ncbi.nlm.nih.gov/pubmed/?term=22136862
WITH LEONINE FACIES AND
TREATED WITH LOW-DOSE
SUBCUTANEOUS ALEMTUZUMAB.
Oliveira A, Lobo I, Alves R, Lima M,
Selores M. Dermatol Online J. 2011
Nov 15;17(11):6. PMID: 22136862
2011 TREATMENT OF RECALCITRANT
http://www.ncbi.nlm.nih.gov/pubmed/?term=22134573
GENERALIZED GRANULOMA
ANNULARE WITH ADALIMUMAB.
Torres T, Pinto Almeida T, Alves R,
Sanches M, Selores M. J Drugs
Dermatol. 2011 Dec;10(12):1466-8.
PMID: 22134573
2011 UNS... E OS OUTROS. Guedes M.
http://www.scielo.gpeari.mctes.pt/scielo.php?script=sci_arttext&pid=S0872-07542011000100016&lng=en&nrm=iso
Nascer e Crescer, Mar 2011, vol.20,
no.1, p.57-57. ISSN 0872-0754.
2011 HYPER-IGE SYNDROME: REPORT
http://www.journalmc.org/index.php/JMC/article/view/213/165
OF THREE CASES ADN REVIEW
OF THE LITERATURE. Brandão M,
Marinho A, Vita P, Farinha F,
Vasconcelos J, Vasconcelos C,
Journal of Medical Cases 2011; 2 (4):
151-155. doi: 10.4021/jmc213w
7. Equipamento
Equipamento
Nº Recibo
Data
Observações
NÃO HÁ EQUIPAMENTO ADQUIRIDO PARA O GRUPO BLDH
8. Descrição detalhada das actividades desenvolvidas
BLOOD, LYMPHOPOIETIC AND HEMATOPOIETIC DISORDERS (BLHD)
RG-HESC-Norte-Porto-215-2923
DESCRIÇÃO DO GRUPO DE INVESTIGAÇÃO
The BLHD group is dedicated to clinical research in blood, lymphopoietic and hematopoietic disorders and integrates health professionals from clinical
and laboratory sectors. For the last years the group developed research activities mainly in five areas: lymphoid malignancies, hemostase, red blood cell
(RBC) disorders, bone marrow (BM) failure syndromes, and immunopathology.
Lymphoid malignancies
The CHP has a large number of patients with leukemia and lymphoma, whose diagnosis is supported by differentiated labs. The Laboratory of Cytometry
is a reference lab for the diagnosis of T- and NK-cell lymphoproliferative disorders (LPD) and there is a multidisciplinary consulting for cutaneous
lymphomas.
In this area we focused on the immunophenotypic (IF) characterization of the normal mature T- and NK- cells, as well as on the IF criteria for the
diagnosis and classification of the T-cell and NK-cell LPD, such as large granular lymphocyte (LGL) leukemia (LGLL) and cutaneous T cell lymphoma
(CTCL).
With this purpose, we integrated the EuroFlow consortium, whose objective is the development and standardization of flow cytometry (FC) tests for
diagnosis and classification of hematological malignancies. In order to better understand the mechanisms by which leukemia and lymphoma cells
infiltrate different organs and tissues, we have studied the expression of chemokine receptors (CKR) on the neoplastic cells from different types of T-cell
LPD, and addressed the role of single nucleotide polymorphisms (SNP) of genes coding for the immunoregulatory molecules in LGLL.
In addition, we have tested the value of FC studies for the diagnosis and classification of lymphoma, when compared to histopathology studies on lymph
node biopsies. Especial attention was dedicated to the diagnosis of central nervous system lymphoma, by studying systematically, by FC, the cerebral
biopsies. Data are now being analyzed.
Partners: Centro Invest. Cancer, Salamanca, ES; Erasmus MC, Univ. Med. Center, Rotterdam, NL; Hosp. Univ. Virgen de las Nieves, Granada, ES.
Consortia: Euroflow.
Bone marrow failure síndromes
The Hospital has a significant number of patients with congenital and acquired BM failure syndromes, including Paroxystic Nocturnal
Hemoglobinuria (PNH), Fanconi Anemia (FA) and Myelodysplastic Syndromes (MDS). The hospital laboratories have a large experience in
diagnosing and monitoring of patients with PNH, as well as in characterizing the abnormal maturation patterns observed in the BM of patients
with MDS. In addition, the Laboratory of Cytogenetic of ICBAS/UP is a reference Lab for the diagnosis of FA.
In this area we have been dedicated to the study of PNH and FA, and participated in the International Fanconi Anemia Register (IFAR).
Fanconi Anemia is a genetically heterogeneous disease characterized by congenital abnormalities, progressive BM failure and predisposition
to cancer. Chromosome instability is a major defect, and FA cells are hypersensitive to inter-strand cross-linking agents, such as
diepoxybutane (DEB).
PNH is a rare disease caused by acquired mutations in the gene encoding for glycosylphosphatidylinositol (GPI) that lead to deficiency of the
GPI-anchored proteins in the RBC membrane. Clinically, PNH is characterized by intravascular hemolytic anemia and increased risk for
thrombosis. It may develop on its own or in association with other BM disorders such as aplastic anemia and MDS. Today, the gold standard
for the diagnosis of PNH is FC.
Partners: Dpt. Genetics, Univ. Aut. Barcelona, ES; Dept. Physiology, Fac. Medicina y Odontología, Univ. Valencia, ES; Inst. Nazionale Tumori,
Fondazione G. Pascale, Napoles, IT; Lab. Toxicologia, Fac. Farmácia, Univ. Porto, PT.
Red blood cell disorders
The Hospital has a large number of patients with anemia and the hospital´ laboratories have a large experience on the study of such conditions.
Our research activity has addressed the maturation of the RBC in the BM and in the peripheral blood, as well as the study of congenital RBC membrane
defects such as Hereditary Spherocytosis (HS). The key questions were: Is FC useful to study the BM erythropoiesis and the terminal maturation of
reticulocytes into mature RBC? What about RBC changes due to ageing? What are the factors determining disease severity in HS? Can FC be used for
the diagnosis of HS?
Partners: Laboratory of Hematology, Fac. Farmácia, Univ. Porto, PT.
Hemostase
The Hematology Department of CHP is a reference center for the diagnosis and treatment of hemorrhagic diseases derived either from
plasmatic (e.g. Hemophilia and von Willebrand disease, vWD) and platelet glycoprotein and granule (i.e., storage pool diseases, SPD) defects.
Our research activity consisted on the participation in clinical trials and observational studies for Hemophilia and on the evaluation of risks
factors for thrombosis and hemorrhage. New studies of platelets and endothelial cells (EC) are being developed. The key questions were:
What are the mechanisms involved in thrombosis and hemorrhage? Can EC be used as biomarkers for thrombosis? What is the best
treatment for acquired hemophilia?
Partners: EAAC Facility, Fac. Life Sciences, Univ. Manchester, UK; Serv. Hematologia y Hemoterapia, Comp. Hosp. Juan Canalejo, Coruña,
ES; Angelo Bianchi Bonomi, Univ. Milan, IT.
Immunopathology
The Laboratory of Immunology of the Hospital is a reference for the diagnosis of immunodeficiencies and immune-mediated diseases. The hospital has
a large number of patients with immunodeficiency, either primary or secondary, as well as with autoimmune diseases (AID) and allergy.
In the last years we have participated in multiple research projects in this area, most of which are presently undergoing: role of T cells in allergy; role of
T cells and EC in Systemic Sclerosis (SS); immunological abnormalities in patients with Systemic Lupus Erythematous (SLE); in vitro differentiation of
blood monocytes into dendritic cells and cytokine production of stimulated monocytes; expression of different types of killer receptors on blood CD56+
NK-cells and T-cells from patients with Multiple Sclerosis (MS); vitamin D and immune deregulation in SLE, T-cell abnormalities in high risk pregnancies;
role of the pro-inflammatory CD14+CD16+ monocytes in chronic inflammatory intestinal disease (CIID) and obesity; characterization of the intestinal
lymphocytic infiltrates from patients with CIID and correlation with the levels of TCR glycosylation; T- and B-cell abnormalities in patients with Common
Variable Immunodeficiency (CID) and their correlations with clinical manifestations; clinical and immunological phenotype in a pediatric population with
22q11 deletion; AID and auto-antibodies in children with chronic granulomatous disease (CGD) and their families (multicenter study conducted in
collaboration with the Karolinska University).
Concerning infectious diseases, our studies have addressed the epidemiology of the hepatitis B infection (HBV) infection in the Northern of Portugal, as
well as of the human immunodeficiency virus (HIV) and invasive pneumococcal disease (IPD) in Portugal. We have also been participating in the
Portuguese Group for Primary Immunodeficiencies (GPIP), as well as in the ESID and the Portuguese Registers for Primary Immunodeficiencies
(REPORID).
Partners: The Rockefeller Univ., St. Giles Lab. Human Genetics of Infectious Diseases, New York, USA; Univ. Paris René Descartes, Fac. Médecine,
Hôp. Necker-Enfants Malades, INSERM U550, U768 and U783, Paris, FR; Central Lab. Netherlands Blood Transfusion Service and Lab. Experimental
and Clinical Immunology, Acad. Medical Center, Amsterdam, NL; Hospital Vall d'Hebron, Pediatric Infectious Diseases and Immunodeficiencies Unit,
Barcelona, ES; Karolinska University; Lab. of Immunology and Immunogenetics, ICBAS/UP; Research Group Glycobiology of Cancer, IPATIMUP, and
Dpt. Biochemistry, FMUP, Porto, PT.
Portuguese Working Groups: Working Group on Invasive Pneumococcal Disease in Children (GTDPIC); Working Group on HIV infection in Children
(GTIVIHC); Portuguese Group for Primary Immunodeficiencies (GPIP).
PRINCIPAIS RESULTADOS ALCANÇADOS
During the 3 years (2011-2013), 79 papers were published in peer-reviewed journals, from which 68 papers (86%) were indexed in the MedLine (PMID
indicated in brackets), with a median IF of 2.053 in 2011, 2.711 in 2012 and 3.035 in 2013. About 20% of papers resulted from the collaboration with
foreign groups and another 20% involved other national teams. In addition, the results were presented in scientific meetings and several MsD and PhD
thesis are presently ongoing. We also organized scientific meetings and courses, supervised academic projects, trained health professionals and
students and participated in academic juries.
Lymphoid malignancies
The results from the Euroflow consortium are being published (22552007) and a new flow cytometry (FC) software (Infinicyt) is already commercialized.
Our effort was oriented to the definition of the best IF protocols to diagnose and classify the T- and NK-cell LPD, such as the LGLL, and other T- and
NK-cell leukemia and lymphoma.
Continuing our previous studies on the LGLL (16437145; 12875995; 12111871; 11696446), we evaluated, in collaboration with other groups, the SNP of
genes coding for the immunoregulatory molecules in patients with CD4+ vs. CD8+ T-LGLL. (18361934); our results suggested that the SNP studied are
not associated with the development of T-LGLL. Concerning the role of CKR expression in determining the clinical manifestations (tissue tropism and
organ involvement) of T-LGLL, in comparison to peripheral T-cell lymphoma (PTCL) (18842429); we observed that T-LGLL cells express mainly late
inflammatory CKR whereas PTCL cells usually have one or more organ homing CKR.
Concerning CTCL, we implemented a protocol for the treatment of the Sezary Syndrome (SS), with low-doses subcutaneous alemtuzumab (anti-CD52
mAb). This study revealed that alemtuzumab induces responses in the majority of SS´ patients and suggested that FC analysis of CD52 expression on
Sezary cells can be used to predict response to treatment (23062898; 22136862). We also tested the effectiveness of Aprepitant in alleviating the
intractable pruritus observed in CTCL (22177649). In addition, we participated in a clinical trial in CTCL (EudraCT: 2011-001076-18). We also published
case reports of patients with cutaneous B- (22398233; 19945162), T- (22136862; 22062773) or anaplastic large cell (21764128) lymphomas and
dendritic cell neoplasms (22577284) with unique characteristics.
Bone marrow failure syndromes
Concerning FA, we presented the results from the DEB induced chromosome instability and breakage studies, allowing for the diagnosis of 34 cases of
FA (22015027) and characterized the audiologic abnormalities observed in these patients (19086307). Using propidium iodide, bromodeoxyuridin and 7amino-actinomycin D based FC-based protocols we have been analyzing the cell cycle of blood lymphocytes from patients with FA, cultured in different
conditions, with or without DEB.
In collaboration with other research groups we described the protective effect of the RBC (21039995) and anti-oxidant molecules against the
genotoxicity of DEB to human lymphocytes (21807063; 22591656), as well as the genotoxic activity of various substances (22565221; 21707428;
9146986). In addition, we participated in collaborative studies, to describe the origin, functional role, and clinical impact of the FANCA mutations in FA
patients (21273304).
Red blood cell disorders
Concerning the investigation of patients with anemia, we collaborated in studies on HS in order to better characterize the biomarkers for disease severity
(21138793), the effects of the RBC membrane protein destabilization (20346007; 18387321) and chronic inflammation (21704613) in determining the
disease outcome, as well as the role of the (TA)nTAA polymorphism of UGT1A1 gene promoter region in determining the bilirubin levels in HS
(19931474). We also contributed for the identification of new mutations in patients with talassemia (23181747), syderoblastic anemia (19693999) and
iron-refractory iron-deficiency anemia (IRIDA) (22765023), as well as for the study of rare forms of hemolytic anemia (23253864). In addition, we
investigated the immune and inflammatory mechanisms underlying anemia severity and response to treatment in patients with kidney disease
(20649681; 18375155; 18205031).
Hemostase
In that concerning the hemorrhagic disorders, we participated in several clinical trials (EudraCT: 2009-011186-88; 2010-020558-33; 2005-005697-71)
and observational collaborative studies (ESCHQoL, OBSITI, SIPPET, EACH2) in patients with Hemophilia. Some of the results obtained have already
been published including those from the EACH2 (22517903; 22321904; 22618709; 22901076) and the ESCHQoL (22639833).
Our research effort on thrombosis focused on the study of the EC. Using FC, we quantified and characterized the circulating EC (CEC) and EC
progenitors in patients with venous thrombo-embolism (VTE) as well as in patients with Myeloproliferative Neoplasms (MPN); the results suggest that
CEC counts reveal EC injury in patients with VTE and MPN and that CEC may express different activation-related phenotypes
(10.1371/journal.pone.0081574).
Immunopathology
Our collaboration with other groups in the area of Primary Immunodeficiencies (PID) allowed for the publication of papers in scientific journals with high
Impact Factor. These papers report on the characterization of the clinical features and outcome (21057262), infections (18669862; 19633526) and B cell
defects (23002119) and other immunological disturbances (18591412) observed in different types of PID. In the area of AID, we dedicated our attention
to the study of autoimmune lymphoproliferative syndrome (22525637), then contributing for the identification of disease biomarkers (19176318). We
have also characterized some of the immune abnormalities observed in AID (19474774) and described several unique clinical cases (1859141;
22227968; 22674017; 18031500; 22995923).
Concerning the epidemiology of HBV infection, genotypes A and D were found to be the most prevalent in the North of Portugal. Patients infected with
genotype D had higher levels of HBV DNA and HBeAg was associated with genotype D, viral load, ALT and AST (19475628; 19475628). 21107506.
Several important data were also obtained with the epidemiological studies on HIV and IPD in children.
PHD THESES COMPLETED UNDER THE SUPERVISION OF INTEGRATED MEMBERS
PHD THESIS CONCLUDED WITH THE SUPERVISION OF INTEGRATED UMIB MEMBERS (N=4)
1.
PhD student: Ana Filipa Brinco de Oliveira Ponte. PhD program: Biomedical Sciences (ICBAS/UP). PhD thesis: CHROMOSOME INSTABILITY
IN FANCONI ANEMIA: SEARCHING DRUGS TO PREVENT THE PROGRESSION OF THE DISEASE. Faculty/University: ICBAS/UP.
Supervisors: Beatriz Porto (ICBAS/UP; UMIB/ICBAS/UP). Dates: 2007/2008-2012 (concluded 19-07-2012).
2.
PhD student: Patrícia Clara dos Santos Coelho. PhD program: Biomedical Sciences (ICBAS/UP). PhD thesis: BIOMONITORING OF
ENVIRONMENTAL CONTAMINATION RESULTING FROM MINING ACTIVITIES ON EXPOSED POPULATIONS. Faculty/University:
ICBAS/UP. Supervisors: João Paulo Teixeira (INRJ); Beatriz Porto (ICBAS/UP; UMIB/ICBAS/UP). Dates: 2006/2007-2013 (concluded 23-112013).
3.
PhD student: Sofia Castanheira Pais. PhD program: Educational Sciences (FPCE/UP). PhD thesis: VIVÊNCIA E QUALIDADE DE VIDA
ESCOLAR, EMPODERAMENTO E PARTICIPAÇÃO: O CASO DAS CRIANÇAS E JOVENS COM DOENÇA CRÓNICA E SUAS FAMÍLIAS.
Faculty/University: FPCE/UP. Supervisors: Isabel Menezes (FPCE/UP); Margarida Guedes (HSA/CHP; ICBAS/UP; UMIB/ICBAS/UP). Dates:
2007/2007-2012 (concluded 23/04/2012).
PHD THESIS CONCLUDED OF UMIB MEMBERS (N=1)
1.
PhD student / UMIB member: Ana Paula Mota (HSA/CHP; UMIB/ICBAS/UP). PhD program: Biomedical Sciences, ICBAS/UP. PhD thesis:
GENÓTIPOS DO VÍRUS DA HEPATITE B, VARIÁVEIS ASSOCIADAS, CARACTERÍSTICAS E DISTRIBUIÇÃO NUMA AMOSTRA DA
POPULAÇÃO PORTUGUESA. Supervisors: Jorge Areias (HSA/CHP; ICBAS/UP; UMIB/ICBAS/UP); Margarida Cardoso (ICBAS/UP).
Faculty/University: ICBAS/UP. Dates: 2006-2011 (concluded 08-07-2011).
BOOKS AND CHAPTERS IN BOOKS
2012
1.
LABORATÓRIO DE CITOMETRIA DO SERVIÇO DE HEMATOLOGIA CLÍNICA DO HOSPITAL DE SANTO ANTÓNIO: 20 ANOS DE HISTÓRIA.
Authors: Lima M. Editor: Fórum Hematológico do Norte. 1st Edition. Year: 2012. Depósito legal: PT 339815/12.
2.
RECOMENDAÇÕES PORTUGUESAS PARA O TRATAMENTO DA INFECÇÃO POR VIH1 E VIH2 2012. Marques L. Brochure. Programa
Nacional para a infecção VIH/SIDA. Electronic edition. Available in: http://www.aidsportugal.com/Modules/WebC_Docs/GetDocument.aspx?DocumentId=2828 .
2011
3.
A INFEÇÃO VIH NA CRIANÇA E NO ADOLESCENTE. Authors: Grupo de Trabalho sobre Infeção VIH na Criança (GTVIHC). Coordinators: Rocha
G; Gonçalo Marques J; Marques L, Prata F, Tavares M. Editor: Asic – Associação de Saúde Infantil de Coimbra. 1st Edition. Year: 2011. ISBN:
978-989-20-2656-5. Depósito Legal: PT 333862/11. Available in:
http://www.spp.pt/UserFiles/file/Protocolos/Infecao_VIH_Crianca_Adolescente_Marco_2011.pdf
4.
HEMOGLOBINÚRIA PAROXÍSTICA NOCTURNA: VÁRIAS FACES DA MESMA DOENÇA, DO DIAGNÓSTICO AO TRATAMENTO. Authors:
Queirós ML, Lima M. Editor: Fórum Hematológico do Norte. 1st Edition. Year: 2011. ISBN: 978-989-20243-7-0. Depósito legal: PT 328231/11.
ORGANISATION OF SCIENTIFIC ACTIVITIES (TRAINING COURSES, SYMPOSIUMS, CONFERENCES, SEMINARS, ETC., ORGANISED BY THE
RESEARCH GROUP)
1.
SIMPÓSIOS INTERNACIONAIS DE TROMBOSE E HEMOSTASE / REUNIÕES DO FÓRUM HEMATOLÓGICO DO NORTE. (Porto, Portugal:
31/03- 01/04/2011).
2.
REUNIÕES ANUAIS DA SOCIEDADE PORTUGUESA DE HEMATOLOGIA (Porto, Portugal. 08/11/2012 - 10/11/2012).
3.
REUNIÕES ANUAIS DA SOCIEDADE PORTUGUESA DE IMUNOLOGIA (Porto, Portugal. 25-27/11/2012).
4.
EUROFLOW MEETINGS. (Porto, Portugal. 12-15/03/2013).
5.
CONGRESSOS NACIONAIS DE DOENÇAS INFECCIOSAS E MICROBIOLOGIA CLÍNICA / CONGRESSOS NACIONAIS SOBRE SIDA (Porto,
Portugal. 12-15/12/2012).
6.
CONGRESSOS NACIONAIS DE PEDIATRIA (Albufeira, Portugal. 6-8/10/2011).
7.
REUNIÕES DE GRUPOS DE TRABALHO: DOENÇA PNEUMOCÓCICA INVASIVA (Braga, Portugal. 18/05/2011).
8.
CURSOS: REUMATOLOGIA PEDIÁTRICA (Porto, Portugal. 18/11/2011); INFECÇÃO POR VIH NA CRIANÇA. (Braga, Portugal. 21/05/2011);
FORMAÇÃO CONTÍNUA EM PEDIATRIA “ENCONTROS À 6ª FEIRA (Porto, Portugal. 28/10/2011-25/05/2012).
9.
JORNADAS NACIONAIS DE INFECCIOLOGIA PEDIATRICA (XII) - IMUNIDADE & INFECÇÃO (Braga, Portugal. 19-21/05/2011).
RESEARCH CONTRACTS WITH NATIONAL OR INTERNATIONAL ENTITIES
CONSORTIA (n=1)
1.
Euroflow consortium (UMIB members: Margarida Lima, Ana Helena Santos). Dates: 2009-. State in November 2013: Ongoing.
CLINICAL TRIALS (n=8)
2.
Clinical trial: INHIBITOR DEVELOPMENT IN PREVIOUSLY UNTREATED PATIENTS (PUPS) OR MINIMALLY BLOOD COMPONENT-TREATED
PATIENTS (MBCTPS) WHEN EXPOSED TO PLASMA-DERIVED VON WILLEBRAND FACTOR-CONTAINING FACTOR VIII (VWF/FVIII)
CONCENTRATES AND TO RECOMBINANT FACTOR VIII (RFVIII) CONCENTRATES: AN INDEPENDENT, INTERNATIONAL, MULTICENTRE,
PROSPECTIVE, CONTROLLED, RANDOMISED, OPEN LABEL, CLINICAL TRIAL. Medical condition: Severe Hemophilia A. EudraCT number:
2009-011186-88. Protocol number: ABB-09-001. Sponsor: Fondazione Centro Emofilia e Trombosi Angelo Bianchi Bonomi. UMIB investigators:
Manuel Campos; Sara Morais. Dates: 2009-. State in November 2013: Ongoing.
3.
Clinical trial: A-LONG: AN OPEN-LABEL, MULTICENTER EVALUATION OF THE SAFETY, PHARMACOKINETICS, AND EFFICACY OF
RECOMBINANT FACTOR VIII FC FUSION PROTEIN (RFVIIIFC) IN THE PREVENTION AND TREATMENT OF BLEEDING IN PREVIOUSLY
TREATED SUBJECTS WITH HEMOPHILIA A. Medical condition: Severe Hemophilia A. EudraCT number: 2010-020558-33. Protocol number:
997HA301. Sponsor: Biogen Idec Hemophilia, Inc. UMIB investigators: Manuel Campos; Sara Morais. Dates: 2011-. State in November 2013:
Concluded.
4.
Clinical trial: RAHF-PFM: ANTIHEMOPHILIC FACTOR (RECOMBINANT), PLASMA/ALBUMIN FREE METHOD: A PHASE 3/4, PROSPECTIVE,
CONTROLLED, RANDOMIZED, MULTI-CENTER STUDY TO COMPARE THE EFFICACY AND SAFETY OF CONTINUOUS INFUSION (CI)
VERSUS INTERMITTENT BOLUS INFUSION (BI) IN SUBJECTS WITH SEVERE OR MODERATELY SEVERE HAEMOPHILIA AN
UNDERGOING UNILATERAL PRIMARY KNEE REPLACEMENT. Medical condition: Severe or moderately severe Hemophilia A. EudraCT
number: 2005-005697-71. Protocol number: 060402. Sponsor: Baxter Innovations GmbH. Baxter Healthcare Corporation, Áustria: UMIB
investigators: Manuel Campos; Sara Morais. Dates: 2009-. State in November 2013: Ongoing.
5.
Clinical trial: A PHASE 2, SINGLE-ARM, OPEN-LABEL, MULTICENTER STUDY OF THE HISTONE DEACETYLASE INHIBITOR (HDACI) JNJ26481585 IN SUBJECTS WITH PREVIOUSLY TREATED STAGE IB-IVA CUTANEOUS T-CELL LYMPHOMA. Medical condition: Stage Ib-IVa
Cutaneous T-cell Lymphoma. EudraCT Number: 2011-001076-18. Protocol number: 26481585LYM2001. Promotor: Janssen-Cilag International.
Sponsor: Janssen-Cilag International. UMIB Investigators: Rosário Alves; Margarida Lima. Dates: 2011-2012. State in November 2013: Concluded.
6.
Clinical trial: JUVENIL IDIOPATHIC ARTHRITIS (JIA) REGISTRY (STRIVE). A LONG-TERM, MULTI-CENTER, LONGITUDINAL POSTMARKETING, OBSERVATIONAL REGISTRY TO ASSESS LONG TERM SAFETY AND EFFECTIVENESS OF HUMIRA® (ADALIMUMAB) IN
CHILDREN WITH MODERATELY TO SEVERELY ACTIVE POLYARTICULAR OR POLYARTICULAR-COURSE JUVENILE IDIOPATHIC
ARTHRITIS (JIA) – STRIVE. Medical condition: Juvenil Idiopathic Arthritis. Promotor: AbbVie (prior sponsor, Abbott). Sponsor: AbbVie (prior
sponsor, Abbott). UMIB investigators: Margarida Guedes. State in November 2013: Ongoing.
7.
Clinical trial: A PHASE II, OPEN-LABEL TRIAL, TO EVALUATE THE SAFETY, TOLERABILITY AND ANTIVIRAL ACTIVITY OF TMC125 IN
ANTIRETROVIRAL EXPERIENCED HIV-1 INFECTED CHILDREN AND ADOLESCENTS / ESTUDO CLÍNICO DE FASE II, ABERTO PARA
AVALIAR A SEGURANÇA, TOLERABILIDADE E ACTIVIDADE ANTIVRAL DO TMC125 EM CRIANÇAS E ADOLESCENTES INFECTADOS
PELO VIH-1 E COM EXPERIÊNCIA TERAPÊUTICA. Medical condition: HIV-1 infected children and adolescents. EudraCT number: 2009-01312616. Protocol number: TMC125-TiDP35-C239. Promotor: Tibotec Pharmaceuticals c/o Tibotec BVBA / Janssen Cilag. UMIB investigators: Laura
Marques. Dates: 2009-. State in November 2013: Ongoing.
8.
Clinical trial: KONCERT: A KALETRA ONCE DAILY RANDOMISED TRIAL OF THE PHARMACOKINETICS, SAFETY AND EFFICACY OF
TWICE-DAILY VERSUS ONCE-DAILY LOPINAVIR/RITONAVIR TABLETS DOSED BY WEIGHT AS PART OF COMBINATION ANTIR. EudraCT
number: 2009-013648-35. Protocol number: PENTA 18. Promotor: PENTA foundation. Sponsor: PENTA foundation. UMIB investigators: Laura
Marques. Dates: 2010-. State in November 2013: Completed.
OBSERVATIONAL AND REGISTRY STUDIES (n=3)
9.
Observational / Registry study: EUROPEAN STUDY OF CLINICAL, HEALTH ECONOMIC AND QUALITY OF LIFE OUTCOMES IN HEMOPHILIA
TREATMENT (ESCHQoL). Sponsor: ISTH. UMIB investigators: Manuel Campos; Sara Morais. Dates: 2005-2006. State in November 2013:
Completed.
10. Observational / Registry study: OBSERVATIONAL IMMUNE TOLERANCE INDUCTION RESEARCH PROGRAM (OBSITI). Promotor: Paediatric
Centre of the Johann Wolfgang-Goethe University Frankfurt, Germany; Haemophilia Centre Rhine-Main (HZRM), Frankfurt-Mörfelden, Germany.
Sponsor: Octapharma AG. Study coordinator: Wolfhart Kreuz and Carmen Escuriola-Ettingshausen Johann Wolfgang Goethe-University, Frankfurt,
Germany. UMIB investigators: Manuel Campos; Sara Morais. Dates: 2005-. State in November 2013: Ongoing.
11.
Observational / Registry study: SURVEY OF INHIBITORS IN PLASMA PRODUCT EXPOSED TODDLERS (SIPPET). Promotor: Angelo Bianchi
Bonomi Hemophilia and Thrombosis Center. Sponsor: Fondazione Angelo Bianchi Bonomi. Study coordinator: Pierr Mannucio Mannucci,
University of Milan, Italy. UMIB investigators: Manuel Campos; Sara Morais. Dates: 2009-2014. State in November 2013: Ongoing.
RESEARCH FELLOWS
1.
Magdalena Anna Leander (PhD). From 1 April 2011 to 31 April 2012 (12 months). Fórum Hematológico do Norte.
2.
Ana Raquel Martins Figueiredo Fonseca (MsD). 2012: 6 months (1 July 2012 to 31 December 2012) (6 months); 2013: 2 months (1 January
2013 to 28 February 2013). FCT
PARTNERS / COLLABORATIONS
HEMATOLOGY
Hemato-oncology
International collaborations
o
Centro de Investigación del Cancer (CIC) (Salamanca, Spain) (Alberto Orfao; Julia Almeida).
o
Erasmus MC, University Medical Center, Department of Immunology, Unit of Molecular Immunology (Rotterdam, The Netherlands)
(Jacques van Dongen)
o
Hospital Universitario de Salamanca (USAL) (Salamanca, Spain) (Alberto Orfao; Julia Almeida).
o
Hospital Universitario Virgen de las Nieves (Granada, Spain) (Francisco Ruiz Cabello; Pillar Garrido).
o
Centro de Estudios de Mastocitosis de Castilla la Mancha (CLMast) (Toledo, Spain) (Luís Escribano)
o
European Competence Network on Mastocytosis (ECNM) (Viena de Áustria, Áustria) (Peter Valent)
National collaborations
o
Instituto Português de Oncologia Francisco Gentil de Lisboa, Consulta Multidisciplinar de Linfomas Cutâneos (Lisboa, Portugal)
(Fernanda Sasche, Mariana Cravo and Rute Alvarez)
o
Instituto Português de Oncologia Francisco Gentil de Lisboa (Lisboa, Portugal), Serviço de Hematologia, Lisboa, Portugal. (Maria
Gomes da Silva, Paulo Lúcio)
o
Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Cancer Glycobiology Research Group, Porto,
Portugal. (Salomé Pinho)
Hemostasis
International collaborations
o
Complejo Hospitalario Juan Canalejo, Servicio de Hematologia e Hemoterapia (La Coruña, Spain) (Francisco Javier Battle)
o
Hôpital Cardiologique, Laboratory Pathologie Cellulaire de l'Hémostase (Pessac, France) (Allan Nurden)
o
University of Manchester, Faculty of Life Sciences, European Action on Anticoagulation Central Facility (EAAC) (Manchester, UK) (Leon
Poller)
o
University of Milan, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center (Milan, Italy) (Pier Mannucio Mannucci)
National collaborations
o
No collaborations in this area.
Bone marrow failure syndromes
International collaborations
o
Instituto Nazionale Tumori (IRCCS), Fondazione G. Pascale, (Napoles, Italy) (Giovanni Pagano)
o
Universidad Autónoma de Barcelona, Department of Genetics (Barcelona, Spain) (Jordi Surralés Calonge)
o
University of Valencia, Facultad de Medicina y Odontología, Department of Phisiology (Valencia, Spain) (Federico Pallardo)
National collaborations
o
Universidade do Porto, Faculdade de Farmácia (FF/UP), Department of Biological Sciences, Laboratory of Toxicology (Porto, Portugal)
(Félix Carvalho)
o
Universidade do Porto, Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP), Department of Microscopy, Laboratory of
Cytogenetics (Porto, Portugal) (Beatriz Porto)
IMMUNOPATHOLOGY
International collaborations
o
Central Laboratory of the Netherlands Blood Transfusion Service and Laboratory of Experimental and Clinical Immunology, Academic
Medical Center (Amsterdam, The Netherlands) (Dirk Roos).
o
Hospital Vall d'Hebron, Pediatric Infectious Diseases and Immunodeficiencies Unit (Barcelona, Spain).
o
The Rockefeller University, St. Giles Laboratory of Human Genetics of Infectious Diseases (New York, USA) (Jean Laurent Casanova)
o
Université Paris René Descartes, Faculté de Médecine, Hôpital Necker-Enfants Malades, INSERM U550 (Human Genetics of Infectious
Diseases) (Paris, France) (Jean Laurent Casanova)
o
Université Paris René Descartes, Faculté de Médecine, Hôpital Necker-Enfants Malades, INSERM U768 (Normal and Pathological
Development of the Immune System) (Paris, France) (Alain Fischer)
o
Université Paris René Descartes, Faculté de Médecine, Hôpital Necker-Enfants Malades, INSERM U783 (Development of the Immune
System) (Paris, France) (Claude-Agnès Reynaud).
National collaborations
o
Centro Hospitalar do Porto (CHP), Hospital de Santo António (HSA), Unidade de Imunologia Clínica (UIC) e Grupo de Investigação em
Imunologia Clínica.
o
Instituto Gulbenkian da Ciência (Oeiras, Portugal) (Constantin Fezel).
o
Instituto Português de Oncologia Francisco Gentil de Lisboa (Lisboa, Portugal), Serviço de Hematologia, Lisboa, Portugal. (Maria
Gomes da Silva, Paulo Lúcio).
o
Universidade do Porto, Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP), Department of Immunophisiology and Pharmacology,
Laboratory of Immunology (Porto, Portugal) (Manuel Vilanova; Paula Ferreira)
o
Universidade do Porto, Instituto de Ciências Biomédicas Abel Salazar (ICBAS/UP), Department of Pathology and Molecular
Immunology, Laboratory of Immunogenetics (Porto, Portugal) (Berta Martins).
o
Universidade do Porto, Instituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), Grupo de Investigação
Glicobiologia do Cancro, Porto, Portugal. (Salomé Pinho).
9. Ficheiros Anexos (opcional)
Nome
Ponto do RF
Descrição
Validar e Lacrar Relatório Final - Componente Científica
A fim de dar cumprimento ao estipulado no Artº. 20º do mesmo regulamento vimos informar que o relatório final relativo às atividades
realizadas no âmbito do projeto estratégico no período 2011/2013 (1 de janeiro de 2011 a 31 de dezembro de 2013) está já disponibilizado
para preenchimento e
deverá ser lacrado até às 17 horas do dia 31 de janeiro de 2014.
Relatório Científico Final 2011-13 – UMIB
Research Group Title: Working Group for Clinical Research (GIC)
Principal Investigator: Margarida Lima
Research Area: Health Sciences
Home Institution: Instituto de Ciências Biomédicas Abel Salazar
Brief explanation
In 2006, a department (DEFI, Departamento de Ensino, Formação e Investigação) was created in the Hospital de Santo António (HSA, now
integrated at the Centro Hospitalar do Porto, CHP) in order to coordinate the teaching, training and research activities. By that time, most of the clinical
research activities were not organized, in the sense that they were not conducted by a research team, according to a specific protocol, neither had separately budgeted or
specific funding. Also in 2006, the UMIB was a relatively small research Unit with 46 members (13 PhD) in the area of the Human and Veterinary
Health Sciences, structurally subdivided into four groups: Pharmacology and Neurosciences (role of the purines in various biological processes),
Anatomy (experimental viral hemorrhagic disease, vibroacustic disease and immune toxicity of heavy metals), Cell Biology (reproductive biology,
with emphasis to spermatogenesis) and Veterinary Virology (infectious diseases in the field of veterinary medicine).
At the beginning of 2007, when the DEFI was just starting its activity, the UMIB began a process of internal reorganization in order to accommodate
research areas that were emerging mainly as a consequence of the ligation between the ICBAS and the HSA. For instance, the Pharmacology &
Neurosciences group was investigating the role of the purinergic signaling in the control of synaptic transmission (Neurology), overactive bladder
and erectile dysfunction (Urology); the Anatomy group was studying the effect of the gastric hormones in bariatric surgery (Endocrinology), as well
as the anatomic and inflammatory events in the myelomeningocele (Neurosurgery), and was planning to investigate the myocardial
revascularization through cardiac venous system. At the same time, the Laboratory of Immunogenetics of the ICBAS was just starting to investigate
epilepsy (Neurology and Neurosurgery) and autoimmune diseases (Immunology and Chemistry). Thus, some hospital investigators from these
clinical areas were invited to be registered and the UMIB groups were reformulated.
Shortly thereafter, the UMIB manifested the intention to expand the collaborations with the Hospital to other areas, by incorporating more clinical
investigators and promoting translation programs. Consequently, in June 2007, all the hospital investigators were formally invited to inscribe at the
UMIB, and dozens of them responded positively to the call. By the same time, the rules for the creation of research groups were released at the
hospital. By July 2007, four research groups were approved and subsequently affiliated to the UMIB, three of them in specific research areas
(“Parkinson Disease Study Group”, PDSG; “Blood, Lymphopoietic and Hematopoietic Disorders”, BLHD; and “Nephrology, Dialysis and
Transplantation”, NDT) and one of them as a general clinical research group, this being designated “Working Group for Clinical Research” (Grupo
de Investigação Clínica, GIC) (Table 1).
Mainly as a consequence of the incorporation of hospital researchers the number of UMIB members increased from 46 (13 PhD) in 2006, to 73 (23
PhD) and then to 152 (31 PhD) in 2007, from which 100 (15 PhD) were from the CHP, reaching the maximum (200; 50 PhD) in 2008, and
stabilizing thereafter with a tendency to decrease. Simultaneously, the number of UMIB research groups increased from 4 in 2006 to 10 in 2007, 2
groups being extinguished at the end of 2010. At the end of 2012, the UMIB comprised 8 research groups and included 148 researchers (44 PhD).
Table 1: UMIB groups from 2003 to 2013
Group
Group designation
Principal
number
Host institution
investigator
Date of
Status in December
approval
2013
2003
Extinguished
2003-2006
2007-2010
2011-2013
215-2465
Anatomy
Anatomy I: Structural pathology
Extinguished (12/2010)
Artur Águas
ICBAS/UP
215-2642
-
Anatomy II: Experimental Medicine
Anatomy: Experimental Medicine
Artur Águas
ICBAS/UP
215-2408
Cell Biology
Biology and Genetics of
Biology and Genetics of
Mário Sousa
ICBAS/UP
2003
Active
Reproduction
Reproduction
Pharmacology and Neurosciences
Pharmacology and Neurosciences
Paulo Correia Sá
ICBAS/UP
2003
Active
Infectious diseases
Extinguished
Gertrude
ICBAS/UP
2003
(12/ 2010)
Thompson
ImmunoGenetics, Inflammation and
ImmunoGenetics, Inflammation and
Berta Martins
ICBAS/UP
2007
Active
Autoimmunity (IGIA)
Autoimmunity (IGIA)
Parkinson's disease study group
Parkinson's disease study group
António Bastos
HSA/CHP
2007
Active
(PDSG)
(PDSG)
Lima (2007-2012)
Margarida Lima
HSA/CHP
2007-
Active
Luísa Lobato
HSA/CHP
2007-
Active
Margarida Lima
HSA/CHP
2007
Extinguished (***)
(*)
215-2560
Pharmacology and
2007
Active
Neurosciences
215-2448
215-2748
215-2956
Veterinary Virology
-
-
Extinguished
(**)
Sara Cavaco
(2012-)
215-2923
215-2990
215-2945
-
-
-
Blood, lymphopoietic &
Blood, lymphopoietic &
hematopoietic disorders (BLHD)
hematopoietic disorders (BLHD)
Nephrology, Dialysis &
Nephrology, Dialysis &
Transplantation (NDT)
Transplantation (NDT)
Working Group for Clinical
Working Group for Clinical
Research (GIC)
Research (GIC)
Extinguished (12/2012 – 06/2013)
Abbreviations: CHP, Centro Hospitalar do Porto; HSA, Hospital de Santo António; ICBAS, Instituto de Ciências Biomédicas Abel Salazar; UMIB, Unidade Multidisciplinar de Investigação Biomédica; UP, Universidade
do Porto.
(*) The “Anatomy I: Structural Pathology” group was extinguished by the end of 2010, following the comments made by the Evaluation Panel, in 2008, regarding the need for reorganization of the two groups of Anatomy
(Anatomy I: Structure Pathology and Anatomy II: Experimental Medicine) in order to focus their research interests and to strengthen the potential impact of the group in the scientific community. Fusion of these two groups
was not difficult to achieve, since both groups had the same PI (Prof. Artur Águas) and a very similar composition with respect to PhD researchers. The group adopted the designation “Anatomy: Experimental Medicine”.
(**) In December 2010, the PI (Gertrude Thompson) and most of the researchers of the group “Infectious Diseases” asked permission to move to another research unit more focused on biological diversity and animal
research. Therefore, this group stopped its activity at UMIB at the end of 2010.
(***) The “Working Group of Clinical Analysis” was created in 2007, in order to integrate the clinical investigators that have registered at the UMIB and were not affiliated with specific groups. For logistical reasons, it was
subsequently decided that all the investigators from the hospital will be included in this group, independently of being or not integrated into other specific groups. The head of the Department for Teaching, Training and
Research (DEFI) of the CHP (Prof. Margarida Lima) assumed the responsibility for the GIC, whose aim was not to perform, but rather to promote and organize the clinical research at the CHP. The group was supposed to
be extinguished within a 3-year period, which had prolonged for another 3 years, till July of 2013, when Prof. Margarida Lima left the position of director of the DEFI.
The GIC was created in order to integrate the clinical investigators that have registered at the UMIB and that were not affiliated with specific groups.
However, for logistical reasons, it was subsequently decided that all the investigators from the hospital will be included in this group, independently
of being or not integrated into other specific groups. The head of the DEFI (Margarida Lima) assumed the responsibility for the GIC, whose aim was
not to perform, but rather to promote and organize the clinical research at the CHP.
The following priorities were defined: to organize research teams; to provide common facilities & support services for clinical research; to promote
scientific education and training for researchers; to collect and disseminate information about the academic and scientific activity of the hospital; to
encourage inter-institutional partnerships; and to provide funding for clinical research. The group was supposed to be extinguished within a 3-year
period, which had prolonged for another 3 years, till July of 2013.
A) ORGANIZATION OF RESEARCH TEAMS IN THE HOSPITAL
The GIC was initially formed by the amalgamation of already existing research investigators, which were supposed to organize themselves into
structured research groups, on a step-wise approach. The teams should have a scientific leader and were obligated to define their research scope
& aims, to plan their activity by conceiving research projects in order to answer clinical relevant questions and to report periodically their activity.
From 2008 to date, 9 research teams were approved in the Hospital (2008: 6 groups; 2010: 2 groups; 2013: 1 group) (Table 2): Anemia
physiopathology, Biopathology of systemic autoimmune diseases, Hemochromatosis, Immunoallergology, Neurobiology of human behaviour,
Primary immunodeficiencies, Clinical Immunology, Intensive Care and Neuropediatrics.
Table 2: Research teams approved in the Hospital from 2008 to 2013
Research team
Date of
Principal investigator
National Partners
State
approval
Anemia physiopathology
Biopathology of systemic autoimmune diseases
2008
2008*
in
December
2013
Alice Santos Silva, FF/UP; Margarida Lima,
FF/UP, IBMC/UP (Biology of Inflammation and Reproduction),
CHP
FMUC
Active
Elsa Bronze, FF/UP; Conceição Cerveira,
FF/UP, IBMC/UP (Biology of Inflammation and Reproduction)
Extinguished in 2012
Active
CHP
Hemochromatosis
2008
Graça Porto, CHP
IBMC/UP (Basic & Clinical Research on Iron Biology)
Immunoallergology
2008
Helena Falcão, CHP
FMUP
Neurobiology of human behavior
2008
Sara Cavaco, CHP
UMIB/ICBAS/UP
Extinguished in 2012
(ImmunoGenetics,
Inflammation
and
Active
UMIB/UP (Blood, Lymphopoietic and Hematopoietic Disorders,
Active
Autoimmunity, IGIA)
Primary immunodeficiencies (PID)
2008
Esmeralda Neves, CHP
BLHD)
IBMC/UP (Immunobiology)
Clinical Immunology
2010
Carlos Vasconcelos, CHP
UMIB/ICBAS/UP
(ImmunoGenetics,
Inflammation
and
Active
Autoimmunity, IGIA)
IGC (Lupus And Autoreactive Immune Repertoires)
Intensive Care
2010
Irene Aragão, CHP
SBIM/FMUP
Active
Neuropediatrics (NeuroPED)
2013 (*)
Teresa Temudo, CHP
CDC/CHUC ECS/ICVS/UP, CIFI2D, FEUP, LABIOMEP, FADEUP
Active
* Proposed in 2012, approved in 2013.
Abbreviations: CIFI2D/UP, Centro de Investigação, Formação, Inovação e Intervenção em Desporto do Porto (HESC-Norte-Porto-4068); ECS/ICVS/UM, Escola de Ciências da Saúde do Instituto de Ciências da Vida e da
Saúde da Universidade do Minho; FADEUP, Faculdade de Desporto e Educação Física da Universidade do Porto; FEUP, Faculdade de Engenharia da Universidade do Por to; FF/UP, Faculdade de Farmácia
da Universidade do Porto; FMUC, Faculdade de Medicina da Universidade de Coimbra; FMUP, Faculdade de Medicina da Universidade do Porto; IBMC/UP, Instituto de Biologia Molecular e Celular da Universidade do
Porto; ICBAS/UP, Instituto de Ciências Biomédicas da Universidade do Porto; UMIB/ICBAS/UP, Unidade Multidisciplinar da Universidade do Porto; LABIOMEP, Laboratório de Biomecânica da Universidade do Porto;
CDC/CHUC, Centro de Desenvolvimento da Criança do Centro Hospitalar e Universitário de Coimbra; SBIM/FMUP, Serviço de Bioestatística e Informática Médica da Faculdade de Medicina da Universidade do Porto.
These teams incorporated investigators from the CHP, as well as from other national academic and research centers, such as ECS/ICVS/UM,
FADEUP, FEUP, FFUP, FMUC, FMUP, ICBAS/UP, CIFI2D, IBMC/UP, LABIOMEP and UMIB/ICBAS/UP.
Nevertheless, some problems compromised the possibility of organizing more research teams inside the hospital and/or proposing these teams as
independent groups inside the UMIB:
a) Firstly, in most cases the natural leaders were not PhD and/or the team did not have enough PhD investigators to be considered as independent
research group by the FCT;
b) Secondly, in some areas (e.g. Neurosciences), the research effort was fragmented thought more or less structured areas (e.g. Epilepsy,
Cerebrovascular diseases, Neuroimmunology, Neuroanesthesia, etc.) and no agreement was reached between the natural leaders in order to
create research groups;
c) Thirdly, some of the clinical investigators chose to integrate other UMIB groups (e.g. IGIA: Clinical Immunology and Neurobiology of Human
Behavior; BLDH: Anemia physiopathology, Immunoallergology and Primary Immunodeficiencies; P&N: Urology and Neurology and Orthopedics;
PDSG: Neurology and Neurosurgery).
d) Finally, other clinical investigators decided to integrate groups from other FCT Units with which they already had long-standing collaboration (e.g.
IBMC/UP – Hemochromatosis; Neurosciences/Headaches; Anemia physiopathology; INEB/UP – Orthopedics).
B) RESEARCH FACILITIES & SUPPORT SERVICES
A Research Coordination Unit (Gabinete Coordenador da Investigação, GCI) was created in 2007 at the CHP, where different areas were
subsequently organized in order to provide support to research: coordination of clinical trials, analysis of research proposals, project management,
biostatistics, and collection of output indicators, among others. Simultaneously, the Hospital made available common facilities and services,
including a training center, an auditorium and a library.
B1. RESEARCH COORDINATION UNIT
Clinical trials core: The conduct of high quality clinical trials is essential to the overall mission of the Hospital. Thus, for the last years our
investment was in creating, inside the GCI, a core facility for coordination and supervision of clinical trials which provides centralized protocol
development and implementation services, data management, reporting, and administrative oversight. It also promotes education and training for
clinical research coordinators, research nurses, and individual investigators. In order to provide support to clinical trials, a team of study
coordinators and research nurses was created in 2012, which is now being expanded. Specific objectives are to: 1) facilitate activation and conduct
of clinical trials in the hospital; 2) promote awareness and availability of active studies; 3) facilitate enrolment of eligible patients onto clinical trials;
and 4) promote quality assurance, research compliance, and adherence to Good Clinical Practices (GCP). In this area, the CHP became a member
of the PtCRIN (Portuguese Clinical Research Infrastructure Network), a national research infrastructure aiming to facilitate and improve quality in
clinical research and to increase research collaboration. http://web.fcm.unl.pt/ptcrin/
Research proposals core: This team provides technical and scientific support to clinical investigators and students for the elaboration of research
proposals and analyses the research studies that are submitted at the CHP, before being analyzed by the Ethical Committee.
Biostatistics core: The biostatistics core provides statistical support to the investigators regarding the preparation of study design and data
analysis. With that purpose, the CHP contracted a PhD consultant in Biostatistics.
Project management core: This core supports clinical researchers in the preparation of grant applications. It is also in charge to identify funding
opportunities, as well as of managing the funded projects, including grant payments, monitoring the expenses and organising the archiving of
supporting documents.
Open Access core: In order to increase the visibility, accessibility and dissemination of the academic and scientific activity of the Hospital
community and to facilitate the management and access to information, in 2010 the CHP became an active member of the RCAAP, a FCCN
supported project aimed to collect, aggregate and index Open Access scientific contents from institutional repositories. Since 2007, hundreds of
documents were archived at the CHP repository, including manuscripts, congress books, master and doctoral thesis, among others.
http://repositorio.chporto.pt/
Dissemination of opportunities: New software was developed in order to disseminate by e-mail the opportunities (e.g. courses, conferences,
funding programs, etc.) to the hospital community.
Scientific journals: NASCER E CRESCER is a quaternary journal focused to all health professionals with an interest in the area of Maternal and
Child Health that publishes scientific articles related to Pediatrics, Perinatology, Mental Health of Children and Adolescents, and Bioethics. It is
published regularly since 1991, being indexed by EMBASE/ Excerpta Medica since 1996, SCOPUS, LATINDEX Catalog since 2004, and Scielo
since 2011. http://www.scielo.gpeari.mctes.pt/scielo.php?script=sci_serial&pid=0872-0754&lng=en&nrm=iso. In October 2008, the Journal
becomes under the technical coordination of the DEFI. From 2008 to 2012, the editorial and the scientific boards were reformulated as did the
scope and the policy and the instructions for the authors.
B2. COMMON FACILITIES AND SERVICES
Auditorium and Training Center: The auditorium and training center facilities were reformulated and reequipped. At the Auditorium, the
conference room accommodates seat capacity for 150 participants; n addition, the upper floor, with optional dividing walls, accommodates three
separate sessions. At the Training Center, 4 additional rooms are available, one of them being equipped with 14 laptop computers. All these
facilities are equipped with computers with Internet connection, slide and overhead projectors, data-shows and projection screens and multi-media,
being available for congresses, seminars, courses and other events.
Library: New library facilities, which are open to the hospital staff as well as to students, were inaugurated in July 2008 and totally reequipped.
Printed resources include about 800 periodicals and over 5,000 monographs, books and manuals, beyond historical documents. On-line resources
include: B-On/FCCN (http://www.b-on.pt/) (signed by the CHP from 2007 to 2010; shared with the UP since then); UptoDate/WKH
(http://www.uptodate.com/) (evidence-based, physician-authored clinical decision support resource developed by the Wolters Kluwer Health, WKH)
(since September 2009); OvidSP/LWW (http://www.ovid.com/) (online access to over 250 medical and nursing journals published by Lippincott
Williams & Wilkins, LWW) (since 2010) and Clinical Key/Elsevier (https://www.clinicalkey.com/) (online access to over 1,000 books, 500 journals,
thousands of videos, and millions of images from medical specialties) (since December 2012) platforms.
The CHP Library Web Page and the Virtual CHP Library were made available in 2010. Using AtoZ/EBSCO, a Web-based tool for organizing and
providing links to library’s e-resources, they facilitate the access to all the on-line resources subscribed by the CHP (e.g. UpToDate/WKH,
OvidSP/LWW, ClinicalKey/Elsevier, etc.), beyond other free on-line resources (e.g. PubMed and MeSH), allowing to search by subject / term and
linking to the full text of numerous online publications in the field of Health, Medical and Biomedical Sciences.
E) SCIENTIFIC EDUCATION AND RESEARCH TRAINING
The GCI provided education and training for the clinical researchers by organizing advanced courses on organization and coordination of clinical
trials, elaboration of research proposals, biostatistics, etc. (Tables 3 and 4) In addition, the Auditorium and the Learning Center gave the logistic
support to hundreds of scientific and academic events promoted by the Hospital community.
In 2007, a discipline for the initiation on clinical research (Disciplina de Iniciação à Investigação Clínica, DIIC) was created an optional discipline for
the medical students of the ICBAS/UP. From 2007 to 2012, 31 medical students conceived and realized their research projects; at the end of 2013,
10 additional projects are being conceived and 9 projects are going-on. Since 2009, a congress is organized every year, where the students
present their research proposals or the results obtained (Journeys of Initiation to Clinical Research, JIIC).
https://sites.google.com/site/jiicmargaridalima/
Our proactive attitude to encourage the attainment of academic degrees by health professionals resulted in a high number of clinicians, nurses and
technicians engaging in post-graduation courses, master and doctoral programs (please see below).
Table 3: Courses and congresses promoted by the GCI from 2007 to 2012*
Year
Courses (number)
Congresses and seminars (number)
2007
Clinical trials (1)
-
2008
Clinical trials (1); Research projects (1)
-
2009
Research projects (1)
Initiation to Clinical Research (for students) (1)
2010
Clinical Trials (2)
Initiation to Clinical Research (for students) (1)
2011
Clinical Trials (3), EndNote Web (2);
Initiation to Clinical Research (for students) (1)
2012
Biostatistics (2); Authorship (1); EndNote Web (1); PubMed (1); SPSS (2); Web of Science (1); Zotero (1)
Initiation to Clinical Research (for students) (1)
Regenerative Medicine (3)
Table 4: ORGANISATION OF SCIENTIFIC DISSEMINATION ACTIVITIES (TRAINING COURSES, SYMPOSIUMS, CONFERENCES,
SEMINARS, etc.)
2013
1.
JORNADAS DE INICIAÇÃO À INVESTIGAÇÃO CLÍNICA (5ªs). Promoter: DIIC/MIM/ICBAS/UP e GCI/DEFI/CHP. Place: Auditório Prof. Doutor Alexandre Moreira, HSA, CHP, Porto, Portugal.
Date: 28/06/2013.
2.
CURSO DE ENSAIOS CLÍNICOS PARA INVESTIGADORES. Promoter: GCI/DEFI/CHP e BIAL. CHP, Porto, Portugal. Place: Auditório Prof. Doutor Alexandre Moreira e Centro de Formação,
DEFI, CHP, Porto, Portugal. Date: 01/02/2013.
3.
CURSO DE ENSAIOS CLÍNICOS PARA COORDENADORES DE ENSAIOS. Promoter: GCI/DEFI/CHP e BIAL. DEFI/CHP. Place: Auditório Prof. Doutor Alexandre Moreira e Centro de Formação,
DEFI, CHP, Porto, Portugal. Date: 31/01/2013 e 01/02/2013.
4.
SPSS: ANÁLISE ESTATÍSTICA DE DADOS COM A UTILIZAÇÃO DO SPSS E DO MS EXCEL (3ª edition). Promoter: GCI/DEFI/CHP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal.
2012
5.
CONCEPÇÃO, REDACÇÃO E PUBLICAÇÃO DE ARTIGOS CIENTÍFICOS. Promoter: XXIV Reunião Anual de Pediatria do CHP e GCI/DEFI/CHP. Place: Ipanema Park Hotel Porto, Portugal.
Date: 21/11/2012.
6.
ZOTERO: APLICAÇÃO INFORMÁTICA PARA RECUPERAÇÃO E GESTÃO DE REFERÊNCIAS BIBLIOGRÁFICAS. Promoter: GCI/DEFI/CHP. Date: 20/10/2012.
7.
DIREITOS DE AUTOR: PUBLICAÇÕES CIENTÍFICAS, AUTORIA E DIREITOS DE AUTOR. Promoter: GCI/DEFI/CHP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 22/09/2012.
8.
JORNADAS DE INICIAÇÃO À INVESTIGAÇÃO CLÍNICA (4ªs). Promoter: DIIC/MIM/ICBAS/UP e GCI/DEFI/CHP. Place: Auditório Prof. Doutor Alexandre Moreira, HSA, CHP, Porto, Portugal.
Date: 29/06/2012.
9.
ENDNOTE WEB (3ª EDIÇÃO): FUNCIONALIDADES E CARACTERÍSTICAS DA APLICAÇÃO INFORMÁTICA PARA RECUPERAÇÃO E GESTÃO DE REFERÊNCIAS BIBLIOGRÁFICAS.
Promoter: GCI/DEFI/CHP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 11, 13 e 15/06/2012.
10.
SEMINÁRIOS INEB/ICBAS/CHP 2012: CONTROVÉRSIAS AO ALMOÇO – FACTOS E MITOS EM … MEDICINA REGENERATIVA – QUAIS OS LIMITES BIOLÓGICOS DA REGENERAÇÃO?
Promoter: INEB/UP, ICBAS/UP e GCI/DEFI/CHP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal. Place: Auditório Prof. Doutor Alexandre Moreira, HSA, CHP, Porto, Portugal. Date:
06/06/2012.
11.
SEMINÁRIOS INEB/ICBAS/CHP 2012: CONTROVÉRSIAS AO ALMOÇO – FACTOS E MITOS EM … MEDICINA REGENERATIVA – TERAPIA CELULAR. Promoter: INEB/UP, ICBAS/UP e
GCI/DEFI/CHP. Place: Auditório Prof. Doutor Alexandre Moreira, HSA, CHP, Porto, Portugal. Date: 09/05/2012.
12.
SPSS: ANÁLISE ESTATÍSTICA DE DADOS COM A UTILIZAÇÃO DO SPSS E DO MS EXCEL, Promoter: GCI/DEFI/CHP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 7, 9, 14,
16, 21, 23 e 28/05/2012.
13.
SEMINÁRIOS INEB/ICBAS/CHP 2012: CONTROVÉRSIAS AO ALMOÇO – FACTOS E MITOS EM … MEDICINA REGENERATIVA – COMO REGENERAR TECIDOS E ÓRGÃOS HUMANOS?
Promoter: INEB/UP, ICBAS/UP e GCI/DEFI/CHP. Place: Auditório Prof. Doutor Alexandre Moreira, HSA, CHP, Porto, Portugal. Date: 04/04/2012.
14.
CURSO AVANÇADO DE BIOESTATÍSTICA E SUAS APLICAÇÕES EM CIÊNCIAS DA SAÚDE. Promoter: GCI/DEFI/CHP e ICBAS/UP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal.
Date: 05/03/2012-17/03/2012 (27h).
15.
PUBMED. Promoter: GCI/DEFI/CHP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 02-04/03/2012.
16.
WEB OF SCIENCE: FUNCIONALIDADES E CARACTERÍSTICAS DA BASE DE DADOS E DA PESQUISA DE E POR CITAÇÕES. Promoter: GCI/DEFI/CHP. Place: Centro de Formação, DEFI,
CHP, Porto, Portugal. Date: 28/02/2012-01/03/2012.
17.
CURSO DE INTRODUÇÃO À BIOESTATÍSTICA E SUAS APLICAÇÕES EM CIÊNCIAS DA SAÚDE. Promoter: GCI/DEFI/CHP e ICBAS/UP. Place: Centro de Formação, DEFI, CHP, Porto,
Portugal. Date: 30/01/2012-11/02/2012.
2011
18.
CURSO DE ENSAIOS CLÍNICOS (4a. Edição): Promoter: GCI/DEFI/CHP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 10/10/2011.
19.
JORNADAS DE INICIAÇÃO À INVESTIGAÇÃO CLÍNICA (3ªs). Promoter: GCI/DEFI/CHP. Place: Auditório Prof. Doutor Alexandre Moreira, HSA, CHP, Porto, Portugal. Date: 01/07/2011.
20.
ENDNOTE WEB (2ª edição). FUNCIONALIDADES E CARACTERÍSTICAS DA APLICAÇÃO INFORMÁTICA PARA RECUPERAÇÃO E GESTÃO DE REFERÊNCIAS BIBLIOGRÁFICAS.
Promoter: GCI/DEFI/CHP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 27 e 29/06/2012.
21.
ENDNOTE WEB (1ª edição). FUNCIONALIDADES E CARACTERÍSTICAS DA APLICAÇÃO INFORMÁTICA PARA RECUPERAÇÃO E GESTÃO DE REFERÊNCIAS BIBLIOGRÁFICAS.
Promoter: GCI/DEFI/CHP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 20 e 22/06/2012.
2010
22.
CURSO DE ENSAIOS CLÍNICOS CHP (3ª edição): Promoter: GCI/DEFI/CHP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 26/11/2010.
23.
JORNADAS DE INICIAÇÃO À INVESTIGAÇÃO CLÍNICA (2ªs): Promoter: DIIC/MIM/ICBAS/UP e GCI/DEFI/CHP. Place: Auditório Prof. Doutor Alexandre Moreira, HSA, CHP, Porto, Portugal.
Date: 02/07/2010.
24.
ENSAIOS CLÍNICOS: Curso de Ensaios Clínicos CHP (2ª edição): Promoter: GCI/DEFI/CHP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 30/06/2010.
2009
25.
JORNADAS DE INICIAÇÃO À INVESTIGAÇÃO CLÍNICA (1ªs). Promoter: DIIC/MIM/ICBAS/UP e GCI/DEFI/CHP. Place: Auditório Prof. Doutor Alexandre Moreira, HSA, CHP, Porto, Portugal.
Date: 26/06/2009.
26.
PROJECTOS DE INVESTIGAÇÃO: ELABORAÇÃO DE PROPOSTAS (2ª edição). Promoter: GCI/DEFI/CHP. Place: Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 19-22 e 27/01/2009.
2008
27.
PROJECTOS DE INVESTIGAÇÃO II: ELABORAÇÃO DE PROPOSTAS” (1ª edição). Promoter: GCI/DEFI/CHP. Centro de Formação, DEFI, CHP, Porto, Portugal. Date: 24-27/11/2008;
02/12/2008.
28.
“ABC DO HOSPITAL”: 20 sessions held throughout the year in 2008, involving 83 Departments, Services, Sectors and Units and were attended by about 1000 participants. Promoter: Direcção
clínica do CHP e DEFI/CHP. Place: Auditório Prof. Doutor Alexandre Moreira, HSA, CHP, Porto, Portugal.
2007
29.
COLÓQUIOS DO HGSA: INVESTIGAÇÃO EM SAÚDE. Promoter: Clinical Direction HSA and DEFI/CHP. Place: Auditório Prof. Doutor Alexandre Moreira, HSA, CHP, Porto, Portugal. Date:
2006
30.
COLÓQUIOS DO HGSA: CUIDADOS DE SAÚDE. Promoter: Clinical Direction HSA and DEFI/CHP. Place: Auditório Prof. Doutor Alexandre Moreira, HSA, CHP, Porto, Portugal. Date:
D) SCIENTIFIC OUTPUT
For the last years, an effort was made in order to improve records of research activities and scientific production of the Hospital, by registering
systematically the research studies performed, the scientific papers published in peer-reviewed scientific journals and the academic graduations.
With this purpose, new software (REFI) was developed in 2010 and 2011 to record the teaching, training and research activities conducted at
Hospital, being used since 2012 for the elaboration of the annual reports. Software for submission and approval of the research studies at the
hospital is now being conceived.
Research studies: From 2007 to 2012, the number of research studies/year increased from 111 to 312: clinical trials with drugs and medical
devices: 20 to 28, research projects and observational studies: 39 to 124; academic projects: 52 to 160. Total number: 1198 (155 + 411 + 632)
(Table 5).
Table 5: Number of research studies at the CHP from 2007 to 2012
Year
2007
2008
2009
2010
2011
2012
2007-2012
Clinical trials with
drugs
18
22
23
23
30
25
141
Studies with medical
devices
2
2
2
2
3
3
14
Research projects and
observational studies
39
48
62
64
74
124
411
Academic
projects
52
76
87
116
141
160
632
Total
111
148
174
205
248
312
1198
Papers published: From 2007 to 2012, the number of papers published annually in peer reviewed scientific journals with peer-review increased
from 170 to 259 (indexed in the Medline: 92 to 187; non-indexed in the Medline: 78 to 72). Total number: 1221 (779 + 442). (Table 6)
Table 6: Number of papers in periodicals with peer-review from 2007 to 2012
Year
Indexed in the MedLine
Non-indexed in the MedLine
Total
2007
92
78
170
2008
99
78
177
2009
103
68
171
2010
139
93
232
2011
159
53
212
2012
186
72
258
2007-2012
778
442
1220
1988-1997: 509 (51/year) (365 MedLine + 153 non-MedLine); 1998-2007 (10 years): 1374 (137/year) (822 MedLine + 552 nonMedLine); 2007-2012 (6 years): 1219 (203/year) (777 MedLine + 442 non-MedLine)
Books published: A Guide for Good Research Clinical Practices was edited in 2010. In the same year another book was edited, collecting all the
papers published from the CHP professionals between 1988 and 2007; since than, a book is edited yearly on the subject.
http://repositorio.chporto.pt/bitstream/10400.16/859/1/GUIA%20DE%20BOAS%20PR%C3%81TICAS%20EM%20INVESTIGA%C3%87%C3%83O
%20cLINICA%20DO%20CHP.pdf
Academic graduations: Between 2007 and 2012, 75 health professionals from the CHP enrolled in PhD programs and 18 PhD theses were
concluded (Table 7); at the end of 2012, 78 PhD theses were ongoing. Also from 2007 to 2012, 133 health professionals from the CHP enrolled in
MsD programs and 123 MsD graduations were obtained (Table 7); at the end of 2012, 33 MsD dissertations were ongoing. At the end of 2013, the
CHP has 41 PhD (38 MD, 1 administrator, 2 technicians) and 151 MsD.
Table 7: Number of academic graduations from health professionals of the CHP
Year
PhD
MsD
Ongoing
Concluded
Starting date (total) Ongoing
Concluded
Starting date (total)
Initiated Initiated Finished
Initiated Initiated Finished
Before 2007
11
71
55
82
12
72
31
84
2007
3
3
5
6
5
22
8
27
2008
11
2
4
13
10
24
10
34
2009
16
2
1
18
9
18
20
27
2010
20
1
2
21
12
22
40
34
2011
13
0
3
13
11
0
19
11
2012
4
0
3
4
NA
0
26
0
2013
NA
0
6
NA
NA
0
4
NA
2007-2012
67
8
18
75
47
86
123
133
Till 2012
78
79
73
157
59
158
154
217
Till 2013
NA
79
79 (*)
NA
59 (**)
158
158 (***)
217
NA, data not available; (*) 23/12/2013: 40 active health professionals with PhD; (**) 23/12/2013: 33 going on + 26 dropouts (***)
23/12/2013: 151 active professionals with MsD.
National survey on scientific and technological activities (IPCTN): From 2007 to 2011 the number of researchers (in full time equivalents, FTE)
at the CHP increased from 37.0 to 72.8 FTE and the total expenses with I&D increased from 1.854.442 to 7.801.801 €/year, corresponding to the
first position in the national ranking in the majority of the evaluated parameters. Data from the 2012 survey are not yet available.
http://www.dgeec.mec.pt/np4/206/ (Table 8)
Table 8: Results from the national survey on scientific and technological activities (IPCTN)*
IPCTN
I&D Units
Research
(Year)
(n, %)
projects (n)
Researchers (n)
Researchers (FTE)
NR
2007
PhD researchers
(FTE)
NR
Researchers (mean %
Expenses (€)
NR
1.854.442
NA
3.556.430
1º
5.449.273
1º
6.189.333
1º
7.801.801
3º
NA
NA
TDR)
25
100
199
37,0
NA NA
NA (40%)
2008
32
157
198
34,3
3º NA
NA 6,0
(52%)
2009
35
204
274
51,8
1º NA
NA 10,8
(56%)
2010
38
290
322
64,3
1º 4,6
6º
15,0
(60%)
2011
28
NA
365
72,8
3º 5,9
6º
15,0
(43%)
2012
NA
NA
NA
NA
NA
NA NA
* Data from GPEARI/MCTES; NA, Not yet available; TDR, Time dedicated to research; FTE, Full Time Equivalents
E) INTER-INSTITUCIONAL PARTNERSHIPS
The research activity in the Hospital is developed in collaboration with other national and foreign academic, research and health care centers, as
well as with professional and scientific societies and working groups. In addition, the Hospital collaborates with a large number of public and private
schools, at different levels: teaching of disciplines and courses, collaborating in academic projects, training health professionals (medical doctors,
lab technicians, nurses, etc.) and students, etc. In the last two years, the Hospital signed collaboration protocols with nearly 50 polytechnic and
university schools.
Some of the collaborations established with other FCT Research Units included: Cardiology - IPATIMUP; Gastroenterology - IPATIMUP;
Hematology - IBMC/UP and UMIB; Immunology – IGC and UMIB/UP; Neurology – IBMC/UP and UMIB/UP; Orthopedics - INEB/UP and UMIB;
F) RESEARCH FUNDING
A)
Hospital funding (FID) – Grants: 343.300€ (individual grants: 253.300€; grants for research projects: 80.000€; grants for PhD projects:
40.000€)
B)
Hospital funding (FID) – Awards: 100.000€ (investigators: 75.000€; clinical departments: 25.000€)
C)
Hospital funding – Library resources: 1.600.000€ (printed: 720.000€; electronic: 880.000€)
D)
ICBAS/UP funding – Research grants (research projects for medical students, DIIC): 67.500 €.
E)
FCT funding – Research grants (research projects): 196.069,00€
F)
European Union funding – Research grants (research projects): 67.405 €
From 2008 to 2012, hospital expenses with library resources totalized ~ 1.400.000€ (Table 9).
Table 9: CHP funding for library resources
Printed resources
On-line resources
B-On
UpToDate
AtoZ
OvidSP
ClinicalKey
Year
Periodicals and others(*)
(FCCN)
(WKH)
(EBSCO)
(LWW)
(Elsevier)
Total
2007
120000,00
97122,88
-
-
-
-
217122,88
2008
120000,00
97122,88
-
-
-
-
217122,88
2009
120000,00
121540,80
45500,00
-
-
-
287040,80
2010
120000,00
216144,00
45500,00
2765,07
23952,50
-
408361,57
2011
120000,00
-
63145,43
2765,07
28982,53
-
214893,03
2012
120000,00
-
63145,43
2765,07
28982,53
48040,00
262933,03
2007-2012
720000,00
531930,56
217290,86
8295,21
81917,56
48040,00
1607474,19
2007-2012
720000,00
2008-2012
600000,00
434807,68
217290,86
81917,56
48040,00
1390351,31
2008-2012
600000,00
887474,19
8295,21
1607474,19
790351,31
1390351,31
By creating a Fund for Research and Development (FID) (financial support from the pharmaceutical industry, mainly from clinical trials), during the
same period, the CHP attributed individual grants, mainly for post-graduation programs (213.300€), grants for research projects (80.000€), PhD
studies (40.000€) (Table 10) and for research fellows (3 grants in 2012, totalizing 40.750€, which were renewed in 2013), as well as awards for the
hospital departments (25.000€) and investigators (75.000€) (Tables 11 and 12). Simultaneously, the remaining funds from research studies (clinical
trials and observational studies) promoted and funded by external entities (mainly pharmaceuticals) were made available to the services to be
applied in teaching, training and research activities, as well as to contract research fellows. In addition, the hospital received grants for research
projects from the FCT (196.069€).and from the European Community (67.405 €) (Tables 13 and 14).
Table 10: CHP funding (FID) for individual grants and grants for research projects and doctoral thesis*
Year
Individual grants & scholarships (€)
Research projects (€)
PhD projects (€)
Total founding (€)
2007
40.000€
-
-
40.000€
2008
40.000€
-
-
40.000€
2009
40.000€
20.000€
10.000€
70.000€
2010
40.000€
20.000€
10.000€
70.000€
2011
46.650€
20.000€
10.000€
76.650€
2012
46.650€
20.000€
10.000€
76.650€
2007-2012
253.300€
80.000€
40.000€
373.300€
2008-2012
213.300€
80.000€
40.000€
343.300€
* Training programs; doctoral, master and other post-graduation courses
Abbreviations: FID, Fundo para a Investigação e Desenvolvimento (Fund for Research and Development)
Table 11: CHP funding (FID) for awards for CHP departments and investigators
Year
Awards for the clinical department with the best scientific activity
Awards for the investigators with the best publication
Total founding
2007
-
-
-
2008
5.000€
15.000€
20.000€
2009
5.000€
15.000€
20.000€
2010
5.000€
15.000€
20.000€
2011
5.000€
15.000€
20.000€
2012
5.000€
15.000€
20.000€
2007-2012
25.000€
75.000€
100.000€
2008-2012
25.000€
75.000€
100.000€
Abbreviations: FID, Fundo para a Investigação e Desenvolvimento (Fund for Research and Development)
Table 12. Awards for the investigators with the best publications
Year
CHP investigator (Author)
Published manuscript
(€)
2007
-
-
-
2008
Teresa Temudo
Stereotypies in Rett syndrome: analysis of 83 patients with and without detected MECP2 mutations
10.000€
2009
Estevão Lima
Endoscopic closure of transmural bladder wall perforations
10.000€
2010
Ana Mota
Epidemiological Study of Genotypes of Hepatitis B Vírus in Norther Portugal
10.000€
Angélica Rodrigues
Bilateral Submandibulectomy for the Treatment of Drooling in Children With Neurological Disability
-
2011
Idalina Beirão
Erythropoietin production by distal nephron in normal and familiar amyloidotic adult human kidneys
7.500€
La Fuente de Carvalho
Diabetes exacerbates the functional deficiency of NO/cGMP pathway associated with erectile dysfunction in human corpus cavernosum and penile arteries
2.500€
2012
Ana Martins da Silva
Olfactory dysfunction in multiple sclerosis: association with secondary progression
7.500€
Maria de La Salete Martins
One Hundred Eleven Simultaneous Pancreas-Kidney Transplantations: 10-Year Experience From a Single Center in Portugal
2.500€
(*) Approximate values (values in 2013 were similar to those indicated for 2012).
Table 13: FCT funding for research projects
Reference number
Project title
PIC/IC/82858/2007
Tendências na incidência e prognóstico dos Acidentes
Neurológicos: o segundo estudo de base populacional no
norte de Portugal
GALENO - Modelação e controlo para administração
personalizada de fármacos (Nº registo
Variabilidade fenotípica e genes modificadores na
Polineuropatia Amiloidótica Familiar
Prevenção/intervenção precoces em distúrbios de
comportamento: eficácia de programas parentais e escolares
Superfícies de nanohidroxiapatite com características
antibacterianas para presenção de infecção óssea associada a
biofilmes (NaNOBiofilm)
Total
PTDC/SAUBEB/103667/2008
PTDC/SAUGMG/100240/2008
PTDC/PSIPED/102556/2008
PTDC/SAUBMA/111233/2009
Host
institution
HSA/CHP
Total
funding €
178.000
Funding for
the CHP €
160.368
FU/UP
185.000
8.640
IBMC/UP
199.275
15.061
FPCE/UC
165.031
6.000
INEB/UP
150.000
6.000
877.360 €
196.069 €
Table 14: European Community funding for research projects
Reference
number
Project title
WebSite
Host
institution
Starting
date
Duration
Grant
Agreement
2008 13 05
DSDP - Day
Surgery Data
Project
http://www.dsdp.eu/
ARSS,
Venezia,
Italia
01-092009
Grant
Agreement
2009 11 04
DSP - Day Safe
Project
http://www.daysafe.eu/
ARSS,
Venezia,
Italia
01-102010
TOTAL
ARSS, Agenzia Regionale Socio-Sanitaria del Veneto.
36 months
Total funding
(EC
funding)€
?
Funding
for the
CHP€
25.308
36 months
(EC: 300.000)
1.094.740
42.097
(EC: 650.000)
(EC: 950.000)
67.405
Relatório Científico Final 2011-13 – UMIB
Research Group Title: Nephrology, Dialysis and Transplantation
Principal Investigator: Luisa Lobato
Research Area: Health Sciences
Home Institution: Instituto de Ciências Biomédicas Abel Salazar