Browsing by Author "Pinho-Costa, P."
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- Aqueous humor erythropoietin levels in open-angle glaucoma patients with and without TTR V30M familial amyloid polyneuropathyPublication . Beirão, J.; Moreira, L.; Oliveira, J.; Menéres, M.; Pessoa, B.; Matos, M.; Pinho-Costa, P.; Torres, P.; Beirão, I.Purpose: Glaucoma is the leading cause of irreversible blindness in familial amyloidotic polyneuropathy (FAP) patients. Erythropoietin (EPO) is a cytokine that has been shown to play a role in neuroprotection and is endogenously produced in the eye. EPO levels in the aqueous humor are increased in eyes with glaucoma. In this study, we evaluated the EPO concentration in the aqueous humor of FAP and non-FAP patients, with and without glaucoma. Methods: Undiluted aqueous humor samples were obtained from 42 eyes that underwent glaucoma surgery, phacoemulsification, or vitrectomy. EPO concentration in the aqueous humor and blood were measured using the Immulite 2000 Xpi using an automatic analyzer (Siemens Healthcare Diagnostics). Results: The mean EPO concentration in the aqueous humor of non-FAP glaucoma eyes group 2(75.73±13.25 mU/ml)was significantly higher than non-FAP cataract eyes (17.22±5.33 mU/ml; p<0.001), FAP glaucoma eyes (18.82±10.16 mU/ml; p<0.001), and FAP nonglaucoma eyes (20.62±6.22 mU/ml; p<0.001). There was no statistically significant difference between FAP nonglaucoma eyes versus non-FAP cataract eyes (p = 0.23) and FAP glaucoma eyes versus FAP nonglaucoma eyes (p = 0.29). In the glaucoma groups, there was no correlation between the aqueous humor EPO concentration and the ocular pressure (p = 0.95) and mean deviation (p = 0.41). There was no correlation between the EPO serum concentration and EPO aqueous humor concentration in our patients (p = 0.77). Conclusions: Unlike other glaucomatous patients, FAP patients with glaucoma do not show increased and potentially neuroprotective endocular EPO production in the aqueous humor and may need more aggressive glaucoma management
- CCR5-Delta32: Implications in SLE developmentPublication . Carvalho, C.; Calvisi, S.L.; Leal, B.; Bettencourt, A.; Marinho, A.; Almeida, I.; Farinha, F.; Pinho-Costa, P.; Silva, B.M.; Vasconcelos, C.Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease with strong genetic and environmental components. Previous studies have shown increased levels of several chemokines in active SLE. C-C chemokine receptor type 5 (CCR5) is involved in the recruitment of inflammatory cells into tissues, and mechanisms modulating CCR5 expression and function may interfere in SLE development, influencing the clinical course of the disease. The aim of this study was to evaluate the possible association between the CCR5{increment}32 base-pair deletion polymorphism and SLE disease in a group of Portuguese patients. A total of 219 patients with SLE and 205 healthy individuals were studied. The frequency of CCR5[del]32 heterozygotes was lower in patients with SLE than in controls (8% vs. 15% OR = 0.5162; P = 0.0319), suggesting a protective association between CCR5[del]32 allele and SLE. These results highlight the protective role of Th1 cells that express CCR5 in SLE pathogenesis.
- Convergent evolution of IL-6 in two leporids (Oryctolagus and Pentalagus) originated an extended proteinPublication . Neves, F.; Abrantes, J.; Pinheiro, A.; Almeida, T.; Pinho-Costa, P.; Esteves, P.J.Interleukin 6 (IL-6) is a class-I helical cytokinewith a broad spectrum of biological activities and a gene structure conserved throughout vertebrates, with five coding exons. IL-6 from European rabbits belonging to the subspecies Oryctolagus cuniculus cuniculus was previously shown to differ from other mammals by extending an additional 27 amino acids. However, in other leporids (Sylvilagus spp and Lepus spp) that diverged from the European rabbit ~12 million years ago this mutation was not present. In this study, we extended the study of IL-6 for the Oryctolagus cuniculus algirus subspecies and five additional lagomorphs’ genera(Brachylagus, Bunolagus, Pentalagus, Romerolagus, and Ochotona). We confirmed the presence of the mutated stop codon in both O. c. cuniculus and O. c. algirus.We found that the typical stop codon is present in Sylvilagus bachmani and Lepus europaeus, in agreement with previous reports, but also in Bunolagus, Brachylagus, and Ochotona. Remarkably, in Pentalagus we detected a deletion of the stop codon causing an extension of IL-6 for 17 extra residues. Our results indicate that the IL-6 extension in those species occurred by two independent events: one occurred between 2 and 8 million years ago in the ancestral of the Oryctolagus subspecies, and the other occurred in a Pentalagus ancestral at a maximum of 9 million years ago. The absence of this IL-6 extension in Bunolagus, sister genus of Oryctolagus, shows that this evolutionary event happened by convergence suggesting some functional relevance.
- Influence of interleukin-6 gene polymorphisms in epicardial adipose tissue and coronary artery calcification in patients with psoriasisPublication . Torres, T.; Bettencourt, N.; Ferreira, J.; Carvalho, C.; Mendonça, D.; Pinho-Costa, P.; Vasconcelos, C.; Selores, M.; Silva, B.Psoriasis is currently considered a systemic inflammatory disorder associated with several comorbidities and increased risk of cardiovascular disease (CVD)1 cytokines are overexpressed cutaneous and systemically and may be responsible for skin lesions but also for psoriasis-associated conditions surrounding the heart, is now regarded as an important factor in the pathogenesis of coronary atherosclerosis and CVD, through inflammatory burden proximal to the coronary arteries, and has been shown to be increased in psoriasis patients independently of abdominal visceral fat (AVF) and to be associated with sub-clinical atherosclerosis IL-6 has been implicated in the pathogenesis of psoriasis1 but also of abdominal obesity atherosclerosis and CVD4 30% of total circulating concentrations in healthy subjects thought to be influenced by polymorphisms in their gene loci, and this may contribute to the development of psoriasis, but also excess adiposity and psoriasis has been investigated that could predict which patients are at risk of developing psoriasis-linked cardiovascular comorbidities may permit an earlier management, with important clinical implications. This study aimed to evaluate the potential contribution of four IL-6 genetic variants (rs1800795[-174G>C], rs1800796[-572G>C], rs2069827[-1426G>T], rs2069840[-1753C>G]) in psoriasis susceptibility and its influence in EAT and coronary artery calcification (CAC) in severe psoriasis patients.
- Influence of TNF-α gene polymorphisms in coronary artery calcification in psoriasis patientsPublication . Torres, T.; Bettencourt, N.; Ferreira, J.; Carvalho, C.; Mendonca, D.; Pinho-Costa, P.; Vasconcelos, C.; Selores, M.; Silva, B.Psoriasis is a systemic inflammatory disorder associated with numerous medical comorbidities and increased risk of cardiovascular disease (CVD. Psoriasis’ systemic inflammation may play an important role in the accelerated atherosclerosis observed in these patients2 as inflammatory processes play a key role in atherogenesis. Psoriasis and atherosclerosis share some pathological features including endothelial dysfunction, alteration in angiogenesis and some inflammatory pathways. TNF-a is a potent pro-inflammatory cytokine that has been implicated in psoriasis and atherosclerosis pathogenesis and its synthesis is tightly regulated at gene transcription level. TNF-a gene promoter region contains several single-nucleotide polymorphisms (SNP) that influence TNF-a production. Several TNF-a gene polymorphisms have been associated with psoriasis and CVD. A recent meta-analysis suggested that TNF-a rs1800629(308G/A) polymorphism was associated with decreased risk of psoriasis, whereas TNF-a rs361525(238G/A) was associated with increased risk. Regarding TNF-a rs1799964 (1031T/C) polymorphism, existing data are limited and contradictory.8 Since psoriasis morbidity and mortality are strongly linked to accelerated atherosclerosis, determining the genetic contribution for cardiovascular morbidity in psoriasis patients becomes an issue of major importance. The aim of this study was to evaluate the contribution of TNF-a rs361525(238G/A), TNF-a rs1800629(308G/A) and TNFa rs1799964(1031T/C) gene polymorphisms to coronary artery calcification (CAC) in severe psoriasis patients.
- Renal amyloidosis: classification of 102 consecutive casesPublication . Tavares, I.; Vaz, R.; Moreira, L.; Pereira, P.; Sampaio, S.; Vizcaíno, J.; Oliveira, J.; Pinho-Costa, P.; Lobato, L.[PT] As amiloidoses são um grupo heterogéneo de doenças classificadas de acordo com a composição das suas proteínas amiloidogénicas. Frequentemente, os tecidos preservados em parafina são usados para identificação imunohistoquímica. A análise de ADN deve ser sempre considerada se houver suspeita de amiloidose hereditária. Dado que os rins são um dos órgãos mais frequentemente envolvidos nas amiloidoses sistémicas, procedemos à classificação imunohistoquímica de 102 casos consecutivos de doença amiloide confirmada por biópsia renal. A análise de ADN foi realizada para confirmar o diagnóstico de amiloidose hereditária. As características demográficas, doença subjacente e dados clínicos à data da biópsia foram obtidos pela revisão retrospetiva dos registos médicos. O tipo de amiloidose obtido por identificação imunohistoquímica foi AA em 60 (58,8%) doentes, AL em 21 (20,6%), AFib em quatro (3,9%), ATTR em dois (2,0%), AApoAI em um (2,0%), ALys em um (2,0%), e em um (2,0%) coexistiam os tipos AL e AA. Em 12 (11,7%) não foi identificado o tipo de amiloide: oito (7,8%) por imunohistoquímica negativa e quatro (3,9%) devido a amostra insuficiente. A análise de ADN confirmou os casos AFib e ATTR pela identificação das mutações pontuais FGA p.Glu545Val e TTR p.Met51Val, respetivamente. A média de idade à data do diagnóstico foi 53,3 anos (49,4 para AA, 63,0 para AL e 53,9 para AFib). As infeções crónicas foram a principal causa de amiloidose AA, sobretudo a tuberculose, e foi apenas identificada uma AA familiar associada a síndrome de Muckle-Wells. A síndrome nefrótica foi a manifestação clínica mais frequente, independentemente do tipo de amiloide. Na nossa série, a amiloidose AA continua a ser a amiloidose sistémica mais frequente. Seis doentes tiveram amiloidose hereditária inequívoca. A imunohistoquímica não identificou a proteína precursora em quase 8% dos doentes; contudo, a utilização de um painel de anticorpos mais alargado poderá melhorar o diagnóstico.
- The role of KIR2DS1 in multiple sclerosis - KIR in Portuguese MS patientsPublication . Bettencourt, A.; Martins Silva, A.; Carvalho, C.; Leal, B.; Santos, E.; Pinho-Costa, P.; Silva, B.Killer Immunoglobulin-like Receptor (KIR) genes may influence both resistance and susceptibility to different autoimmune diseases, but their role in the pathogenesis of Multiple Sclerosis (MS) is still unclear. We investigated the influence of KIR genes on MS susceptibility in 447 MS Portuguese patients, and also whether genetic interactions between specific KIR genes and their HLA class I ligands could contribute to the pathogenesis of MS. Weobserved a negative association between the activating KIR2DS1 gene and MS (adjusted OR = 0.450, p = 0.030)independently from the presence of HLA-DRB1*15 allele. The activating KIR2DS1 receptor seems to confer protection against MS most probably through modulation of autoreactive T cells by Natural Killer cells.