Browsing by Author "Martinho, A"
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- Drug reaction with eosinophilia and systemic symptoms caused by spironolactone: Case reportPublication . Fernandes, RA; Regateiro, FS; Faria, E; Martinho, A; Gonçalo, Margarida; Todo‐Bom, A
- Genetic markers in chronic urticariaPublication . Machado, D; Pereira, C; Martinho, A; Loureiro, G; Tavares, B; Santos, P; Calado, G; Chieira, C; Baganha, MF; Pais, M
- Genetic polymorphisms in CYP3A5 and MDR1 genes and their correlations with plasma levels of tacrolimus and cyclosporine in renal transplant recipientsPublication . Mendes, J; Martinho, A; Simões, O; Mota, A; Breitenfeld, L; Pais, LImmunosuppressive drugs, such as tacrolimus (FK506) and cyclosporine (CsA), play an essential role in graft survival, preventing rejection. Large interindividual differences in drug-metabolizing enzymes as well as in drug transporters make the task of reaching the optimal concentrations difficult. The bioavailability of CsA and FK506 seems to be associated with the cytocrhome P450 IIIA (CYP3A) gene. It has also been described that the Multi Drug Resistance 1 (MDR1) gene that encodes for polyglycoprotein-P (P-gp) may influence the metabolizing action of FK506 and CsA. Therefore, we sought, to correlate single nucleotide polymorphisms (SNPs) in the CYP3A and MDR1 genes with the concentrations of FK506 and CsA. For this purpose we analyzed 2 groups of renal transplant recipients by sequencing: one receiving a CsA immunosuppressive regime, and other, an FK506-immunosuppression. This study showed that subjects in the FK506 group who had encoded the 1236C>T substitution in the MDR1 gene displayed 44.4% higher drug concentrations compared with ("wild-type") individuals. Individuals carrying the 2677G>T,A mutation showed FK506 concentrations that were 44.7% higher than the wild-type individuals. Concerning the CsA group, individuals carrying the 22915A>C substitution displayed CsA concentrations 52.1% higher than wild-type individuals
- Genótipos do VHC: Histopatologia hepática e perfil imunológico em quatro grupos de doentesPublication . Carvalho, A; Martinho, A; Leitão, J; Cipriano, MA; Coimbra, H; Porto, AAIM: Study on the prevalence of MCV genotypes, and correlation with liver pathology and immunological parameters. PATIENTS AND METHODS: 77 chronic hepatitis C patients (52 males, 25 females), mean age 44 +/- 14 years, belonging to four groups: (1) 23 (11 males) without other aetiology, (II) 19 (18 males) excessive drinkers, (III) 18 (12 males) haemodialysed, (IV) 17 (11 males) renal transplantation patients Genotyping was done by PCR (primers of the core, and hybridisation with specific probes). Serum Igs A, G, and M (by nephelometry), and peripheral blood lymphocyte (PBL) subsets (by flow cytometry) were determined. RESULTS: One genotype was found in 62 patients (1b 69.2%, 1a 21.5%, 2a 3.1%, 2b 3.1%, 3a 9.2%), and two genotypes in 4 patients (1b + 3a in 1 of group 1, 1b + 2a in 2 and 1a + 3a in 1 of group 111). Twelve cases (15.6%) were not identified (NI). Relative prevalence was not different in the four groups, but in 7 drug addicts 1 b was not found (Ia in 71.4%, 3 a 28.6%) The relationship between genotypes and age was significant (p < 0.05): in the 34 patients with less than 40 years, 1b was found in 38.2%, in the others in 41.2%, and NI in 20.6%; in those with 40-60 years, 1b was found in 68.8%, in the others in 15.6%, M in 15.6%; in those above 60 years, 1b was found in 90.9%, in the others in 9.1%. Of those identified, only genotype 1 (1a and 1b) was associated to moderate or severe activity, and infected 11/13 cases of cirrhosis or severe fibrosis. IgM (g/dL) was lower in 1b than in the others: 1.58 + 1.23 vs. 2.53 + 1.93 (p < 0.01). PBL (per mm3) were lesser in 1b than in the others, with significance for the CD8+: 540t239 vs. 739 + 420 (p < 0.01). CONCLUSIONS: Genotype 1b was the most prevalent in Portuguese patients, more significantly in the elderly, and was absent in drug addicts. The prevalence of genotypes is similar in general patients, in chronic haemodialysed, in renal transplantation recipients and in alcoholics. More severe liver pathology was associated with 1b and 1a genotypes. IgM and CD8+ had lower mean values in 1b infected patients. Other genotypes are certainly important in Portugal.
- Lifelong training improves anti-inflammatory environment and maintains the number of regulatory T cells in masters athletesPublication . Minuzzi, LG; Rama, L; Bishop, NC; Rosado, F; Martinho, A; Paiva, A; Teixeira, AMPURPOSE: The purpose of this study was to quantify and characterize peripheral blood regulatory T cells (Tregs), as well as the IL-10 plasma concentration, in Masters athletes at rest and after an acute exhaustive exercise test. METHODS: Eighteen Masters athletes (self-reported training: 24.6 ± 1.83 years; 10.27 ± 0.24 months and 5.45 ± 0.42 h/week per each month trained) and an age-matched control group of ten subjects (that never took part in regular physical training) volunteered for this study. All subjects performed an incremental test to exhaustion on a cycle ergometer. Blood samples were obtained before (Pre), 10 min into recovery (Post), and 1 h after the test (1 h). RESULTS: Absolute numbers of Tregs were similar in both groups at rest. Acute exercise induced a significant increase in absolute numbers of Tregs at Post (0.049 ± 0.021 to 0.056 ± 0.024 × 109/L, P = 0.029 for Masters; 0.048 ± 0.017 to 0.058 ± 0.020 × 109/L, P = 0.037 for control) in both groups. Treg mRNA expression for FoxP3, IL-10, and TGF-β in sorted Tregs was similar throughout the trials in both groups. Masters athletes showed a higher percentage of subjects expressing the FoxP3 (100% for Masters vs. 78% for Controls, P = 0.038) and TGF-β (89% for Masters vs. 56% for Controls, P = 0.002) after exercise and a higher plasma IL-10 concentration (15.390 ± 7.032 for Masters vs. 2.411 ± 1.117 for control P = 0.001, ES = 2.57) at all timepoints. KLRG1 expression in Tregs was unchanged. CONCLUSION: Our findings showed that Masters athletes have elevated anti-inflammatory markers and maintain the number of Tregs, and may be an adaptive response to lifelong training.
- Prevalência e significado clínico da infecção pelo vírus da "hepatite" G em diversos grupos de doentesPublication . Carvalho, A; Martinho, A; Cipriano, MA; Coimbra, H; Porto, A
- Tolerogenic versus Inflammatory Activity of Peripheral Blood Monocytes and Dendritic Cells Subpopulations in Systemic Lupus ErythematosusPublication . Carvalheiro, T; Rodrigues, A; Lopes, A; Velada, I; Ribeiro, A; Martinho, A; Inês, L; Pereira da Silva, JA; Pais, ML; Paiva, AAbnormalities in monocytes and in peripheral blood dendritic cells (DC) subsets have been reported in systemic lupus erythematosus (SLE). We aim to clarify the tolerogenic or inflammatory role of these cells based on ICOSL or IFN-α and chemokine mRNA expression, respectively, after cell purification. The study included 18 SLE patients with active disease (ASLE), 25 with inactive disease (ISLE), and 30 healthy controls (HG). In purified plasmacytoid DC (pDC) was observed a lower ICOSL mRNA expression in ASLE and an increase in ISLE; similarly, a lower ICOSL mRNA expression in monocytes of ALSE patients was found. However, a higher ICOSL mRNA expression was observed in ASLE compared to HG in myeloid DCs. Interestingly, clinical parameters seem to be related with ICOSL mRNA expression. Regarding the inflammatory activity it was observed in purified monocytes and CD14(-/low) CD16(+) DCs an increase of CCL2, CXCL9, and CXCL10 mRNA expression in ASLE compared to HG. In myeloid DC no differences were observed regarding chemokines, and IFN-α mRNA expression. In pDC, a higher IFN-α mRNA expression was observed in ASLE. Deviations in ICOSL, chemokine, and IFN-α mRNA expression in peripheral blood monocytes and dendritic cells subpopulations in SLE appear to be related to disease activity.