Browsing by Author "Branco, T"
Now showing 1 - 8 of 8
Results Per Page
Sort Options
- Differences in Nevirapine Biotransformation as a Factor for its Sex-Dependent Dimorphic Profile of Adverse Drug ReactionsPublication . Marinho, AT; Rodrigues, PM; Caixas, U; Antunes, A; Branco, T; Harjivan, S; Marques, MM; Monteiro, EC; Pereira, SAOBJECTIVES: Nevirapine is widely used for the treatment of HIV-1 infection; however, its chronic use has been associated with severe liver and skin toxicity. Women are at increased risk for these toxic events, but the reasons for the sex-related differences are unclear. Disparities in the biotransformation of nevirapine and the generation of toxic metabolites between men and women might be the underlying cause. The present work aimed to explore sex differences in nevirapine biotransformation as a potential factor in nevirapine-induced toxicity. METHODS: All included subjects were adults who had been receiving 400 mg of nevirapine once daily for at least 1 month. Blood samples were collected and the levels of nevirapine and its phase I metabolites were quantified by HPLC. Anthropometric and clinical data, and nevirapine metabolite profiles, were assessed for sex-related differences. RESULTS: A total of 52 patients were included (63% were men). Body weight was lower in women (P = 0.028) and female sex was associated with higher alkaline phosphatase (P = 0.036) and lactate dehydrogenase (P = 0.037) levels. The plasma concentrations of nevirapine (P = 0.030) and the metabolite 3-hydroxy-nevirapine (P = 0.035), as well as the proportions of the metabolites 12-hydroxy-nevirapine (P = 0.037) and 3-hydroxy-nevirapine (P = 0.001), were higher in women, when adjusted for body weight. CONCLUSIONS: There was a sex-dependent variation in nevirapine biotransformation, particularly in the generation of the 12-hydroxy-nevirapine and 3-hydroxy-nevirapine metabolites. These data are consistent with the sex-dependent formation of toxic reactive metabolites, which may contribute to the sex-dependent dimorphic profile of nevirapine toxicity.
- Efavirenz Concentrations in HIV-Infected Patients With and Without Viral HepatitisPublication . Pereira, SA; Caixas, U; Branco, T; Germano, I; Lampreia, F; Papoila, AL; Monteiro, EAIMS: Data on efavirenz in HIV/viral hepatitis co-infected patients is non-consensual, probably due to liver function heterogeneity in the patients included. METHODS: A case control study was performed on 27 HIV-infected patients, with controlled and homogenous markers of hepatic function, either mono-infected or co-infected with HBV/HCV, to ascertain the influence of viral hepatitis on efavirenz concentrations over a 2-year follow-up period. RESULTS: No differences were found in efavirenz concentrations between groups both during and at the end of the follow-up period: control (2.43 +/- 1.91 mg l(-1)) vs. co-infected individuals (2.37 +/- 0.37 mg l(-1)). CONCLUSION: It was concluded that HBV/HCV infections in themselves do not predispose to an overexposure to efavirenz.
- Effect of Efavirenz on High-Density Lipoprotein Antioxidant Properties in HIV-Infected PatientsPublication . Pereira, SA; Batuca, JR; Caixas, U; Branco, T; Delgado-Alves, J; Germano, I; Lampreia, F; Monteiro, ECWHAT IS ALREADY KNOWN ABOUT THIS SUBJECT: * In previous work, we showed a long-term and concentration-dependent beneficial effect of the non-nucleoside reverse transcriptase inhibitor efavirenz (EFV) on high-density lipoproteins (HDL) in human immunodeficiency virus (HIV)-infected patients. * Furthermore, it has been suggested that instead of the current practice of only measuring HDL-chelesterol values, the evaluation of HDL function, namely its antioxidant properties, might be an improved tool for identifying subjects at increased risk for cardiovascular events. * Paraoxonase-1 (PON-1) is an enzyme associated with HDL that is responsible for HDL antioxidant function. WHAT THIS STUDY ADDS: * In the present work, we studied the effect of EFV on the activity of PON-1 and showed, for the first time, that EFV-based antiretroviral therapy is associated with a better antioxidant function, i.e. with a higher PON-1 activity. AIMS: A long-term and concentration-dependent beneficial effect of efavirenz (EFV) on cholesterol associated with high-density lipoprotein (HDL-c) in human immunodeficiency virus (HIV)-infected patients has been documented. Furthermore, it has been suggested that, instead of the current practice of only measuring HDL-c values, the evaluation of HDL quality might be an improved tool for identifying subjects at increased risk of cardiovascular events. Paraoxonase-1 (PON-1) is an enzyme associated with HDL that is involved in the onset of cardiovascular disease and responsible for HDL antioxidant function. The aim of the present study was to investigate the effect of EFV on the circulating activity of PON-1 in HIV-infected patients. METHODS: The patients included were adults with a documented HIV-1 infection, nontreated or treated with antiretroviral regimens including EFV 600 mg once daily as first therapeutic regimen for at least 3 months. The influence of treatment with EFV, HDL-c and CD4 cell count on PON-1 activity was analysed. RESULTS: HIV-infected White patients treated with EFV had higher PON-1 activity [77.35 U l(-1) (65.66, 89.04)] (P < 0.05) and higher PON-1 activity : HDL-c ratio [1.88 (1.49, 2.28)] (P < 0.01) than untreated patients. PON-1 activity was higher in Black patients (P < 0.001) and in patients with a CD4 cell count >500 cells ml(-1) (P= 0.0120). CONCLUSIONS: EFV-based antiretroviral regimens are associated with HDL particles with a better antioxidant function, i.e. with a higher PON-1 activity. The PON-1 activity of Black patients is higher than that found in Whites regardless of treatment. Ethnicity should be taken into consideration when studying drug effects on PON-1 activity.
- Evidence for Nevirapine Bioactivation in Man: Searching for the First Step in the Mechanism of Nevirapine ToxicityPublication . Caixas, U; Antunes, A; Marinho, A; Godinho, A; Grilo, N; Marques, M; Oliveira, MC; Branco, T; Monteiro, E; Pereira, SDespite its efficacy, including in the prevention of vertical transmission, the antiretroviral nevirapine is associated with severe idiosyncratic hepatotoxicity and skin rash. The mechanisms underlying nevirapine toxicity are not fully understood, but drug bioactivation to reactive metabolites capable of forming stable protein adducts is thought to be involved. This hypothesis is based on the paradigm that drug reactive metabolites have the potential to bind to self-proteins, which results in drug-modified proteins being perceived as foreign by the immune system. The aim of the present work was to identify hemoglobin adducts in HIV patients as biomarkers of nevirapine haptenation upon bioactivation. The ultimate goal is to develop diagnostic methods for predicting the onset of nevirapine-induced toxic reactions. All included subjects were adults on nevirapine-containing antiretroviral therapy for at least 1month. The protocol received prior approval from the Hospital Ethics Committees and patients gave their written informed consent. Nevirapine-derived adducts with the N-terminal valine of hemoglobin were analyzed by an established liquid chromatography-electrospray ionization-tandem mass spectrometry method and characterized on the basis of retention time and mass spectrometric fragmentation pattern by comparison with adduct standards prepared synthetically. The nevirapine adducts were detected in 12/13 patient samples, and quantified in 11/12 samples (2.58±0.8 fmol/g of hemoglobin). This work represents the first evidence of nevirapine-protein adduct formation in man and confirms the ability of nevirapine to modify self-proteins, thus providing clues to the molecular mechanisms underlying nevirapine toxicity. Moreover, the possibility of assessing nevirapine-protein adduct levels has the potential to become useful for predicting the onset of nevirapine-induced adverse reactions.
- Infecção Cutânea por Mycobacterium MarinumPublication . Baptista, J; Serrão, V; Branco, T; Guerra, FMycobacterum marinum é uma micobactéria atípica, saprófita em meios aquáticos, capaz de provocar infecções em humanos durante o contacto com água ou peixes contaminados. A infecção cutânea, também conhecida por “granuloma das piscinas”, com nódulos inflamatórios ou placas verrucosas, é a mais comum, podendo ser igualmente atingidas estruturas profundas, causando tenosinovites, artrites e osteomielites. Um elevado índice de suspeição clínica e história sócio-ocupacional compatível são importantes para o diagnóstico. Estão descritas várias modalidades terapêuticas, sendo a antibioterapia sistémica o tratamento de escolha, por vezes coadjuvado pela cirurgia; a resolução espontânea é possível. Os autores apresentam o caso clínico de um doente de 38 anos, infectado pelo vírus HIV, com nódulos inflamatórios na mão direita e disseminação esporatricóide ao longo do membro superior homolateral. Após constatar contacto com peixes de aquário, colocou-se o diagnóstico de infecção cutânea por M. marinum, que foi confirmado por exame histopatológico e cultura. Observou-se, entretanto, a resolução espontânea do quadro clínico, não tendo sido feito qualquer tratamento dirigido à micobacteriose. Não há história de recidiva aos 2 anos de follow-up.
- Long-Term and Concentration-Dependent Beneficial Effect of Efavirenz on HDL-Cholesterol in HIV-Infected PatientsPublication . Pereira, SA; Branco, T; Côrte-Real, R; Germano, I; Lampreia, F; Caixas, U; Monteiro, EAIMS: To investigate the long-term effects of efavirenz on cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL-C) and triglycerides (TG). METHODS: Thirty-four HIV-infected patients who commenced efavirenz therapy were monitored for 36 months. RESULTS: In patients with baseline HDL-C<40 mg.dL-1 an increase in HDL-C from 31+/-1 mg.dL-1 to 44+/-2 mg.dL-1 (95% confidence interval 5.9, 21.9, P<0.01) was observed and remained throughout the follow-up period. Median efavirenz plasma concentration was 1.98 mg.L-1 and a direct correlation between percentage of HDL-C variation or TC/HDL-C ratio and efavirenz plasma concentrations was found. CONCLUSIONS: There is evidence of a long-term and concentration-dependent beneficial effect of efavirenz on HDL-C in HIV-infected patients.
- A Pessoa Afásica e a ReabilitaçãoPublication . Branco, T; Guerreiro, DAbordar as questões cerebrais é algo de complexo e fascinante e apesar de nos levar a um mundo amplamente desbravado por diversas personalidades, continua a suscitar o nosso interesse. Designa-se por Afasia a alteração da comunicação resultante de uma lesão cerebral, cujas manifestações se fazem sentir a vários níveis: verbal, gestual, visual e gráfico. As tentativas frustradas de comunicação repercutem-se negativamente na vida da Pessoa podendo-a levar à depressão. Actualmente é possível o enfermeiro especialista em reabilitação ajudar a minorar o impacto psicossocial resultante da perturbação da linguagem assegurando o processo comunicacional da pessoa afásica com a família, através das técnicas terapêuticas existentes. O presente artigo pretende abordar a temática da Pessoa com Afasia e as respectivas intervenções de enfermagem.
- A Verdade ao Doente. Um Dilema Ético de EnfermagemPublication . Mendes, I; Gomes, M; Branco, T