Tenofovir monotherapy for hepatitis B after 1 year does not produce renal dysfunction, but is associated with hyperparathyroidism not related to vitamin D.

INTRODUCTION: Viral hepatitis B (VHB) represents a major public health problem. Studies from HIV multidrug patients have associated the use of tenofovir disoproxil fumarate (TDF) with renal dysfunction and phosphate wasting. OBJECTIVE: The aim of this study was to examine the effect of year-long TDF monotherapy on renal function in VHB patients. PATIENTS AND METHODS: We evaluated adult patients diagnosed with VHB before treatment initiation (T0), and after 3 and 12 months (T3 and T12) of TDF initiation. Estimated glomerular filtration rate (eGFR) was estimated by serum cystatin C and creatinine. In addition, urinary electrolytes and tubular biomarkers (cystatin C, ß2-microglobulin and neutrophil gelatinase-associated lipocalin) were analyzed, as well as parathyroid hormone (PTH) and 25(OH)vitamin D levels. RESULTS: After 1 year, 32 patients completed the study, 22 (68.7%) men and 12 (37.5%) Whites, mean age 44.1±12.0 years. We found that serum electrolytes were similar at baseline and 3 or 12 months after initiation of TDF monotherapy. In addition, urinary fractional excretions of electrolytes as well as proteinuria, albuminuria, urinary ß2-microglobulin, and urinary cystatin C showed no significant differences across the treatment timeline. There were also no statistical differences in the eGFR. There was a statistically significant increase in the PTH (Friedman's test, P=0.012), but the 25(OH)vitamin D levels were in the normal range in the beginning and did not change at the follow-up. Moreover, there was no correlation between the initial levels of vitamin D and the corresponding increases in the PTH values. CONCLUSION: If used as monotherapy in hepatitis B patients for a 12-month period, TDF is not associated with changes in either eGFR or a panel of urinary biomarkers. Serum and urinary electrolytes also remained unchanged. Of note, a significant increase in the PTH was found, although not related to the 25(OH)vitamin D initial status.

Oxidative stress in the pathophysiology of metabolic syndrome: which mechanisms are involved? / Estresse oxidativo na fisiopatologia da síndrome metabólica: quais mecanismos estão envolvidos?

ABSTRACTMetabolic syndrome (MS) is a combination of cardiometabolic risk factors, including obesity, hyperglycemia, hypertriglyceridemia, dyslipidemia and hypertension. Several studies report that oxidative condition caused by overproduction of reactive oxygen species (ROS) plays an important role in the development of MS. Our body has natural antioxidant system to reduce oxidative stress, which consists of numerous endogenous and exogenous components and antioxidants enzymes that are able to inactivate ROS. The main antioxidant defense enzymes that contribute to reduce oxidative stress are superoxide dismutase (SOD), catalase (CAT) and gluthatione peroxidase (GPx). The high-density lipoprotein cholesterol (HDL-c) is also associated with oxidative stress because it presents antioxidant and anti-inflammatory properties. HDL-c antioxidant activity may be attributed at least in part, to serum paraoxonase 1 (PON1) activity. Furthermore, derivatives of reactive oxygen metabolites (d-ROMs) also stand out as acting in cardiovascular disease and diabetes, by the imbalance in ROS production, and close relationship with inflammation. Recent reports have indicated the gamma-glutamyl transferase (GGT) as a promising biomarker for diagnosis of MS, because it is related to oxidative stress, since it plays an important role in the metabolism of extracellular glutathione. Based on this, several studies have searched for better markers for oxidative stress involved in development of MS.

RESUMOA síndrome metabólica (SM) representa uma conjunção de fatores de risco cardiometabólicos, incluindo obesidade, hiperglicemia, hipertrigliceridemia, dislipidemia e hipertensão. Vários estudos reportam que a condição oxidativa causada pela superprodução de espécies reativas de oxigênio (EROs) desempenha importante papel no desenvolvimento da SM. Nosso organismo apresenta sistema antioxidante natural para diminuir o estresse oxidativo, o qual consiste em numerosos componentes endógenos e exógenos e enzimas antioxidantes que são capazes de inativar as EROs. As principais enzimas de defesa antioxidante que contribuem para o processo de redução do estresse oxidativo são a superóxido dismutase (SOD), a catalase (CAT) e a glutationa peroxidase (GPx). O colesterol associado à lipoproteína de alta densidade (HDL-c) também está relacionado com o estresse oxidativo por apresentar propriedades antioxidantes e anti-inflamatórias. A atividade antioxidante do HDL-c pode ser atribuída, pelo menos em parte, à atividade da paraoxonase 1 (PON1) sérica. Além disso, os metabólitos derivados de oxigênio reativo (d-ROMs) também se destacam como atuantes nas doenças cardiovasculares e no diabetes, pelo desequilíbrio na produção de EROs, tendo relação importante com a inflamação. Relatos recentes vêm apontando a gama-glutamiltransferase (GGT) como biomarcador promissor para diagnóstico da SM, pois esta se associa ao estresse oxidativo, uma vez que desempenha papel relevante no metabolismo extracelular de glutationa. Com base nisso, vários estudos vêm buscando melhores marcadores do estresse oxidativo e sua relação com o desenvolvimento da SM.

Searching for monooxygenases and hydrolases in bacteria from an extreme environment.

Microbial oxidation potentials of extremophiles recovered from Pampo Sul oil field, Campos Basin, Brazil, in pure culture or in consortia, were investigated using high-throughput screening (HTS) and multibioreactions. Camphor (1), cis-jasmone (2), 2-methyl-cyclohexanone (3), 1,2-epoxyoctane (4), phenylethyl acetate (5), phenylethyl propionate (6), and phenylethyl octanoate (7) were used to perform multibioreaction assays. Eighty-two bacterial isolates were recovered from oil and formation water samples and those presenting outstanding activities in HTS assays were identified by sequencing their 16S rRNA genes. These results revealed that most microorganisms belonged to the genus Bacillus and presented alcohol dehydrogenase, monooxygenase, epoxide hydrolase, esterase, and lipase activities.