Interaction of non-ionic surfactants with hepatic CYP in Prochilodus scrofa

Cytochromes P450 (CYP) constitute a superfamily of hemeproteins that play a vital role in the metabolism of a wide variety of endogenous and xenobiotic compounds. Xenobiotic metabolism and the role of CYP are of particular interest in studies regarding the prevention of the damage caused by chemical pollutants. We investigated, in this study, the interaction of Triton X-100 and Tween 80 with CYP and antioxidant defenses in Curimbata, a Brazilian fish. Aiming to clarify the effects of non-ionic surfactants in the monooxigenase system of fish through in vitro study, the effects of Triton X-100 and Tween 80 were analyzed using monooxygenases and antioxidant system as experimental model. Total CYP and EROD were strongly inhibited by Triton X-100 and Tween 80 in a concentration-dependent way; the content of CYP was reduced until zero while EROD activity was completely inhibited in the presence of Triton X-100 and more than 40% inhibited in the presence of Tween 80. Each surfactant causes a different effect on each antioxidant enzyme. No effect was detected in SOD activity in the presence of even Triton X-100 or Tween 80. Triton X-100 increase catalase activity, while Tween 80 decreases this enzyme activity. The molecular structure of the surfactants causes the alteration of this system, since they are able to interact with the microsomal protein, especially with monooxigenase's components, altering their conformation and, consequently destroying their function. Our results suggest that surfactants can interact with components of the microsomal system leading to inhibition of CYP. Therefore, CYP activity, which has been used as a biomarker of xenobiotic exposure, should be used as a marker in association with other enzymes. (C) 2004 Elsevier Ltd. All rights reserved.18685986

A new method to purify hepatic CYP1A of Prochilodus scrofa, a Brazilian freshwater fish

Cytochromes P450 constitute a superfamily of the phase I enzymes whose primary task is the detoxification of both endogenous and xenobiotic compounds. Fish, among non-mammalian species, have received great interest because they are a direct food source for humans as well as conveyors of toxic chemicals to human beings. The aim of the present study was the purification of the hepatic isoform, of CYP1A in Prochilodus scrofa (Prochilodontidae), a Brazilian fish, using only one chromatographic step. The purification of CYP1A was done by Reverse Phase HPLC on a C18 column. Purified CYP1A was characterized with respect to electrophoretic, immunochemical and biocatalyst properties. CYP1A fractions produced a single uniform band on SDS-PAGE with an apparent molecular mass of 58 kDa. Purified CYP1A of P scrofa showed strong cross-reactivity with antibodies directed against CYP1A from trout. The fraction was also encapsulated in two different reconstituted systems; one composed of neutral lipids and another of negatively charged lipids. In both of them, we could detect EROD activity but not PROD activity, which confirms that the CYP1A was purified with all its enzyme activity. There was an increase of activity when CYP1A and NADPH cytochrome P450 (CYP) reductase were encapsulated in negatively charged lipids, which confirms that the charge of lipid is essential to CYP1A activity. All these characteristics strongly suggest that this new procedure is efficient for purifying hepatic CYP1A from R scrofa, showing that the CYP1A isoform of this fish has a highly conserved protein region. (C) 2004 Elsevier Inc. All rights reserved.1381677

Familial colorectal cancer type X:genetic profiles and phenotypic features

Heredity is a major cause of colorectal cancer, but although several rare high-risk syndromes have been linked to disease-predisposing mutations, the genetic mechanisms are undetermined in the majority of families suspected of hereditary cancer. We review the clinical presentation, histopathologic features, and the genetic and epigenetic profiles of the familial colorectal cancer type X (FCCTX) syndrome with the aim to delineate tumor characteristics that may contribute to refined diagnostics and optimized tumor prevention.Modern Pathology advance online publication, 18 April 2014; doi:10.1038/modpathol.2014.49

Medicamentos excepcionais para doença renal crônica: gastos e perfil de utilização em Minas Gerais, Brasil Dispensing of exceptional drugs for chronic renal failure: expenditures and patients' profile in Minas Gerais State, Brazil

No Brasil, os medicamentos para o tratamento da doença renal crônica são disponibilizados gratuitamente pelo Sistema Único de Saúde (SUS). Este estudo teve como objetivos descrever os gastos públicos com esses medicamentos em Minas Gerais, Brasil, e o perfil dos usuários; objetivou, também, analisar os fatores associados ao gasto médio mensal individual. Observou-se que o gasto total com os medicamentos estudados (R$41,6 milhões) representa uma parcela significativa do gasto total com procedimentos ambulatoriais no SUS (9,6$ 41.6 million, or U$25 million) represents a significant portion of total spending on outpatient procedures in the National health System (9.6%). Most patients are young adult males with arterial hypertension as the main cause of chronic renal failure. Multivariate analysis showed a trend towards lower spending on elderly patients, those with diabetes as the main underlying disease, those using iron hydroxide, and in municipalities with a lower human development index, or HDI (p < 0.05). Finally, the study indicated the importance of management tools that allow monitoring the trajectory of individual patients in the health system and support appropriate health policymaking