Methionine- and choline-deficient diet induces hepatic changes characteristic of non-alcoholic steatohepatitis

CONTEXT: Non-alcoholic steatohepatitis is a disease with a high incidence, difficult diagnosis, and as yet no effective treatment. So, the use of experimental models for non-alcoholic steatohepatitis induction and the study of its routes of development have been studied. OBJECTIVES: This study was designed to develop an experimental model of non-alcoholic steatohepatitis based on a methionine- and choline-deficient diet that is manufactured in Brazil so as to evaluate the liver alterations resulting from the disorder. METHODS: Thirty male C57BL6 mice divided in two groups (n = 15) were used: the experimental group fed a methionine- and choline-deficient diet manufactured by Brazilian company PragSoluções®, and the control group fed a normal diet, for a period of 2 weeks. The animals were then killed by exsanguination to sample blood for systemic biochemical analyses, and subsequently submitted to laparotomy with total hepatectomy and preparation of the material for histological analysis. The statistical analysis was done using the Student's t-test for independent samples, with significance level of 5%. RESULTS: The mice that received the methionine- and choline-deficient diet showed weight loss and significant increase in hepatic damage enzymes, as well as decreased systemic levels of glycemia, triglycerides, total cholesterol, HDL and VLDL. The diagnosis of non-alcoholic steatohepatitis was performed in 100% of the mice that were fed the methionine- and choline-deficient diet. All non-alcoholic steatohepatitis animals showed some degree of macrovesicular steatosis, ballooning, and inflammatory process. None of the animals which were fed the control diet presented histological alterations. All non-alcoholic steatohepatitis animals showed significantly increased lipoperoxidation and antioxidant enzyme GSH activity. CONCLUSION: The low cost and easily accessible methionine- and choline-deficient diet explored in this study is highly effective in inducing steatosis and steatohepatitis in animal model, alterations that are similar to those observed in human livers

Achieving the optimal power of patent rights

This article examines how policy instruments governing the grant and enforcement of patent rights affect the ex ante incentive to invest in inventive activity. In order to encourage investment into the creation of an asset, capitalism extends to firms and individuals the right to appropriate the returns from owning that asset. Preventing theft, and accordingly, the expropriation of one's profits, hinges on being able to define the asset. For tangible assets, this mechanism is certain since the boundaries around what are (and are not) part of the asset can be precisely articulated and title to the ownership is mostly complete. However, this is not the case for intangible assets such as intellectual property because the boundary between a new asset and existing ones is often ambiguous when expressed in written form. From a welfare perspective, granting patent rights gives rise to a further issue. Unlike property rights over tangible assets, patents create deadweight social losses by temporarily blocking imitation and preventing others from using a non-rivalrous resource. These deadweight losses arise because the patent system operates by creating a distortion (a monopoly right) to correct a distortion. Given the existence of legislation enshrining patent owners' rights, the power of a patent is determined in two stages: first, acquiring the title to the right (patent granting) and, second, getting competitors to accede to the right by modifying their behavior (patent enforcement). These two stages occur over a continuum of administrative, legal and quasi-legal activities including drafting the patent application, examining (and opposing) the application at the patent office, and enforcing the patent