Prevalence of metabolic syndrome in the interior of Croatia: the Baranja region.

Metabolic syndrome (MS), a constellation of metabolic risk factors associated with development of cardiovascular diseases and Type 2 diabetes (T2D), has emerged as a public health problem of enormous proportions in developed and developing countries. We have reported previously its prevalence in several island populations of the Eastern Adriatic coast of Croatia. In spite of leading a relatively traditional life style pattern including adherence to a Mediterranean diet, the prevalence of MS in these populations is high and comparable to that in developed nations. However, data on prevalence of MS among the mainland Croatian populations is limited. Therefore, we conducted a study in an outbred population comprising of Croats, Hungarians and Serbs from the Baranja region of mainland Croatia. Although this is an ethnically heterogeneous population, the constituent groups exchange mates and therefore, are not reproductively isolated. The life style patterns are also similar. Overall prevalence of MS, assessed by the National Cholesterol Education Program (NCEP) criteria, is 40% (35% in males and 42% in females) with Body Mass Index (BMI) as the predictor of obesity and 42% (52% in males and 39% in females) with Waist Hip Ratio (WHR) as the predictor of obesity. It is likely that, in addition to genetic risk factors, a host of environmental factors that include dietary habits and relatively urban life style in a modernized society have influenced the levels of the constituent metabolic traits leading to an increased prevalence of MS.

A novel G418 conjugate results in targeted selection of genetically protected hepatocytes without bystander toxicity.

G418, an aminoglycoside neomycin analogue, is an antimicrobial agent that interferes with protein synthesis and has been used extensively for selection of mammalian cell lines that possess neomycin resistance (NR). It is potent and nonspecific in its effects that occur through tight binding to ribosomal elements. Because of the potent intracellular effect, we wondered whether G418 could be used to select a specific cell type based on receptor-mediated endocytosis. The objective of this study was to target G418 specifically to liver cells via asialoglycoprotein receptors (AsGR) which are known to be highly selective for these cells. A novel G418 conjugate was synthesized chemically by coupling G418 to a galactose-terminating carrier protein, asialoorosomucoid (AsOR), in a molar ratio of 5:1. AsOR-G418 conjugates inhibited viability of AsGR (+) cells by 84.3%, while inhibition in AsGR (-) cells was only by 19%. In AsGR (+) cells, stably transfected with a NR gene, the conjugate decreased viability by less than 9%. Furthermore, incubation of conjugate in cocultures of AsGR (+), and AsGR (-) cells did not result in the loss of viability of neighboring AsGR (-) cells. Our data demonstrate for the first time that G418 can be covalently bound to AsOR to form a conjugate for hepatocyte-specific targeting and toxicity. AsOR-G418 conjugates may be useful tools for genetic manipulation of human liver cells in the presence of nonhepatic cells.

Potential role of RNAi in the treatment of HCV infection.

Chronic HCV infection is a leading cause of chronic hepatitis and its sequelae, liver cirrhosis and hepatocellular carcinoma. Current therapeutic options are limited, associated with significant adverse effects and costly. Accordingly, there is strong impetus to develop novel therapeutic strategies that act through alternate mechanisms. RNAi has been widely used for the analysis of gene function and represents a potentially promising approach for the treatment of HCV infection. siRNAs are short RNA duplexes approximately 21 nts long. When introduced into mammalian cells, siRNA can silence specific gene expression. Although efficient suppression of HCV replicon RNA in cell culture has been demonstrated with siRNAs, there is much work to be done to improve delivery, limit off-target effects and minimize development of virus resistance. Here, we review the use of RNAi as a tool to inhibit HCV gene expression and discuss the potential advantages and obstacles for this new potential therapeutic approach against HCV infection.

Potential applications of siRNA in hepatitis C virus therapy.

Small interfering RNAs (siRNAs) are short RNA duplexes approximately 21 nucleotides long. When introduced into mammalian cells, siRNA can silence specific gene expression. Hepatitis C virus (HCV) replicates in the cytoplasm of liver cells without integration into the host genome. Because the HCV genome is a single-stranded RNA that functions both as a messenger RNA and as a viral replication template, destruction of HCV RNA could eliminate not only virally directed protein synthesis, but also viral replication. It has been demonstrated that siRNAs interfere with HCV gene expression and replication, and this review will describe the use of RNAi as a tool to inhibit HCV gene expression.