The effect of zinc and/or vitamin E supplementation on biochemical parameters of selenium-overdosed rats.

The normotensive (Wistar) and spontaneously hypertensive (SHR) rats were examined to assess the response of the organism to selenium (Se) overdose. Moreover, the effect of zinc (Zn) and vitamin E, i.e. dietary components interacting in many biochemical processes with Se, on the Se uptake was evaluated. The control group was fed an untreated diet, and the diets of two other groups were overdosed with Se in the form of sodium selenite (9 mg/kg) and supplemented with Zn (13 mg/kg). Two experimental groups were fed a diet supplemented with Zn (13 mg/kg) and Se at an adequate level (0.009 mg/kg); a half of the animals was supplemented with vitamin E. The results showed significant differences in the Se contents between the rat strains in case of Se-overdosed groups, where in the liver and kidney tissue Se contents of SHR rats exceeded 3- and 7-fold the normotensive ones. The Se uptake was altered by the vitamin E; no effect of Zn was observed. Activities of antioxidant enzymes were determined in the animal tissues indicating different patterns according to rat strain, tissue analysed, and administered Se dose. Thus, Se overdose, for instance, via an incorrectly prepared dietary supplement, can result in serious imbalances of the biochemical status of the animals.

Identification of novel biomarker candidates for hypertrophic cardiomyopathy and other cardiovascular diseases leading to heart failure.

In-depth proteome discovery analysis represents new strategy in an effort to identify novel reliable specific protein markers for hypertrophic cardiomyopathy and other life threatening cardiovascular diseases. To systematically identify novel protein biomarkers of cardiovascular diseases with high mortality we employed an isobaric tag for relative and absolute quantitation (iTRAQ) proteome technology to make comparative analysis of plasma samples obtained from patients suffering from non-obstructive hypertrophic cardiomyopathy, stable dilated cardiomyopathy, aortic valve stenosis, chronic stable coronary artery disease and stable arterial hypertension. We found 128 plasma proteins whose abundances were uniquely regulated among the analyzed cardiovascular pathologies. 49 of them have not been described yet. Additionally, application of statistical exploratory analyses of the measured protein profiles indicated the relationship in pathophysiology of the examined cardiovascular pathologies.

LPS structure influences protein secretion in Salmonella enterica.

In this study we have compared protein secretion in the wild type of S. Typhimurium and the rfaC mutant. We found out that the rfaC mutant was defective in protein secretion. In addition, the rfaC mutant was defective in its invasion into an IPEC-J2 porcine epithelial cell line and also in motility in semisolid agar. Consistent with this, reduced flagella numbers were observed in the rfaC mutant. In the rfaC mutant, there were no defects in flagellin expression as detected by western blot and immune electron microscopy which demonstrated equal amounts of flagellin in the cytoplasm of both the rfaC mutant and the wild-type S. Typhimurium. However, in the wild-type strain only, the flagellin was assembled to spatially restricted areas on the inner side of cytoplasmic membrane. The oligosaccharide core of LPS is therefore required for the assembly of flagella and T3SS secretion machinery followed by protein secretion.

Application of proteomics in biomarker discovery: a primer for the clinician.

Ever since proteomics was proven to be capable of characterizing a large number of differences in both protein quality and quantity, it has been applied in various areas of biomedicine, ranging from the deciphering molecular pathogenesis of diseases to the characterization of novel drug targets and the discovery of potential diagnostic biomarkers. Indeed, the biomarker discovery in human plasma is clearly one of the areas with enormous potential. However, without proper planning and implementation of specific techniques, the efforts and expectations may very easily be hampered. Numerous earlier projects aimed at clinical proteomics, characterized by exaggerated enthusiasm, often underestimated some principal obstacles of plasma biomarker discovery. Consequently, ambiguous and insignificant results soon led to a more critical view in this field. In this article, we critically review the current state of proteomic approaches for biomarker discovery and validation, in order to provide basic information and guidelines for both clinicians and researchers. These need to be closely considered prior to initiation of a project aimed at plasma biomarker discovery. We also present a short overview of recent applications of clinical proteomics in biomarker discovery.

Genetic analysis of cardiovascular risk factor clustering in spontaneous hypertension.

The SHR is the most widely studied animal model of hypertension. In this strain, as in many humans with essential hypertension, increased blood pressure has been reported to cluster with other risk factors for cardiovascular disease, including insulin resistance and dyslipidemia. However, the genetic mechanisms that mediate this clustering of risk factors for cardiovascular disease or the hypertension "metabolic syndrome" remain poorly understood. In the current studies, we have demonstrated (1) that a gene or genes responsible for a whole spectrum of cardiovascular risk factors mapped to a limited segment of the centromeric region of rat chromosome 4, (2) that a spontaneous deletion in the gene for Cd36 that encodes a fatty acid transporter and is located directly at the peak of QTL linkages on chromosome 4 has been indirectly linked to the transmission of insulin resistance, defective fatty acid metabolism, and increased blood pressure, and (3) based on complementation analysis in two transgenic lines expressing wild-type Cd36 on the genetic background of the SHR strain harboring the deletion variant of Cd36, we have established that defective Cd36 can be a determinant of disordered fatty acid metabolism, glucose intolerance, and insulin resistance in spontaneous hypertension.

Hematocrit and hemoglobin values are negatively correlated with insulin resistance in spontaneous hypertension.

It has been recently reported that increased hematocrit and hemoglobin values often accompany insulin resistance and compensatory hyperinsulinemia in humans. In the current study, we analyzed the relationship between hematocrit/hemoglobin on the one hand and insulin resistance, dyslipidemia, and hypertension on the other hand in HXB/BXH recombinant inbred (RI) strains derived from the spontaneously hypertensive rat (SHR) and the Brown Norway (BN) rat. The SHR progenitor strain had a significantly increased hematocrit values and it was also hypertensive and insulin-resistant when compared with the BN progenitor. The distribution of hematocrit and hemoglobin values among RI strains was continuous, suggesting a polygenic mode of inheritance. Analysis of RI strains revealed that hemoglobin was negatively correlated with insulin and insulin/glucose ratio, and that hematocrit was negatively correlated with insulin-stimulated glucose uptake in isolated adipocytes. There was no relationship between hematological parameters and blood pressure or lipid phenotypes in RI strains. The findings of the current study suggest that hematocrit and hemoglobin values might be added to the clustering variables related to the insulin resistance syndrome in the SHR strain.