A novel method for the analysis of clinical biomarkers to investigate the effect of diet on health in a rat model

Experiments into the relationship between diet and health have been an area of high interest for a long time. In this study, we investigate the application of multivariate data analysis to differentiate between rat populations fed on two different diets: normal rat diet (control) and Western affluent diet (WAD). Two sets of data were acquired and analysed: one from a biochemical clinical analyser, taking measurements of blood-based biochemical markers; the other from the analysis of the volatile organic compounds (VOCs) emitted from faecal samples from the same animals using selected ion flow tube mass spectrometry (SIFT-MS). Five classes were considered: weanlings, 12 month controls, 12 month WADs, 18 month controls, and 18 month WADs. Data from the biochemical analyser, weanlings and 18 month WAD fed rats showed significant differences from the other measurement classes. This was shown in both the exploratory analysis and through multivariate classification. Classification of control diet versus WAD diets suggested there are differences between classes with 92% accuracy for the 12 month classes and 91% for the 18 month classes. Cholesterol markers, especially as low density lipoprotein-cholesterol (LDL), were the main factor in influencing WAD samples. The data from the SIFT-MS analysis also produced very good classification accuracies. Classification of control diet versus WAD diets using the H3O+ precursor ion data suggested there are differences between classes with 71% accuracy for the 12 month classes and 100% for the 18 month classes. These findings confirm that total cholesterol and LDL-cholesterol are elevated in the 18 month WAD-fed rats. We therefore suggest that the analysis of VOCs from faecal samples in conjunction with multivariate data analysis may be a useful alternative to blood analysis for the detection of parameters of health

The extracellular matrix and insulin resistance

The extracellular matrix (ECM) is a highly dynamic compartment that undergoes remodeling as a result of injury and repair. Over the past decade, mounting evidence in humans and rodents suggest that ECM remodeling is associated with diet-induced insulin resistance in several metabolic tissues. Additionally, integrin receptors for the ECM have also been implicated in the regulation of insulin action. This review will address what is currently known about the ECM, integrins and insulin action in the muscle, liver and adipose tissue. Understanding how ECM remodeling and integrin signaling regulates insulin action may aid in the development of new therapeutic targets for the treatment of insulin resistance and type 2 diabetes

Azathioprine and 6-mercaptopurine-induced intrahepatic cholestasis of pregnancy: Case report and review of the literature

Objective: Azathioprine, a prodrug of 6-mercaptopurine (6-MP), is used in the treatment of inflammatory bowel disease and may be continued during pregnancy. Acute cholestatic liver injury has been reported to occur with azathioprine. We aimed to examine azathioprine related cholestasis effect on pregnancy complications and outcome. Case report: We present a unique case of 6-MP-induced severe intrahepatic cholestasis of pregnancy (ICP) that required meticulous combined therapy including plasma exchange. The symptoms resolved following 6-MP withdrawal. A literature review revealed 11 pregnancies complicated by early-induced severe ICP among women treated with azathioprine or 6-MP. Conclusion: We recommend weekly bile acid level tests for pregnant women treated with azathioprine or 6-MP, beginning early in the second trimester of pregnancy, and the prompt discontinuation of treatment upon establishment of an ICP diagnosis