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Salisbury Silver posted an update 1 week, 1 day ago
3% during weekdays (stool). The number of patients with a sample that was positive for GIP increased over the 4-week study period (urine samples in week 1 vs week 4, P less then .05). Patients with symptoms had more weeks in which GIP was detected in stool than patients without symptoms (P less then .05). Numbers of samples that were positive for GIP correlated with titers of deamidated gliadin peptide IgA in patients’ blood samples, but not with levels of tissue transglutaminase. CONCLUSIONS Patients with celiac disease on a long-term GFD are still frequently exposed to gluten. Assays to detect GIP in stool and urine might be used to assist dietitians in assessment of GFD compliance. The Hepatitis B Virus (HBV) ribonuclease H (RNaseH) is a promising but unexploited drug target. Here, we synthesized and analyzed a library of 57 amide-containing α-hydroxytropolones (αHTs) as potential leads for HBV drug development. Fifty percent effective concentrations ranged from 0.31 to 54 μM, with selectivity indexes in cell culture of up to 80. Activity against the HBV RNaseH was confirmed in semi-quantitative enzymatic assays with recombinant HBV RNaseH. The compounds were overall poorly active against human ribonuclease H1, with 50% inhibitory concentrations of 5.1 to >1,000 μM. BVDU The αHTs had modest activity against growth of the fungal pathogen Cryptococcus neoformans, but had very limited activity against growth of the Gram – bacterium Escherichia coli and the Gram + bacterium Staphylococcus aureus, indicating substantial selectivity for HBV. A molecular model of the HBV RNaseH templated against the Ty3 RNaseH was generated. Docking the compounds to the RNaseH revealed the anticipated binding pose with the divalent cation coordinating motif on the compounds chelating the two Mn++ ions modeled into the active site. These studies reveal that that amide αHTs can be strong, specific HBV inhibitors that merit further assessment toward becoming anti-HBV drugs. In spite of a decrease in the prevalence and incidence seen in recent years, chronic hepatitis B (CHB) still remains a major healthcare challenge, prevalent mostly in developing but also in developed regions. CHB is associated with significant morbidity and mortality, secondary to the complications of disease progression; cirrhosis and hepatocellular carcinoma (HCC). Historically, antiviral treatment has been restricted to patients with active hepatitis, established liver disease, fibrosis or cirrhosis and/or the risk of HCC development. As a result, patients with hepatitis B ‘e’ antigen (HBeAg) -positive chronic infection, formerly referred to as the ‘immune tolerant’ disease phase, have been excluded from treatment, since immune tolerant CHB had been considered ‘benign’ with no ostensible progressive liver disease. However, recent advances in ‘decoding’ the immunopathogenesis of CHB challenged the accuracy of this classical perception it is now well-recognised that HBeAg-positive chronic infection is not characterized by immunological tolerance and that events associated with tumourigenesis are already present during this early disease phase. These findings have led to a paradigm shift in 2017, the European Association for the Study of the Liver (EASL) recommended a change in the nomenclature and clinical categorisation of CHB and proposed lowering the threshold for antiviral treatment to include patients with HBeAg-positive chronic infection. It is anticipated that this could delay or even prevent disease progression and the development of HCC, alongside the potential to achieve functional cure (hepatitis B ‘surface’ antigen loss with or without development of hepatitis B ‘surface’ antibody). The current article reviews relevant literature and discusses the reasons for considering early treatment in CHB. Traditional anti-arrhythmic drugs are classified by the Vaughan-Williams classification scheme based on their mechanisms of action, which includes effects on receptors and/or ion channels. Some known anti-arrhythmic drugs do not perfectly fit into this classification scheme. Other medications/molecules with established non-anti-arrhythmic indications have shown anti-arrhythmic properties worth exploring. In this narrative review, we discuss the molecular mechanisms and evidence base for the anti-arrhythmic properties of traditional non-antiarrhythmic drugs such as inhibitors of the renin angiotensin system (RAS), statins and polyunsaturated fatty acids (PUFAs). In summary, RAS antagonists, statins and PUFAs are ‘upstream target modulators’ that appear to have anti-arrhythmic roles. RAS blockers prevent the downstream arrhythmogenic effects of angiotensin II – the main effector peptide of RAS – and the angiotensin type 1 receptor. Statins have pleiotropic effects including anti-inflammatory, immunomodulatory, modulation of autonomic nervous system, anti-proliferative and anti-oxidant actions which appear to underlie their anti-arrhythmic properties. PUFAs have the ability to alter ion channel function and prevent excessive accumulation of calcium ions in cardiac myocytes, which might explain their benefits in certain arrhythmic conditions. Clearly, whilst a number of anti-arrhythmic drugs exist, there is still a need for randomised trials to establish whether additional agents, including those already in clinical use, have significant anti-arrhythmic effects. The effects of oleoylethanolamide (OEA) on NAFLD are yet to be examined in human. The objective of the present study was to examine the effects of OEA supplementation along with weight loss intervention on the expression of PPAR-α, uncoupling proteins 1and 2 (UCP1 and UCP2) genes in the peripheral blood mononuclear cells (PBMCs), metabolic parameters, and anthropometric indices among obese patients with NAFLD. In this triple-blind placebo-controlled randomized clinical trial, 76 obese patients newly diagnosed with NAFLD were randomly allocated into either OEA or placebo group along with calorie-restricted diets for 12 weeks. At pre-and post-intervention phase, mRNA expression levels of PPAR-α, UCP1, and UCP2 genes in the PBMCs, serum levels of metabolic parameters as well as diet and appetite sensations were assessed. There was a significant increase in the expression levels of PPAR-α, UCP1, and UCP2 genes in the PBMCs, compared to the placebo at the endpoint. A significant decrease in the anthropometric indices, energy and carbohydrate intakes, glycemic parameters, except for hemoglobin A1c concentration was also observed in the OEA group, compared to the placebo group.