Nonsteroidal anti-inflammatory drugs (NSAIDs) are drugs with analgesic, anti-inflammatory, and antipyretic activity. Their effect is achieved by the reduction in synthesis of prostanoids. Inhibition of prostanoids is responsible for a substantial risk of adverse effects. The risk of side effects affecting the gastrointestinal tract and kidneys has long been known. The possibilities of blood pressure elevation and the development of congestive heart failure are also widely recognized. Increased incidence of acute myocardial infarction in clinical trials with rofecoxib drew attention to the potential cardiotoxicity of selective cyclooxygenase-2 inhibitors, and similarly, concerns have been raised regarding the cardiovascular safety of non-selective NSAIDs. The safety of NSAIDs with regards to cardiovascular events has been studied in recent years in a large number of retrospective and prospective clinical studies and meta-analyses. The results indicate that cardiotoxicity is a class effect, but the magnitude of the risk is widely variable between individual NSAID drugs. This article aims to summarize the available data on the risk of adverse cardiovascular events with NSAIDs, the clinical impact of these events and possible underlying mechanisms.

ObjectiveBeyond the taste buds, sweet taste receptors (STRs; T1R2/T1R3) are also expressed on enteroendocrine cells, where they regulate gut peptide secretion but their regulatory function within the intestine is largely unknown.MethodsUsing T1R2-knock out (KO) mice we evaluated the role of STRs in the regulation of glucose absorption in vivo and in intact intestinal preparations ex vivo.ResultsSTR signaling enhances the rate of intestinal glucose absorption specifically in response to the ingestion of a glucose-rich meal. These effects were mediated specifically by the regulation of GLUT2 transporter trafficking to the apical membrane of enterocytes. GLUT2 translocation and glucose transport was dependent and specific to glucagon-like peptide 2 (GLP-2) secretion and subsequent intestinal neuronal activation. Finally, high-sucrose feeding in wild-type mice induced rapid downregulation of STRs in the gut, leading to reduced glucose absorption.ConclusionsOur studies demonstrate that STRs have evolved to modulate glucose absorption via the regulation of its transport and to prevent the development of exacerbated hyperglycemia due to the ingestion of high levels of sugars.

Background Non-caloric artificial sweeteners (NCAS) are widely used as a substitute for dietary sugars to control body weight or glycemia. Paradoxically, some interventional studies in humans and rodents have shown unfavorable changes in glucose homeostasis in response to NCAS consumption. The causative mechanisms are largely unknown, but adverse changes in gut microbiota have been proposed to mediate these effects. These findings have raised concerns about NCAS safety and called into question their broad use, but further physiological and dietary considerations must be first addressed before these results are generalized. We also reasoned that, since NCAS are bona fide ligands for sweet taste receptors (STRs) expressed in the intestine, some metabolic effects associated with NCAS use could be attributed to a common mechanism involving the host. Results We conducted a double-blind, placebo-controlled, parallel arm study exploring the effects of pure saccharin compound on gut microbiota and glucose tolerance in healthy men and women. Participants were randomized to placebo, saccharin, lactisole (STR inhibitor), or saccharin with lactisole administered in capsules twice daily to achieve the maximum acceptable daily intake for 2 weeks. In parallel, we performed a 10-week study administering pure saccharin at a high dose in the drinking water of chow-fed mice with genetic ablation of STRs (T1R2-KO) and wild-type (WT) littermate controls. In humans and mice, none of the interventions affected glucose or hormonal responses to an oral glucose tolerance test (OGTT) or glucose absorption in mice. Similarly, pure saccharin supplementation did not alter microbial diversity or composition at any taxonomic level in humans and mice alike. No treatment effects were also noted in readouts of microbial activity such as fecal metabolites or short-chain fatty acids (SCFA). However, compared to WT, T1R2-KO mice were protected from age-dependent increases in fecal SCFA and the development of glucose intolerance. Conclusions Short-term saccharin consumption at maximum acceptable levels is not sufficient to alter gut microbiota or induce glucose intolerance in apparently healthy humans and mice. Trial registration Trial registration number NCT03032640, registered on January 26, 2017.

The racing season is considered a critical period for racing pigeons due to the susceptibility to stress and weakening of the birds. One of the ways how to support their health and avoid problems involves supplementation of mineral-vitamin preparations based on selenium and vitamin E, which act as important antioxidants and protect cells against damage. This study investigated the influence of peroral supplementation of selenium at a dose of 0.3 mg Se.kg−1 feed dry matter (DM) in the form of Na2SeO3 and vitamin E 300 mg.ml−1 added to water at a rate of 4 ml.l−1 during 60 days. The supplemented group comprised 14 pigeons and their results were compared with a control group of 14 pigeons fed non-supplemented commercial feed. Blood samples were collected and examined at the beginning of the supplementation period, one day before a 300 km race and after the race. Pigeons from the supplemented group exhibited increased plasma levels of Se and vitamin E, as well as the activity of glutathione peroxidase (GSH-Px) before and after the 300 km race in comparison with the controls. Comparison of the activity of the enzymes: alanine aminotransferase (ALT), aspartate aminotransferase (ASP), alkaline phosphatase (ALP), and creatinine kinase (CK) at the beginning of the supplementation and one day before the race showed no changes. A significant (P < 0.05) increase in the activity of all investigated enzymes were observed after the race in both groups.

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