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Purpose: Autophagy and heat shock protein (HSP) response are proteostatic systems involved in the acute and adaptive responses to exercise. These systems may upregulate sequentially following cellular stress including acute exercise, however, currently few data exist in humans. This study investigated the autophagic and HSP responses to acute intense lower body resistance exercise in peripheral blood mononuclear cells (PBMCs) with and without branched-chain amino acids (BCAA) supplementation. Methods: Twenty resistance-trained males (22.3 ± 1.5 yr; 175.4 ±.7 cm; 86.4 ± 15.6 kg) performed a bout of intense lower body resistance exercise and markers of autophagy and HSP70 were measured immediately post- (IPE) and 2, 4, 24, 48, and 72 h post-exercise. Prior to resistance exercise, 10 subjects were randomly assigned to BCAA supplementation of 0.22 g/kg/d for 5 days pre-exercise and up to 72 h following exercise while the other 10 subjects consumed a placebo (PLCB). Results: There were no difference in autophagy markers or HSP70 expression between BCAA and PLCB groups. LC3II protein expression was significantly lower 2 and 4 h post-exercise compared to pre-exercise. LC3II: I ratio was not different at any time point compared to pre-exercise. Protein expression of p62 was lower IPE, 2, and 4 h post-exercise and elevated 24 h post-exercise. HSP70 expression was elevated 48 and 72 h post-exercise. Conclusions: Autophagy and HSP70 are upregulated in PBMCs following intense resistance exercise with autophagy increasing initially post-exercise and HSP response in the latter period. Moreover, BCAA supplementation did not affect this response. [ABSTRACT FROM AUTHOR]

The leitmotifs of magnetic resonance imaging (MRI) contrast agent-induced complications range from acute kidney injury, symptoms associated with gadolinium exposure (SAGE)/gadolinium deposition disease, potentially fatal gadolinium encephalopathy, and irreversible systemic fibrosis. Gadolinium is the active ingredient of these contrast agents, a non-physiologic lanthanide metal. The mechanisms of MRI contrast agent-induced diseases are unknown. Mice were treated with a MRI contrast agent. Human kidney tissues from contrast-naïve and MRI contrast agent-treated patients were obtained and analyzed. Kidneys (human and mouse) were assessed with transmission electron microscopy and scanning transmission electron microscopy with X-ray energy-dispersive spectroscopy. MRI contrast agent treatment resulted in unilamellar vesicles and mitochondriopathy in renal epithelium. Electron-dense intracellular precipitates and the outer rim of lipid droplets were rich in gadolinium and phosphorus. We conclude that MRI contrast agents are not physiologically inert. The long-term safety of these synthetic metal–ligand complexes, especially with repeated use, should be studied further. [ABSTRACT FROM AUTHOR]

Introduction: Legume lectins can have toxic effects when consumed without adequate cooking, occasionally leading to an acute gastroenteritis. Lectins are sugar binging proteins and may use this property to execute their toxic effects; these toxic effects may be secondary to increased gut bacteria and intestinal permeability. However, whether or not sucrose rescues these toxic effects by decreasing gut bacterial concentration and intestinal permeability is unknown.Aim: Our aim was to test the hypothesis that sucrose may reduce toxic effects of legume lectins by protecting barrier function, bacterial overgrowth and bacterial translocation.Methods: Twenty-four rats were randomized to an ad libitum diet of either standard rat chow, a chow containing 26% crude red kidney beans or a chow containing 26% crude red kidney beans supplemented with 1 mM sucrose in drinking water for 24 h. After 12-h fast, rats were gavaged with sugar probes; breath gas and urine were collected for 5 h. Intestine and liver tissues were then collected. Mucosa-associated total bacterial count were measured by targeting the 16s rRNA gene. Four groups of in vitro Caco-2 cell lines were treated with PBS, 200 μg/ml phytohemagglutinin (PHA), 1 mM sucrose and both 200 μg/ml PHA and 1 mM sucrose, respectively, and trans-epithelial resistance was measured.Results: Rats fed crude red kidney beans for 24 h showed significant weight loss when compared to controls (P < 0.05), as well as increased intestinal permeability (P < 0.05), increased bacterial load (P < 0.05) and increased bacterial translocation to the liver (P < 0.05). Sucrose rescues the drop in trans-epithelial resistance due to PHA in CaCO2-cells (P < 0.05).Conclusions: Sucrose reduced crude red kidney beans induced increase in intestinal permeability, bacterial load and translocation. Since red kidney beans are an important source of dietary protein in the world, their potential toxicity when inadequately cooked may be rescued by a suitable complementary diet. [ABSTRACT FROM AUTHOR]

Severe hyperthermia disrupts the intestinal barrier, allowing bacterial lipopolysaccharides (LPS) to enter the bloodstream. Since the symptoms of heat stroke resemble those of endotoxic shock, there is a common belief that endotoxaemia induces heat stroke. Therefore, we studied the effects of different doses, from moderate to sublethal, of Escherichia coli LPS and an antipyretic (indomethacin) upon the temperature equilibrium of the brain and body of rats exposed to a constant ambient temperature of 38 °C. The animals were then heated until they developed heat stroke, which was identified using a critical thermal maximum (CTM) behavioural test. In separate experiments on defence against endotoxaemia, we compared plasma lipid composition in rats exposed to a sublethal dose of LPS, hyperthermia and heat stroke. Neither LPS nor indomethacin, injected into rats while they were in a hyperthermic steady-state condition of 40–41 °C, influenced their thermal equilibrium. Unexpectedly, moderate doses of LPS significantly elevated the thermal tolerance of rats, such that the mean (SEM) CTM value of body temperature was raised from 42.7 (0.3) °C to 43.1 (0.1) °C (P < 0.05). Indomethacin and huge doses of LPS failed to induce any change in this parameter. The sublethal dose of LPS did not induce mortality in rats subjected to heat stroke. Hyperthermic steady-state conditions and heat stroke alone significantly decreased plasma concentrations of cholesterol, triglyceride and high-density lipoproteins, while the concentrations of low-density lipoproteins increased. A similar pattern of changes was recorded in normothermic rats injected with a sublethal dose of LPS. In conclusion, endotoxaemia in heat-stressed rats induces neither a secondary increase in their core temperature nor a decrease in their ultimate thermal tolerance. Low-density lipoproteins are likely to protect heat-stressed animals against endotoxin-induced death. [ABSTRACT FROM AUTHOR]