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Gadolinium-based contrast agents are increasingly used in clinical practice. While these pharmaceuticals are verified causal agents in nephrogenic systemic fibrosis, there is a growing body of literature supporting their role as causal agents in symptoms associated with gadolinium exposure after intravenous use and encephalopathy following intrathecal administration. Gadolinium-based contrast agents are multidentate organic ligands that strongly bind the metal ion to reduce the toxicity of the metal. The notion that cationic gadolinium dissociates from these chelates and causes the disease is prevalent among patients and providers. We hypothesize that non-ligand-bound (soluble) gadolinium will be exceedingly low in patients. Soluble, ionic gadolinium is not likely to be the initial step in mediating any disease. The Kidney Institute of New Mexico was the first to identify gadolinium-rich nanoparticles in skin and kidney tissues from magnetic resonance imaging contrast agents in rodents. In 2023, they found similar nanoparticles in the kidney cells of humans with normal renal function, likely from contrast agents. Wesuspect these nanoparticles are the mediators of chronic toxicity from magnetic resonance imaging contrast agents. This article explores associations between gadolinium contrast and adverse health outcomes supported by clinical reports and rodent models. [ABSTRACT FROM AUTHOR]

The effects of physiologically relevant increase in temperature (37-41 [degrees]C) on intestinal epithelial tight junction (TJ) barrier have not been previously studied. Additionally, the role of heat-shock proteins (HSPs) in the regulation of intestinal TJ barrier during heat stress remains unknown. Because heat-induced disturbance of intestinal TJ barrier could lead to endotoxemia and bacterial translocation during physiological thermal stress, the purpose of this study was to investigate the effects of modest, physiologically relevant increases in temperature (37-41[degrees]C) on intestinal epithelial TJ barrier and to examine the protective role of HSPs on intestinal TJ barrier. Filter-grown Caco-2 intestinal epithelial cells were used as an in vitro intestinal epithelial model system to assess the effects of heat exposure on intestinal TJ barrier. Exposure of filter-grown Caco-2 monolayers to modest increases in temperatures (37-41[degrees]C) resulted in a significant time- and temperature-dependent increases in Caco-2 TJ permeability. Exposure to modest heat (39 or 41[degrees]C) resulted in rapid and sustained increases in HSP expression; and inhibition of HSP expression produced a marked increase in heat-induced increase in Caco-2 TJ permeability (P < 0.001). Heat exposure (41[degrees]C) resulted in a compensatory increase in Caco-2 occludin protein expression and an increase in junctional localization. Inhibition of HSP expression prevented the compensatory upregulation of occludin protein expression and produced a marked disruption in junctional localization of occludin protein during heat stress. In conclusion, our findings demonstrate for the first time that a modest, physiologically relevant increase in temperature causes an increase in intestinal epithelial TJ permeability. Our data also show that HSPs play an important protective role in preventing the heat-induced disruption of intestinal TJ barrier and suggest that HSP mediated upregulation of occludin expression may be an important mechanism involved in the maintenance of intestinal epithelial TJ barrier function during heat stress. Caco-2; heat-shock protein; tight junction protein

This study evaluated the effect of weighted vest running (WVR) on fatty acid oxidation (FAox) and caloric expenditure at predesignated steady-state exercise intensities. Seventeen recreationally trained runners (9 men and 8 women) performed 4 separate graded exercise tests (GXTs) separated by at least 24 hours. The first GXT was a VO2max test to establish running velocities (percentage of max) at the prespecified exercise intensities (60, 65, 70, 75, and 80% VO2max). The following randomized WVR trials included a control (no vest), 5% body mass (BM) vest, and 10% BM vest using 3-minute incrementally increasing steady-state stages. Indirect calorimetry was used to measure both FAox (g·min-1) and caloric expenditure (kcal·min-1) at each stage. The ANOVA/ANCOVA analysis revealed that intensity had the largest effect on and FAox (p, 0.001) while WVR had a significant main effect on both caloric expenditure and FAox (p, 0.05). Pairwise comparisons revealed that the 10% BM significantly increased caloric expenditure for all exercise intensities compared with control and 5% BM (except 60% VO2max), while FAox decreased in the 10% BM 70 and 75% VO2max intensities only. Marginal rsquared (R²m) demonstrate that when sex + fat-free mass (FFM) + fat mass (FM) were included as covariates, sex was a significant predictor of caloric expenditure but was further explained by the large FFM (kg) differences between the sexes significantly influencing caloric expenditure (R²m = 0.87, p, 0.001). Exercise intensity, body composition (FFM + FM), and external mass placement are relevant considerations for runners looking to maximize FAox and caloric expenditure. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the effect of adding a Wingate sprint (W) before or after a circuit weight training (C) session on acute serum human growth hormone (HGH) concentration. Seven resistance-trained men performed a familiarization trial followed by 4 experimental trials: (a) W trial; (b) C trial; (c) WC trial; and (d) CW trial. The W resistance was set at 0.7 Nm/kg body mass. The C required a warm-up set of 10 repetitions at 40% 1RM and 2 sets of 10 repetitions at 70% 1RM consisting of bench press, bent-over barbell row, smith machine squat, seated dumbbell shoulder press, Romanian deadlift, and latissimus dorsi pull-down. Serum HGH was measured pre- and 5 (P5), 10 (P10), 20 (P20), 30 (P30), 45 (P45), and 60 min (P60) post-trial. All trials resulted in a significant increase in serum HGH compared to rest (P<0.05). The CW trial resulted in: (a) significantly higher serum HGH than the W and the C trials at P20 (P<0.05); (b) significantly higher HGH compared to the C and the WC trials at P30 (P<0.05); (c) significantly higher HGH area under the curve (AUC) compared to the C and the W trials (P<0.05); and (d) significantly higher peak HGH compared to the C trial (P<0.05). These results suggest that adding a Wingate sprint following a circuit weight training session may be particularly effective at acutely increasing serum HGH. [ABSTRACT FROM AUTHOR]

Effect of heat stress on LPS-induced febrile response in D-galactosamine-sensitized rats. Am J Physiol Regulatory Integrative Comp Physiol 280: R338-R344, 2001.--We have previously reported that heat conditioning augments lipopolysaccharide (LPS)-induced fewer in rats, which is accompanied by an accumulation of heat shock protein (HSP) in the liver and the reduction of the plasma level of tumor necrosis factor (TNF-[Alpha]) (Kluger MJ, Rudolph K, Soszynski D, Conn CA, Leon LR, Kozak W, Wallen ES, and Moseley PL. Am J Physiol Regulatory Integrative Comp Physiol 273: R858-R863, 1997). In the present study we have tested whether inhibition of protein synthesis in the liver can reduce the effect of this heat conditioning on the LPS-induced febrile response in the rat. D-galactosamine (D-gal) was used to selectively inhibit liver protein synthesis, D-gal (500 mg/kg) or PBS as control was administered intraperitoneally 1 h before heat stress. LPS (50 [micro]g/kg ip) was injected 24 h post-heat exposure. Treatment with D-gal blunted the febrile response to LPS. Moreover, heat-conditioned rats treated first with D-gal and subsequently with LPS demonstrated a profound fall in core temperature 10-18 h post-LPS. A significant increase of serum TNF-[Alpha] accompanied this effect of D-gal on fever. Heat-conditioned animals receiving D-gal showed an inhibition in inducible HSP-70 in the liver. These data support the role of hepatic function in modulating the febrile response to LPS. heat shock proteins; liver; heart; kidney; tumor necrosis factor-[Alpha], interleukin-6, temperature regulation; fever; lipopolysaccharide