Ventilation-perfusion inequality in the human lung is not increased following no-decompression-stop hyperbaric exposure

Venous gas bubbles occur in recreational SCUBA divers in the absence of decompression sickness, forming venous gas emboli (VGE) which are trapped within pulmonary circulation and cleared by the lung without overt pathology. We hypothesized that asymptomatic VGE would transiently increase ventilation-perfusion mismatch due to their occlusive effects within the pulmonary circulation. Two sets of healthy volunteers (n = 11, n = 12) were recruited to test this hypothesis with a single recreational ocean dive or a baro-equivalent dry hyperbaric dive. Pulmonary studies (intrabreath VA/Q (iV/Q), alveolar dead space, and FVC) were conducted at baseline and repeat 1- and 24-h after the exposure. Contrary to our hypothesis VA/Q mismatch was decreased 1-h post-SCUBA dive (iV/Q slope 0.023 ± 0.008 ml−1 at baseline vs. 0.010 ± 0.005 NS), and was significantly reduced 24-h post-SCUBA dive (0.000 ± 0.005, p < 0.05), with improved VA/Q homogeneity inversely correlated to dive severity. No changes in VA/Q mismatch were observed after the chamber dive. Alveolar dead space decreased 24-h post-SCUBA dive (78 ± 10 ml at baseline vs. 56 ± 5, p < 0.05), but not 1-h post dive. FVC rose 1-h post-SCUBA dive (5.01 ± 0.18 l vs. 5.21 ± 0.26, p < 0.05), remained elevated 24-h post SCUBA dive (5.06 ± 0.2, p < 0.05), but was decreased 1-hr after the chamber dive (4.96 ± 0.31 L to 4.87 ± 0.32, p < 0.05). The degree of VA/Q mismatch in the lung was decreased following recreational ocean dives, and was unchanged following an equivalent air chamber dive, arguing against an impact of VGE on the pulmonary circulation

Venous gas embolism as a predictive tool for improving CNS decompression safety

A key process in the pathophysiological steps leading to decompression sickness (DCS) is the formation of inert gas bubbles. The adverse effects of decompression are still not fully understood, but it seems reasonable to suggest that the formation of venous gas emboli (VGE) and their effects on the endothelium may be the central mechanism leading to central nervous system (CNS) damage. Hence, VGE might also have impact on the long-term health effects of diving. In the present review, we highlight the findings from our laboratory related to the hypothesis that VGE formation is the main mechanism behind serious decompression injuries. In recent studies, we have determined the impact of VGE on endothelial function in both laboratory animals and in humans. We observed that the damage to the endothelium due to VGE was dose dependent, and that the amount of VGE can be affected both by aerobic exercise and exogenous nitric oxide (NO) intervention prior to a dive. We observed that NO reduced VGE during decompression, and pharmacological blocking of NO production increased VGE formation following a dive. The importance of micro-nuclei for the formation of VGE and how it can be possible to manipulate the formation of VGE are discussed together with the effects of VGE on the organism. In the last part of the review we introduce our thoughts for the future, and how the enigma of DCS should be approached

Nutritional considerations during prolonged exposure to a confined, hyperbaric, hyperoxic environment: Recommendations for saturation divers

Saturation diving is an occupation that involves prolonged exposure to a confined, hyperoxic, hyperbaric environment. The unique and extreme environment is thought to result in disruption to physiological and metabolic homeostasis, which may impact human health and performance. Appropriate nutritional intake has the potential to alleviate and/or support many of these physiological and metabolic concerns, whilst enhancing health and performance in saturation divers. Therefore, the purpose of this review is to identify the physiological and practical challenges of saturation diving and consequently provide evidence-based nutritional recommendations for saturation divers to promote health and performance within this challenging environment. Saturation diving has a high-energy demand, with an energy intake of between 44 and 52 kcal/kg body mass per day recommended, dependent on intensity and duration of underwater activity. The macronutrient composition of dietary intake is in accordance with the current Institute of Medicine guidelines at 45-65 % and 20-35 % of total energy intake for carbohydrate and fat intake, respectively. A minimum daily protein intake of 1.3 g/kg body mass is recommended to facilitate body composition maintenance. Macronutrient intake between individuals should, however, be dictated by personal preference to support the attainment of an energy balance. A varied diet high in fruit and vegetables is highly recommended for the provision of sufficient micronutrients to support physiological processes, such as vitamin B12 and folate intake to facilitate red blood cell production. Antioxidants, such as vitamin C and E, are also recommended to reduce oxidised molecules, e.g. free radicals, whilst selenium and zinc intake may be beneficial to reinforce endogenous antioxidant reserves. In addition, tailored hydration and carbohydrate fueling strategies for underwater work are also advised

Curcumin activates the p38MPAK-HSP25 pathway in vitro but fails to attenuate diabetic nephropathy in DBA2J mice despite urinary clearance documented by HPLC

<p>Abstract</p> <p>Background</p> <p>Curcumin has anti-inflammatory, anti-oxidant, and anti-proliferative properties, and depending upon the experimental circumstances, may be pro- or anti-apoptotic. Many of these biological actions could ameliorate diabetic nephropathy.</p> <p>Methods/Design</p> <p>Mouse podocytes, cultured in basal or high glucose conditions, underwent acute exposure to curcumin. Western blots for p38-MAPK, COX-2 and cleaved caspase-3; isoelectric focusing for HSP25 phosphorylation; and DNase I assays for F- to G- actin cleavage were performed for <it>in vitro </it>analyses. <it>In vivo </it>studies examined the effects of dietary curcumin on the development of diabetic nephropathy in streptozotocin (Stz)-induced diabetes in DBA2J mice. Urinary albumin to creatinine ratios were obtained, high performance liquid chromatography was performed for urinary curcuminoid measurements, and Western blots for p38-MAPK and total HSP25 were performed.</p> <p>Results</p> <p>Curcumin enhanced the phosphorylation of both p38MAPK and downstream HSP25; inhibited COX-2; induced a trend towards attenuation of F- to G-actin cleavage; and dramatically inhibited the activation of caspase-3 in <it>vitro</it>. In curcumin-treated DBA2J mice with Stz-diabetes, HPLC measurements confirmed the presence of urinary curcuminoid. Nevertheless, dietary provision of curcumin either before or after the induction of diabetes failed to attenuate albuminuria.</p> <p>Conclusions</p> <p>Apart from species, strain, early differences in glycemic control, and/or dosing effects, the failure to modulate albuminuria may have been due to a decrement in renal HSP25 or stimulation of the 12/15 lipoxygenase pathway in DBA2J mice fed curcumin. In addition, these studies suggest that timed urine collections may be useful for monitoring curcumin dosing and renal pharmacodynamic effects.</p

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a global epidemic that poses a major challenge to health-care systems. Improving metabolic control to approach normal glycaemia (where practical) greatly benefits long-term prognoses and justifies early, effective, sustained and safety-conscious intervention. Improvements in the understanding of the complex pathogenesis of T2DM have underpinned the development of glucose-lowering therapies with complementary mechanisms of action, which have expanded treatment options and facilitated individualized management strategies. Over the past decade, several new classes of glucose-lowering agents have been licensed, including glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium/glucose cotransporter 2 (SGLT2) inhibitors. These agents can be used individually or in combination with well-established treatments such as biguanides, sulfonylureas and thiazolidinediones. Although novel agents have potential advantages including low risk of hypoglycaemia and help with weight control, long-term safety has yet to be established. In this Review, we assess the pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with T2DM within the context of disease pathogenesis and natural history. In addition, we briefly describe treatment algorithms for patients with T2DM and lessons from present therapies to inform the development of future therapies