Zhang et al. found that plasma concentrations of the thiamine antimetabolite oxythiamine are significantly increased in patients with end-stage renal disease. These investigators discuss the potential sources of oxythiamine and the consequences of its plasma elevation. This commentary addresses the significance of these findings and expands on the potential role of gut microbiome in the generation of this antithiamine metabolite.

Exercise training stimulates angiogenesis in locomotor muscles. We hypothesize that skeletal myofiber expressed vascular endothelial growth factor is necessary for this angiogenic response to exercise training and overall improvements in exercise capacity. A conditional skeletal myofiber-specific VEGF gene deletion adult mouse model (HSA-Cre-ERT² X VEGFLoxP), in which skeletal muscle VEGF levels are reduced by >80%, was used to test this hypothesis. After 8 weeks of exercise training, skmVEGF-/- mice were unable to improve maximal speed or endurance. Wild-type littermates showed 18% and 99% increases in speed and endurance, respectively (p < 0.01). Capillary measurements revealed the angiogenic response (C:F) to training was attenuated in the plantaris of skmVEGF-/- mice (VEGF +/+ EX, 38%; skmVEGF-/- EX, 18%; p < 0.01), and completely inhibited in the gastrocnemius (VEGF +/+ EX, 43%, p < 0.01; skmVEGF-/- 7%, n.s.). Capillarity was unaffected under sedentary conditions. SkmVEGF-/- mice displayed increased BrdU+ cells (total cell proliferation), vimentin+ cells (fibroblast proliferation) and [alpha]- smooth muscle actin (arterial remodeling), which was amplified with training. Contraction-induced blood flow, measured by optical imaging of near-infrared fluorescent nanospheres, was inhibited in skmVEGF-/- mice. Contractile function of isolated soleus and extensor digitorum longus remained unchanged. SkmVEGF-/- mice had increased sedentary [Beta]-hydroxyacyl-CoA dehydrogenase activity, but training-induced augmentation was completely blocked. Improvements in citrate synthase and phosphofructokinase activity was inhibited and unaltered, respectively. These data suggest VEGF is necessary to augment capillary number and improve exercise capacity in response to exercise training, and plays an essential role in maintaining the vascular system in adult mice

Background

The low physical activity (LPA) more or less affects every community. Because of high prevalence of cardiovascular diseases in Iran and their relationship with LPA, this study aimed to measure precisely the epidemic size of LPA and determine its relationship with six other coronary artery disease (CAD) risk factors among an urban population aged 15 to 75 years in Kerman, Iran.

Methods

Using household survey, 5895 adults were randomly recruited through single-stage cluster sampling from 250 postal codes. Demographic characteristics, blood pressure, blood glucose, cholesterol, triglyceride, smoking, opium use, mental status and physical activities at work, rest and recreation were assessed and ranked as low, moderate and intense. Adjusted odds ratio (AOR) was reported as a measure of the relationship between LPA and other CAD risk factors.

Results

The prevalence of low, moderate, and intense physical activity were 42.1% (40.3-43.9), 45.0% (43.6-47.4) and 12.4% (11.1-13.9), respectively. LPA showed a sudden rise from 36.8% to 45.4% after the age of 25 years. On average, women had less physical activity than men (45.1% vs. 39.2%, P= 0.01). Participants with low physical activity compared to those without physical activity had significantly higher chance of anxiety [odds ratio 1.39; confidence interval (95% CI) 1.08-1.79; P = 0.01], hypertension (1.59; 1.08-2.35; P = 0.02), hyper-cholesterolemia (1.37; 1.06-1.76; P = 0.02), cigarette smoking (1.52; 1.07-2.11; P = 0.01), opium addiction (1.47; 1.07-2.02; P = 0.02) and overweight/obesity (1.34; 1.05-1.71; P = 0.02).

Conclusion

LPA was very common in the studied population and almost half of the adults were at risk for CAD because of insufficient level of physical activity. Such risky life-style pattern makes the emerging of CAD epidemic unavoidable, if effective interventions not being in place timely to this community.

End-stage renal disease (ESRD) is associated with a significant propensity for development of atherosclerosis and cardiovascular mortality. The atherogenic diathesis associated with ESRD is driven by inflammation, oxidative stress, and dyslipidemia. Reduced high-density lipoprotein cholesterol (HDL-C) level and high-density lipoprotein (HDL) dysfunction are the hallmarks of ESRD-related dyslipidemia. Clinical and laboratory studies have revealed that ESRD is associated with significantly reduced serum apolipoprotein A-I (ApoA-I) and HDL-C level as well as altered HDL composition. Furthermore, although ESRD is associated with impaired HDL antioxidant and anti-inflammatory properties in most patients, in a small subset, HDL may in fact have a pro-oxidant and proinflammatory effect. Therefore, it is no surprise that serum HDL-C level is not a dependable indicator of cardiovascular disease burden in ESRD, and markers such as HDL function are critical to accurately identifying patients at risk for cardiovascular disease and mortality in ESRD.

Ascorbic acid (AA) accumulation in intestinal epithelial cells is an active transport process mainly mediated by two sodium-dependent vitamin C transporters (SVCT-1 and SVCT-2). To date, little is known about the effect of gut microbiota generated lipopolysaccharide (LPS) on intestinal absorption of water-soluble vitamins. Therefore, the objective of this study was to investigate the effects of bacterially-derived LPS on AA homeostasis in enterocytes using Caco-2 cells, mouse intestine and intestinal enteroids models. Pre-treating Caco-2 cells and mice with LPS led to a significant decrease in carrier-mediated AA uptake. This inhibition was associated with a significant reduction in SVCT-1 and SVCT-2 protein, mRNA, and hnRNA expression. Furthermore, pre-treating enteroids with LPS also led to a marked decrease in SVCT-1 and SVCT-2 protein and mRNA expression. Inhibition of SVCT-1 and SVCT-2 occurred at least in part at the transcriptional level as promoter activity of SLC23A1 and SLC23A2 was attenuated following LPS treatment. Subsequently, we examined the protein and mRNA expression levels of HNF1α and Sp1 transcription factors, which are needed for basal SLC23A1 and SLC23A2 promoter activity, and found that they were significantly decreased in the LPS treated Caco-2 cells and mouse jejunum; this was reflected on level of the observed reduction in the interaction of these transcription factors with their respective promoters in Caco-2 cells treated with LPS. Our findings indicate that LPS inhibits intestinal carrier- mediated AA uptake by down regulating the expression of both vitamin C transporters and transcriptional regulation of SLC23A1 and SLC23A2 genes.

We examined the association of dyadic-level factors with syringe sharing among people who inject drugs (PWID) in Kerman, Iran. In a cross-sectional study, we collected data on 329 drug-injecting dyads by individual face-to-face interviews. An injecting dyad was defined as 2 PWID who knew each other and injected drugs together during the last 6 months. If they reported at least 1 occasion of syringe sharing, the dyad was considered high-risk. Dyadic-level factors associated with syringe sharing were assessed using cross-classified multilevel logistic regression. The rate of syringe sharing was significantly higher for dyads who were more intimate (adjusted odds ratio [AOR] 4.5, CI 95%, 2.3-8.6), who had instrumental support (AOR 2.1, 95% CI 1.1-4.5), and who pooled money for drugs (AOR 4.1, 95% CI 2.0-8.3). The rate was lower in same-sex dyads (AOR 0.4, 95% CI 0.2-0.9) and in dyads who shared health information (AOR 0.5, 95% CI 0.2-0.9). Findings highlight close-peer influences on syringe-sharing behavior.