Selenoprotein I is essential for murine embryogenesis.

Selenoprotein I (SELENOI) is an ethanolamine phosphotransferase that catalyzes the third reaction of the Kennedy pathway for the synthesis of phosphatidylethanolamine. Since the role of SELENOI in murine embryogenesis has not been investigated, SELENOI-/+ mating pairs were used to generate global KO offspring. Of 323 weanling pups, no homozygous KO genotypes were found. E6.5-E18.5 embryos (165 total) were genotyped, and only two E18.5 KO embryos were detected with no discernable anatomical defects. To screen embryos prior to uterine implantation that occurs ~ E6, blastocyst embryos (E3.5-E4.4) were flushed from uteruses of pregnant females and analyzed for morphology and genotype. KO embryos were detected in 5 of 6 pregnant females, and 7 of the 32 genotyped embryos were found to be SELENOI KO that exhibited no overt pathological features. Overall, these results demonstrate that, except for rare cases (2/490 = 0.4%), global SELENOI deletion leads to early embryonic lethality.

Selenium, Selenoproteins, and Immunity.

Selenium is an essential micronutrient that plays a crucial role in development and a wide variety of physiological processes including effect immune responses. The immune system relies on adequate dietary selenium intake and this nutrient exerts its biological effects mostly through its incorporation into selenoproteins. The selenoproteome contains 25 members in humans that exhibit a wide variety of functions. The development of high-throughput omic approaches and novel bioinformatics tools has led to new insights regarding the effects of selenium and selenoproteins in human immuno-biology. Equally important are the innovative experimental systems that have emerged to interrogate molecular mechanisms underlying those effects. This review presents a summary of the current understanding of the role of selenium and selenoproteins in regulating immune cell functions and how dysregulation of these processes may lead to inflammation or immune-related diseases.

Enhanced external counterpulsation (EECP) improves biomarkers of glycemic control in patients with non-insulin-dependent type II diabetes mellitus for up to 3 months following treatment.

AIMS: The purpose of the present study was to evaluate the potential clinical benefits of EECP on glycemic parameters [fasting plasma glucose (FPG), postprandial glucose (PPG120), glycosylated hemoglobin (HbA1c)] in patients with a clinical diagnosis of type II diabetes mellitus (T2DM). METHODS: Thirty subjects (60.7 ± 1.9 years) with T2DM were randomly assigned (2:1 ratio) to receive either 35 1-h sessions of EECP (n = 20) or time-matched control of standard care (n = 10). FPG, PPG120, and HbA1c were evaluated before and at 48 h, 2 weeks, 3 and 6 months following EECP treatment or time-matched control. RESULTS: EECP significantly decreased FPG (-14.6 and -12.0 %), PPG120 (-14.6 and -13.5 %), and HbA1c (-11.5 and -19.6 %) 48 h following EECP and 2 weeks following EECP, respectively. HbA1c remained significantly reduced at 3 months following EECP (-14.3 %). The homeostasis model assessment of insulin resistance (-31.1 %) and whole-body composite insulin sensitivity index (+54.2 %) were significantly improved 48 h following EECP. Nitrite/nitrate (NO x ) was significantly increased 48 h following EECP (+48.4 %) and 2 weeks (+51.9 %) following EECP treatment. CONCLUSIONS: Our findings provide novel evidence that EECP improves glycemic control in patients with T2DM that persist for up to 3 months following treatment.

Flow-mediated dilation is associated with endothelial oxidative stress in human venous endothelial cells.

Flow-mediated dilation (FMD) is recognized as a non-invasive endothelial function bioassay. However, FMD's relationship with endothelial cell oxidative stress in humans is yet to be determined. Here, we sought to determine if FMD was associated with endothelial nitric oxide synthase (eNOS) and endothelial oxidative stress in humans. Twenty-seven apparently healthy young men (26.5±5.9 years) underwent brachial artery FMD testing and endothelial cell biopsy from a forearm vein. Non-normalized FMD (%) and three different brachial artery FMD normalizations were performed: (1) peak shear rate (%/SR); (2) area under the SR curve until peak dilation (%/AUC); and (3) AUC 30 seconds before peak dilation (%/AUC30). Immunofluorescence quantification was used to assess eNOS expression and nitrotyrosine (NT), a criterion marker of endothelial oxidative stress. Values for eNOS and NT expression were reported as a ratio of endothelial cell to human umbilical vein endothelial cell average pixel intensity. NT expression was significantly correlated with FMD normalized by AUC30 (r = -0.402, p<0.05). Other FMD normalizations and non-normalized FMD were not significantly correlated with NT expression (r range = -0.364 to -0.142, all p>0.05). There were no significant correlations between eNOS expression and normalized and non-normalized FMD (r range = -0.168 to -0.066, all p>0.05). In conclusion, brachial artery FMD is associated with venous endothelial cell oxidative stress. However, this association is observed only when FMD is normalized by AUC30.

Enhanced external counterpulsation improves endothelial function and exercise capacity in patients with ischaemic left ventricular dysfunction.

Enhanced external counterpulsation (EECP) therapy decreases angina episodes and improves quality of life in patients with left ventricular (LV) dysfunction (LVD). However, studies have not elucidated the mechanisms of action and overall effects of EECP in patients with LVD. The purpose of the present study was to investigate the effects of EECP on endothelial function in peripheral conduit arteries and exercise capacity (peak Vo2 ) in patients with LVD. Patients with ischaemic LVD (ejection fraction (EF) 34.5 ± 4.2%; n = 9) and patients with symptomatic coronary artery disease (CAD) and preserved LV function (EF 53.5 ± 6.6%; n = 15) were studied before and after 35 sessions (1 h) of EECP. Brachial and femoral artery flow-mediated dilation (bFMD and fFMD, respectively) were evaluated using high-resolution ultrasound. Enhanced external counterpulsation elicited similar significant improvements in the following FMD parameters in the CAD and LVD groups (P ≥ 0.05 between groups for all): absolute bFMD (+53% and +70%, respectively), relative bFMD (+50% and +74%, respectively), bFMD normalized for shear rate (+70% and +61%, respectively), absolute fFMD (+33% and +21%, respectively) and relative fFMD (+32% and +17%, respectively). In addition, EECP significantly improved plasma levels of nitrate/nitrite (+55% and +28%) and prostacyclin (+50% and +70%), as well as peak Vo2 (+36% and +21%), similarly in both the CAD and LVD groups (P ≥ 0.05 between groups for all). Despite reduced LV function, EECP therapy significantly improves peripheral vascular function and functional capacity in CAD patients with ischaemic LVD to a similar degree to that seen in CAD patients with preserved LV function.

Enhanced external counterpulsation improves peripheral resistance artery blood flow in patients with coronary artery disease.

Enhanced external counterpulsation (EECP) increases coronary artery perfusion and improves endothelium-dependent vasodilation in peripheral muscular conduit arteries. It is unknown whether vasodilatory capacity is improved in the peripheral resistance vasculature. Here we provide novel evidence from the first randomized, sham-controlled study that EECP increases peak limb blood flow and improves endothelium-dependent vasodilation in both calf and forearm resistance arteries in patients with coronary artery disease.