Mitochondrial potassium channel opener diazoxide preserves neuronal-vascular function after cerebral ischemia in newborn pigs

Background and Purpose-N-Methyl-D-aspartate (NMDA) elicits neuronally mediated cerebral arteriolar vasodilation that is reduced by ischemia/reperfusion (I/R). This sequence has been preserved by pretreatment with the ATP-sensitive potassium (K-ATP) channel opener aprikalim, although the mechanism was unclear. In the heart, mitochondrial K-ATP channels (mitoK(ATP)) are involved in the ischemic preconditioning-like effect of K+ channel openers. We determined whether the selective mitoK(ATP) channel opener diazoxide preserves the vascular dilation to NMDA after I/R. Methods-Pial arteriolar diameters were determined with the use of closed cranial window/intravital microscopy in anesthetized piglets. Vascular responses to NMDA were assessed before and 1 hour after 10 minutes of global cerebral ischemia induced by raising intracranial pressure. Subgroups received 1 of the following pretreatments before I/R: vehicle; 1 to 10 mu mol/L diazoxide; and coapplication of 100 mu mol/L 5-hydroxydecanoic acid (5-HD), a K-ATP antagonist with diazoxide. Results-NMDA-induced dose-dependent pial arteriolar dilation was not affected by diazoxide treatment only but was severely attenuated by I/R, In contrast, diazoxide dose-dependently preserved the NMDA vascular response after I/R; at 10 mu mol/L, diazoxide arteriolar responses were unaltered by I/R. The effect of diazoxide was antagonized by coapplication of 5-HD with diazoxide. Percent preservation of 100 mu mol/L NMDA-induced vasodilation after I/R was 53 +/- 19% (mean +/- SEM, n = 8) in vehicle-treated controls versus 55 +/- 10%, 85 +/- 5%, and 99 +/- 15% in animals pretreated with 1, 5, and 10 mu mol/L diazoxide (n = 8, n = 8, and n = 12, respectively) and 60 +/- 15% in the group treated with 5-HD+diazoxide (n = 5). Conclusions-The mitoK(ATP) channel opener diazoxide in vivo preserves neuronal function after I/R, shown by pial arteriolar responses to NMDA, in a dose-dependent manner. Thus, activation of mitoK(ATP) channels may play a role in mediating the protective effect of other K+ channel openers

Jan Misugi in Captain Tsubasa as an Educational Example for Children with Congenital Heart Disease

Introduction: Visual narratives such as manga, comics and cartoons can play an important role in educating readers on various aspects of life including medicine and disabilities. Methods: We reviewed the animated series entitled "Captain Tsubasa", focusing our analysis on the episodes which introduced the character Jun Misugi, a football player suffering from an unspecified congenital heart disease (CHD). Discussion: For a child with a CHD, the practice of sports could be risky but also an opportunity to improve heart function and reach personal fulfillment. CHD have an important impact on children's quality of life, and sports participation has beneficial effects on quality of life, weight loss, and exercise capacity, in patients with CHD. Restricting sports could have a negative impact on quality of life, and on the disease acceptance in children with CHD. The story of Jan Misugi could be considered as an educational medical tool to sensitize children with CHD who face sport' restriction.Peer reviewe

The human hand and foot in evolution and art : the effects of wearing footwear

The structures of the human hands and feet are shaped by evolution and its effects on the brain, skeleton and other structures, and on behavior. We used measurements obtained of hands and feet from living humans in Europe, the Americas (South and North) and Australia and images of hands and feet in cave art, paintings, and photographs obtained from the Web including some from Africa. We used the ratios of the third finger/width of hand and second toe/width of foot. We hypothesized that hand ratios would not have changed over millennia whereas, because of the use of footwear and mechanical locomotion, the ratios obtained from feet could have changed significantly. Here we report that statistical analyses and modeling confirmed our initial hypothesi

Insulin Resistance and Hyperinsulinemia in Patients with Chronic Liver Disease and Hepatocellular Carcinoma

ObjectivesTo investigate the role of insulin resistance (IR) and insulin plasma levels (IRI) in patients with chronic liver disease (CLD) and hepatocellular carcinoma (HCC).MethodsWe recruited the following patients: 125 with HCC, 128 with liver cirrhosis (LC) and 133 with chronic hepatitis C (CHC). IR was assessed by the HOMA-IR method. To define IR and hyperinsulinemia we selected as a cut-off level, the value of the 80th percentile for HOMA-IR (2.72) and IRI (11.18) in 113 healthy subjects.ResultsThe mean levels of HOMA-IR and IRI increase progressively among CHC (2.7 ± 2.9 and 11.5 ± 10.5, respectively), LC (5.4 ± 4.5 and 17.6 ± 11.2) and HCC (6.4 ± 9.8 and 18.2 ± 18.8). In the upper quintiles for HOMA-IR and IRI, the frequency of patients in the LC and HCC groups was twice as much in CHC cases. HCC with DM2 have the greatest percentage above the 80th percentile of HOMA-IR, their quintiles distribution is inverted and HOMA-IR mean values are significantly higher in comparison with HCC without DM2 cases.DiscussionOur study shows that the association between IR and CLD begins in the early stages of liver fibrosis. DM2 increases HOMA-IR and IRI mean levels in HCC patients and these metabolic factors could play a major role in the link between diabetes mellitus and hepatocarcinoma

Circadian rhythm of autonomic activity in non diabetic offsprings of type 2 diabetic patients

The aim of the present study was to evaluate, by heart rate variability (HRV) with 24-hours ECG Holter (HRV), the circadian autonomic activity in offspring of type 2 diabetic subjects and the relation with insulin-resistance. METHODS: 50 Caucasian offsprings of type 2 diabetic subjects were divided in two groups: insulin-resistant offsprings (IR) and non insulin-resistant offsprings (NIR). Autonomic nervous activity was studied by HRV. Time domain and spectral analysis (low frequency, LF, and high frequency, HF, provide markers of sympathetic and parasympathetic modulation when assessed in normalized units) were evaluated. RESULTS. Time domain showed a reduction of total SDNN in IR (p < 0.001) and NIR (p 0.047) versus controls. Spectral analysis showed a total and night LF higher in IR and NIR than in control group (all p < 0.001). CONCLUSION. In frequency domain, the analysis of sympathetic (LF) and parasympathetic (HF) component evidenced an association between the offspring of type 2 diabetic subjects and a sympathetic overactivity. A global reduction and alteration of circadian rhythm of autonomic activity are present in offspring of type 2 diabetic patients with and without insulin resistance. The data of our study suggested that an autonomic impairment is associated with the familiarity for type 2 diabetes independently to insulin resistance and that an impairment of autonomic system activity could precede the insulin resistance

The calculation of Solvency Capital Requirement using Copulas

Our aim is to present an alternative methodology to the standard formula imposed to the insurance regulation (the European directive knows as Solvency II) for the calculus of the capital requirements. We want to demonstrate how this formula is now obsolete and how is possible to obtain lower capital requirement through the theory of the copulas, function that are gaining increasing importance in various economic areas. A lower capital requirement involves the advantage for the various insurance companies not to have unproductive capital that can therefore be used for the production of further profits. Indeed the standard formula is adequate only with some particular assumptions, otherwise it can overestimate the capital requirements that are actually needed as the standard formula underestimates the effect of diversification