Rebreathing-Induced Hypoxia Improves Insulin Sensitivity in Adults with Type 2 Diabetes

Hypoxia stimulates glucose uptake through an insulin-independent pathway. PURPOSE: To examine the acute effect of rebreathing-induced hypoxia on plasma glucose and insulin levels in adults with type 2 diabetes. We hypothesized that rebreathing-induced hypoxia would attenuate the increase in glucose and insulin levels during an oral glucose tolerance test. METHODS: Nine individuals with type 2 diabetes (4 women, age: 53±10 years, body mass index: 35±7 kg/m2, HbA1c: 7.1±0.5%) visited the laboratory on two occasions. On both visits, a 2-hour, 75 g oral glucose tolerance test was conducted while simultaneously performing a rebreathing-induced hypoxia protocol (RIH) or breathing room air (Norm). Venous blood samples were collected 0, 30, 60, 90, and 120 min following ingestion of the high-glucose drink to measure plasma glucose and insulin levels. The rebreathing-induced hypoxia protocol consisted of two series of five 2-min rebreathing bouts in a low-volume, closed circuit system interspersed with two minutes of breathing room air. The first and second series of rebreathing bouts were performed within the first 30 min and 30-60 min after ingestion of the high-glucose drink, respectively. RESULTS: Rebreathing-induced hypoxia resulted in a nadir oxygen saturation of 88±4% and a nadir fraction of inspired oxygen of 12±5%. Plasma glucose responses to the oral glucose tolerance test were not different between conditions, however, insulin levels were lower during rebreathing-induced hypoxia than normoxia (RIH vs. Norm: 0: 17±13 vs. 21±14; 30: 37±28 vs. 42±26; 60: 57±32 vs. 77±52; 90: 88±67 vs. 116±81; and 120: 114±96 vs. 136 ±111 ulU/ml, p=0.03), suggesting an acutely improved insulin sensitivity. Accordingly, the insulin area under the curve was lower during rebreathing-induced hypoxia than normoxia (124±84 vs. 157±102, p=0.02). CONCLUSION: Exposure to short and intermittent rebreathing-induced hypoxia following ingestion of a high-glucose drink acutely improves insulin sensitivity in adults with type 2 diabetes. Rebreathing-induced hypoxia could therefore represent a novel and simple strategy to improve glycemic control in individuals living with type 2 diabetes

Measurement of the local aortic stiffness by a non-invasive bioelectrical impedance technique

Aortic stiffness measurement is well recognized as an independent predictor of cardiovascular mortality and morbidity. Recently, a simple method has been proposed for the evaluation of the local aortic stiffness (AoStiff) using a non-invasive bioelectrical impedance (BI) technique. This approach relies on a novel interpretation of the arterial stiffness where AoStiff is computed from the measurement of two new BI variables: (1) the local aortic flow resistance (AoRes) exerted by the drag forces onto the flow; (2) the local aortic wall distensibility (AoDist). Herein, we propose to detail and compare these three indices with the reference pulse wave velocity (PWV) measurement and the direct assessment of the aortic drag forces (DF) and distensibility (DS) obtained by the magnetic resonance imaging technique. Our results show a significant correlation between AoStiff and PWV (r = 0.79; P < 0.0001; 120 patients at rest; mean age 44 ± 16 years), and also between AoRes and DF (r = 0.95; P = 0.0011) and between AoDist and DS (r = 0.93; P = 0.0022) on eight patients at rest (mean age 52 ± 19 years). These first results suggest that local aortic stiffness can be explored reliably by the BI technique

Effect of age on the hemodynamic and sympathetic responses at the onset of isometric handgrip exercise.

Cardiac and peripheral vasomotor factors contribute to the rapid pressor response at the onset of isometric handgrip exercise. We tested the hypothesis that age enhances the sympathetic and vasoconstrictor response at the onset of isometric handgrip exercise so that the pressor response is maintained, despite a diminished cardiac function. Twelve young and twelve older (24 ± 3 and 63 ± 8 yr) individuals performed 20-s isometric handgrip exercise at 30, 40, or 50% of maximal voluntary contraction force. Muscle sympathetic nerve activity (MSNA) was measured using microneurography. Mean arterial pressure (MAP) and cardiac output (Q) were assessed continuously by finger plethysmography and total peripheral resistance was calculated. MAP increased with the onset of handgrip; this increase was associated with handgrip intensity and was similar in both groups. Heart rate and Q increased with increasing handgrip intensity in both groups, but increases were greater in young vs. older individuals (age × handgrip intensity interaction, P \u3c 0.05). MSNA burst frequency increased (P \u3c 0.01), while MSNA burst incidence tended to increase (P = 0.06) with increasing handgrip intensity in both groups. The change in MSNA between baseline and handgrip, for both frequency and incidence, increased with increasing handgrip intensity for both groups. There was no effect of handgrip intensity or age on total peripheral resistance. The smaller heart rate and Q response during the first 20 s of handgrip exercise in older individuals was not accompanied by a greater sympathetic activation or vasoconstrictor response. However, increases in MAP were similar between groups, indicating that the pressor response at the onset of handgrip exercise is preserved with aging

La faute médicale caractérisée en droit français est-elle liée à des qualifications d'intensité et de gravité ?

Medical misconduct in criminal law could be qualified as characterized by judge. It would be determined by the fact that the medical practitioner exposes a patient to health danger with full consciousness. This medical misconduct could be done during positive act or guilty abstention. But the legislator didn’t clarify the term “characterized” of fault in the bill. Precise definitions were established by dispute at law. In the medical field, an analysis was performed when indirect causality was involved by supreme judge. The majority of court rulings were based on criminal negligence which couldn’t be ignored by the medical doctor that endangers health patient. Intensity and gravity in criminal negligence were systematically demonstrated. That could be considered as the term “characterized” in the medical fault

Proton Motive Force-Dependent Hoechst 33342 Transport by the ABC Transporter LmrA of Lactococcus lactis

The fluorescent compound Hoechst 33342 is a substrate for many multidrug resistance (MDR) transporters and is widely used to characterize their transport activity. We have constructed mutants of the adenosine triphosphate (ATP) binding cassette (ABC)-type MDR transporter LmrA of Lactococcus lactis that are defective in ATP hydrolysis. These mutants and wild-type LmrA exhibited an atypical behavior in the Hoechst 33342 transport assay. In membrane vesicles, Hoechst 33342 transport was shown to be independent of the ATPase activity of LmrA, and it was not inhibited by orthovanadate but sensitive to uncouplers that collapse the proton gradient and to N,N'-dicyclohexylcarbodiimide, an inhibitor of the F0F1-ATPase. In contrast, transport of Hoechst 33342 by the homologous, heterodimeric MDR transporter LmrCD showed a normal ATP dependence and was insensitive to uncouplers of the proton gradient. With intact cells, expression of LmrA resulted in an increased rate of Hoechst 33342 influx while LmrCD caused a decrease in the rate of Hoechst 33342 influx. Cellular toxicity assays using a triple knockout strain, i.e., L. lactis ΔlmrA ΔlmrCD, demonstrate that expression of LmrCD protects cells against the growth inhibitory effects of Hoechst 33342, while in the presence of LmrA, cells are more susceptible to Hoechst 33342. Our data demonstrate that the LmrA-mediated Hoechst 33342 transport in membrane vesicles is influenced by the transmembrane pH gradient due to a pH-dependent partitioning of Hoechst 33342 into the membrane.

Efflux in Acinetobacter baumannii can be determined by measuring accumulation of H33342 (bis-benzamide)

10.1093/jac/dkt052Journal of Antimicrobial Chemotherapy6871594-160