Impact of Intermittent Hypoxia on the Glycemic Response to an Oral Glucose Tolerance Test

Hypoxia triggers glucose uptake independently from the action of insulin. PURPOSE: To determine the acute effect of intermittent hypoxia, defined as alternating short bouts of breathing hypoxic and room air, on plasma glucose levels during an oral glucose tolerance test in healthy individuals. We hypothesized that exposure to intermittent hypoxia would attenuate the increase in glucose levels in response to an oral glucose tolerance test. METHODS: Nine individuals (5 men, age: 24 ± 4 years, height: 175 ± 9 cm, weight: 71.0 ± 13.5 kg, HbA1c: 5.4 ± 0.1%) participated in the study. Participants visited the laboratory on two occasions. On both visits, a 2-hour oral glucose tolerance test was performed, with venous blood samples collected 0, 30, 60, 90 and 120 minutes following the ingestion of a 75 g glucose drink. On visit 1, an intermittent hypoxia (IH) protocol, consisting of eight 4-minute hypoxic cycles at a targeted arterial oxygen saturation of 80% interspersed with breathing room air to resaturation, was performed following ingestion of the glucose drink. On visit 2, an intermittent normoxia protocol consisting of eight 4-minute normoxic cycles interspersed with breathing room air was performed following ingestion of the glucose drink. Visit order was randomized and participants were blinded to the condition. RESULTS: As expected, intermittent hypoxia resulted in a lower arterial oxygen saturation than intermittent normoxia (IH: 83 ± 3, IN: 98 ± 1%, p \u3c 0.01) which corresponded to lower levels of inspired oxygen (IH: 10.9 ± 0.7, IN: 20.9 ± 0.3%, p \u3c 0.01). Plasma glucose responses to the oral glucose tolerance test were not different between conditions (IH vs. IN: 0: 90 ± 7 vs. 89 ± 6; 30: 135 ± 21 vs. 137 ± 24; 60: 110 ± 28 vs. 108 ± 25; 90: 96 ± 18 vs. 88 ± 14; and 120: 101 ± 19 vs. 83 ± 14 mg/dl, p = 0.29). Intermittent hypoxia triggered an increase in cardiac output (6.1 ± 0.9 to 6.8 ± 1.3 L/min, p \u3c 0.01) caused by an increase in heart rate (67 ± 10 to 79 ± 12 bpm, p \u3c 0.01). CONCLUSION: Contrary to our hypothesis, intermittent exposure to hypoxia did not attenuate the increase in plasma glucose levels during an oral glucose tolerance test in individuals with normal glycemic control. It remains to be determined whether intermittent hypoxia can attenuate the increase in plasma glucose levels in response to an oral glucose tolerance test in individuals with impaired glucose tolerance

The Influence of Intermittent Hypoxia on Erythropoietin Levels in Older Adults

Few minutes of hypoxia exposure stabilizes hypoxia-inducible factors, resulting in erythropoietin (EPO) gene transcription and production. A brief intermittent hypoxia exposure increased EPO levels in young healthy adults, suggesting that a single session of intermittent hypoxia has the potential to increase oxygen-carrying capacity. PURPOSE: To determine the effect of a single session of intermittent hypoxia on serum EPO levels and hemoglobin mass among older adults. We hypothesized that a single session of intermittent hypoxia would raise serum EPO levels and lead to an increase in hemoglobin mass in older adults. METHODS: Seventeen participants (8 women, age: 54 ± 8 years, height: 177 ± 10 cm, weight: 76 ± 14 kg, BMI: 24 ± 4 kg/m2) were randomly assigned to an intermittent hypoxia group (IH, n=11) or an intermittent normoxia group (IN, n=6). Intermittent hypoxia consisted of eight 4-minute cycles at a targeted arterial oxygen saturation of 80% interspersed with normoxic cycles to resaturation. Air was made hypoxic by titrating nitrogen into the breathing circuit. Intermittent normoxia consisted of the same protocol, but nitrogen was not added to the breathing circuit. Pulmonary gas exchange, arterial oxygen saturation, and hemodynamics were continuously measured throughout both protocols. EPO levels were measured before and 4.5 hours after the beginning of each protocol. Hemoglobin mass was assessed via carbon monoxide rebreathing the day before and seven days following intermittent hypoxia or normoxia. RESULTS: Intermittent hypoxia lowered arterial oxygen saturation (­­98 ±­ 1 to 82 ± 3 %, p\u3c0.01), which resulted in a lower fraction of inspired oxygen (20.8 ±­ 0.1 to 10.9 ± 1.0 %, p\u3c0.01). There was no significant change in EPO levels in either condition (IH:10.4 ±­ 2.9 to 13.3 ± 4.2; IN: 5.6 ±­ 2.4 to 6.5 ± 2.9 mU/ml, main effect for time p=0.12). Similarly, there was no change in hemoglobin mass in response to both conditions (IH: 752 ±­ 189 to 754 ± 189; IN: 858 ± 177 to 879 ± 157 g, main effect for time p=0.87). Intermittent hypoxia did not affect mean arterial pressure (87 ± 15 to 88 ± 14 mmHg, p=0.18) or cardiac output (5.5 ± 1.5 to 5.7 ± 1.5 L/min, p=0.22), but increased heart rate (62 ± 9 to 68 ± 9 bpm, p\u3c0.01). CONCLUSION: A single session of eight 4-minute cycles of intermittent hypoxia did not increase serum EPO levels in older adults

Efficient design and evaluation of countermeasures against fault attacks using formal verification

This paper presents a formal verification framework and tool that evaluates the robustness of software countermeasures against fault-injection attacks. By modeling reference assembly code and its protected variant as automata, the framework can generate a set of equations for an SMT solver, the solutions of which represent possible attack paths. Using the tool we developed, we evaluated the robustness of state-of-the-art countermeasures against fault injection attacks. Based on insights gathered from this evaluation, we analyze any remaining weaknesses and propose applications of these countermeasures that are more robust

Hypoxic Preconditioning Attenuates Ischemia-reperfusion Injury in Older Adults

Sudden restoration of blood flow to an ischemic vessel paradoxically damages endothelial cells. In young healthy adults, ischemic preconditioning, caused by repeated periods of brief ischemia induced by local cuff inflation prior to reperfusion, attenuates endothelial dysfunction following an ischemia-reperfusion injury. However, ischemic preconditioning does not consistently protect against ischemia-reperfusion injury in older adults. Intermittent systemic hypoxemia, induced via brief bouts of breathing low levels of oxygen, attenuates endothelial dysfunction following an ischemia-reperfusion injury in young adults. PURPOSE: To determine whether intermittent hypoxia protects against ischemia-reperfusion injury in older adults. METHODS: Twelve older adults (5 women, age: 57 ± 9 years, height: 173 ± 8 cm, body weight: 75.8 ± 13.4 kg) visited the laboratory on two separate occasions. Endothelium-dependent vasodilation was assessed by brachial artery flow-mediated dilation using a semiautomated diagnostic ultrasound system before and after 20 minutes of upper arm blood flow occlusion to induce an ischemia-reperfusion injury. Blood flow occlusion was preceded by either intermittent hypoxia, consisting of three 4-minute hypoxic cycles at a targeted arterial oxygen saturation of 80% interspersed with 4-minute room air cycles, or intermittent normoxia, consisting of three 4-minute normoxic cycles separated by 4-minute room air cycles. RESULTS: Intermittent hypoxia resulted in an arterial oxygen saturation of 80 ± 2%, which corresponded to oxygen levels of 11.4 ± 0.7%. When preceded by intermittent normoxia, blood flow occlusion reduced flow-mediated dilation by 4.1 ± 2.6% (6.5 ± 1.7 to 2.4 ± 1.7%). In contrast, flow-mediated dilation was reduced by 2.0 ± 1.5% when blood flow occlusion was preceded by intermittent hypoxia (5.6 ± 1.7 to 3.6 ± 2.3%, P = 0.03). When compared to intermittent normoxia, intermittent hypoxia resulted in a greater heart rate (60 ± 10 vs. 68 ± 10 bpm, P \u3c 0.01) but did not affect cardiac output (5.1 ± 1.4 vs. 5.8 ± 1.8 L/min, P = 0.11). CONCLUSION: Hypoxic preconditioning attenuated the reduction in flow-mediated dilation induced by a 20-minute blood flow occlusion in older adults. Thus, exposure to intermittent hypoxia represents a promising strategy to protect against ischemia-reperfusion injury in populations at risk for ischemic events

Strontium ranelate decreases the incidence of new caudal vertebral fractures in a growing mouse model with spontaneous fractures by improving bone microarchitecture

Summary Young mice over-expressing Runx2 fail to gain bone relative to wild type mice with growth and present spontaneous fractures. It allows, for the first time in rodents, direct assessment of anti-fracture efficacy of strontium ranelate which was able to decrease caudal vertebrae fracture incidence through an improvement of trabecular and cortical architecture. Introduction The aim was to investigate whether strontium ranelate was able to decrease fracture incidence in mice over-expressing Runx2, model of severe developmental osteopenia associated with spontaneous vertebral fractures. Methods Transgenic mice and their wild type littermates were treated by oral route with strontium ranelate or vehicle for 9 weeks. Caudal fracture incidence was assessed by repeated X-rays, resistance to compressive loading by biochemical tests, and bone microarchitecture by histomorphometry. Results Transgenic mice receiving strontium ranelate had significantly fewer new fractures occurring during the 9 weeks of the study (−60%, p < 0.05). In lumbar vertebrae, strontium ranelate improves resistance to compressive loading (higher ultimate force to failure, +120%, p < 0.05) and trabecular microarchitecture (higher bone volume and trabecular number, lower trabecular separation, +60%, +50%, −39%, p < 0.05) as well as cortical thickness (+17%, p < 0.05). In tibiae, marrow cavity cross-section area and equivalent diameter were lower (−39%, −21%, p < 0.05). The strontium level in plasma and bone was in the same range as the values measured in treated postmenopausal women. Conclusions This model allows, for the first time, direct assessment of anti-fracture efficacy of strontium ranelate treatment in rodents. In these transgenic mice, strontium ranelate was able to decrease caudal vertebral fracture incidence through an improvement of trabecular and cortical architecture

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

Mechanical integrity of thin inorganic coatings on polymer substrates under quasi-static, thermal and fatigue loadings

The interplay between residual stress state, cohesive and adhesive properties of coatings on substrates is reviewed in this article. Attention is paid to thin inorganic coatings on polymers, characterized by a very high hygro-thermo-mechanical contrast between the brittle and stiff coating and the compliant and soft substrate. An approach to determine the intrinsic, thermal and hygroscopic contributions to the coating residual stress is detailed. The critical strain for coating failure, coating toughness and coating/substrate interface shear strength are derived from the analysis of progressive coating cracking under strain. Electro-fragmentation and electro-fatigue tests in situ in a microscope are described. These methods enable reproducing the thermo-mechanical loads present during processing and service life, hence identifying and modeling the critical conditions for failure. Several case studies relevant to food and pharmaceutical packaging, flexible electronics and thin film photovoltaic devices are discussed to illustrate the benefits and limits of the present methods and models. © 2010 Elsevier B.V. All rights reserved

Isolation of DNA sequences on human chromosome 21 by application of a recombination-based assay to DNA from flow-sorted chromosomes

By merging two efficient technologies, bivariate flow sorting of human metaphase chromosomes and a recombination-based assay for sequence complexity, we isolated 28 cloned DNA segments homologous to loci on human chromosome 21. Subregional mapping of these DNA segments with a somatic cell hybrid panel showed that 26 of the 28 cloned DNA sequences are distributed along the long arm of chromosome 21, while the other 2 hybridize with sequences on the short arm of both chromosome 21 and other chromosomes. This new collection of probes homologous to chromosome 21 should facilitate molecular analyses of trisomy 21 by providing DNA probes for the linkage map of chromosome 21, for studies of nondisjunction, for chromosome walking in clinically relevant subregions of chromosome 21, and for the isolation of genes on chromosome 21 following the screening of cDNA libraries.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47623/1/439_2004_Article_BF00366237.pd