Nonaxisymmetric Neutral Modes in Rotating Relativistic Stars

We study nonaxisymmetric perturbations of rotating relativistic stars. modeled as perfect-fluid equilibria. Instability to a mode with angular dependence $\exp(im\phi)$ sets in when the frequency of the mode vanishes. The locations of these zero-frequency modes along sequences of rotating stars are computed in the framework of general relativity. We consider models of uniformly rotating stars with polytropic equations of state, finding that the relativistic models are unstable to nonaxisymmetric modes at significantly smaller values of rotation than in the Newtonian limit. Most strikingly, the m=2 bar mode can become unstable even for soft polytropes of index $N \leq 1.3$, while in Newtonian theory it becomes unstable only for stiff polytropes of index $N \leq 0.808$. If rapidly rotating neutron stars are formed by the accretion-induced collapse of white dwarfs, instability associated with these nonaxisymmetric, gravitational-wave driven modes may set an upper limit on neutron-star rotation. Consideration is restricted to perturbations that correspond to polar perturbations of a spherical star. A study of axial perturbations is in progress.Comment: 57 pages, 9 figure

Microparticles and vascular dysfunction in obstructive sleep apnoea

Obstructive sleep apnoea (OSA) is independently associated with various cardiovascular diseases, including myocardial infarction and stroke. OSA may promote atherosclerosis risk factors such as hypertension, diabetes and dyslipidaemia, and may have direct proatherogenic effects on the vascular wall. A growing number of studies have recently focused on the role of microparticles (MPs) in the atherogenic process. MPs are small plasma membrane vesicles that can be released by a variety of vascular or blood cells, and contain both membrane and cytosolic elements. Case–control studies have shown that platelet-, endothelium- and leukocyte-derived MP levels are increased in OSA. Experimental evidence has demonstrated that MPs from OSA patients induce endothelial dysfunction, inflammation and vascular hyperreactivity when injected into mice. In this review, we provide an overview of the main characteristics of MPs, their expression in OSA and their potential role in the atherogenic process associated with OSA

Long-term outcome of noninvasive positive pressure ventilation for obesity hypoventilation syndrome

BACKGROUND: Few data are available on the long-term outcome of noninvasive positive pressure ventilation (NPPV) for obesity hypoventilation syndrome (OHS). This study was designed to determine long-term survival, treatment adherence, and prognostic factors in patients with OHS in whom NPPV was initiated in an acute setting vs under stable clinical conditions.METHODS: One hundred thirty consecutive patients with OHS (56 women) who started NPPV between January 1995 and December 2006 either under stable conditions (stable group, n = 92) or during ICU management of acute hypercapnic exacerbation (acute group, n = 38) were retrospectively analyzed. RESULTS: Arterial blood gases and the Epworth sleepiness scale were both significantly improved after 6 months of NPPV. With a mean follow-up of 4.1 +/- 2.9 years, 24 (18.5%) patients died and 24 (18.5%) discontinued NPPV. On Kaplan-Meier analysis, 1-, 2-, 3-, and 5-year survival probabilities were 97.5%, 93%, 88.3%, and 77.3%, respectively. Mortality was lower than that described in a previous series of patients with untreated OHS. Supplemental oxygen therapy was the only independent predictor of mortality. The probability of continuing NPPV was 80% at 3 years with a high rate of daily use ( > 7 h). Female sex was predictive of lower long-term adherence to NPPV. The acute and stable groups did not differ in terms of arterial blood gases and Epworth sleepiness scale at 6 months, long-term survival, and treatment adherence. CONCLUSIONS: The results of this study support long-term NPPV as an effective and well-tolerated treatment of OHS whether initiated in the acute or chronic setting

Pneumopathie médicamenteuse sous traitement par venlafaxine et propranolol

Introduction Venlafaxine and propranolol have rarely been identified as causes of pulmonary pathology. We describe a case of drug-induced pneumonitis occurring in a patient treated with these two medications. Case report A 55 years old woman with liver cirrhosis treated with venlafaxine for 1 year and propranolol for 1 month was admitted to the intensive care unit because of acute respiratory failure. A Mycoplasma pneumoniae pneumonitis was diagnosed. After initial improvement under antibiotics, a new deterioration of respiratory status was observed 4 days after the reintroduction of venlafaxine and propranolol. Spontaneous recovery occurred after these treatments were withheld. Co administration of venlafaxine and propranolol, 2 drugs with affinity for the same cytochrome P450 isoenzyme (CYP2D6), may have contributed to drug accumulation and pulmonary toxicity. The liver cirrhosis of our patient may also have contributed to decreased cytochrome P450 enzymatic activity. Conclusions Venlafaxine and propranolol share the same metabolic pathway and their co-administration may be complicated by drug induced pneumonitis

Influence of micropaticles harvested from patients affected by obstructive sleep apnea syndrome on endothelial function and vascular reactivity

Obstructive sleep apnea syndrome (OSAS) is a highly prevalent disease characterized by recurrent episodes of partial or complete obstruction of the upper airways during sleep, leading to oxygen desaturation, sleep fragmentation and clinical endothelial dysfunction. Microparticles (MPs) are membrane vesicles released during cell activation and apoptosis. Elevated levels of circulating MPs have been detected in pathologies associated with vascular alterations. We investigated the effects of MPs on endothelial function and vascular reactivity in OSAS. Blood samples were obtained either from 38 OSAS patients without any other cardiovascular comorbidities and 23 healthy subjects. A desaturation index above 10 per hour defined OSAS patients. MPs concentration and origin were assessed using flow cytometer. Male Swiss mice were injected i.v. with MPs from OSAS or healthy subjects, or with saline solution, and sacrified after 24hours. Endothelial function and vascular reactivity were studied on aortic rings and small mesenteric resistance (SMA) arteries by myography and arteriography, respectively. Patients with OSAS did not display increased circulating levels of MPs compared to healthy subjects including those from pro-coagulant, platelet, endothelial, leukocyte and erythrocyte origins. Interestingly, MPs from granulocytes and activated leukocytes were significantly enhanced in OSAS patients. Activated leukocyte MPs positively correlated with oxygen desaturation index. In aorta, MPs from OSAS patients but not those from healthy subjects significantly reduced endothelium-dependent relaxation to acetylcholine. MPs from OSAS increased sensitivity of the aorta in response to serotonin that was greater compared to the effect of MPs from healthy subjects. In SMA, MPs from OSAS but not those from healthy subjects impaired flow-induced dilation without any effect on myogenic tone. Although SMA from mice treated with healthy subjects MPs did not affect flow-induced dilation, these vessels showed a reduced prostacyclin-component that was completely compensated by the NO-component of the response. The endothelial dysfunction induced by MPs from OSAS was caused by the reduction of both NO- and prostacyclin- but not the endothelium-derived hyperpolarizing factor-components of the response in SMA. These data provide evidence that circulating MPs from OSAS patients influence both endothelial function and vascular reactivity

Nocturnal release of leukocyte-derived microparticles in males with obstructive sleep apnoea

Multiple pathophysiological mechanisms have been proposed to contribute to the increased cardiovascular morbidity in obstructive sleep apnoea (OSA), including autonomic dysfunction, inflammation, oxidative stress and endothelial dysfunction 1. Microparticles (MPs) are small membrane vesicles that are shed from circulating cells or from the components of the vessel wall in response to activation and apoptosis. There is growing evidence in support of a potential role of MPs in the field of cardiovascular diseases. Increased levels of MPs derived from various cell types are found in patients at risk of cardiovascular diseases 2. By modulating inflammation, coagulation, vasomotor reactivity and angiogenesis, MPs might directly contribute to cardiovascular diseases 2. Recent case–control studies suggest a potential involvement of MPs in OSA-associated cardiovascular morbidity 3–6. An increase in morning levels of MPs derived from activated leukocytes has been demonstrated in otherwise healthy male OSA patients with marked nocturnal desaturations 5. In vitro, nitric oxide (NO) production by endothelial cells incubated with MPs from OSA patients correlates negatively with circulating levels of activated leukocyte-derived MPs 5. Ex vivo, mice previously injected with MPs from OSA patients display endothelial dysfunction, reduced endothelial NO release and increased adhesion molecule expression 5

Circulating microparticles from patients with obstructive sleep apnea enhance vascular contraction: mandatory role of the endothelium

Obstructive sleep apnea (OSA) is characterized by repetitive apnea-hypopnea cycles during sleep associated with oxygen desaturation and sleep disruption. We evaluated the role of circulating microparticles (MPs) from patients with OSA in the regulation of vascular function. MPs from whole blood from patients with OSA or control subjects were injected i.v. into mice. Injection of MPs from patients with OSA induced ex vivo vascular hyperreactivity in aortas with functional endothelium but, in contrast, hyporeactivity in vessels without functional endothelium. Vascular hyperreactivity was blunted in the presence of a nitric oxide synthase inhibitor alone or combined with the cyclooxygenase inhibitor indomethacin. MPs from patients with OSA reduced endothelial nitric oxide synthase activity and nitric oxide production, increased aortic cyclooxygenase-1 and cyclooxygenase-2 expression, and increased thromboxane A(2) and prostacyclin production. Blockade of thromboxane A(2) receptor did not affect the serotonin response in arteries from OSA MP-treated mice. A superoxide dismutase mimetic reduced the vascular hyperreactivity induced by MPs from patients with OSA but had no effect on contraction in vessels from control and non-OSA MP-treated mice. These data provide evidence that circulating MPs from patients with OSA induce ex vivo vascular hyperreactivity with the obligatory role of the endothelium and subtle interactions between the nitric oxide and cyclooxygenase pathways and metabolites. These results highlight the participation of MPs in vascular dysfunction associated with OSA

Microparticles from patients with metabolic syndrome induce vascular hypo-reactivity via Fas/Fas-ligand pathway in mice

Peer reviewedPublisher PD

Independent association between obstructive sleep apnea severity and glycated hemoglobin in adults without diabetes

OBJECTIVE: We tested the hypothesis of an independent cross-sectional association between obstructive sleep apnea (OSA) severity and glycated hemoglobin (HbA(1c)) in adults without known diabetes. RESEARCH DESIGN AND METHODS: HbA(1c) was measured in whole-blood samples from 2,139 patients undergoing nocturnal recording for suspected OSA. Participants with self-reported diabetes, use of diabetes medication, or HbA(1c) value ≥6.5% were excluded from this study. Our final sample size comprised 1,599 patients. RESULTS: A dose-response relationship was observed between apnea-hypopnea index (AHI) and the percentage of patients with HbA(1c) >6.0%, ranging from 10.8% for AHI <5 to 34.2% for AHI ≥50. After adjustment for age, sex, smoking habits, BMI, waist circumference, cardiovascular morbidity, daytime sleepiness, depression, insomnia, sleep duration, and study site, odds ratios (95% CIs) for HbA(1c) >6.0% were 1 (reference), 1.40 (0.84-2.32), 1.80 (1.19-2.72), 2.02 (1.31-3.14), and 2.96 (1.58-5.54) for AHI values <5, 5 to <15, 15 to <30, 30 to <50, and ≥50, respectively. Increasing hypoxemia during sleep was also independently associated with the odds of HbA(1c) >6.0%. CONCLUSIONS: Among adults without known diabetes, increasing OSA severity is independently associated with impaired glucose metabolism, as assessed by higher HbA(1c) values, which may expose them to higher risks of diabetes and cardiovascular disease

Dynamic regulation of mitochondrial network and oxidative functions during 3T3-L1 fat cell differentiation

Mitochondria have been shown to be impaired in insulin resistance-related diseases but have not been extensively studied during the first steps of adipose cell development. This study was designed to determine the sequence of changes of the mitochondrial network and function during the first days of adipogenesis. 3T3-L1 preadipocytes were differentiated into adipocytes without using glitazone compounds. At days 0, 3, 6, 9, and 12, mitochondrial network imaging, mitochondrial oxygen consumption, membrane potential, and oxidative phosphorylation efficiency were assessed in permeabilized cells. Gene and protein expressions related to fatty acid metabolism and mitochondrial network were also determined. Compared to preadipocytes (day 0), new adipocytes (days 6 and 9) displayed profound changes of their mitochondrial network that underwent fragmentation and redistribution around lipid droplets. Drp1 and mitofusin 2 displayed a progressive increase in their gene expression and protein content during the first 9 days of differentiation. In parallel with the mitochondrial network redistribution, mitochondria switched to uncoupled respiration with a tendency towards decreased membrane potential, with no variation of mtTFA and NRF1 gene expression. The expression of PGC1α and NRF2 genes and genes involved in lipid oxidation (UCP2, CD36, and CPT1) was increased. Reactive oxygen species (ROS) production displayed a nadir at day 6 with a concomitant increase in antioxidant enzyme gene expression. This 3T3-L1-based in vitro model of adipogenesis showed that mitochondria adapted to the increased number of lipid droplets by network redistribution and uncoupling respiration. The timing and regulation of lipid oxidation-associated ROS production appeared to play an important role in these changes