La forme non musculaire de la kinase de la chaine légère de la myosine (MLCKnm) est une kinase principalement exprimée par les cellules endothéliales dont le rôle principal est de phosphoryler la chaine légère de myosine. Cette phosphorylation modifie la conformation des têtes de myosine, augmente l’interaction actine/myosine, et induit une rétraction des cellules endothéliales. Ce processus augmente la perméabilité de la barrière endothéliale. L’activation de MLCKnm permet l’infiltration de cellules inflammatoires en réponse à certains stimuli dont le lipopolysaccharide (LPS) bactérien. Dans ce modèle expérimental de sepsis, la déficience de MLCKnm dans un modèle murin protège les souris injectées avec du LPS, associée à une prévention des stress oxydant et nitrosant ainsi que de l’activation de voies de signalisation inflammatoire. Cependant les mécanismes moléculaires mis en jeu ne sont pas totalement connus. Dans le contexte inflammatoire, le syndrome d’apnées/hypopnées obstructives du sommeil, caractérisé par une obstruction des voies aériennes lors du sommeil menant à une hypoxie intermittente (HI), partage certaines caractéristiques dans l’activation inflammatoire observée lors du sepsis. L’HI modifie le métabolisme des cellules endothéliales en diminuant la biodisponibilité du monoxyde d’azote, augmentant le stress oxydant ainsi que la production de certains facteurs inflammatoires. A long terme, une réponse inflammatoire systémique est observée augmentant les risques d’athérosclérose. L’objectif de ce travail est d’étudier l’implication de MLCKnm dans l’inflammation vasculaire dans deux modèles physiopathologiques, induits par le LPS et l’HI. / Non muscular myosin light chain kinase (nmMLCK) is aprotein mainly expressed by endothelial cells whose roleis to phosphorylate myosin light chain. This phosphorylation modifies the conformation of myosin heads, increasing actin/myosin interaction, and inducing endothelial cells retraction. This process increases endothelial barrier permeability. The activation of nmMLCK increases inflammatory cell infiltration in response to several stimuli such as the bacterial lipopolysaccharide (LPS). In this experimental model of sepsis, nmMLCK deficiency in a murine model protects mice injected with LPS, associated with oxidative and nitrative stresses prevention as well as inflammatory pathway inhibition. However, molecular mechanisms are not fully known. In this inflammatory context, obstructive sleep apnea hypopnea syndrome, characterized by obstruction of upper airway during sleep leading to intermittent hypoxia (IH), share several characteristics in inflammatory activation observed during sepsis. IH modifies the metabolism of endothelial cells decreasing nitric oxide bioavailability, increasing oxidative stress aswell as inflammatory mediators. Long-term, systemic inflammatory response is observed increasing atherosclerosis risk. The objective of this work is to study the implication of nmMLCK in vascular inflammation in two pathophysiological models induced by LPS and IH.

Sleep apnea syndrome, or sleep apneic syndrome, is a serious illness that causes a high risk of cardiovascular disease development in patients. This disease is characterized by a breathless breathing disorder and falls into a class of disorder that accompanies sleep disturbances. Sleep apnea syndrome (SAS) affects 5-15% of the population, and 50-80% of patients with type 2 diabetes mellitus (T2DM) or severe obesity. SAS has a causal contribution to the development of disorders in glucose metabolism and T2DM. Diabetes mellitus type 2 is a complex metabolic disorder in which the organism is unable to process glucose as under normal physiological conditions due to a relative insulin deficiency and simultaneous peripheral insulin resistance. Insulin resistance is eventually compensated for by increased insulin secretion, which leads to the development of hyperglycemia after failure of this compensation. T2DM is very often associated with the presence of obesity, arterial hypertension, dyslipidemia and hyperuricemia. The aim of this study is to determine if the presence of SAS in non-diabetic subjects and patients with type 2 diabetes mellitus leads to disorders in the metabolism of fatty acids in the skeletal muscle. The results of the study contribute to the understanding of the molecular mechanisms...

Objetivo: describir la frecuencia de factores de riesgo cardiovascular en pacientes con Síndrome isquémico coronario agudo (SICA) de dos hospitales del Perú. Materiales y métodos: se realizó un estudio descriptivo transversal. Participaron 100 pacientes hospitalizados con SICA, en quienes se exploraron factores de riesgo cardiovascular. También se utilizó la escala ronquido somnolencia y escala de somnolencia de Epworth (versión peruana) para evaluar síntomas relacionados a apnea de sueño. Resultados: la frecuencia de los factores de riesgo cardiovascular más prevalentes entre los participantes fueron: obesidad según índice cintura cadera 98,86% (87/88), edad mayor a 55 años en varones y 65 años en mujeres, 78% (78/100), hipertensión arterial 71% (71/100), Dislipidemia 55,67% (54/97), sedentarismo 50,51% (49/97). La frecuencia de roncadores crónicos fue de 85,56% (83/97). Conclusiones: el factor de riesgo cardiovascular más frecuente fue la obesidad según Índice cintura-cadera y el menos frecuente fue el tener antecedente familiar de SICA. La frecuencia de ronquido en estos pacientes fue elevada.

No description available.

Obstructive sleep apnea (OSA) and asthma are potentially linked at several levels. The pathophysiology of these two conditions seems to overlap significantly, as airway obstruction, inflammation, obesity, and several other factors are implicated in the development of both diseases. Gastroesophageal reflux disease (GERD), cardiovascular complications, obesity itself, and the underlying inflammatory processes are all complex contributory factors that provide hypothetical links. Furthermore, a collateral rise in prevalence of both OSA and asthma has been noticed during the past few years, occurring in association with the emerging epidemic of obesity, a common risk factor for both conditions. OSA and asthma share many other risk factors as well. We propose a hypothetical OSA-asthma relationship that has implications on the diagnosis and management of patients presenting with either condition singly. Clinicians should be aware that OSA might complicate asthma management. Based on this hypothesis, we suggest that the treatment of the individual patient who experiences both asthma and OSA needs to be multidisciplinary and comprehensive. This hypothetical association of asthma and OSA, though described anecdotally, has not been systematically studied. In particular, the influence of continuous positive airway pressure therapy (for sleep apnea) on asthma outcomes (such as quality of life, steroid utilization, emergency room visits) and fatality needs to be studied further.

This qualitative descriptive (QD) study examined the experience of the woman newly diagnosed with obstructive sleep apnea (OSA). The study employed Leventhal’s Self- Regulatory Theory to understand women’s illness representation of OSA, cognitive and emotional coping, and situational appraisal skills in coming to terms with OSA. The specific aims were to: 1) Describe the illness representation of women with a recent diagnosis (within one year) of OSA; 2) Describe the cognitive perceptions and emotional response to diagnosis and treatment of OSA in this sample of women; and, 3) Describe the meaning of OSA and the coping strategies used by this sample of women. The overarching theme of this study of a life-altering diagnosis required participants to process the health threatening information in both a conceptual and concrete process for dealing with both the physical and emotional aspects. The first two subthemes that emerged were Making sense of it, and Making it work as the women came to terms with their symptoms, diagnosis, and adapted to their treatment. For this sample of women, both acceptance (acknowledging the diagnosis of OSA and embracing treatment), and denial (not convinced of diagnosis or need for treatment, seeking alternatives) were factors in how they made sense of the situation. The making it work subtheme dealt with the women’s experiences adapting to treatment both physically and emotionally, including the appraisal, reconsideration and adjustments when they encountered difficulties and delays. A fluid iterative process included women participants describing how they appraised their situation often moving back and forth between acceptance, denial, seeking alternatives, struggling with treatment and moving forward. In both of these subthemes, family support and the stigma of OSA and CPAP were involved in how the women accepted and adapted to treatment. The third subtheme that emerged was Paying it forward as many women felt the obligation to help themselves by adapting a healthier lifestyle for themselves, their families and to assist others impacted by OSA. Women spoke of paying it forward by offering information and support to others not yet diagnosed, or are struggling with diagnosis and treatment. Many of these women were staunch advocates for other women to be tested, for HCPs to be more aware, to be more attuned to women’s sleep history, and to refer women for treatment. Implications of these findings include enhancing recognition and awareness by women of OSA symptoms, the need for diagnostic evaluation, and partner awareness as an important component of diagnosis and successful treatment for women. Study findings support recognition of women’s presentation of OSA including unusual symptoms for earlier diagnosis and treatment. Sleep partner awareness and support appear to be relevant to women in acceptance of a life altering diagnosis. Further exploration of modifiable factors such as prompt diagnosis and individualized treatment of women with OSA could also impact potential co-morbidities. Provision of further education and awareness by HCPs and insurance companies that women may not present with classic symptoms of OSA is also needed. Targeted interventions specific to women’s experiences with OSA include development of screening tools, care guidelines and treatments that enhance applicability, acceptability, and patient satisfaction. Future advocacy work will also require supporting women in “paying it forward” to help other women diagnosed with OSA.

No description available.

No description available.

No description available.

Obstructive sleep apnea (OSA) is a disorder that affects a significant portion of middle-aged adult population. Patients exhibit recurring episodes of upper airway obstruction during sleep that decrease blood oxygen concentration (hypoxia) and are terminated by brief arousals. Epidemiologically, OSA has been extensively linked to cardiovascular dysfunction and is an independent risk factor for the development of hypertension. The proposed mechanism of cardiovascular dysfunction in patients is chronic sympathoexcitation and altered vascular tone, with a predominance of the vasoconstrictor endothelin-1 (ET-1) and removal of the vasodilator nitric oxide (NO). Means to reduce the effects of ET-1 and increase synthesis of NO may have beneficial effects on the cardiovascular co-morbidity commonly associated with OSA. OBJECTIVES: The major aim of this study was to assess the relative importance of circulating biomarkers of ET-1 and NO in hemodynamic function in OSA patients. Potential production of ET-1 by circulating mononuclear cells was also measured to assess their contribution to plasma ET-1 levels. Biomarker levels before and after 12 wk of continuous partial airway pressure (CPAP) therapy were used to assess standard treatment. Mild/moderate exercise training was initiated with CPAP therapy in a subgroup of OSA patients to evaluate the potential benefits of physical activity on hemodynamic function and NO and ET-1 levels. METHODS: Overall, 16 newly diagnosed OSA patients (5 female, 11 male; age 45.4 ± 2.7 yr; RDI 24.6 ± 4.0 events/hr) were selected for study. Seven apparently healthy control volunteers (5 female, 2 male; age 39.43 ± 2.6 yr) screened for OSA served as control subjects. Blood pressure was recorded over one complete day and prior to, during, and following maximal exercise testing on a cycle ergometer. Blood samples were taken prior to exercise testing and assessed for nitrate and nitrite by HPLC and for big endothelin-1 and ET-1 by ELISA. Relative gene expression of preproendothelin-1 was measured by real-time RT-PCR. Following initial testing, patients were stratified into either a standard therapy group (nCPAP) or a standard therapy group with a mild/moderate intensity aerobic training regimen (nCPAP+Ex). Baseline testing was repeated following 12 wk of treatment. Statistical significance was set at p < 0.05 a priori. RESULTS: 24 hr ambulatory systolic and diastolic blood pressure were elevated in OSA patients vs. control subjects (systolic: 128.9 ± 3.8 mmHg vs. 108.8 ± 1.3 mmHg, respectively; diastolic: 97.5 ± 2.0 mmHg vs. 82.1 ± 1.9 mmHg, respectively). OSA patients experienced significant elevations in systolic (OSA 209.7 ± 5.7 mmHg; Control 174.5 ± 6.2 mmHg) and mean arterial pressures (OSA 125.8 ± 3.2 mmHg; Control 109.05 ± 4.5 mmHg) at peak exercise. No differences in nitrate, nitrite, or big endothelin-1 were noted. Plasma endothelin-1 concentrations were below assay detection limit. Big endothelin-1 levels were significantly correlated with BMI in both OSA patients (r=0.955; p=0.001) and control subjects (r=0.799; p=0.045). Relative gene expression of preproendothelin-1 was not elevated in OSA patients (0.40 ± 0.20 fold increase over control subjects). Group nCPAP usage was above minimum therapeutic threshold, but was non-uniform in both groups, with an overall range of 182 to 495 min mean usage per night. A mild/moderate exercise training program failed to elicit a training response through standard hemodynamic or cardiopulmonary indices. Plasma nitrite levels rose from 55.3 ± 4.7 μg/ml to 71.0 ± 7.6 μg/ml in the nCPAP group. CONCLUSIONS: Moderate OSA is associated with elevated blood pressure at rest and during exercise stress that bears no relationship to circulating biomarkers of NO and ET-1 or immune preproendothelin production in patients without diagnosed hypertension. nCPAP therapy failed to elicit significant improvements in hemodynamic function, with or without moderate exercise. Plasma nitrite levels rose following nCPAP therapy, indicating a possible increase in basal nitric oxide formation. Higher intensity exercise regimens may be needed to elicit the positive benefits of exercise training in OSA patients without significant cardiovascular dysfunction. / Ph. D.