Cromakalim (BRL 34915) restores in vitro the membrane potential of depolarized human skeletal muscle fibres

The purpose of the present study was to analyze the effects of cromakalim (BRL 34915), a potent drug from a new class of drugs characterized as K+ channel openers, on the electrical activity of human skeletal muscle. Therefore, intracellular recordings were used to measure the effects of cromakalim on the membrane potential and input conductance of fibres from human skeletal muscle biopsies. Cromakalim in a concentration above 1 mol/l induced an increase in membrane K+ conductance. This effect resulted in a membrane hyperpolarization. The magnitude of this polarization depended on the difference between resting and K+ equilibrium potential. The effect had a rapid onset and was quickly reversible after washing. Fibres from two patients with hyperkalaemic periodic paralysis showed an excessive membrane depolarization during and also after exposure to an slightly elevated extracellular K+ concentration. In the latter situation, cromakalim repolarized the fibres to the normal resting potential. Tolbutamide (1 mmol/l) and Ba2+ (3 mmol/l) strongly antagonized the effect of cromakalim. The data show that cromakalim hyperpolarizes depolarized human skeletal muscle fibres maintained in vitro. The underlying mechanism is probably an activation of otherwise silent, ATP-regulated K+ channels. Such an effect may be of therapeutic benefit in a situation in which a membrane depolarization causes muscle paralysis

Nerve damage induced skeletal muscle atrophy is associated with increased accumulation of intramuscular glucose and polyol pathway intermediates

Perturbations in skeletal muscle metabolism have been reported for a variety of neuromuscular diseases. However, the role of metabolism after constriction injury to a nerve and the associated muscle atrophy is unclear. We have analyzed rat tibialis anterior (TA) four weeks after unilateral constriction injury to the sciatic nerve (DMG) and in the contralateral control leg (CTRL) (n = 7) to investigate changes of the metabolome, immunohistochemistry and protein levels. Untargeted metabolomics identified 79 polar metabolites, 27 of which were significantly altered in DMG compared to CTRL. Glucose concentrations were increased 2.6-fold in DMG, while glucose 6-phosphate (G6-P) was unchanged. Intermediates of the polyol pathway were increased in DMG, particularly fructose (1.7-fold). GLUT4 localization was scattered as opposed to clearly at the sarcolemma. Despite the altered localization, we found GLUT4 protein levels to be increased 7.8-fold while GLUT1 was decreased 1.7-fold in nerve damaged TA. PFK1 and GS levels were both decreased 2.1-fold, indicating an inability of glycolysis and glycogen synthesis to process glucose at sufficient rates. In conclusion, chronic nerve constriction causes increased GLUT4 levels in conjunction with decreased glycolytic activity and glycogen storage in skeletal muscle, resulting in accumulation of intramuscular glucose and polyol pathway intermediates

Adenosine, ‘pertussis-sensitive’ G-proteins, and K+ conductance in central mammalian neurones under energy deprivation

There is a striking similarity between the effects of adenosine and of hypoxia or glucose depletion on membrane potential and conductance of hippocampal neurones in tissue slices of rat brain. Both induce a membrane hyperpolarization by an increase in potassium conductance. It seemed likely, therefore, that a rise in extracellular adenosine concentration during energy deprivation may link neuronal metabolism with membrane K+ conductance. To test this hypothesis, we have now investigated the effects of hypoxia/glucose deprivation on hippocampal neurones from pertussis toxin-treated rats. In such slices adenosine had no effect on postsynaptic membrane potential and input resistance. Nevertheless, hypoxia or glucose depletion were as effective as in controls. These data provide evidence against adenosine as the main mediator between cell metabolism and potassium conductance

A Micropulse eye-safe all-fiber molecular backscatter coherent temperature lidar

In this paper, we analyze the performance of an all-fiber, micropulse, 1.5 μm coherent lidar for remote sensing of atmospheric temperature. The proposed system benefits from the recent advances in optics/electronics technology, especially an all-fiber image-reject homodyne receiver, where a high resolution spectrum in the baseband can be acquired. Due to the presence of a structured spectra resulting from the spontaneous Rayleigh-Brillouine scattering, associated with the relevant operating regimes, an accurate estimation of the temperature can be carried out. One of the main advantages of this system is the removal of the contaminating Mie backscatter signal by electronic filters at the baseband (before signal conditioning and amplification). The paper presents the basic concepts as well as a Monte-Carlo system simulation as the proof of concept

Enhancement of K+ conductance improves in vitro the contraction force of skeletal muscle in hypokalemic periodic paralysis

An abnormal ratio between Na+ and K+ conductances seems to be the cause for the depolarization and paralysis of skeletal muscle in primary hypokalemic periodic paralysis. Recently we have shown that the k+ channel opener cromakalim hyperpolarizes mammalian skeletal muscle fibers. Now we have studied the effects of this drug on the twitch force of muscle biopsies from normal and diseased human skeletal muscle. Cromakalim had little effect on the twitch force of normal muscle whereas it strongly improved the contraction force of fibers from patients suffering from hypokalemic periodic paralysis. Recordings of intracellular K+ and Cl- activities in human muscle and isolated rat soleus muscle support the view that cromakalim enhances the membrane K+ conductance (gK+). These data indicate that K+ channel openers may have a beneficial effect in primary hypokalemic periodic paralysis

Psychometric properties of the questionnaire for needs of family members of patients hospitalized in critical units, abbreviated version

Indexación: Scopus; Scielo.El ingreso de una persona a una Unidad de Paciente Crítico genera efectos en su círculo familiar más cercano, siendo el acceso a la información y trato empático algunas de las necesidades de los familiares de los pacientes hospitalizados. El Critical Care Family Needs Inventory (CCFNI), versión breve, permite evaluar la satisfacción de necesidades de los familiares de pacientes hospitalizados en estas unidades y se considera una herramienta útil para obtener una visión de este grupo. Objetivo: Describir la adaptación cultural y evaluar las propiedades psicométricas del CCFNI, versión breve, en familiares de pacientes hospitalizados en Unidades de Cuidados Intensivos del Hospital Dr. Hernán Henríquez Aravena, Temuco, Chile. Material y método: Diseño de corte transversal. Se realizó la adaptación cultural del instrumento y luego se aplicó a 77 familiares, posterior a la firma del consentimiento informado. Se determinó validez de constructo y confiabilidad del instrumento. Resultados: Fueron excluidos los ítems 11 y 14. El análisis factorial exploratorio evidenció cuatro componentes cuyos alfa de Cronbach fueron 0,7; 0,7; 0,6 y 0,3. Conclusión: La traducción y adaptación realizada debe continuar su estudio psicométrico incorporando un número mayor de familiares de pacientes hospitalizados para confirmar la ex clusión de los ítems y comprobar su estructura multidimensional. Este instrumento constituye una herramienta para valorar las necesidades de familiares de pacientes hospitalizados en Unidades Críticas.The admission of a patient to the Intensive Care Unit has an effect on its inner family circle, the access to information and an empathic treatment being some of the needs of the relatives of the patient in this unit. The short version of the Critical Care Family Needs Inventory (CCFNI) allows to evaluate the satisfaction of those needs by the relatives of the patients in this units and it is considered a useful tool to obtain an overview of this group. Objective: To describe the cultural adaptations and to evaluate the psychometric properties of the short version of the CCFNI in hospitalized patients' relatives in Dr. Hernán Henríquez Aravena's Hospital, Temuco, Chile. Method: This research uses a cross-sectional survey design. The tool was first culturally adapted and then applied to 77 relatives during the time span of five months, after a written consent was provided. Validity of the construct and reliability of the tool are determined. Results: Items 11 and 14 were excluded. The exploratory factorial analysis showed four components whose Alphas of Cronbach were 0.7; 0.7; 0.6 and 0.3. Conclusion: The translation and adapted version applied must continue its psychometric study incorporating a bigger number of relatives of hospitalized patients to confirm the exclusion of items and to check its multidimensional structure. This instrument is a tool to value the needs of relatives of patients hospitalized in Critical Units.https://scielo.conicyt.cl/scielo.php?script=sci_arttext&pid=S0717-95532017000300077&lng=en&nrm=iso&tlng=e

Statin-induced myopathic changes in primary human muscle cells and reversal by a prostaglandin F2 alpha analogue

Statin-related muscle side effects are a constant healthcare problem since patient compliance is dependent on side effects. Statins reduce plasma cholesterol levels and can prevent secondary cardiovascular diseases. Although statin-induced muscle damage has been studied, preventive or curative therapies are yet to be reported. We exposed primary human muscle cell populations (n = 22) to a lipophilic (simvastatin) and a hydrophilic (rosuvastatin) statin and analyzed their expressome. Data and pathway analyses included GOrilla, Reactome and DAVID. We measured mevalonate intracellularly and analyzed eicosanoid profiles secreted by human muscle cells. Functional assays included proliferation and differentiation quantification. More than 1800 transcripts and 900 proteins were differentially expressed after exposure to statins. Simvastatin had a stronger effect on the expressome than rosuvastatin, but both statins influenced cholesterol biosynthesis, fatty acid metabolism, eicosanoid synthesis, proliferation, and differentiation of human muscle cells. Cultured human muscle cells secreted ω-3 and ω-6 derived eicosanoids and prostaglandins. The ω-6 derived metabolites were found at higher levels secreted from simvastatin-treated primary human muscle cells. Eicosanoids rescued muscle cell differentiation. Our data suggest a new aspect on the role of skeletal muscle in cholesterol metabolism. For clinical practice, the addition of omega-n fatty acids might be suitable to prevent or treat statin-myopathy

Developments in Australian Buddhism: facets of the diamond

This book examines the adaptation of Buddhism to the Australian socio-cultural context, within the broader context of Buddhism's development in Westernized countries. The book also examines the methodological approaches currently used for studying this process and suggests a synthesis of the approaches used for studying convert and ethnic Buddhist groups. Spuler begins with an example of how Buddhism has adapted to the Australian context, illustrating both seemingly logical adaptations and incongruities. The process that has given rise to this hybridised tradition is examined, and the book provides a history of Buddhism's development. It then focuses on data gathered during field work, on the adaptation of Diamond Sangha Zen Buddhist groups in Australia, and compares this with other Western Buddhist groups, using existing models of cross-cultural acculturation. This book is timely as it provides a much-needed update on Buddhism in Australia. This information is vital for international comparative studies with Buddhism in other countries. It also includes previously unpublished information about the Diamond Sangha Zen Buddhist organisation, one of the largest Zen lineages in the West. Its founding teacher, Robert Aitken, is often cited as a key figure in the history of Western Zen. This book will be of interest to Buddhist practitioners and students and scholars of Buddhist studies, as well as anyone interested in processes of acculturation