Evaluación de la función respiratoria en pacientes con patologías neuromusculares / Evaluation of Respiratory Function in Patients with Neuromuscular Diseases

Introducción: La Enfermedades Neuromusculares se caracterizan por la pérdida progresiva de la fuerza muscular, la morbi-mortalidad aumenta con la exageración de la debilidad muscular determinando mayor riesgo de complicaciones respiratorias. Es de suma importancia evaluar e interpretar adecuadamente la función pulmonar y ventilatoria para poder realizar intervenciones que pueda prevenir dichas complicaciones. Objetivos: El objetivo del estudio fue reportar el estado funcional respiratorio de un grupo de pacientes con ENM en control ambulatorio y relacionar estos hallazgos con umbrales clínicamente relevantes de complicaciones respiratorias, reforzando intervenciones basadas en opiniones de expertos. Materiales y métodos: Se realizó un estudio Descriptivo-Observacional de corte transversal, donde fueron evaluados en forma ambulatoria, de marzo del 2017 a agosto del 2018, 30 niños y adolescentes con enfermedades neuromusculares. Resultados: El 46% del total de pacientes presenta capacidad tusígena no funcional con alto riesgo de complicaciones. No obstante, sólo el 10% del total de pacientes fueron aptos para realizar adecuadamente estudios de espirometría. Durante las pruebas espirométricas, sólo el 50% de los pacientes logró mantener 6 segundos la espiración. Conclusión: Si bien la espirometría es la principal prueba de función pulmonar y una alta proporción de pacientes presentó alteraciones en su morfología, su realización en estados avanzados de enfermedad fue poco factible. Para detectar umbrales de complicaciones respiratorias graves, la medición del flujo generado durante la tos resultó mejor. Conclusión: Si bien la espirometría es la principal prueba de función pulmonar y una alta proporción de pacientes presentó alteraciones en su morfología, su realización en estados avanzados de enfermedad fue poco factible. Para detectar umbrales de complicaciones respiratorias graves, la medición del flujo generado durante la tos resultó mejor.

Introduction: Neuromuscular Diseases are characterized by the progressive loss of muscle mass, morbidity and mortality increases with the progress of muscle weakness due to the increased risk of respiratory complications, so it is very important to properly evaluate and interpret the measurements of lung functions and ventilation to be able to carry out a specific treatment that can reduce respiratory complications. Objectives: The purpose of this work is to present the results of the measurements of flows, volumes, respiratory capacities and spirometric patterns in outpatients with neuromuscular diseases and to verify their usefulness to detect vital risks. Materials and methods: A cross-sectional Descriptive-Observational study was carried out, where 30 children and adolescents with neuromuscular diseases were evaluated on an outpatient basis, from March 2017 to August 2018. Results: 46% of all patients presented a non-functional cough with a high risk of complications and only 10% of all patients were eligible for spirometry studies. During the spirometric tests, 50% of the patients managed to maintain expiration for 6 seconds. In 70% of the patients, abnormalities in the Flow-Volume curve could be detected. Conclusion: Although spirometry is the main pulmonary function test, its usefulness and efficacy in neuromuscular diseases depends on the findings of specific alterations in the morphology of the flow-volume curve, which in many cases are not possible to distinguish.

Shiga toxin glycosphingolipid receptors in microvascular and macrovascular endothelial cells: differential association with membrane lipid raft microdomains.

Vascular damage caused by Shiga toxin (Stx)-producing Escherichia coli is largely mediated by Stxs, which in particular, injure microvascular endothelial cells in the kidneys and brain. The majority of Stxs preferentially bind to the glycosphingolipid (GSL) globotriaosylceramide (Gb3Cer) and, to a lesser extent, to globotetraosylceramide (Gb4Cer). As clustering of receptor GSLs in lipid rafts is a functional requirement for Stxs, we analyzed the distribution of Gb3Cer and Gb4Cer to membrane microdomains of human brain microvascular endothelial cells (HBMECs) and macrovascular EA.hy 926 endothelial cells by means of anti-Gb3Cer and anti-Gb4Cer antibodies. TLC immunostaining coupled with infrared matrix-assisted laser desorption/ionization (IR-MALDI) mass spectrometry revealed structural details of various lipoforms of Stx receptors and demonstrated their major distribution in detergent-resistant membranes (DRMs) compared with nonDRM fractions of HBMECs and EA.hy 926 cells. A significant preferential partition of different receptor lipoforms carrying C24:0/C24:1 or C16:0 fatty acid and sphingosine to DRMs was not detected in either cell type. Methyl-ß-cyclodextrin (MßCD)-mediated cholesterol depletion resulted in only partial destruction of lipid rafts, accompanied by minor loss of GSLs in HBMECs. In contrast, almost entire disintegration of lipid rafts accompanied by roughly complete loss of GSLs was detected in EA.hy 926 cells after removal of cholesterol, indicating more stable microdomains in HBMECs. Our findings provide first evidence for differently stable microdomains in human endothelial cells from different vascular beds and should serve as the basis for further exploring the functional role of lipid raft-associated Stx receptors in different cell types.

Vibration effects of lab equipment on dissolution testing with USP paddle method.

Environmental vibration induced by laboratory equipment, building construction, or even by the analysts themselves is one of the more complicated factors affecting dissolution testing. It is difficult to control and/or calibrate by mechanical means or performance-based methods. In this study, dissolution apparatus vibration levels were measured in the frequency range from 10 to 270 Hz along all three axes using commercially available, single-axis accelerometers. The vibration distribution on the dissolution vessel plate was mapped, and acceleration was subsequently measured during dissolution runs involving NCDA#2 (10 mg prednisone) tablets using the paddle method. Several types of laboratory equipment were used to induce vibration during dissolution testing and vibration levels along the X-, Y-, and Z-axes of the vessel plate were measured in an attempt to establish possible correlation with dissolution results. In the frequency range studied, root mean square (RMS) acceleration values above 0.01 g, in either vertical or horizontal direction, typically affected dissolution results.