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RESUMEN Introducción: La hipertensión pulmonar (HP) abarca un grupo heterogéneo de enfermedades que genera discapacidad y aumento de la morbimortalidad. La rehabilitación cardiorrespiratoria (RC) es un recurso terapéutico subutilizado en esta condición. Objetivo: Estimar los efectos de un programa de RC en una prueba de caminata de campo y en la calidad de vida de pacientes con diagnóstico de HP de los grupos I y IV. Materiales y Métodos: Los pacientes fueron evaluados antes y después de la intervención mediante la prueba de caminata de 6 minutos (PC6M) y el Saint George's Respiratory Questionnaire (SGRQ). El programa de RC consistió en 8 semanas de ejercicios supervisados con modalidad institucional. Resultados: Se incluyeron 19 pacientes con diagnóstico de HP precapilar por cateterismo cardíaco derecho, 18 mujeres (94,7%) con una media de edad de 45,5 ± 14,3 años. Trece (68,4%) presentaron HP del grupo I, y 6 (31,6%) HP del grupo IV. Se observaron cambios estadísticamente significativos en la PC6M (diferencia de medias -DM- 31 ± 27,3 metros; p <0,001), y en el SGRQ (DM 8,2 ± 10,2; p<0,01). No se reportaron eventos adversos graves durante el programa. Conclusiones: Nuestro estudio sugiere que un programa de RC supervisado en pacientes con HP podría mejorar la distancia caminada y la calidad de vida.
ABSTRACT Background: Pulmonary hypertension (PH) comprises a heterogeneous group of diseases resulting in disability and increased morbidity and mortality. Cardiopulmonary rehabilitation (CR) is a therapeutic resource not widely used in this condition. Objective: The aim of this study was to evaluate the effects of a CR program on a walking test and on the quality of life in patients with group 1 and group 4 PH Methods: Patients were evaluated before and after the intervention with the six-minute walk test (6MWT) and Saint George's Respiratory Questionnaire (SGRQ). The program consisted of 8 weeks of supervised exercises within the institution. Results: Nineteen patients with precapillary PH diagnosed by right heart catheterization were included; 18 were women (94.7%) with a mean age of 45.5±14.3 years. Thirteen (68.4%) patients had group 1 PH and 6 (31.6%) had group 4 PH. There were statistically significant changes in the 6MWT [mean difference (MD) 31±27.3 m; p<0.001], and in the SGRQ (MD 8.2±10.2; p<0.01). No adverse events were reported during the program. Conclusions: Our study suggests that a supervised CR program in patients with PH could improve the distance walked and the quality of life.
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Isothermal Titration Calorimetry (ITC) is widely employed to assess antimicrobial affinity for lipopolysaccharide (LPS); nevertheless, experiments are usually limited to commercially available-LPS chemotypes. Herein we show a method that uses Differential Scanning Calorimetry (DSC) to characterize homogeneity artificial vesicles of LPS (LPS-V) extracted from isogenic mutant bacterial strains before analyzing the antimicrobial binding by ITC. This method allows us to characterize the differences in the Polymyxin-B binding and gel to crystalline liquid (ßâα) phase profiles of LPS-V made of LPS extracted from Escherichia coli isogenic mutant strains for the LPS biosynthesis pathway, allowing us to obtain the comparable data required for new antimicrobial discovery. A method for:â¢Obtaining LPS vesicles from isogenic mutant bacterial strains.â¢Characterize artificial LPS vesicles homogeneity.â¢Characterize antimicrobial binding to LPS.
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Phosphoethanolamine (pEtN) decoration of E. coli Lipopolysaccharide (LPS) provides resistance to the antimicrobial Polymyxin B (PolB). While EptA and EptB enzymes catalyze the addition of pEtN to the Lipid A and Kdo (pEtN-Kdo-Lipid A), EptC catalyzes the pEtN addition to the Heptose I (pEtN-HeptI). In this study, we investigated the contribution of pEtN-HeptI to PolB resistance using eptA/eptB and eptC deficient E. coli K12 and its wild-type parent strains. These mutations were shown to decrease the antimicrobial activity of PolB on cells grown under pEtN-addition inducing conditions. Furthermore, the 1-N-phenylnapthylamine uptake assay revealed that in vivo PolB has a reduced OM-permeabilizing activity on the ΔeptA/eptB strain compared with the ΔeptC strain. In vitro, the changes in size and zeta potential of LPS-vesicles indicate that pEtN-HeptI reduce the PolB binding, but in a minor extent than pEtN-Kdo-Lipid A. Molecular dynamics analysis revealed the structural basis of the PolB resistance promoted by pEtN-HeptI, which generate a new hydrogen-bonding networks and a denser inner core region. Altogether, the experimental and theoretical assays shown herein indicate that pEtN-HeptI addition promote an LPS conformational rearrangement, that could act as a shield by hindering the accession of PolB to inner LPS-targets moieties.