ER-dependent membrane repair of mycobacteria-induced vacuole damage.

IMPORTANCE: Tuberculosis still remains a global burden and is one of the top infectious diseases from a single pathogen. Mycobacterium tuberculosis, the causative agent, has perfected many ways to replicate and persist within its host. While mycobacteria induce vacuole damage to evade the toxic environment and eventually escape into the cytosol, the host recruits repair machineries to restore the MCV membrane. However, how lipids are delivered for membrane repair is poorly understood. Using advanced fluorescence imaging and volumetric correlative approaches, we demonstrate that this involves the recruitment of the endoplasmic reticulum (ER)-Golgi lipid transfer protein OSBP8 in the Dictyostelium discoideum/Mycobacterium marinum system. Strikingly, depletion of OSBP8 affects lysosomal function accelerating mycobacterial growth. This indicates that an ER-dependent repair pathway constitutes a host defense mechanism against intracellular pathogens such as M. tuberculosis.

Quantitative Spatio-temporal Analysis of Phagosome Maturation in Live Cells.

Phagocytosis and phagosome maturation are central processes to the development of the innate and adaptive immune response. Phagosome maturation is a continuous and dynamic process that occurs rapidly. In this chapter we describe fluorescence-based live cell imaging methods for the quantitative and temporal analysis of phagosome maturation of beads and M. tuberculosis as two phagocytic targets. We also describe simple protocols for monitoring phagosome maturation: the use of the acidotropic probe LysoTracker and analyzing the recruitment of EGFP-tagged host proteins by phagosomes.

ILC1 drive intestinal epithelial and matrix remodelling.

Organoids can shed light on the dynamic interplay between complex tissues and rare cell types within a controlled microenvironment. Here, we develop gut organoid cocultures with type-1 innate lymphoid cells (ILC1) to dissect the impact of their accumulation in inflamed intestines. We demonstrate that murine and human ILC1 secrete transforming growth factor ß1, driving expansion of CD44v6+ epithelial crypts. ILC1 additionally express MMP9 and drive gene signatures indicative of extracellular matrix remodelling. We therefore encapsulated human epithelial-mesenchymal intestinal organoids in MMP-sensitive, synthetic hydrogels designed to form efficient networks at low polymer concentrations. Harnessing this defined system, we demonstrate that ILC1 drive matrix softening and stiffening, which we suggest occurs through balanced matrix degradation and deposition. Our platform enabled us to elucidate previously undescribed interactions between ILC1 and their microenvironment, which suggest that they may exacerbate fibrosis and tumour growth when enriched in inflamed patient tissues.

[Extrapyramidal adverse reactions to metoclopramide. A pharmacovigilance survey]. / Farmacovigilancia activa de metoclopramida 10 mg oral en pacientes del Programa de Alivio del Dolor y Cuidados Paliativos o diabetes mellitus tipo 2 en cinco hospitales del Servicio de Salud Viña del Mar-Quillota.

BACKGROUND: In 2013 the Chilean regulatory sanitary agency issued a warning concerning dose adjustment and use restriction to avoid severe adverse effects of metoclopramide such tardive dyskinesia. AIM: To study dyskinesia type adverse effects in a population using metoclopramide. MATERIAL AND METHODS: A cross sectional observational study was conducted among patients pertaining to palliative care and diabetes mellitus programs and consuming 10 mg/day or more of metoclopramide. Patients were interrogated looking for extrapiramidal signs and symptoms using a questionnaire validated by two neurologists. RESULTS: In 40% of diabetic patients with gastroparesia and 35% of palliative care patients, extrapyramidal adverse reactions to metoclopramide were suspected. Palliative Care patients suffered the largest number of adverse events. The period of use and individual doses of the drug were largely above Chilean regulatory agency recommendations in all cases. CONCLUSIONS: A significant number of patients using metoclopramide could experience extrapyramidal adverse reactions.

Farmacovigilancia activa de metoclopramida 10 mg oral en pacientes del Programa de Alivio del Dolor y Cuidados Paliativos o diabetes mellitus tipo 2 en cinco hospitales del Servicio de Salud Viña del Mar-Quillota / Extrapyramidal adverse reactions to metoclopramide: a pharmacovigilance survey

Background: In 2013 the Chilean regulatory sanitary agency issued a warning concerning dose adjustment and use restriction to avoid severe adverse effects of metoclopramide such tardive dyskinesia. Aim: To study dyskinesia type adverse effects in a population using metoclopramide. Material and Methods: A cross sectional observational study was conducted among patients pertaining to palliative care and diabetes mellitus programs and consuming 10 mg/day or more of metoclopramide. Patients were interrogated looking for extrapiramidal signs and symptoms using a questionnaire validated by two neurologists. Results: In 40% of diabetic patients with gastroparesia and 35% of palliative care patients, extrapyramidal adverse reactions to metoclopramide were suspected. Palliative Care patients suffered the largest number of adverse events. The period of use and individual doses of the drug were largely above Chilean regulatory agency recommendations in all cases. Conclusions: A significant number of patients using metoclopramide could experience extrapyramidal adverse reactions.

Anestesia para el trasplante renal: revision / Anesthesia for renal transplant: revision

Se analizan en forma retrospectiva las historias clinicas y los registros de anestesia para realizar 40 trasplantes renales entre Abril de 1985 y Abril de 1989. Los pacientes estaban sometidos a hemodialisis periodica, representativos de una fase final de falla renal cronica con un alto indice de alteraciones cardiovasculares y bioquimico, seleccionado para trasplante renal intrafamiliar y de cadaver, segun protocolo por su compabilidad inmunologica, edad, estado clinico, consentimiento familiar y condiciones anatomo-quirurgicos de donantes y receptores. La mayoria recibio anestesia general con barbiturico intravenoso, relajante muscular, agentes inhalatorios con suplemento narcotico, otros en menor numero, anestesia raquidea o peridural y en pequena proporcion una combinacion de las tecnicas. No ocurrieron decesos intraoperatorios, una muerte postoperatoria en recuperar se atribuyo a diuresis excesiva y profunda hipokalemia; no se presentaron complicaciones cardiovasculares y respiratorias inmediatas. Un pequeno numero de pacientes requirio nuevos procesos anestesicos inmediatos y taridos por sospecha de rechazo agudo compresion o torsion venosa y arterial, obstruccion ureteral, coagulos sanguineos vesicales o fistulas del trayecto uretero-vesical. A dos enfermos se les retiro tardiamente el injerto trasplantado