Kinetics and protective role of autophagy in a mouse cecal ligation and puncture-induced sepsis

INTRODUCTION: It is not well understood whether the process of autophagy is accelerated or blocked in sepsis, and whether it is beneficial or harmful to the immune defense mechanism over a time course during sepsis. Our aim was to determine both the kinetics and the role of autophagy in sepsis. METHODS: We examined autophagosome and autolysosome formation in a cecal ligation and puncture (CLP) mouse model of sepsis (in C57BL/6N mice and GFP-LC3 transgenic mice), using western blotting, immunofluorescence, and electron microscopy. We also investigated the effect of chloroquine inhibition of autophagy on these processes. RESULTS: Autophagy, as demonstrated by increased LC3-II/LC3-I ratios, is induced in the liver, heart, and spleen over 24 h after CLP. In the liver, autophagosome formation peaks at 6 h and declines by 24 h. Immunofluorescent localization of GFP-LC3 dots (alone and with lysosome-associated membrane protein type 1 (LAMP1)), as well as electron microscopic examination, demonstrate that both autophagosomes and autolysosomes are increased after CLP, suggesting that intact autophagy mechanisms operate in the liver in this model. Furthermore, inhibition of autophagy process by chloroquine administration immediately after CLP resulted in elevated serum transaminase levels and a significant increase in mortality. CONCLUSIONS: All autophagy-related processes are properly activated in the liver in a mouse model of sepsis; autophagy appears to play a protective role in septic animals

プレホスピタル ノ ゲンバ ニオケル ガイショウ ショリョウ

From our experience of emergency cases, the careful prehospital care and treatment are critical factors in good recovery. Diagnosis of the blunt injury, triage, initial therapy and the decision of the adequate institusion are principal for paramedics. We participated in the trauma seminar for japanese paramedics. In the seminar, we learned the method of the primary care for traumatic patient modified from BTLS (Basic trauma life support), which is called PTCJ ( Prehospital Trauma Care Japan). Recently, we used the long-board to secure the neck and the back of the injured-patient. It is helpful for safe transportation because we can prevent the aggravation of spinal injury by keeping the patient’s neck straight. We applied the PTCJ in 3 cases, and the outcomes were satisfactory. We regard the PTCJ should be applied more widely

Retinoic acid embryopathy: report of two cases associated with the use of isotretinoin

The authors report two cases associated with the use of isotretinoin before or during the gestational period, with its characteristic aspects and variations, of one male and one female child. This report aims at raising the awareness of medical professionals about the possible risk of isotretinoin administration to fertile-aged women considering the severity of malformations in the different systems of the human body.Os autores apresentam dois casos associados ao uso da isotretinoína antes ou durante o período gestacional, com seus aspectos característicos e variações, sendo uma criança do sexo feminino e outra do sexo masculino. Descritos para divulgação no meio médico das possíveis complicações do uso da isotretinoína nas mulheres em idade fértil levando em conta a gravidade das malformações nos diferentes sistemas do corpo humano

Dynamin 1 is important for microtubule organization and stabilization in glomerular podocytes

Dynamin 1 is a neuronal endocytic protein that participates in vesicle formation by scission of invaginated membranes. Dynamin 1 is also expressed in the kidney; however, its physiological significance to this organ remains unknown. Here, we show that dynamin 1 is crucial for microtubule organization and stabilization in glomerular podocytes. By immunofluorescence and immunoelectron microscopy, dynamin 1 was concentrated at microtubules at primary processes in rat podocytes. By immunofluorescence of differentiated mouse podocytes (MPCs), dynamin 1 was often colocalized with microtubule bundles, which radially arranged toward periphery of expanded podocyte. In dynamin 1-depleted MPCs by RNAi, alpha-tubulin showed a dispersed linear filament-like localization, and microtubule bundles were rarely observed. Furthermore, dynamin 1 depletion resulted in the formation of discontinuous, short acetylated alpha-tubulin fragments, and the decrease of microtubule-rich protrusions. Dynamins 1 and 2 double-knockout podocytes showed dispersed acetylated alpha-tubulin and rare protrusions. In vitro, dynamin 1 polymerized around microtubules and cross-linked them into bundles, and increased their resistance to the disassembly-inducing reagents Ca(2+)and podophyllotoxin. In addition, overexpression and depletion of dynamin 1 in MPCs increased and decreased the nocodazole resistance of microtubules, respectively. These results suggest that dynamin 1 supports the microtubule bundle formation and participates in the stabilization of microtubules

Paracoccidioidomicose – acometimento encefálico e medular: relato de caso

The paracoccidioidomycosis (PCM) is a systemic granulomatous mycosis, with Brazil being responsible for 80% of the cases reported in the world. Even in endemic zones its incidence is low (3-4 new cases/million up to 1-3 new cases/100 thousand inhabitants per year). We will report the case of a 54 year old woman, from the rural area in the North region of the state of Goiás, Central area of Brazil. During investigation for the medullar compressive syndro-me, a tumor lesion at the thoracic level was identified, submitted to resection, and diagnostically confirmed as neuroparacoccidioi-domycosis in the anatomical pathology analysis. She was admitted for rehabilitation with the diagnosis of T9 Asia B Paraplegia. During her stay, exams were performed (computerized tomography (CT) of the brain and thorax) to investigate the state of other organs. A thorax CT showed an aspect suggesting PCM with micronodules with center-lobular location and some opaqueness in “tree-in-bud” formation with moderate distortion of the pulmonary architecture, in addition to spots of attenuation in “opaque glass” appearance with non-homogeneous distribution. A cranial CT also suggested PCM in an active phase: nodular areas in nuclear-capsule to the left and corresponding thalamus, with reactional edema and important peripheral emphasis. This disease is a public health problem in Brazil due to is incapacitating potential. It is difficult to diagnose, especially when it attacks the CNS, since this is an uncommon manifestation (pulmonary symptoms are most commonly found).A paracoccidioidomicose (PCM) é uma micose sistêmica, tipo granulomatosa, sendo o Brasil responsável por 80% dos casos relatados no mundo. Mesmo em zonas endêmicas, sua incidência é baixa (3-4 novos casos/milhão até 1-3 novos casos/100mil habitantes ao ano). Relatamos um caso do sexo feminino, 54 anos, procedente do meio rural, região norte do estado de Goiás, centrooeste do Brasil. Durante investigação para síndrome compressiva medular foi identificada lesão tumoral em nível torácico, submetida à ressecção e firmado o diagnóstico de neuroparacoccidioidomicose no anatomopatológico. Foi admitida para reabilitação com diagnóstico de Paraplegia T9 Asia B. Durante a internação foram realizados exames (tomografia computadorizada (TC) de crânio e tórax) para investigação de acometimento de outros órgãos. A TC de tórax demonstrou aspecto sugestivo de PCM com micronódulos de localização centro-lobular e algumas opacidades em “árvore em brotamento” com discreta distorção da arquitetura pulmonar, além de focos de atenuação em “vidro fosco” de distribuição não homogênea. A TC crânio também se mostrou sugestiva de acometimento da PCM em fase ativa: áreas nodulares em cápsulonuclear à esquerda e tálamo correspondente, com edema reacional e importante realce periférico. A doença é um problema de saúde pública no Brasil devido ao seu potencial incapacitante, sendo o diagnóstico difícil especialmente quando acomete SNC, por ser uma manifestação pouco comum (maior acometimento pulmonar)

On the origin and evolution of the asteroid Ryugu: A comprehensive geochemical perspective

Presented here are the observations and interpretations from a comprehensive analysis of 16 representative particles returned from the C-type asteroid Ryugu by the Hayabusa2 mission. On average Ryugu particles consist of 50% phyllosilicate matrix, 41% porosity and 9% minor phases, including organic matter. The abundances of 70 elements from the particles are in close agreement with those of CI chondrites. Bulk Ryugu particles show higher δ18O, Δ17O, and ε54Cr values than CI chondrites. As such, Ryugu sampled the most primitive and least-thermally processed protosolar nebula reservoirs. Such a finding is consistent with multi-scale H-C-N isotopic compositions that are compatible with an origin for Ryugu organic matter within both the protosolar nebula and the interstellar medium. The analytical data obtained here, suggests that complex soluble organic matter formed during aqueous alteration on the Ryugu progenitor planetesimal (several 10’s of km), <2.6 Myr after CAI formation. Subsequently, the Ryugu progenitor planetesimal was fragmented and evolved into the current asteroid Ryugu through sublimation

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe