Lymphocytes, apoptosis and sepsis: making the jump from mice to humans

Sepsis is an important clinical problem with a mortality rate of 20% to 30%. Lymphocyte apoptosis has been recognized as an important step in the pathogenesis of experimental sepsis, by inducing a state of 'immune paralysis' that renders the host vulnerable to invading pathogens. The importance of lymphocyte apoptosis in human disease is now confirmed by Weber and colleagues, who demonstrate extensive apoptosis in circulating lymphocytes from patients with severe sepsis. Weber and colleagues' data set the basis for further studies aimed at modulating lymphocyte apoptosis in sepsis

Mechanical ventilation interacts with endotoxemia to induce extrapulmonary organ dysfunction

INTRODUCTION: Multiple organ dysfunction syndrome (MODS) is a common complication of sepsis in mechanically ventilated patients with acute respiratory distress syndrome, but the links between mechanical ventilation and MODS are unclear. Our goal was to determine whether a minimally injurious mechanical ventilation strategy synergizes with low-dose endotoxemia to induce the activation of pro-inflammatory pathways in the lungs and in the systemic circulation, resulting in distal organ dysfunction and/or injury. METHODS: We administered intraperitoneal Escherichia coli lipopolysaccharide (LPS; 1 μg/g) to C57BL/6 mice, and 14 hours later subjected the mice to 6 hours of mechanical ventilation with tidal volumes of 10 ml/kg (LPS + MV). Comparison groups received ventilation but no LPS (MV), LPS but no ventilation (LPS), or neither LPS nor ventilation (phosphate-buffered saline; PBS). RESULTS: Myeloperoxidase activity and the concentrations of the chemokines macrophage inflammatory protein-2 (MIP-2) and KC were significantly increased in the lungs of mice in the LPS + MV group, in comparison with mice in the PBS group. Interestingly, permeability changes across the alveolar epithelium and histological changes suggestive of lung injury were minimal in mice in the LPS + MV group. However, despite the minimal lung injury, the combination of mechanical ventilation and LPS resulted in chemical and histological evidence of liver and kidney injury, and this was associated with increases in the plasma concentrations of KC, MIP-2, IL-6, and TNF-α. CONCLUSION: Non-injurious mechanical ventilation strategies interact with endotoxemia in mice to enhance pro-inflammatory mechanisms in the lungs and promote extra-pulmonary end-organ injury, even in the absence of demonstrable acute lung injury

Comparison of direct and indirect models of early induced acute lung injury

The animal experimental counterpart of human acute respiratory distress syndrome (ARDS) is acute lung injury (ALI). Most models of ALI involve reproducing the clinical risk factors associated with human ARDS, such as sepsis or acid aspiration; however, none of these models fully replicates human ARDS. To compare different experimental animal models of ALI, based on direct or indirect mechanisms of lung injury, to characterize a model which more closely could reproduce the acute phase of human ARDS. Adult male Sprague-Dawley rats were subjected to intratracheal instillations of (1) HCl to mimic aspiration of gastric contents; (2) lipopolysaccharide (LPS) to mimic bacterial infection; (3) HCl followed by LPS to mimic aspiration of gastric contents with bacterial superinfection; or (4) cecal ligation and puncture (CLP) to induce peritonitis and mimic sepsis. Rats were sacrificed 24 h after instillations or 24 h after CLP. At 24 h, rats instilled with LPS or HCl-LPS had increased lung permeability, alveolar neutrophilic recruitment and inflammatory markers (GRO/KC, TNF-α, MCP-1, IL-1β, IL-6). Rats receiving only HCl or subjected to CLP had no evidence of lung injury. Rat models of ALI induced directly by LPS or HCl-LPS more closely reproduced the acute phase of human ARDS than the CLP model of indirectly induced ALI

Разработка плана по локализации и ликвидации аварии в зале нагнетателей компрессорного цеха Юргинского ЛПУМГ ООО «Газпром трансгаз Томск»»

Цель выпускной квалификационной работы: разработка порядка действий производственного персонала Юргинского ЛПУМГ в случае аварии на опасном производственном объекте по сценарию аварии "Разгерметизация технологического оборудования в компрессорном цехе с заполнением помещения природным газом и последующим взрывом". В работе выполнен обзор литературы, выполнен расчет критериев взрывопожарной и пожарной опасности в помещении зала нагнетателей компрессорного цеха, разработан порядок действий производственного персонала при аварии по данному сценарию, рассчитан полный ущерб от аварии.The purpose of the final qualification work: development of the procedure for the actions of the production personnel of the Yurginsky LPGMG in the event of an accident at a hazardous production facility under the accident scenario "Depressurization of the process equipment in the compressor shop with the filling of the room with natural gas and subsequent explosion". The work reviews the literature, calculates the fire and explosion hazard criteria in the room of the compressor room of the compressor room, developed the procedure for operating personnel in the event of an accident in this scenario, and calculates the total damage from the accident

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality