Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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Patients with cancer who develop sepsis have a markedly higher mortality than patients who were healthy prior to the onset of sepsis. Potential mechanisms underlying this difference have previously been examined in two preclinical models of cancer followed by sepsis. Both pancreatic cancer/pneumonia and lung cancer/cecal ligation and puncture (CLP) increase murine mortality, associated with alterations in lymphocyte apoptosis and intestinal integrity. ⋯ Cancer septic mice thus have consistently reduced survival compared with previously healthy septic mice, independent of the cancer or sepsis model utilized. Changes in lymphocyte apoptosis are common to cancer model and independent of sepsis model, whereas gut apoptosis is common to sepsis model and independent of cancer model. The host response to the combination of cancer and sepsis is dependent, at least in part, on both chronic comorbidity and acute illness.
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Bacterial pneumonia is one of the most common diagnoses and a leading cause of death in the intensive care unit. NR4A1 is an early response gene that has been identified as a vital regulator of immune and inflammatory responses. This study aims to explore the role of NR4A1 in Escherichia coli (E. coli) pneumonia. ⋯ These data demonstrate that NR4A1 impairs the phagocytic capacity of AMs and disrupts the host defense against invading bacteria, worsening the outcome of E. coli pneumonia in mice.
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Hypoxemia and tissue ischemia during hemorrhage as well as formation of oxygen and nitrogen radicals during resuscitation promote hyperinflammation and, consequently, trigger severe multi-organ failure (MOF). Individuals diagnosed with stress-related disorders or reporting a life history of psychosocial stress are characterized by chronic low-grade inflammation and a reduced glucocorticoid (GC) signaling. We hypothesized that exposure to chronic psychosocial stress during adulthood prior to hemorrhagic shock increases oxidative/nitrosative stress and therefore the risk of developing MOF in mice. ⋯ Chronic psychosocial stress during adulthood is not sufficient to promote hemodynamic complications, organ dysfunction, metabolic disturbances and did not increase the risk of MOF after subsequent hemorrhage and resuscitation. Intravenous norepinephrine to keep target hemodynamics might have led to a certain level of oxidative stress in both groups and, therefore, disguised potential effects of chronic psychosocial stress on organ function after hemorrhagic shock in the present murine trauma model.
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Heat stroke, the most serious type of heat illness, refers to the presence of hyperthermia (core temperature >40°C), accompanied by central nervous system dysfunction. The hippocampus is a particularly vulnerable region in the early stage of heat stroke. Increasing evidence suggests that dysregulation of brain iron metabolism is involved in many neurodegenerative diseases. ⋯ Our data thereby indicate that heat stroke can decrease learning ability and memory in rats. The mechanism may be related to changes of iron levels, as well as Fpn1 and hepcidin expression, in the hippocampus. Furthermore, hepcidin may rapidly decrease cellular Fpn1 protein levels, even under conditions of iron loading, indicating that hepcidin is a more dominant regulator of Fpn1 than is iron.