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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Sepsis is a serious public health issue and the leading cause of death in critically ill patients in intensive care units. Thioredoxin-1 (Trx-1) is a protein of regulating redox, as well as a modulator of inflammation and apoptosis. Our previous study reported that Trx-1 decreased endoplasmic reticulum-mediated inflammation involved in lung in a model of experimental sepsis. ⋯ However, the decreased Bcl-2 expression in sepsis was recovered in Trx-1 Tg mice. Our results suggest that overexpression of Trx-1 provides protection against sepsis through suppressing mitochondria-induced apoptosis pathway in spleen. This study may provide a new target for clinical intervention, as well potential strategies for treatment of sepsis.
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Carbon monoxide (CO) poisoning is a common cause of poison-related mortality. CO binds to hemoglobin in the blood to form carboxyhemoglobin (COHb), impairing oxygen delivery to peripheral tissues. Current treatment of CO-poisoned patients involves oxygen administration to rapidly remove CO and restore oxygen delivery. Light dissociates CO from COHb with high efficiency. Exposure of murine lungs to visible laser-generated light improved the CO elimination rate in vivo. The aims of this study were to apply pulmonary phototherapy to a larger animal model of CO poisoning, to test novel approaches to light delivery, and to examine the effect of chemiluminescence-generated light on the CO elimination rate. ⋯ Successful application of pulmonary phototherapy in larger animals and humans may represent a significant advance in the treatment of CO-poisoned patients.
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Current animal models of sepsis often incorporate antibiotics to be consistent with clinical standards for treatment of patients in the intensive care unit. However, such experimental intervention is commonly initiated very early after infectious insult, which likely blunts the progression of systemic inflammation and downstream pathology. The objective of this study was to establish an animal model of sepsis with delayed therapeutic intervention, allowing a longer disease course and downstream pathology, but still resulting in a high survival rate. ⋯ When fluid resuscitation (physiological saline, s.c.) was performed in combination with antibiotic treatment (twice daily) beginning at these late time-points, the majority of mice survived (75%) and showed bacteremia, cytokinemia, organ dysfunction, and prolonged body weight loss (<90% for 4 weeks). We recommend that this new repeated combination treatment with antibiotics and fluids resuscitation be initiated at a late time point after bacteremia becomes evident because this model more closely mimics the downstream pathological characteristics of severe clinical sepsis yet maintains a high survival rate. This model would be advantageous for studies on severe sepsis and postintensive care illness.