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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Chronic lung diseases cause serious morbidity and mortality, and effective treatments are limited. Induced pluripotent stem cells (iPSCs) lacking the reprogramming factor c-Myc (3-gene iPSCs) can be used as ideal tools for cell-based therapy because of their low level of tumorigenicity. In this study, we investigated whether 3-gene iPSC transplantation could rescue bleomycin-induced pulmonary fibrosis. ⋯ Furthermore, IP-10 neutralization via treatment with IP-10-neutralizing antibodies ameliorated the reparative effect of either 3-gene iPSCs or iPSC-CM on collagen content, neutrophil and monocyte accumulation, pulmonary fibrosis, and recipient survival. Intravenous delivery of 3-gene iPSCs/iPSC-CM alleviated the severity of histopathologic and physiologic impairment in bleomycin-induced lung fibrosis. The protective mechanism was partially mediated by the early moderation of inflammation, reduced levels of cytokines and chemokines that mediate inflammation and fibrosis, and an increased production of antifibrotic IP-10 in the injured lungs.
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Traumatic injury ranks as the number one cause of death for the younger than 44 years age group and fifth leading cause of death overall (www.nationaltraumainstitute.org/home/trauma_statistics.html). Although improved resuscitation of trauma patients has dramatically reduced immediate mortality from hemorrhagic shock, long-term morbidity and mortality continue to be unacceptably high during the postresuscitation period particularly as a result of impaired host immune responses to subsequent challenges such as surgery or infection. Acute alcohol intoxication (AAI) is a significant risk factor for traumatic injury, with intoxicating blood alcohol levels present in more than 40% of injured patients. ⋯ Thus, dissecting the dynamic imbalance produced by AAI during trauma is of critical relevance for a significant proportion of injured victims. This review outlines how AAI at the time of hemorrhagic shock not only prevents adequate responses to fluid resuscitation but also impairs the ability of the host to overcome a secondary infection. Moreover, it discusses the neuroendocrine mechanisms underlying alcohol-induced hemodynamic dysregulation and its relevance to host defense restoration of homeostasis after injury.
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The objective of this study was to analyze the association between candidate gene polymorphisms and susceptibility to acute respiratory distress syndrome (ARDS) in patients with severe sepsis. ⋯ The presence of the allele D of the ACE gene is associated with ARDS in patients with severe sepsis.
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Bronchiolitis obliterans organizing pneumonia (BOOP), a morbid condition when associated with lung transplant and chronic lung disease, is believed to be a complication of ischemia. Our goal was to develop a simple and reliable model of lung ischemia in the Sprague-Dawley rat that would produce BOOP. Unilateral ischemia without airway occlusion was produced by an occlusive slipknot placed around the left main pulmonary artery. ⋯ Toll-like receptor 4 expression was increased in ischemic left lungs over right. An occlusive slipknot around the main left pulmonary artery in rats produces BOOP, providing direct evidence that ischemia without immunomodulation or coinfection is sufficient to initiate this injury. It also affords an excellent model to study signaling and genetic mechanisms underlying BOOP.
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In animal models, administration of nitric oxide (NO) donor agents has been shown to reduce ischemia/reperfusion (I/R) injury. Our aim was to systematically analyze the biomedical literature to determine the effects of NO-donor agent administration on I/R injury in human subjects. We hypothesized that NO-donor agents reduce I/R injury. ⋯ In 20 (77%) of 26 studies and four (67%) of six high-quality studies, patients treated with NO-donor agents experienced reduced I/R injury compared with controls. Zero clinical studies to date have tested NO-donor agent administration in patients with cerebral I/R injury (e.g., cardiac arrest, stroke). Despite a paucity of high-quality clinical investigations, the preponderance of evidence to date suggests that administration of NO-donor agents may be an effective treatment for I/R injury in human subjects.