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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We hypothesize that the nebulization of γ-tocopherol (g-T) in the airway of our ovine model of acute respiratory distress syndrome will effectively improve pulmonary function following burn and smoke inhalation after 96 h. Adult ewes (n = 14) were subjected to 40% total body surface area burn and were insufflated with 48 breaths of cotton smoke under deep anesthesia, in a double-blind comparative study. A customized aerosolization device continuously delivered g-T in ethanol with each breath from 3 to 48 h after the injury (g-T group, n = 6), whereas the control group (n = 5) was nebulized with only ethanol. ⋯ The following clinical parameters were improved with g-T treatment: pulmonary shunt fraction, peak and pause pressures, lung bloodless wet-to-dry weight ratios (2.9 ± 0.87 vs. 4.6 ± 1.4, P < 0.05), and bronchiolar obstruction (2.0% ± 1.1% vs. 4.6% ± 1.7%, P < 0.05). Nebulization of g-T, carried by ethanol, improved pulmonary oxygenation and markedly reduced the time necessary for assisted ventilation in burn- and smoke-injured sheep. Delivery of g-T into the lungs may be a safe, novel, and efficient approach for management of acute lung injury patients who have sustained oxidative damage to the airway.
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Expression of inflammatory cytokines is regulated by transcriptional and posttranscriptional mechanisms. We previously showed that NADPH oxidase-derived superoxide induces inflammatory mediators in response to tumor necrosis factor α (TNF-α) and lipopolysaccharide (LPS). In this study, we examined the role of endothelial NADPH oxidase in the regulation of mRNA stability of three inflammatory mediators: interleukin (IL) 8, IL-6, and intercellular adhesion molecule 1 (ICAM-1). ⋯ In conclusion, NADPH oxidase contributes to destabilization of IL-8 mRNA stability and propose a model for the complex underlying mechanism, which is dependent upon agonist (LPS vs. TNF-α) and target molecule (IL-8 vs. IL-6 and ICAM-1) and involves tristetraprolin, p38, and extracellular signal-regulated kinase 1/2 MAPK.
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Experimental pharmacotherapies for the acute respiratory distress syndrome (ARDS) have not met with success in the clinical realm. We hypothesized that chemically modified tetracycline 3 (CMT-3), an anti-inflammatory agent that blocks multiple proteases and cytokines, would prevent ARDS and injury in other organs in a clinically applicable, porcine model of inflammation-induced lung injury. Pigs (n = 15) were anesthetized and instrumented for monitoring. ⋯ It significantly lowered plasma concentrations of interleukin 1β (IL-1β), tumor necrosis factor α, IL-6, IL-8, and IL-10. This study presents a clinically relevant model of lung injury in which CMT-3 treatment prevented the development of ARDS due in part to reduction of multiple plasma cytokines. Treatment of sepsis patients with CMT-3 could significantly reduce progression from sepsis into ARDS.
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The influence of estrogen signaling on infectious diseases is not fully known. Males seem to be more susceptible to infections than females. This has also been noted for the Scandinavian form of hemorrhagic fever with renal syndrome caused by Puumala hantavirus (PUUV). ⋯ None or very small amounts of ERβ were detected, and ERα and ERβ2 mRNA were elevated in the patient group. The samples from the males were correlated with ERβ2; the female samples, with ERα. Furthermore, the female and male samples are partly separated using multivariate statistic analysis (principal component analysis), supporting findings that clinical symptoms differ depending on sex.
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Myeloid differentiation 2 (MD-2) plays a critical role in orchestrating the innate immune response and the development of sepsis and subsequent organ dysfunction after trauma. The objectives of this prospective study were to identify haplotype tag single-nucleotide polymorphisms (htSNPs) within the entire MD-2 gene and to investigate their clinical relevance in patients with major trauma. A total of 726 patients with major trauma were prospectively recruited and composed of two different geographic populations (Chongqing in southwestern China and Zhejiang in eastern China). ⋯ However, only the rs11465996 polymorphism was shown to be significantly associated with higher sepsis morbidity rate and MOD scores in patients with major trauma in both Chongqing and Zhejiang districts. In addition, the rs11465996 polymorphism was significantly associated with tumor necrosis factor α production by peripheral blood leukocytes in response to bacterial lipoprotein stimulation. Among the three htSNPs of the entire MD-2 gene, only the rs11465996 might be used as relevant risk estimate for the development of sepsis and MOD syndrome in patients with major trauma.