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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This study examined whether acute alcohol (EtOH) intoxication before burn injury potentiates postburn intestinal tissue damage and whether neutrophils have any role in the damage under those conditions. Male rats ( approximately 250 g) were gavaged with EtOH to achieve a blood EtOH level of approximately 100 mg/dL or with saline and received either approximately 12.5% or approximately 25% total body surface area (TBSA) burn or sham injury. Rats were killed at 4 or 24 h after injury, and various parameters were measured. ⋯ The presence of EtOH in rats at the time of burn injury exacerbated the levels of IL-18, MPO activity, and edema at 4 and 24 h after burn injury. Treatment of rats with anti-IL-18 antibodies or with antineutrophil antiserum prevented the increase in the above parameters after EtOH and burn injury, except that the depletion of neutrophils did not prevent the IL-18 increase. In summary, these findings suggest that acute EtOH intoxication exacerbates postburn intestinal tissue damage after burn injury, and that it is, in part, neutrophil mediated.
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Free fatty acids (FFAs) have been shown to produce alteration of heart rate variability (HRV) in healthy and diabetic individuals. Changes in HRV have been described in septic patients and in those with hyperglycemia and elevated plasma FFA levels. We studied if sepsis-induced heart damage and HRV alteration are associated with plasma FFA levels in patients. ⋯ Heart dysfunction was determined by left ventricular stroke work systolic index and HRV index in nonsurvivor patients. A relationship was found between plasma FFA levels, LFnu index, troponin levels, and histological changes. Plasma FFA levels emerged as possible cause of heart damage in sepsis.
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Nucleotide oligomerization domain (NOD) proteins recognize peptidoglycan fragments, resulting in up-regulation of transcription factors, and may enhance the inflammatory response to infection. Specifically, NOD2 has been shown to sense muramyl dipeptide (MDP), which is released during bacterial cell growth and replication. Activation of NOD2 by MDP enhances the inflammatory response caused by LPS (endotoxin). ⋯ When compared with animals receiving low-dose LPS alone, coadministration of MDP (10 mg kg(-1), i.v.) and LPS, or administration of MDP (10 mg kg(-1), i.v.) 24 h before LPS resulted in a significant increase in the degree of organ injury, cytokine release, and lung injury caused by LPS alone. Thus, our results demonstrate that the two bacterial wall components MDP and LPS work in concert to cause multiple organ injury and systemic inflammation. We hope that our results stimulate other studies designed to evaluate the effects of NOD ligands in animal models of inflammation.
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Because studies have shown that 17beta-estradiol (E2) produces anti-inflammatory effects after various adverse circulatory conditions, we examined whether administration of E2 before spinal cord injury (SCI) has any salutary effects in reducing SCI. Spinal cord injury was induced by the application of vascular clips (force of 24 g) to the dura via a four-level T5-T8 laminectomy. To gain a better insight into the mechanism of action of the anti-inflammatory effects of E2, the following end points of the inflammatory process were evaluated: (1) spinal cord inflammation and tissue injury (histological score); (2) neutrophil infiltration (myeloperoxidase activity); (3) expression of iNOS, nitrotyrosine, and COX-2; (4) apoptosis (terminal deoxynucleotidyltransferase-mediated UTP end labeling staining and Bax and Bcl-2 expression); and (5) tissue TNF-alpha, IL-6, IL-1beta, and monocyte chemoattractant protein 1 levels. ⋯ To elucidate whether the protective effects of E2 were mediated via the estrogen receptors, we investigated the effect of an estrogen receptor antagonist, ICI 182,780, on the protective effects of E2. ICI 182,780 (500 microg/kg, s.c., 1 h before treatment with E2) significantly antagonized the effect of the E2 and abolished the protective effect against SCI. Taken together, our results clearly demonstrate that administration of E2 before SCI reduces the development of inflammation and tissue injury associated with spinal cord trauma.