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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Signaling pathways and mediators in LPS-induced lung inflammation in diabetic rats: role of insulin.
Diabetic patients are more susceptible to infections, and their inflammatory response is impaired. This is restored by insulin treatment. In the present study, we investigated the effect of insulin on LPS-induced signaling pathways and mediators in the lung of diabetic rats. ⋯ Treatment of diabetic rats with insulin completely or partially restored all these parameters. In conclusion, data presented show that insulin regulates mitogen-activated protein kinase, phosphatidylinositol 3'-kinase, protein kinase C pathways, expression of the inducible enzymes, cyclooxygenase 2 and iNOS, and levels of IL-6 and CINC-2 in LPS-induced lung inflammation in diabetic rats. These results suggest that the protective effect of insulin in sepsis could be due to modulation of cellular signal transduction factors.
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Crocetin, a constituent of saffron, has been shown not only to prevent reactive oxygen species-induced hepatotoxicity and genotoxicity but also to increase whole-body oxygen consumption and survival. The present study was to determine whether crocetin has beneficial effects on cardiac injury caused by hemorrhagic shock and resuscitation in rats. Anesthetized rats were bled to reduce mean arterial pressure (MAP) to 35 +/- 5 mmHg for 60 min and then resuscitated with their withdrawn shed blood and isotonic sodium chloride solution. ⋯ Myocardial nuclear factor-kappaB activity, iNOS activity, NO, malondialdehyde, TNF-alpha, and IL-6 were significantly elevated, whereas T-SOD activity was suppressed in the control group if compared with those of sham animals. These parameters tended to be normalized in rats administered crocetin. These results suggest that crocetin blocks inflammatory cascades by inhibiting reactive oxygen species production and preserving T-SOD activity to ameliorate the cardiac injury caused by hemorrhage/resuscitation.
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Our previous studies have shown that acute alcohol intoxication (AAI) decreases blood pressure, exacerbates hypotension after hemorrhagic shock, impairs the pressor response to fluid resuscitation, and blunts neuroendocrine activation. We hypothesized that impaired hemodynamic compensation during and after hemorrhagic shock in the acute alcohol-intoxicated host is the result of blunted neuroendocrine activation or, alternatively, of an impaired vascular responsiveness to vasoactive agents. The aim of this study was to examine the effects of AAI, AAI and hemorrhagic shock, and AAI and hemorrhagic shock and resuscitation on reactivity of isolated blood vessel rings to phenylephrine and acetylcholine. ⋯ Acute alcohol intoxication did not produce significant alterations in either pressor or dilator responses in aortic or mesenteric rings. These findings suggest that impaired hemodynamic counterregulation during hemorrhagic shock in AAI is not due to decreased vasopressor responsiveness. However, our results suggest a role for accentuated vasodilatory responses that may be central in progression to decompensatory shock.
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Oxidative stress during reperfusion of ischemia is associated with a phenotypic change in circulating monocytes from CD14++CD16- to a proinflammatory CD14+CD16+ subpopulation resulting in altered immunity and development of organ failure. However, the mechanism responsible remains unknown. We hypothesize that this phenotypic change, modeled by hydrogen peroxide exposure in vitro, is due to oxidative-induced intracellular calcium flux and distinct cytoskeletal and lipid raft changes. ⋯ This increase in CD16 expression was associated with a 27% increase in intracellular TNF-alpha, an alteration in actin polymerization, and the formation of raft macrodomains. These changes induced by H2O2 were inhibited by inhibition of actin polymerization (cytochalasin D and lactrunculin A) and intracellular calcium flux [1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid]. This study provides the first evidence that phenotypic alterations induced by oxidative stress during reperfusion may occur as a result of changes in cytoskeletal architecture due to calcium flux that result in lipid raft alterations rather than solely from demargination and/or production of bone marrow-derived CD16+ monocytes.
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Heart rate complexity (HRC) is an emerging "new vital sign" for critically ill and injured patients. Traditionally, 800-beat data sets have been used to calculate HRC variables, thus limiting their practical use in an emergency. We sought to investigate whether data set reductions diminish the use of HRC to predict mortality in prehospital trauma patients. ⋯ This finding was confirmed for data sets as short as 100 beats by computationally different metrics. SampEn, SOD, and complex demodulation were relatively unaffected by data set reduction. These metrics may be useful for rapid identification of trauma patients with potentially lethal injuries using short EKG data sets.