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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Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a nuclear receptor that regulates diverse biological functions including inflammation. The PPARgamma ligands have been reported to exert cardioprotective effects and attenuate myocardial reperfusion injury. Here, we examined the molecular mechanisms of their anti-inflammatory effects. ⋯ The cardioprotection afforded by ciglitazone was attenuated by the PPAR-gamma antagonist GW-9662. In contrast, GW-9662 did not affect the beneficial effects afforded by 15d-PGJ2. Thus, our data suggest that treatment with these chemically unrelated PPAR-gamma ligands results in diverse anti-inflammatory mechanisms.
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Neutrophil infiltration is a crucial step in the development of organ dysfunction after trauma. We have previously shown that keratinocyte-derived chemokine (KC), a chemoattractant for neutrophils, is up-regulated after trauma-hemorrhage. To determine the role of KC after trauma-hemorrhage, the effect of a KC-neutralizing antibody on the posttraumatic inflammatory response was examined. ⋯ Administration of the anti-KC antibody before trauma-hemorrhage prevented increases in KC plasma levels, which was accompanied by amelioration of neutrophil infiltration and edema formation in lung and liver after trauma-hemorrhage. No effect on other cytokines in plasma or Kupffer cell release was observed. These results suggest that KC plays a pivotal role in neutrophil infiltration and organ damage after trauma-hemorrhage and resuscitation.
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Lung ischemia-reperfusion (I/R) injury plays an important role in many clinical issues. A series of mechanisms after I/R has been uncovered after numerous related studies. Organ preconditioning (PC) is a process whereby a brief antecedent event, such as transient ischemia, oxidative stress, temperature change, or drug administration, bestows on an organ an early or delayed tolerance to further insults by the same or different stressors. ⋯ Less prominent and transient increase in expression of HSP-70 was found in the PC group. We concluded that the intratracheal thermal PC can effectively attenuate I/R-induced lung injury through various mechanisms, including the decrease of various proinflammatory cytokines. The mechanism of its protective effect might be related to the increased expression of HSP-70.
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Shock states are associated with an impaired tissue oxygen supply-demand relationship and perturbations within the microcirculation, leading to global tissue hypoxia, finally resulting in multiple-organ failure or even death. Two of the most frequent causes of shock are acute hemorrhage and sepsis. Although the origin and the pathophysiology of hemorrhagic and septic shock are basically different, the involvement of adenosine triphosphate-sensitive potassium (KATP) channels, as an important regulator of vascular smooth muscles tone, plays a pivotal role under both conditions. ⋯ The differences in the species, the comorbidity, and the difficulty in determining the exact onset of shock in clinical practice and, thus, any duration-related alterations in vascular responses and KATP channel activation may explain the discrepancy between the results obtained from experimental and clinical studies. Currently, two of the most relevant problems related to effective KATP blockade in shock states are represented by (1) the dose itself (benefit-risk ratio) and (2) the route of administration (oral vs. i.v.). This review article critically elucidates the published in vivo studies on the role of KATP channel inhibition in both described shock forms and discusses the advantages and the potential pitfalls related to the treatment of human shock states.
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Randomized Controlled Trial
Preoperative methylprednisolone administration maintains coagulation homeostasis in patients undergoing liver resection: importance of inflammatory cytokine modulation.
Alterations in hemostatic parameters are a common finding after major hepatic resection. There is growing evidence that inflammation has a significant role in inducing coagulation disarrangement that follows major surgery. To determine whether preoperative methylprednisolone administration has a protective effect against the development of coagulation disorders, we evaluated the effect of preoperative steroids administration on changes in hemostatic parameters and plasma levels of inflammatory cytokines in patients undergoing liver surgery. ⋯ Decreases in antithrombin III, platelet count and fibrinogen levels, prolongation of prothrombin time, and increases in the plasma fibrin degradation products were significantly suppressed by the administration of methylprednisolone. Cytokines production was also significantly suppressed by the administration of methylprednisolone, and there was significant correlation between plasma levels of cytokines and coagulation alterations. These findings suggest that preoperative methylprednisolone administration inhibits the development of coagulation disarrangements in patients undergoing liver resection, possibly through suppressing the production of inflammatory cytokines.