losartan-potassium and Systemic-Inflammatory-Response-Syndrome

Environmental heat exposure represents one of the most deadly natural hazards in the United States. Heat stroke is a life-threatening illness that affects all segments of society with few effective treatment strategies to mitigate the long-term debilitating consequences of this syndrome. Although the etiologies of heat stroke are not fully understood, the long-term sequelae are thought to be due to a systemic inflammatory response syndrome (SIRS) that ensues following heat-induced tissue injury. Endotoxin and cytokines have been implicated as key mediators of the heat-induced SIRS, based almost exclusively on correlative data that show high circulating concentrations of these substances in heat stroke patients and animal models. However, endotoxin and cytokine neutralization studies have not consistently supported this hypothesis indicating that the mechanisms of heat stroke morbidity / mortality remain poorly understood. This review discusses the current understanding of the role of endotoxin and cytokines in heat-induced SIRS. Insight is provided into genetic conditions that may predispose to heat stroke and potential therapeutic strategies that may be efficacious against the adverse consequences of this debilitating illness.

Topics: Animals; Cytokines; Disease Models, Animal; Endotoxins; Erythropoietin; Genetic Predisposition to Disease; Glucocorticoids; Heat Stroke; Hot Temperature; Humans; Hypothermia, Induced; Malignant Hyperthermia; Mutation; Polymorphism, Genetic; Prostaglandin Antagonists; Protein C; Recombinant Proteins; Signal Transduction; Systemic Inflammatory Response Syndrome

Sepsis is the systemic inflammatory response to infection and can result in multiple organ dysfunction syndrome with associated high mortality, morbidity and health costs. Erythropoietin is a well-established treatment for the anaemia of renal failure due to its anti-apoptotic effects on red blood cells and their precursors. The extra-haemopoietic actions of erythropoietin include vasopressor, anti-apoptotic, cytoprotective and immunomodulating actions, all of which could prove beneficial in sepsis. Attenuation of organ dysfunction has been shown in several animal models and its vasopressor effects have been well characterised in laboratory and clinical settings. Clinical trials of erythropoietin in single organ disorders have suggested promising cytoprotective effects, and while no randomised trials have been performed in patients with sepsis, good quality data exist from studies on anaemia in critically ill patients, giving useful information of its pharmacokinetics and potential for harm. An observational cohort study examining the microvascular effects of erythropoietin is underway and the evidence would support further phase II and III clinical trials examining this molecule as an adjunctive treatment in sepsis.

Topics: Animals; Apoptosis; Blood Vessels; Erythropoietin; Humans; Sepsis; Systemic Inflammatory Response Syndrome

Since many end stage renal disease (ESRD) patients experi inflammation, malnutrition, and anemia, the interplay of these processes should be considered in the approach to patients treated with erythropoietin (EPO). This article reviews the interrelationship between these factors. The systemic inflammatory response caused by exposure to inflammatory stimuli results in anorexia and metabolic disturbances leading to protein calorie malnut tion as well as sequestration of iron and hyporesponsiveness to EPO. The implications of these effects and possible strategies to optimize anemia management in the presence of these conditions are discussed.

Topics: Anemia, Iron-Deficiency; Clinical Protocols; Drug Monitoring; Erythropoietin; Ferritins; Hematinics; Humans; Iron; Iron-Binding Proteins; Iron-Dextran Complex; Kidney Failure, Chronic; Nutritional Status; Nutritional Support; Protein-Energy Malnutrition; Risk Factors; Systemic Inflammatory Response Syndrome; Treatment Outcome

The anemia of inflammation is related in part to abnormal erythropoiesis in bone marrow. G-CSF regulates granulopoiesis and is increased during systemic inflammation. Here, we have showed that high levels of G-CSF are associated with repression of bone marrow erythropoiesis and expansion of splenic erythropoiesis in

Topics: Animals; Bone Marrow; Erythropoiesis; Erythropoietin; Escherichia coli; Escherichia coli Infections; Granulocyte Colony-Stimulating Factor; Injections, Subcutaneous; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Mice, Knockout; Signal Transduction; Spleen; Systemic Inflammatory Response Syndrome; Toll-Like Receptor 4

Cardioprotective properties of recombinant human Erythropoietin (rhEpo) have been shown in in vivo regional or ex vivo global models of ischemia-reperfusion (I/R) injury. The aim of this study was to characterize the cardioprotective potential of rhEPO in an in vivo experimental model of global I/R approximating the clinical cardiac surgical setting and to gain insights into the myocardial binding sites of rhEpo and the mechanism involved in its cardioprotective effect.. Hearts of donor Lewis rats were arrested with cold crystalloid cardioplegia and after 45 min of cold global ischemia grafted heterotopically into the abdomen of recipient Lewis rats. Recipients were randomly assigned to control non-treated or Epo-treated group receiving 5000 U/kg of rhEpo intravenously 20 min prior to reperfusion. At 5 time points 5-1440 min after reperfusion, the recipients (n=6-8 at each point) were sacrificed, blood and native and grafted hearts harvested for subsequent analysis.. Treatment with rhEpo resulted in a significant reduction in myocardial I/R injury (plasma troponin T) in correlation with preservation of the myocardial redox state (reduced glutathione). The extent of apoptosis (activity of caspase 3 and caspase 9, TUNEL test) in our model was very modest and not significantly affected by rhEpo. Immunostaining of the heart tissue with anti-Epo antibodies showed an exclusive binding of rhEpo to the coronary endothelium with no binding of rhEpo to cardiomyocytes. Administration of rhEpo resulted in a significant increase in nitric oxide (NO) production assessed by plasma nitrite levels. Immunostaining of heart tissue with anti-phospho-eNOS antibodies showed that after binding to the coronary endothelium, rhEpo increased the phosphorylation and thus activation of endothelial nitric oxide synthase (eNOS) in coronary vessels. There was no activation of eNOS in cardiomyocytes.. Intravenous administration of rhEpo protects the heart against cold global I/R. Apoptosis does not seem to play a major role in the process of tissue injury in this model. After binding to the coronary endothelium, rhEpo enhances NO production by phosphorylation and thus activation of eNOS in coronary vessels. Our results suggest that cardioprotective properties of rhEpo are at least partially mediated by NO released by the coronary endothelium.

Topics: Animals; Apoptosis; Atrial Natriuretic Factor; Body Water; Cardiotonic Agents; Coronary Vessels; Disease Models, Animal; Drug Evaluation, Preclinical; Endothelium, Vascular; Erythropoietin; Heart Transplantation; Male; Myocardial Reperfusion Injury; Nitric Oxide; Oxidative Stress; Rats; Rats, Inbred Lew; Recombinant Proteins; Systemic Inflammatory Response Syndrome; Troponin T

The objective of this study was to determine the effect of erythropoietin (Epo) on the intestinal labile zinc and the inflammatory factor in rats after traumatic brain injury (TBI).. Male Sprague-Dawley rats were randomly divided into nine groups: (a) normal group; (b) sham-operation group; (c, d, e, f, and g) TBI group, killed at 1 hour, 6 hour, 24 hour, and 72 hour and 7 days postinjury, respectively; (h and i) TBI + saline and TBI + Epo, killed at 24 hour or 72 hour postinjury. Parietal brain contusion was produced by a free-falling weight on the exposed dura of the right parietal lobe. Intestinal labile zinc, the tumor necrosis factor-alpha, interleukin (IL)-8, and wet/dry weight ratio were investigated in different groups.. The gut contains a certain amount of labile zinc in normal animals and TBI caused obviously gradual increment of intestinal liabled zinc. The levels of inflammatory mediators and the gut wet/dry weight ratio were also found to increase in the trauma group (p < 0.05). There was a highly positive correlation between the abundance of zinc fluorescence and these proinflammation factors. Epo significantly reduced the intestinal labile zinc, the inflammatory mediators, and the gut wet/dry weight ratio compared with TBI group (p < 0.05).. Epo can protect intestine from TBI-induced injury by attenuating intestinal inflammation and labile zinc accumulation in vivo.

Topics: Animals; Brain Concussion; Capillary Permeability; Enzyme-Linked Immunosorbent Assay; Erythropoietin; Homeostasis; Inflammation Mediators; Interleukin-8; Intestinal Mucosa; Male; Microscopy, Fluorescence; Parietal Lobe; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha; Zinc