Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infections remain the leading cause of death among patients admitted to intensive care units (ICU). Infections due to Gram-negative bacteria are both frequent and difficult to treat. The poor outcome of such infections has been attributed to the endotoxin. The high mortality rate related to Gram-negative sepsis has prompted the testing of new, adjunctive therapies to prevent and treat infections in critically ill patients. Immunotherapy or immunoprophylaxis have long been investigated in this context. Passive immunotherapy consists of the administration of immune plasma or serum, or standard or hyperimmune purified immune globulins. Several clinical studies using such preparations to treat critically ill patients are reviewed in this article. While two studies using hyperimmune plasma or serum appeared to be successful, two studies using hyperimmune globulin failed to show a beneficial effect in the treatment or the prevention of Gram-negative septic shock. Regarding the infusion of standard intravenous immune globulin (IVIG) two studies have demonstrated a substantial benefit in the prevention of severe infections; the reduction of nosocomial pneumonia recorded in both trials and the shortness of stay in ICU may also afford savings in hospital costs. The cost effectiveness of such prophylactic administration of IVIG is worthy of further investigation.
 ...
PMID:Polyclonal intravenous immune globulin for prevention and treatment of infections in critically ill patients. 803 38

Gram-negative sepsis/septic shock in the human newborn continues to be a severe medical problem because of significant mortality and morbidity. Since macrophages detoxify endotoxin, a decreased number of macrophages may contribute to the newborn's sensitivity to endotoxin. In this study, peritoneal macrophages were used for the treatment of endotoxic shock in 10-day-old rats, and 24-hr mortality, plasma glucose, and lactate concentrations were monitored. Peritoneal macrophages were harvested from adult or 10-day-old rats. Caseinate-stimulated macrophages from adult and 10-day-old rats significantly decreased the mortality of 10-day-old rat endotoxic shock from 90% to 37.5% and 44.4%, respectively. Resident macrophages from adult and 10-day-old rats also decreased the mortality from 90% to 12.5% and 45.4%, respectively. Peritoneal macrophages from adult rats significantly ameliorated hypoglycemia during endotoxic shock in a dose-dependent manner. Macrophage treatment decreased plasma endotoxin concentration (P < 0.05). Macrophage treatment was important for host defense.
 ...
PMID:Macrophage treatment in suckling rat endotoxic shock. 814 52

Gram-negative shock is thought to result primarily from the effects of endotoxin, a component of the bacterial outer membrane. Accordingly, therapies aimed at inhibiting, neutralizing, or clearing endotoxin have been extensively explored. Despite over 30 years of research, no antiendotoxin approach to the treatment of human septic shock is of proven benefit. In recent randomized clinical trials of monoclonal antibodies against endotoxin, therapeutic efficacy was not convincingly demonstrated. This result, however, does not eliminate the possibility that other antiendotoxin therapies may be effective. The antibodies used in these clinical trials do not appear to neutralize endotoxin in vitro and are not reproducibly protective in animal models of sepsis. Newer agents with well-defined mechanisms of antiendotoxin activity may help clarify the role of endotoxin in septic shock and prove useful therapy for some patients.
 ...
PMID:Antiendotoxin therapies for septic shock. 816 53

Heparin is used clinically in horses to treat hemostatic abnormalities associated with severe gastrointestinal disease, septicemia, and endotoxemia. The primary anticoagulant effect of heparin is through the suppression of thrombin-dependent amplification of the coagulation cascade, and inhibition of thrombin-mediated conversion of fibrinogen to fibrin. Heparin may be of benefit in preventing the complications associated with hypercoagulable states such as jugular vein thrombosis, laminitis, and organ failure. Heparin may also be beneficial in the prevention of intraabdominal adhesions after gastrointestinal surgery, and in amelioration of hemodynamic abnormalities associated with endotoxic shock. Because a sequential rise in serum heparin concentration occurs during a uniform dosage regimen, a decreasing dosage regimen is recommended. The initial dose recommended is 150 U heparin/kg body weight subcutaneously, followed by 125 U heparin/kg body weight subcutaneously, every 12 hours for six doses. The dose should be decreased to 100 U heparin/kg body weight subcutaneously, every 12 hours, after the seventh dose. Anemia, hemorrhage, thrombocytopenia, and painful swelling at injection sites are complications of heparin administration in horses.
 ...
PMID:Heparin: a review of its pharmacology and therapeutic use in horses. 817 60

Despite the use of potent antibiotics and intensive supportive care, mortality remains high among septic shock patients, especially those with endotoxemia. To remove endotoxin directly from the blood, a material consisting of polymyxin B that is immobilized on fibers (PMX-F) and that can selectively detoxify endotoxin was developed. In a preliminary clinical study, 16 patients with septic multiple organ failure were treated with direct hemoperfusion using a PMX-F column. This therapy significantly decreased the endotoxin level from 76 pg/mL to 21 pg/mL after 2 hours of direct hemoperfusion. The hyperdynamic state of the cardiac index, which is a characteristic of endotoxic shock, returned to normal levels after treatment. In septic shock patients with a systolic pressure of less than 100 mm Hg, the systolic arterial pressure increased significantly from the pretreatment level. The alleviation of fever caused by this therapy continued until the day after treatment. Of the 16 patients who underwent this therapy, 9 were alive 2 weeks after this therapy and 7 patients were discharged from the hospital alive. Hemoperfusion with PMX may be an effective treatment for sepsis and septic shock.
 ...
PMID:Treatment of sepsis by extracorporeal elimination of endotoxin using polymyxin B-immobilized fiber. 817 86

Lipopolysaccharide (LPS, endotoxin) is a major component of the outer membrane of gram-negative bacteria. Although it interacts with many types of cells and is linked to numerous events associated with sepsis and endotoxic shock, the mechanisms underlying these actions are poorly understood. We found that Ca-signaling induced by endotoxin in guinea-pig neutrophils and macrophages is caused by cross-recognition of LPS with platelet activating factor (PAF) receptors. However, the synthesis of tumor necrosis factor-alpha or the priming effect of O2- production was not affected by PAF antagonists. Thus, at least two distinct pathways are involved in the actions of LPS, one via the PAF receptor, while the other is independent of a PAF receptor and Ca-signaling.
 ...
PMID:Two distinct signal transduction pathways for the activation of guinea-pig macrophages and neutrophils by endotoxin. 826 81

Gram-negative sepsis/septic shock in the newborn continues to be a major medical problem, causing high mortality. Hyperglycemia followed by hypoglycemia is a common symptom in endotoxic shock. However, the mechanism of newborn glucoregulatory response to endotoxin has not been well understood. Paradoxically, monocyte-phagocytes can contribute to shock by overwhelming secretion of cytokines and also host defense by detoxifying endotoxin. Since monocyte-phagocyte function is immature in the newborn, this study was performed to evaluate Kupffer cell's role in liver glycogenolysis during endotoxic shock. Endotoxin (LPS) induced hyperglycemia in 10-day-old rats, and increased net glucose output in the isolated perfused liver. 1) Cytarabine decreased Kupffer cell function (decreased hepatic colloid carbon uptake) and blunted LPS-increased liver net glucose output in the Cytarabine + LPS-treated group (104 +/- 4 vs. 146 +/- 3 micrograms/min/g wet liver in the LPS-treated group: P < .001). 2) Indomethacin (IND) suppressed LPS-induced liver net glucose output in the LPS + IND-treated group (133 +/- 5 vs. 146 +/- 3 micrograms/min/g wet liver, P < .05). Thus, prostaglandins were suggested to contribute to glycogenolysis in the 10-day-old rat liver. 3) Phorbol 12-myristate 13-acetate (PMA) increased liver net glucose output (166 +/- 4 micrograms/min/g wet liver), and H-7, a protein kinase C inhibitor, blunted PMA-induced liver glucose output (140 +/- 2 micrograms/min/g wet liver, P < .05). H-7 enhanced LPS-induced liver net glucose output (196 +/- 9 micrograms/min/g wet liver, P < .01). Therefore, protein kinase C may not be the dominant cell signaling system for LPS stimulation in suckling rat Kupffer cells.
 ...
PMID:Lipopolysaccharide alters suckling rat liver glycogenolysis. 832 90

Interleukin-1 (IL-1) is a mediator of endotoxin shock and IL-1 receptor blockade has been shown to have therapeutic efficacy against endotoxic shock and sepsis in laboratory models. The current studies were designed to characterize the efficacy of a murine monoclonal IL-1 receptor antibody (IL-1rab) against endotoxin (LPS) lethality and to investigate whether combined anticytokine therapy using the IL-1rab and a highly specific polyclonal rabbit anti-mouse TNF antibody (TNF Ab) could provide additive or synergistic efficacy against LPS lethality in C57B1/6 female mice. A single intraperitoneal (ip) dose of IL-1rab, 0.1 or 0.2 mg, significantly reduced lethality from LPS, 30 to 40 mg/kg ip, compared to nonimmune IgG, 0.1 or 0.2 mg, in control mice (P2 < 0.05). Treatment with IL-1rab was effective when administered from 6 hr before to 1 hr after LPS. After LPS, circulating levels of IL-6 were significantly lower in IL-1rab-treated mice [IL-6 (ng/ml) 2 h after LPS: IgG, 100 +/- 25, IL-1rab, 41 +/- 8; 4 h after LPS: IgG, 46 +/- 13, IL-1rab, 8 +/- 1; P2 < 0.05 and 0.03, respectively]. Northern blot analysis showed that IL-1rab markedly lowered IL-6 gene expression after LPS. Combined treatment with IL-1rab and TNF Ab did not result in any improvement in survival after LPS compared to either agent alone. These results indicate that an IL-1 receptor antibody has therapeutic efficacy against LPS and significantly decreases IL-6 production.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Interleukin-1 receptor antibody (IL-1rab) protection and treatment against lethal endotoxemia in mice. 833 25

Candidemia in humans is often associated with an endotoxic shock-like syndrome, comparable to gram-negative sepsis. Tumor necrosis factor-alpha (TNF alpha) has been implicated as a mediator in the endotoxic shock syndrome. The possible role of TNF alpha causing early deaths was explored in a murine model of acute infection with Candida albicans. In vitro data from three mouse strains (BALB/c, C3H/HeJ, and C3H/HeN) and in vivo data from BALB/c mice were obtained. Peritoneal macrophages from all three strains produced TNF alpha in vitro when stimulated with C. albicans. After intravenous infection with 10(8) cfu of C. albicans, mice died within 12 h. TNF concentrations in sera from these mice were significantly greater than in controls. Pretreatment of BALB/c mice with anti-murine TNF alpha did not alter mortality of C. albicans-infected mice, but pretreatment with murine TNF alpha reduced mortality. Therefore, in contrast to what was anticipated, TNF alpha may serve a protective role in murine candidiasis.
 ...
PMID:Induction of tumor necrosis factor-alpha in murine Candida albicans infection. 848 50

The concept of the systemic inflammatory response (SIRS) has recently been defined with suggested new terminology and criteria for diagnosis, and this has gained acceptance in the international literature. The importance of Gram-positive organisms as a cause of the SIRS has become increasingly recognised in recent years. This report describes a case of severe staphylococcal infection with a clinical picture similar to 'classic' endotoxic shock associated with Gram-negative organisms. We use this report to discuss the management of severe sepsis with organ dysfunction, outline the clinical complications and specific therapy of staphylococcal infections, discuss the new terminology, and compare and contrast the features of SIRS associated with varying causes.
 ...
PMID:Systemic response to gram-positive and gram-negative infections--comparison and contrast. 860 54


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>