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

To assess the role of combined immunomodulator and antibiotic therapy in sepsis, glucan--a beta 1,3 polyglucose--and gentamicin were administered in a model of murine peritonitis. ICR/HSD mice received one of four treatment regimens: 5% dextrose; gentamicin 0.02 mg intramuscularly (sub-MIC) 2 hours before peritonitis; glucan 0.1 mg intraperitoneally 24 hours before peritonitis; combined glucan-gentamicin treatment. All animals were challenged with 1 X 10(8) Escherichia coli intraperitoneally. Long-term survival was significantly enhanced in the combined therapy group (56%, p less than 0.05) when compared with D5W (0%), gentamicin alone (0%), or glucan alone (9%). Macrophage secretory activity, as assayed by interleukin-1 (IL-1) production, was significantly enhanced by combined therapy when compared with the other three treatment groups. Combined therapy significantly reduced E. coli bacteremia at 8 hours after inoculation, when compared with the other three groups. Availability of host neutrophils was assessed by peripheral counts and bone marrow proliferation assay. Combined glucan-gentamicin significantly enhanced bone marrow proliferation when compared with the other three groups and this enhancement correlated with increased circulating neutrophils. Combined immunomodulator and antibiotic therapy had synergistic effects on survival in E. coli peritonitis. This combined therapy enhanced macrophage secretory activity and bone marrow proliferation. Clinical use of immunomodulators may alter conventional use and dosage of antibiotics.
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PMID:Synergistic effect of nonspecific immunostimulation and antibiotics in experimental peritonitis. 330 98

Starling's hypothesis of forces governing fluid movement across capillary membranes suggests that any unopposed decrease in intracapillary colloid oncotic pressure (COP) or increase in capillary permeability should result in increased interstitial fluid. Iso-oncotic increase in pulmonary artery wedge (PAW) causes pulmonary dysfunction. Isobaric reduction of COP with normal capillary permeability does not result in pulmonary interstitial edema. Because sepsis is a frequent antecedent of clinical pulmonary dysfunction, the question was asked: does reduction in the COP-PAW gradient in the presence of sepsis result in increased pulmonary dysfunction? Twenty baboons were studied: group 1--control, group 2--4-h constant infusion of E. coli, group 3--plasmapheresis alone, group 4--plasmapheresis followed by sepsis. Ringer's lactate was infused to keep PAW constant. Arterial and mixed venous blood gases were drawn and the intrapulmonary shunt (QS/QT) was calculated. The data were compared using Tukey's HSD test and one way analysis of variance. Plasmapheresis alone resulted in a 68% reduction in COP (15 +/- 2.9 (SD) torr to 4.6 +/- 0.6 in group 3 and 16.5 +/- 4.3 to 5.7 +/- 0.9 in group 4, p less than 0.05). Sepsis resulted in an increase in QS/QT in all septic animals. There was no increased QS/QT in those animals that had sepsis added to plasmapheresis, group 4 (p less than 0.05). These data indicate that sepsis leads to pulmonary dysfunction but that this dysfunction appears to be independent of colloid oncotic forces.
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PMID:Does reduced colloid oncotic pressure increase pulmonary dysfunction in sepsis? 700 18

In late sepsis, it has been established that the liver plays a major role in the initiation of multiorgan failure, which is the most lethal complication in hospitals. The molecular mechanism underlying liver failure that results from sepsis remains elusive. This study was undertaken to identify the bona fide differentially expressed genes in the 18-h septic liver by suppression subtractive hybridization, and the data were corroborated by Northern blot analysis. The differential gene expression profile renders a clue as to the genes involved in septic liver failure. The cecal ligation and puncture (CLP) model of a polymicrobial septic rat was used, with the late sepsis referring to animals sacrificed at 18 h after CLP. We have identified three upregulated genes (TII-kininogen, serine protease inhibitor 2.2 [Spi2.2], and alpha 2 macroglobulin [alpha M]) and six down-regulated genes (hydroxysteroid dehydrogenase [3 alpha HSD], EST189895/mouse RNase4, bile acid-CoA-amino acid N-acyltransferase [kan-1/rBAT], IF1, albumin, and alpha 2u-globulins [alpha 2u-G PGCL1]). Among these genes, the 3 alpha HSD and kan-1/rBAT are involved in bile acid metabolism. The IF1 plays a crucial role in any disease that involves ATP hydrolysis by F1F0-ATPase. The alpha 2M, TII-kininogen, and Spi2.2 are protease inhibitors. The functions of the alpha 2u-G PGCL1 and EST189895/mouse RNase4 genes are unknown. The present results suggest that the roles of disturbance of bile acid metabolism/synthesis and the abolishment of ATP production may contribute to liver failure during late sepsis.
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PMID:Isolation of bona fide differentially expressed genes in the 18-hour sepsis liver by suppression subtractive hybridization. 1516 84

Myocardial dysfunction is a major consequence of septic shock and contributes to the high mortality of sepsis. We have previously reported that glucan phosphate (GP) significantly increased survival in a murine model of cecal ligation and puncture (CLP)-induced sepsis. In the present study, we examined the effect of GP on cardiac dysfunction in CLP-induced septic mice. GP was administered to ICR/HSD mice 1 h before induction of CLP. Sham surgically operated mice served as control. Cardiac function was significantly decreased 6 h after CLP-induced sepsis compared with sham control. In contrast, GP administration prevented CLP-induced cardiac dysfunction. Macrophage migration inhibitory factor (MIF) has been implicated as a major factor in cardiomyocyte apoptosis and cardiac dysfunction during septic shock. CLP increased myocardial MIF expression by 88.3% (P < 0.05) and cardiomyocyte apoptosis by 7.8-fold (P < 0.05) compared with sham control. GP administration, however, prevented CLP-increased MIF expression and decreased cardiomyocyte apoptosis by 51.2% (P < 0.05) compared with untreated CLP mice. GP also prevented sepsis-caused decreases in phospho-Akt, phospho-GSK-3beta, and Bcl-2 levels in the myocardium of septic mice. These data suggest that GP treatment attenuates cardiovascular dysfunction in fulminating sepsis. GP administration also activates the phosphoinositide 3-kinase/Akt pathway, decreases myocardial MIF expression, and reduces cardiomyocyte apoptosis.
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PMID:Glucan phosphate attenuates cardiac dysfunction and inhibits cardiac MIF expression and apoptosis in septic mice. 1676 37