Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Glucan, a beta 1 leads to 3 polyglucosidic component of Saccharomyces cerevisiae, was evaluated for its ability to provide nonspecific resistance to S. aureus septicemia in AKR/J mice. Intravenous injection of glucan (0.45 mg/mouse) 7 and 4 days prior to intravenous challenge with S. aureus (1.0 x 10(9)) resulted in a significantly increased survival as compared to control mice. Histological examination of the kidneys revealed that glucan decreased tissue necrosis associated with systemic staphylococcal disease. A post-treatment regimen of glucan significantly enhanced survival of AKR/J mice with lymphocytic leukemia as well as leukemic mice with experimentally induced systemic staphylococcal infection. The effect of glucan on S. aureus septicemia was also evaluated in cyclophosphamide-treated mice. Glucan increased peripheral leukocyte counts as well as significantly enhanced survival of cyclophosphamide-treated mice with systemic S. aureus infection. Histopathological examination revealed that glucan administration markedly inhibited renal and hepatic pathology in cyclophosphamide-treated mice following intravenous challenge with S. aureus. These data denote that glucan provides nonspecific resistance to bacterial sepsis in normal, leukemic as well as immunosuppressed mice.
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PMID:Glucan induced modification of experimental Staphylococcus aureus infection in normal, leukemic and immunosuppressed mice. 54 28

Bacterial infection decreases insulin-mediated glucose uptake (IMGU) by skeletal muscle and produces whole body insulin resistance. Because circulating catecholamines are elevated by the septic insult, the present study was performed to determine the potential role of the beta-adrenergic system in eliciting these changes. Before induction of sepsis, an infusion containing saline, propranolol, or atenolol was started and continued throughout the experimental protocol. Sepsis increased the basal rate of glucose production and utilization and impaired IMGU by peripheral tissues. The peripheral insulin resistance in septic rats was manifested by an increase in the dose producing 50% of maximal response and a decrease in the maximal responsiveness. Infusion of propranolol, a nonselective beta-adrenergic antagonist, attenuated the sepsis-induced increase in basal glucose turnover by 70% and completely prevented the decrease in IMGU by the whole body. In contrast, atenolol, a selective beta 1-antagonist, did not alter the glucose metabolic response to infection. Under basal conditions, propranolol prevented or attenuated the increase in glucose uptake by the gastrocnemius, diaphragm, skin, liver, lung, spleen, and ileum normally observed in septic rats. In addition, propranolol prevented the decrease in IMGU by various muscles and skin in septic animals. These results suggest that adrenergic stimulation, probably mediated by a beta 2-adrenergic mechanism, is partially responsible for the sepsis-induced increases in basal whole body glucose turnover and plays a prominent role in the development of peripheral insulin resistance in this condition.
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PMID:Sepsis-induced insulin resistance in rats is mediated by a beta-adrenergic mechanism. 132 50

Streptococcus suis is a common cause of sepsis, meningitis, and other serious infections in young piglets and also causes meningitis in humans. The cell-binding specificity of sialic acid-recognizing strains of Streptococcus suis was investigated. Treatment of human erythrocytes with sialidase or mild periodate abolished hemagglutination. Hemagglutination inhibition experiments with sialyl oligosaccharides indicated that the adhesin preferred the sequence NeuNAc alpha 2-3Gal beta 1-4Glc(NAc). Resialylation of desialylated erythrocytes with Gal beta 1-3(4)GlcNAc alpha 2-3-sialyltransferase induced a strong hemagglutination, whereas no or only weak hemagglutination was obtained with cells resialylated with two other sialyltransferases. Binding of radiolabeled bacteria to blots of erythrocyte membrane proteins revealed binding to the poly-N-acetyllactosamine-containing components Band 3, Band 4.5, and polyglycosyl ceramides and to glycophorin A. The involvement of glycophorin A as a major ligand was excluded by the strong hemagglutination of trypsin-treated erythrocytes and En(a-) erythrocytes defective in glycophorin A. Sensitivity of the hemagglutination toward endo-beta-galactosidase treatment of erythrocytes and inhibition by purified poly-N-acetyllactosaminyl glycopeptides indicated that the adhesin bound to glycans containing the following structure: NeuNAc alpha 2-3Gal beta 1-4GlcNAc beta 1-3Gal beta 1-.
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PMID:Identification of N-acetylneuraminyl alpha 2-->3 poly-N-acetyllactosamine glycans as the receptors of sialic acid-binding Streptococcus suis strains. 140 Apr 20

Mice challenged with Escherichia coli or Staphylococcus aureus were protected against lethal peritonitis by the intravenous administration of 10 micrograms of poly-beta 1-6-glucotriosyl-beta 1-3-glucopyranose (PGG) glucan per animal 4 to 6 h prior to bacterial challenge. Subsequent studies with the rat model for intra-abdominal sepsis indicated that intramuscular doses of 10 to 100 micrograms per animal 24 and 4 h prior to surgical implantation of the bacterial inoculum reduced the early mortality associated with the peritonitis phase of this experimental disease process. Quantitative cultures of blood obtained from challenged rats showed that significantly fewer organisms were present in the blood of PGG glucan-treated animals than in that of untreated animals. Quantitative studies of leukocytes of rats and mice following a single injection of PGG glucan showed a modest transient increase in the total leukocyte count. The possible mechanisms by which protection occurs in the animal model system are discussed.
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PMID:Anti-infective effect of poly-beta 1-6-glucotriosyl-beta 1-3-glucopyranose glucan in vivo. 154 86

The erythrocyte receptors for S-fimbriated Escherichia coli, which causes sepsis and meningitis in newborn infants, were investigated. Neuraminidase and trypsin treatments of erythrocytes abolished the hemagglutination ability of the bacteria. To identify the receptor glycoproteins, we separated erythrocyte membrane proteins by gel electrophoresis, blotted them to nitrocellulose, and incubated them with 125I-labeled bacteria. The only bacterium-binding bands identified corresponded to glycophorin A dimer and monomer, and the binding was abolished by neuraminidase treatment of the blot. Radiolabeled bacteria also bound to purified glycophorin A adsorbed to polyvinyl chloride microwells, and the binding was inhibited by other sialoglycoproteins and isolated sialyloligosaccharides containing the NeuAc alpha 2-3Gal sequence. Oligosaccharides which contain the NeuAc alpha 2-3Gal beta 1-3GalNAc and NeuAc alpha 2-3Gal beta 1-3(NeuAc alpha 2-6)GalNAc sequence and which are identical to the O-linked saccharides of glycophorin A were twofold more effective inhibitors of binding than were other oligosaccharides containing the NeuAc alpha 2-3Gal sequence. The replacement of sialic acid in asialoerythrocytes with a purified Gal beta 1-3GalNAc alpha 2-3 sialyltransferase, which forms the O-linked NeuAc alpha 2-3Gal beta 1-3GalNAc sequence in asialoglycophorins, restored bacterial hemagglutination. These results indicated that the major erythrocyte receptor for S-fimbriated E. coli is the NeuAc alpha 2-3Gal beta 1-3GalNAc sequence of the O-linked oligosaccharide chains of glycophorin A.
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PMID:Identification of the O-linked sialyloligosaccharides of glycophorin A as the erythrocyte receptors for S-fimbriated Escherichia coli. 287 51

Escherichia coli strains that cause sepsis and meningitis in neonatal infants carry S fimbriae that bind to sialyl galactoside units of cell surface glycoproteins. To investigate the possible role of S fimbriae in determining the tissue tropism of neonatal meningitis, we have studied the presence of binding sites for S fimbriae in different tissues of the neonatal rat which is susceptible to meningitis caused by S-fimbriated E. coli. Purified S fimbriae were incubated on cryostat sections of different rat organs and their binding was assessed by indirect immunofluorescence. In the brain of the neonatal rat, S fimbriae specifically bound to the luminal surfaces of the vascular endothelium and of the epithelium lining the choroid plexuses and brain ventricles. The binding was completely inhibited by the trisaccharide NeuAc alpha 2-3Gal beta 1-4Glc, a receptor analogue of S fimbriae, and by a preceding neuraminidase treatment of the sections. A recombinant E. coli strain expressing S fimbriae adhered in large numbers to the same tissue sites in the neonatal brain sections as did the purified fimbriae, whereas the non-fimbriated host strain and a recombinant strain expressing P fimbriae did not adhere to brain tissues. The results suggest that adhesion of S-fimbriated bacteria to the binding sites observed in the neonatal brain has a pathogenetic role during bacterial invasion from circulation into the cerebrospinal fluid.
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PMID:Binding sites in the rat brain for Escherichia coli S fimbriae associated with neonatal meningitis. 289 10

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

Sepsis and lipopolysaccharide (LPS) trigger the systemic release of both cytokines and catecholamines. Cytokines are known to be capable of eliciting a stress hormone response in vivo. The present study sought insight into the effect of noradrenaline on LPS-induced release of tumor necrosis factor alpha (TNF) and interleukin 6 (IL-6) in human whole blood. Whole blood was incubated with LPS for 4 h at 37 degrees C in the presence and absence of noradrenaline and/or specific alpha and beta antagonists and agonists. Noradrenaline caused a dose-dependent inhibition of LPS-induced TNF and IL-6 production. This effect could be completely prevented by addition of the specific beta 1, antagonist metoprolol, while it was not affected by the alpha antagonist phentolamine. Specific beta-adrenergic stimulation by isoprenaline mimicked the inhibiting effect of noradrenaline on LPS-evoked cytokine production, whereas alpha-adrenergic stimulation by phenylephrine had no effect. Fluorescence-activated cell sorter analysis demonstrated that beta-adrenergic stimulation had no effect on LPS binding to and internalization into mononuclear cells or on the expression of CD14, the major receptor for LPS on mononuclear cells. In acute sepsis, enhanced release of noradrenaline may be part of a negative feedback mechanism meant to inhibit ongoing TNF and IL-6 production.
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PMID:Noradrenaline inhibits lipopolysaccharide-induced tumor necrosis factor and interleukin 6 production in human whole blood. 816 70

In a effect to prevent nosocomial pneumonia and sepsis, we treated patients with severe multiple trauma with an immunomodulator--beta 1-3 polyglucose (glucan). Forty-one patients with no infection at admission were stratified using Trauma Score and included in a randomized double-blind controlled trial. They were divided into a control group (n = 20) and a glucan group (n = 21). Pneumonia occurred in 11 of 20 patients in the control group and in two of 21 recipients of glucan (p < 0.01). Sepsis occurred in seven of 20 patients in the control group and in two of 21 patients treated with glucan (p < 0.05). Considering patients with pneumonia and sepsis, a decrease was observed in nosocomial infection from 65.0 to 14.4 percent (p < 0.001). The mortality rate related to infection was 30.0 percent in patients in the control group and 4.8 percent in the group treated with glucan (p < 0.05). The general mortality rate, cerebral deaths excluded, was 42.1 percent in the control group and 23.5 percent in the glucan group.
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PMID:Infection prevention in patients with severe multiple trauma with the immunomodulator beta 1-3 polyglucose (glucan). 821 83

Norepinephrine and epinephrine stimulate alpha- and beta-adrenergic receptors which, in turn, modulate force of contraction in heart muscle cells. However, chronic stimulation may be associated with growth-promoting effects and modulation of the cardiac phenotype. Sympathetic tone is chronically enhanced in chronic heart failure and results in a selective down regulation of beta 1 adrenergic receptors, most likely due to local mechanisms. Beyond reduced beta 1 receptor density and increased levels of inhibitory Gi proteins, there is now evidence that NO can modulate the beta-adrenergic stimulation in the human myocardium. Increased NO activity generated by an inducible NO synthase is associated with a reduced positive inotropic response to beta-agonists, a mechanism which may play an important role in inflammatory states such as myocarditis or sepsis. Experimental data suggests that stimulation of alpha-adrenergic receptors of cardiomyocytes results in cardiac growth and changes in phenotype which, in turn, may affect the functional properties of the myocardium. For example, phenylephrine can upregulate the expression of the sodium/calcium exchanger, while the expression SR Ca2+ ATPase may be reduced. The latter is also affected by angiotensin II. Similar changes in the expression of these crucial proteins for the cardiac calcium homeostasis have been reported in the failing human heart, raising the possibility that the increased sympathetic tone and the activated renin-angiotensin system may be involved in these changes.
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PMID:[Sympathetic nervous system in heart failure: effect of catecholamines and nitric oxide]. 906 72


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