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)

The reticuloendothelial stimulant glucan, a beta-1,3-polyglucose component of the cell wall of Saccharomyces cerevisiae, was evaluated for its ability to modify Staphylococcus aureus-induced lethality in normal and leukemic mice. In normal mice the intravenous injection of glucan (0.45 mg per mouse) 7 and 4 days prior to intravenous challenge with S. aureus (1.0 x 10(9)) resulted in a significantly increased survival. Histological examination of the kidneys revealed that glucan significantly inhibited renal necrosis associated with systemic staphylococcal diseases. Further studies indicated that glucan administration not only enhanced survival of leukemic mice, but also increased survival of leukemic mice with experimentally induced staphylococcal speticemia. These data denote that glucan enhances nonspecific resistance to S. aureus sepsis, promotes survival during leukemic episodes, and increases survival time of leukemic mice with experimentally induced staphylococcal infection.
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PMID:Protective effect of glucan against systemic Staphylococcus aureus septicemia in normal and leukemic mice. 35 59

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

Two multicenter controlled clinical trials of genetically engineered monoclonal antibodies directed against endotoxin, a potent mediator of inflammation in the gram-negative sepsis syndrome, were recently reported in the medical literature. One of these antiendotoxin antibodies was derived from a murine (mouse) source, and the other antibody was derived mainly from a human source (nebacumab [negative bacteria human monoclonal antibody]). This article reviews recent literature concerning the use of these agents in the treatment of gram-negative sepsis syndrome. It also projects economic assessment data regarding the use of nebacumab in the United States.
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PMID:Update on monoclonal antibody therapy in the gram-negative sepsis syndrome. 142 60

Previous experimental and clinical studies have demonstrated the ability of polyclonal antibody directed against the core lipopolysaccharide (LPS)-lipid A component of endotoxin to reduce mortality. We sought to characterize the ability of a single murine monoclonal IgG1 antibody (8A1 MAb) to react to a variety of gram-negative microorganisms, to promote phagocytosis, and to provide protection during experimental murine sepsis. The 8A1 MAb reacted to various gram-negative bacterial whole cell and LPS antigens examined by enzyme-linked immunosorbent assay. Reactivity was highest to Salmonella minnesota Re LPS and lipid A. Phagocytosis was promoted by this monoclonal antibody to several gram-negative bacteria, except Pseudomonas aeruginosa. The 8A1 MAb (2 mg per mouse) enhanced survival during bacteremia due to either Escherichia coli 0111:B4 or Klebsiella pneumoniae, and during endotoxemia due to all types of LPS examined except P aeruginosa. We concluded that a single MAb with anti-lipid A specificity was cross reactive in vitro and cross protective in vivo. A clinical trial comparing polyclonal and monoclonal antibody in high-risk septic patients seems warranted.
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PMID:Immunotherapy of gram-negative bacterial sepsis. A single murine monoclonal antibody provides cross-genera protection. 394

Glucan, a beta-1,3 polyglucose, was evaluated for its ability to enhance resistance of post-operative mice to experimentally induced C. albicans sepsis. Male C57BL/6J mice were injected i.v. with glucan (0.45 mg/mouse) on days 10,7,4 and 1 prior to midline laparotomy and intravenous challenge with 3 X 10(6) C. albicans. The detrimental effect of surgery on survival following C. albicans infection was manifested by a 47% survival in the non-surgery-infected group in contrast to 20% in the surgery-infected group. Protection against C. albicans was observed in the glucan-treated groups. The glucan-treated non-operated mice manifested 100% survival while the surgery group had a 73% survival. Glucan significantly enhanced macrophage phagocytic function in control and operated mice. Laparotomy alone did not significantly depress macrophage phagocytosis. Histopathological studies revealed that glucan markedly inhibited the renal pathology associated with C. albicans challenge both in the presence and absence of laparotomy. These data indicate that glucan increased survival and reduced renal pathology associated with C. albicans challenge in the post-operative period. These observations suggest that Biologic Response Modifiers such as glucan may be effectively employed in patients who are at risk for post-operative infections.
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PMID:Modification of post-operative C. albicans sepsis by glucan immunostimulation. 672 65

The benefits of nitric oxide synthase (NOS) inhibitors in the treatment of endotoxemia or sepsis presumably arise from inhibition of the type II (inducible) NOS. However, inasmuch as the effect of these inhibitors on NOS function in vivo is rarely assessed, NOS activity was evaluated in rats and mice by measuring changes in plasma nitrite and nitrate concentrations ([NOx]) after administration of lipopolysaccharide (LPS). In both species, [NOx] peaked at 20 hr, returning to base line by 48 to 72 hr. The ED50 values (dose that elicited a 50% inhibition of the LPS-dependent increase in [NOx] 6 hr after LPS administration) for L-NG-monomethylarginine acetate, L-NG-nitroarginine methyl ester and aminoguanidine (administered 3 hr after LPS) were 34, 21 and 19 mg/kg in the rat and 32, 5 and 4 mg/kg in the mouse. These compounds also decreased the survival of LPS-challenged animals, which in the case of L-NG-nitroarginine methyl ester was reversed by L-arginine. Dexamethasone (which prevents the induction of type II NOS) also inhibited the LPS-dependent increase in [NOx] with ED50 values of 0.05 mg/kg (rat) and 1 mg/kg (mouse), but did not lead to decreased survival. Thus, inhibition of the type I (neuronal) or type III (endothelial) NOS, rather than the type II isoform, may be a possible mechanism for the animal mortality. These models provide a simple and reproducible means for assessing the in vivo inhibition of type II NOS by various compounds.
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PMID:Lipopolysaccharide-induced changes in plasma nitrite and nitrate concentrations in rats and mice: pharmacological evaluation of nitric oxide synthase inhibitors. 753 50

Bacterial lipopolysaccharide (LPS) stimulates the production and release of endogenous mediators [e.g., tumor necrosis factor (TNF), interleukins-1 and -6 (IL-1 and IL-6), and Platelet Activating Factor [PAF] responsible for the pathophysiologic changes and the mortality associated with sepsis. We recently demonstrated that lysozyme (LZM) bound to LPS (LZM-LPS complex) suppresses LPS-induced tumor necrosis factor-alpha (TNF-alpha) production in vivo. In the present study, we investigated the effect of LZM-LPS complex formation on LPS-induced IL-6 production, both in vitro and in vivo. With the addition of LZM-LPS complex, TNF-alpha and IL-6 release was significantly reduced compared with that by LPS in a dose-dependent manner in mouse macrophage-like cells, RAW264.7. IL-6 production in serum by LPS in carrageenan (CAR)-primed mice peaked at 2 hr following injection. LZM-LPS and LZM-Escherichia coli cell complex (as 1 microgram of LPS per mouse) released significantly reduced concentrations of IL-6 in serum (P < 0.01 and P < 0.001 versus CAR-pretreated LPS- or cell-injected mice). These results emphasize the important role of LZM in vivo in the neutralization of endotoxin. However, in the case of IL-6, by administration of a lethal dose of LPS (as 100 micrograms of LPS per mouse), the IL-6 level was reduced by LZM, but a significant concentration of IL-6 was still released; although the TNF- alpha concentration was negligible in this experimental condition. Thus, it is suggested that LZM might regulate the systemic inflammation induced during Gram-negative bacterial infections by inhibiting the release of cytokines in serum.
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PMID:Lysozyme regulates LPS-induced interleukin-6 release in mice. 762 57

Cytokine production was measured in mice during Salmonella typhimurium sepsis and intoxication. In mice given live S. typhimurium (10 cfu/mouse), by intra-peritoneal injection, serum levels of tumour necrosis factor (TNF)-alpha and interleukin-6 increased steadily from day 1 until day 4. Interferon-gamma levels showed a transient peak on day 3. Interleukin-1-alpha levels were very low. There were high bacterial counts in the livers at day 3 and deaths occurred from day 4 onwards. Intraperitoneal injection of lipopolysaccharide or heat-killed bacteria also induced all of the cytokines, but their time of appearance and levels varied greatly. Cytokine induction by heat-killed bacteria was more marked. Endotoxaemia decreased with time during intoxication and increased during sepsis. Bioactive TNF, as measured by a cytotoxicity assay, was found only in mice given heat-killed bacteria.
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PMID:Cytokine stimulation during Salmonella typhimurium sepsis in Itys mice. 775 14

Leukemia inhibitory factor (LIF) has recently been associated with septic shock in humans. In this study we sought to determine, in mice, the role of LIF in septic shock. During sublethal endotoxemia, serum LIF levels, as determined by radio-receptor competition assay, peaked at 2 h and were low (3 ng/ml), whereas in lethal Escherichia coli septic shock serum LIF levels rose progressively (> 30 ng/ml) in the premorbid phase coincident with the development of tissue injury. Single i.v. injections of high doses (up to 50 micrograms per mouse) of recombinant murine LIF had no obvious acute detrimental effects, whereas continued i.p. administration (30 micrograms per mouse per day) for 3-4 days induced a fatal catabolic state without evidence of preceding hemodynamic collapse or shock. Simultaneous or subsequent administration of high doses of LIF had no effect on mortality from sublethal and lethal E. coli septic shock, whereas prior administration conferred significant protection against lethality (P << 0.001 by log-rank test), an effect that was dose and interval dependent. This protective effect resembled endotoxin tolerance and was characterized by suppression of E. coli-induced serum tumor necrosis factor concentration (P < 0.05), reduction in the number of viable bacteria (P < 0.05), and prevention of sepsis-induced tissue injury. These observations suggest that systemic LIF production is part of the host response to both endotoxin and sepsis-induced tissue injury.
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PMID:Leukemia inhibitory factor protects against experimental lethal Escherichia coli septic shock in mice. 787 78

A human intravenous IgG preparation (Anti-LPS IgG) rich in antibodies to different lipopolysaccharides (LPS) and a normal human intravenous IgG (NIgG) were investigated for their ability to confer passive immunity. Both preparations were given at the time of infection (prophylaxis) or during sepsis (therapy) to burned mice with lethal infection induced by various clinically relevant gram-negative bacteria. When given at the time of infection both IgG preparations (5 mg/mouse) inhibited lethality induced by some bacteria (Pseudomonas aeruginosa serogroup G and B), but not others (Serratia marcescens, Klebsiella pneumonia, Proteus mirabilis), indicating a protection by by strain-specific antibodies. However, no significant protection was seen when mice were treated during sepsis. The range of specific antibody titers to the whole live bacteria and heat-killed (LPS-preserved) bacteria in the NIgG paralleled that of Anti-LPS IgG; however, the magnitude of the antibody titers did not accurately reflect the protective capacity in vivo. Thus, the exact specificity of the protective antibodies is still unknown. The protective effect of both IgG preparations was dose-dependent; at low IgG doses (0.5 mg/mouse) better protection was obtained with Anti-LPS IgG, whilst at higher doses (> or = 1 mg/mouse) both preparations exhibited identical effects. Low doses of either IgG preparation in combination with subtherapeutic doses of piperacillin significantly enhanced early survival (day 2 for NIgG and day 2 + 3 for Anti-LPS IgG) against P. aeruginosa, but the protective effect waned thereafter. We conclude that a strain-specific antibacterial effect in a compromised mouse infection model can be obtained by early passive immunization with human IgG from large plasma pools. It is suggested that Anti-LPS IgG or NIgG may be of benefit in some cases of gram-negative sepsis when administered as prophylaxis together with proper antibiotic treatment.
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PMID:Effect of a human IgG preparation rich in antibodies to a wide range of lipopolysaccharides on gram-negative bacterial sepsis in burned mice. 850 60


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