Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of sub-MICs of ciprofloxacin and tobramycin on the cell surface characteristics and extracellular virulence factors of Pseudomonas cepacia were evaluated. Cells were grown in batch culture under iron-deficient and iron-replete conditions. At sub-MIC levels that did not affect bacterial growth cell surface hydrophobicity decreased under both iron-replete and iron-depleted conditions with ciprofloxacin, but increased with tobramycin under iron-sufficient conditions. Exopolysaccharide synthesis, lipase production and siderophore production were all significantly increased by the presence of ciprofloxacin under both growth conditions. Outer membrane protein and lipopolysaccharide profiles were not affected by exposure to the two antibiotics.
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PMID:Effect of sub-MIC antibiotics on the cell surface and extracellular virulence determinants of Pseudomonas cepacia. 751 77

We sought to characterize factors released by sonicated human erythrocytes that stimulate peripheral blood mononuclear cells (PBMC) to release tumour necrosis factor-alpha (TNF). This response is not inhibited by polymyxin B, indicating that contaminating lipopolysaccharide (LPS) is not responsible. When erythrocyte lysates are fractionated by reverse-phase chromatography using a gradient of n-propanol on Sep-Pak C18 cartridges, the TNF-inducing activity elutes as a single peak. The erythrocyte-derived TNF-inducing activity is unaffected by digestion with proteases but is destroyed by mild base hydrolysis or digestion by lipases, indicating that compounds containing ester-linked acyl chains may be essential. These properties are similar to those of TNF stimulators that we have previously identified in erythrocytes infected with malaria parasites, except that the TNF-inducing activity per cell is about 200 times higher in parasitized erythrocytes than in uninfected erythrocytes. Lipase-digested erythrocyte lysates inhibit the TNF-inducing factors of both normal and malaria-infected erythrocytes, suggesting that lipase digestion creates partial structures which compete with active components for macrophage receptors. Such receptors may recognize a common structure that contains an inositol monophosphate (IMP)-like component, as IMP also inhibits the TNF response to erythrocyte-derived factors and to parasite lysates whereas it does not affect the response to LPS. We conclude that lysed erythrocytes release specific cytokine-inducing factors that may contribute to the fever response to non-infectious tissue injury.
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PMID:Stimulators of tumour necrosis factor production released by damaged erythrocytes. 783 44

A novel fluorescence assay for phospholipase A2 [Wilton (1990) Biochem. J. 266, 435-439] has been used to study the Group-II rat liver mitochondrial enzyme, and a number of novel properties of this enzyme were identified. (1) The enzyme activity was located in the liver macrophages (Kupffer cells) while negligible activity was associated with hepatocytes. (2) Although subcellular fractionation of whole liver confirmed the predominantly mitochondrial location of this enzyme activity, the analysis of the hepatocyte-free Kupffer-cell-enriched fraction revealed a different enzyme distribution, with the majority of activity being associated with the microsomal membrane fraction. (3) Bacterial endotoxin has been previously shown to be scavenged by Kupffer cells in rats. Treatment of rats with bacterial lipopolysaccharide (endotoxin) resulted in a dramatic time- and dose-dependent increase in liver phospholipase A2 activity. (4) It is known that injection of endotoxin into rodents results in elevated serum phospholipase A2 activity, while a similar phenomenon is seen in the condition of septic shock in man. The source of this serum enzyme was unknown. In this study perfusion of livers from rats pretreated with lipopolysaccharide with physiological saline demonstrated a 6-fold increase in phospholipase A2 activity in the perfusate compared with sham-treated controls, with only minor release of hepatic lipase. (5) Western-blot analysis confirmed an increased release of this Group-II phospholipase A2 into the perfusate of lipopolysaccharide-treated rats compared with sham-treated controls. These results suggest that liver Kupffer cells are a major source of the endotoxin-induced serum Group-II phospholipase A2 activity associated with bacterial infection and trauma.
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PMID:Rat liver mitochondrial phospholipase A2 is an endotoxin-stimulated membrane-associated enzyme of Kupffer cells which is released during liver perfusion. 832 56

The effects of in vivo lipopolysaccharide administration on serum lipid metabolism were studied in normal and hepatoma-bearing rats. Changes in serum lipid levels and adipose tissue lipase (lipoprotein lipase and hormone-sensitive lipase) activities following injection of lipopolysaccharide into normal rats resembled those in hepatoma-bearing rats. These results suggest the presence of some common factor(s) involved in the incidence of abnormal lipid metabolism upon lipopolysaccharide injection and hepatoma transplantation.
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PMID:Responses of serum lipids and adipose tissue lipases to lipopolysaccharide administration in normal and hepatoma-bearing rats. 890 Nov 18

Infection with Helicobacter pylori (H. pylori) is now recognized as a major factor in the pathogenesis of gastric disease, and the successful therapy regimens require a combination of H2 blockers with gastroprotective and antimicrobial agents. Ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene) amino]-4-thiazolyl] methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfonamide, CAS 100981-43-9, FI-3542) is the only drug combining acid-suppressant activity with remarkable gastroprotective and anti-H. pylori properties. The drug not only displays a potent anti-H. pylori activity alone, but also exerts a strong potentiating effect on the efficacy of antimicrobial agents commonly used for H. pylori eradication, and the successful ulcer therapy with ebrotidine induces a significant (4-fold) increase in the H. pylori aggregation titer of gastric mucin. Moreover, the drug exhibits a strong inhibitory effect on H. pylori urease activity, the extent of which exceeds that of ranitidine, omeprazole and lansoprazole. Ebrotidine has also been demonstrated to exert a potent inhibitory action on the enzymatic activities directed towards mucus perimeter of gastric mucosal defense, causing a marked inhibition of H. pylori protease, lipase and phospholipase A2 activities. Another important property of ebrotidine is its ability to efficiently counteract the disruptive effects of H. pylori lipopolysaccharide on the integrity of gastric epithelium. This includes countering the interference by the lipopolysaccharide in mucosal integrin receptor interaction with proteins of extracellular matrix and the reversal of H. pylori disruptive effect on the binding of mucin to its gastric epithelial receptor. Furthermore, most recent data indicate that ebrotidine has the ability to reverse the impairment caused by H. pylori in feedback inhibition of gastrin release by somatostatin. This activity of ebrotidine apparently stems from the drug's ability to counter the untoward effect of H. pylori on the binding of somatostatin to its specific receptor on the gastric mucosal G-cells. The unique combination of acid suppressant, gastroprotective and anti-H. pylori activities makes ebrotidine a drug of choice in the treatment of gastric disease caused by H. pylori.
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PMID:Anti-Helicobacter pylori activities of ebrotidine. A review of biochemical and animal experimental studies and data. 920 47

1. We compared the effects of calpain inhibitor I (inhibitor of the proteolysis of I kappa B and, hence, of the activation of nuclear factor kappa B (NF kappa B) and dexamethasone on (i) the circulatory failure, (ii) multiple organ dysfunction and (iii) induction of the inducible isoforms of nitric oxide (NO) synthase (iNOS) and cyclo-oxygenase (COX-2) in anaesthetized rats with endotoxic shock. 2. Injection of lipopolysaccharide (LPS, E. coli, 10 mg kg-1, i.v.) resulted in hypotension and a reduction of the pressor responses elicited by noradrenaline. This circulatory dysfunction was attenuated by pretreatment of LPS-rats with calpain inhibitor I (10 mg kg-1, i.v., 2 h before LPS) or dexamethasone (1 mg kg-1, i.v.). 3. Endotoxaemia also caused rises in the serum levels of (i) urea and creatinine (renal dysfunction), (ii) alanine aminotransferase (ALT), aspartate aminotransferase (AST) (hepatocellular injury), bilirubin and gamma-glutamyl transferase (gamma GT) (liver dysfunction), (iii) lipase (pancreatic injury) and (iv) lactate. Calpain inhibitor I and dexamethasone attenuated the liver injury, the pancreatic injury, the lactic acidosis as well as the hypoglycaemia caused by LPS. Dexamethasone, but not calpain inhibitor I, reduced the renal dysfunction caused by LPS. 4. Endotoxaemia for 6 h resulted in a substantial increase in iNOS and COX-2 protein and activity in lung and liver, which was attenuated in LPS-rats pretreated with calpain inhibitor I or dexamethasone. 5. Thus, calpain inhibitor I and dexamethasone attenuate (i) the circulatory failure, (ii) the multiple organ dysfunction (liver and pancreatic dysfunction/injury, lactic acidosis, hypoglycaemia), as well as (iii) the induction of iNOS and COX-2 protein and activity in rats with endotoxic shock. We propose that prevention of the activation of NF-kappa B in vivo may be useful in the therapy of circulatory shock or of disorders associated with local or systemic inflammation.
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PMID:Effect of calpain inhibitor I, an inhibitor of the proteolysis of I kappa B, on the circulatory failure and multiple organ dysfunction caused by endotoxin in the rat. 920 36

1 Here we compared the effects of various inhibitors of the activity of protein tyrosine kinase on (i) the expression of the activity of the inducible isoform of nitric oxide (NO) synthase (iNOS) caused by endotoxin (lipopolysaccharide, LPS) in cultured macrophages, (ii) the induction of iNOS and cyclooxygenase 2 (COX-2) protein and activity in rats with endotoxaemia, and (iii) the circulatory failure and organ dysfunction caused by LPS in the anesthetized rat. 2 Activation of murine cultured macrophages with LPS (1 microgram ml-1) resulted, within 24 h, in a significant increase in nitrite (an indicator of the formation of NO) in the cell supernatant. This increase in nitrate was attenuated by the tyrphostins AG126, AG556, AG490 or AG1641 or by genistein in a dose-dependent fashion (IC50: approximately 15 microM). In contrast, tyrphostin A1 (an analogue of tyrphostin AG126) or daidzein (an analogue of genistein) had no effect on the rise in nitrite caused by LPS. 3 Administration of LPS (E. coli, 10 mg kg-1, i.v.) caused hypotension and a reduction of the pressor responses elicited by noradrenaline (NA, 1 microgram kg-1, i.v.). Pretreatment of rats with the tyrphostins AG126, AG490, AG556, AG1641 or A1 attenuated the circulatory failure caused by LPS. Although genistein attenuated the vascular hyporeactivity to NA, it did not affect the hypotension caused by LPS. Daidzein did not affect the circulatory failure caused by LPS. 4 Endotoxaemia for 360 min resulted in rises in the serum levels of (i) urea and creatinine (indicators of renal failure), (ii) alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin and gamma-glutamyl transferase (gamma GT) (indicators of liver injury/dysfunction), lipase (an indicator of pancreatic injury) as well as lactate (an indicator of tissue hypoxia). None of the tyrosine kinase inhibitors tested had a significant effect on the rise i the serum levels of urea, but the tyrphostins AG126, AG556 or A1 significantly attenuated the rises in the serum level of creatinine caused by LPS. In addition, all tyrphostins and genistein attenuated the liver injury/failure, the pancreatic injury, the hypoglycaemia and the lactic acidosis caused by LPS. In contrast, daidzein did not reduce the organ injury/dysfunction or the lactic acidosis caused by LPS. 5 Injection of LPS resulted (within 90 min) in a substantial increase in the serum level of tumor necrosis factor alpha (TNF alpha), which was attenuated by pretreatment of LPS-rats with any of the tyrphostins used. Genistein, but not daidzein, also reduced the rise in the serum levels of TNF alpha caused by LPS. Endotoxaemia for 6 h also resulted in a substantial increase in the expression of iNOS and COX-2 protein and activity in the lung, which was attenuated by pretreatment of LPS-rats with the tyrphostins AG126, AG556 or genistein, but not by daidzein. 6 Thus, tyrphostins (AG126, AG556, AG1641 or A1) and genistein, but not daidzein (inactive analogue of genistein), prevent the (i) circulatory failure, (ii) the multiple organ dysfunction (liver and pancreatic dysfunction/injury lactacidosis, hypoglycaemia), as well as (iii) the induction of iNOS and COX-2 protein and activity in rats with endotoxic shock.
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PMID:Effects of tyrphostins and genistein on the circulatory failure and organ dysfunction caused by endotoxin in the rat: a possible role for protein tyrosine kinase. 929 29

Over the last 30 years, Serratia marcescens has become an important cause of nosocomial infection. There have been many reports concerning the identification, antibiotic susceptibility, pathogenicity, epidemiological investigations and typing of this organism. Accurate identification is important in defining outbreaks. The API 20E system has been used widely, but is not individually satisfactory. The growth of S. marcescens in the environment has been investigated in relation to water, disinfectants and plastics such as blood bags. Certain extracellular products are unique to S. marcescens. Pigment (prodigiosin) biosynthesis by S. marcescens has been investigated fully since the emergence of the organism as a cause of infection. Many other aspects of the pathogenicity and virulence of S. marcescens have been studied, including adherence and hydrophobicity, lipopolysaccharide (LPS) and extracellular products. Two modes of adhesion to host epithelial surfaces have been suggested. These are mannose-resistant (MR) pili and mannose-sensitive (MS) pili. LPS, which is responsible for the biological activity of endotoxin, has been investigated fully and 24 somatic antigens have been described. The production of different enzymes by S. marcescens as virulence factors has also been reported, including chitinase, lipase, chloroperoxidase and an extracellular protein, HasA. Antibiotics used to treat serratia infection include beta-lactam agents, aminoglycosides and fluoroquinolones and a variety of different resistance mechanisms have been demonstrated. Typing methods used to study the epidemiology of S. marcescens include biotyping, bacteriocin typing, phage typing, plasmid analysis, polymerase chain reaction amplification of enterobacterial repetitive intergenic consensus sequences (ERIC-PCR) and ribotyping. Serological typing has also been used and this method seems to be a suitable first-line typing method for S. marcescens, although some strains remain untypable. RAPD-PCR has also been applied to a small number of isolates and seems to be a promising method, especially for rapid monitoring of an outbreak and tracing the source of initial infection.
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PMID:Serratia marcescens. 936 30

1. An enhanced production of nitric oxide (NO) from L-arginine, related to the diffuse expression of an inducible NO synthase (iNOS), contributes to the pathogenesis of endotoxic shock. Since iNOS activity depends on extracellular L-arginine, we hypothesized that limiting cellular L-arginine uptake would reduce NO production in endotoxic shock. We investigated the effects of L-lysine, an inhibitor of L-arginine uptake through system y+, on NO production, multiple organ dysfunction and lactate levels, in normal and endotoxaemic rats. 2. Anaesthetized rats challenged with intravenous lipopolysaccharide (LPS, 10 mg kg[-1]) received a 5 h infusion of either L-lysine (500 micromol kg(-1) h(-1), n = 12) or isotonic saline (2 ml kg(-1) h(-1), n = 11). In rats treated with saline, LPS produced a large increase in plasma nitrate and L-citrulline concentrations at 5 h, both markers of enhanced NO production. LPS also caused severe hypotension, low cardiac output and marked hyperlactataemia. All these changes were significantly reduced by L-lysine administration. 3. Endotoxaemia also caused a significant rise in the plasma levels of alanine aminotransferase (ALAT), lipase, urea and creatinine, and hence, liver, pancreatic and renal dysfunction. These changes tended to be less pronounced in rats treated with L-lysine, although the differences did not reach statistical significance. 4. Similar experiments were conducted in 10 rats challenged with LPS vehicle in place of LPS and then treated with L-lysine (500 micromol kg(-1) h(-1), n = 5) or saline (2 ml kg(-1) h(-1), n = 5) for 5 h. In these animals, all the haemodynamic and metabolic variables remained stable and not statistically different between both treatment groups, except for a slight rise in ALAT, which was comparable in L-lysine and saline-treated rats. 5. In conclusion, L-lysine, an inhibitor of cellular L-arginine uptake, reduces NO production and exerts beneficial haemodynamic effects in endotoxaemic rats. L-lysine also reduces hyperlactataemia and tends to blunt the development of organ injury in these animals. Contrastingly, L-lysine has no effects in the absence of endotoxin and thus appears to act as a selective modulator of iNOS activity.
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PMID:Effect of L-lysine on nitric oxide overproduction in endotoxic shock. 937 72

The effects of two nitric oxide synthase (NOS) inhibitors with different isoform selectivity were compared in a murine model of endotoxemia. Mice challenged with 70 mg/kg intraperitoneal (ip) lipopolysaccharide (LPS) were treated 6 h after LPS with either NG-gamma-L-arginine methyl ester (L-NAME, nonselective NOS inhibitor, 10-60 mg/kg), L-canavanine (selective inhibitor of inducible NOS, 50-300 mg/kg), or saline (0.2 mL) given ip. In a subset of mice, plasma concentrations of nitrate (NO breakdown product), lipase (pancreas injury), lactate dehydrogenase, and transaminases (liver injury) were measured 16 h after LPS. Although both inhibitors reduced plasma nitrate, they produced contrasting effects on survival and organ injury. L-NAME enhanced liver damage and tended to accelerate the time of death, while L-canavanine significantly reduced mortality and had no deleterious effects in terms of organ damage. These results indicate that nonselective NOS inhibitors are detrimental in endotoxic shock and support the potential usefulness of selective inducible NOS inhibitors in this setting.
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PMID:Nonselective versus selective inhibition of inducible nitric oxide synthase in experimental endotoxic shock. 941 79


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