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

A novel composite hypertonic solution for intravenous use was tested in two experimental models, one of endotoxic shock and one of shock linked with dehydration, both in anaesthetised calves. Endotoxic shock was induced with Escherichia coli lipopolysaccharide and was characterised by a low cardiac output, hypoxaemia, acidosis and anuria. Treatment with a small volume of the solution increased cardiac output, improved oxygen carriage, corrected acidosis and stimulated renal function. Experimental dehydration in calves was induced by intraperitoneal mannitol and frusemide diuresis, and was characterised by reduced circulating plasma volume, acidosis and poor peripheral perfusion. Treatment with the new solution corrected the acidosis and stimulated peripheral circulation significantly better than treatment with hypertonic or isotonic saline alone, and also expanded the calves' plasma volume. The new solution was also compared with conventional fluid therapy in clinical small animal practice. Twenty cats and dogs with clinical shock were treated with either small volumes of the hypertonic solution or large volumes of isotonic fluids. The animals treated with small volumes of the hypertonic solution responded better than the animals treated with large volumes of isotonic fluid.
 ...
PMID:A hypertonic infusion in the treatment of experimental shock in calves and clinical shock in dogs and cats. 811 68

Antibody neutralization studies have established interferon gamma (IFN-gamma) as a critical mediator of endotoxic shock. The advent of IFN-gamma receptor negative (IFN gamma R-/-) mutant mice has enabled a more direct assessment of the role of IFN-gamma in endotoxin (lipopolysaccharide [LPS]-induced shock. We report that IFN gamma R-/- mice have an increased resistance to LPS-induced toxicity, this resistance manifesting well before the synthesis and release of LPS-induced IFN-gamma. LPS-induced lymphopenia, thrombocytopenia, and weight loss seen in wild-type mice were attenuated in IFN gamma R-/- mice. IFN gamma R-/- mice tolerated 100-1,000 times more LPS than the minimum lethal dose for wild-type mice in a D-galactosamine (D-GalN)/LPS model. Serum tumor necrosis factor (TNF) levels were 10-fold reduced in mutant mice given LPS or LPS/D-GalN. Bone marrow and splenic macrophages from IFN gamma R-/- mice had a four- to sixfold decreased LPS-binding capacity which correlated with similar reduction in CD14. Serum from mutant mice reduced macrophage LPS binding by a further 50%, although LPS binding protein was only 10% reduced. The expression of TNF receptor I (p55) and II (p75) was identical between wild-type and mutant mice. Thus, depressed TNF synthesis, diminished expression of CD14, and low plasma LPS-binding capacity, in addition to blocked IFN-gamma signaling in the mutant mice, likely to combine to manifest in the resistant phenotype of IFN gamma R-/- mice to endotoxin.
 ...
PMID:Interferon gamma receptor deficient mice are resistant to endotoxic shock. 816 30

A rat model of endotoxic shock was used to evaluate the effects of dimethylthiourea, a putative hydroxyl radical scavenger, in the alterations of lung phosphatidylcholine biosynthesis found during endotoxemia. Treatment of rats with dimethylthiourea, just before lipopolysaccharide injection, resulted in a decreased lipid peroxidation and an increase in phosphatidylcholine biosynthesis, although it did not prevent the body weight loss or the increase in lung weight and lung protein content associated with the lung injury induced by lipopolysaccharide. Our results suggest that phosphatidylcholine biosynthesis is impaired by processes in which hydroxyl radicals are implicated, although other oxygen free radical species, not removed by dimethylthiourea, can be also involved in lipopolysaccharide mediated lung injury.
 ...
PMID:Effect of dimethylthiourea in phosphatidylcholine biosynthesis by rat lung during reversible endotoxic shock. 817 23

We investigated the effects of gadolinium chloride (GdCl3.6H2O), which blocks phagocytosis by liver macrophages, on the mortality, blood tumor necrosis factor (TNF) levels, and hepatotoxicity in a lethal endotoxic shock rat model system [10 mg/kg body weight lipopolysaccharide (LPS) intravenously]. With administration of GdCl3, twice at 0.5 or 5 mg/kg, the survival rate 24 h after LPS injection was 56% and 100%, respectively, whereas the level of TNF in blood was not affected. Microscopic investigation of the liver revealed that the focal necrosis of hepatocytes under endotoxemia was completely protected by the administration of GdCl3 at 5 mg/kg. We then investigated the effects of GdCl3 on superoxide (O2-) production by isolated liver macrophages in vitro. The O2- production by liver macrophages isolated from control rats was suppressed by GdCl3 in a dose-dependent manner. GdCl3 also had a cytotoxic effect on these macrophages. The enhanced O2- production by liver macrophages isolated from sublethal endotoxemic (1 mg/kg) rats was suppressed by pretreatment with GdCl3 (5 mg/kg). It was suggested that lethality in endotoxemia cannot be explained only by the degree of increase in blood TNF levels and that the mechanism by which GdCl3 reduces mortality and hepatotoxicity in endotoxemia possibly includes suppression of superoxide production by liver macrophages.
 ...
PMID:Blockade of liver macrophages by gadolinium chloride reduces lethality in endotoxemic rats--analysis of mechanisms of lethality in endotoxemia. 819 98

To measure interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-like activities in canine serum, bioassays were conducted using human melanoma A375S1, IL-6 dependent murine hybridoma MH60.BSF2, and WEHI 164 murine sarcoma subclone 28-4. Clinically normal adult beagles were experimentally induced endotoxic shock by an intravenous injection of lipopolysaccharide or local inflammation by an intramuscular injection of turpentine oil. IL-1-like activity was detected in sera from dogs with endotoxic shock. IL-6 and TNF-like activities were detected in sera from both dogs with endotoxic shock and local inflammation. IL-1-like activity in sera from the dogs with endotoxic shock declined after dilution with either medium or serum obtained before treatment (pre-serum), but the IL-1-like activity was maintained to a greater extent in samples diluted with pre-serum compared to those diluted with medium. TNF-like activity declined equally after dilution with either medium or pre-serum. On the other hand, IL-6-like activity was inhibited at low dilution. It was, therefore, necessary to dilute the serum samples to 1:180 from dogs with endotoxic shock or 1:60 from dogs with local inflammation, in order to minimize the effect of inhibitory factors on IL-6-like activity. IL-6-like activity was neutralized by monoclonal antibody against murine IL-6 receptors. TNF-like activity was neutralized by anti-mouse TNF alpha rabbit serum. However IL-1-like activity was not neutralized by either anti-mouse or anti-human IL-1 rabbit serum.
 ...
PMID:Bioassay for interleukin-1, interleukin-6, and tumor necrosis factor-like activities in canine sera. 820 33

Oxygen-derived radicals have been suggested to produce tissue injury during endotoxic shock by initiating lipid peroxidation. In order to investigate the induction of lipid peroxidation by Escherichia coli 0111:B4 lipopolysaccharide (LPS) on hepatocytes, malondialdehyde (MDA) and superoxide dismutase (SOD) activity have been evaluated in vivo and in vitro using two experimental models: rat liver after the establishment of endotoxic reversible shock, and cultured hepatocytes after treatment with LPS. Liver MDA levels were increased in vivo during the acute-phase of endotoxic shock, decreasing below control values in the recovery phase. An inverse pattern was obtained when SOD activity was measured, consistent with an active system of cellular protection. Similar results were obtained in vitro after treatment of cultured hepatocytes with LPS (50 micrograms/ml), thus indicating that a direct LPS cytotoxic effect on hepatocytes exits during the endotoxic process. The direct LPS interaction induced alterations in Ca2+ permeability of hepatocyte plasma membrane as detected by flow cytometry using the fluorescent probe Indo-1.
 ...
PMID:The induction of lipid peroxidation by E. coli lipopolysaccharide on rat hepatocytes as an important factor in the etiology of endotoxic liver damage. 825 29

Intraperitoneal injection of lipopolysaccharide (LPS) was used to elicit a sublethal, shock-like condition in mice. LPS, 2.5 mg/kg i.p., induced hypothermia, elevated serum TNF-alpha levels and lethality over a 48 h period in male CD-1 mice. The 5-lipoxygenase (LO) inhibitors, WY-50,295 tromethamine and zileuton (100 mg/kg p.o), significantly inhibited hypothermia at 4, 24 and 48 h after LPS. Interestingly, whereas cyclooxygenase (CO) inhibitors (ibuprofen, etodolac, naproxen and tenidap) at 40-80 mg/kg p.o. stimulated hypothermia at 4 h, they significantly reduced the later stages of hypothermia at 24-48 h. Rolipram (PDE-IV inhibitor) and dexamethasone significantly reduced hypothermia at 4-24 h and 1-24 h, respectively. All the anti-inflammatory agents significantly reduced elevated TNF-alpha levels at approximately 70 min post-LPS, except for ibuprofen. In conclusion, these anti-inflammatory standards indicate that LPS-induced shock involves multiple lipid mediators (PG's, LT's and possibly PAF) and secondary cytokine generation. This sublethal model of LPS-induced shock represents a sensitive model for estimating the efficacy of potential drug candidates for the treatment of endotoxic shock.
 ...
PMID:Inhibition of endotoxin-induced hypothermia and serum TNF-alpha levels in CD-1 mice by various pharmacological agents. 827 85

Two isoforms of cyclooxygenase (COX) have been identified in eukaryotic cells: COX-1 encoded by a 2.8-kb mRNA, and a mitogen-inducible COX-2 encoded by a 4-kb mRNA. We have cloned the COX-1 and COX-2 cDNAs from the cDNA library constructed from lipopolysaccharide (LPS)-stimulated rat peritoneal macrophages. The deduced amino acid sequence showed that COX-1 contained 602 amino acids, whereas COX-2 contained 604 amino acids. There is 95% conservation of the nucleotide sequence in the open reading frame of COX-1 between the rat and the mouse, while the homology of the 3' untranslated region is 68% except for a 150 bp segment adjacent to the stop codon which is nonhomologous with the mouse. Transfection of both COX cDNAs into Cos-7 cells resulted in increased COX activity. In rat vascular smooth muscle cells, interleukin-1 beta selectively increased the expression of COX-2, but not that of COX-1, as assessed by enzyme activity, immunoprecipitation of COX proteins, and mRNA analysis. Only the brain among tissues tested exhibits basal expression of COX-2 as the major form of the enzyme. However, COX-2 mRNA was expressed in vivo in the lung and kidney, but not in the heart, after systemic administration of LPS, suggesting that COX-2 but not COX-1 plays a major role in producing COX-derived products of arachidonic acid during endotoxic shock. Thus, the two COX isoforms were differentially expressed, and COX-2 was selectively induced in response to inflammatory stimuli in rats.
 ...
PMID:Cloning two isoforms of rat cyclooxygenase: differential regulation of their expression. 827 23

The adrenal glands have a crucial role for survival during endotoxic shock. Cholesterol is the obligatory intermediary in corticosteroid biosynthesis; thus any alteration in either the availability of cholesterol or in the ability of the adrenal gland to use cholesterol would have a profound effect on corticosteroid production. We have studied the effect of Escherichia coli endotoxin on cholesterol metabolism, injecting lipopolysaccharide (1.6 mg/100 g body) from E. coli 0111:B4 into the tail vein of male Wistar rat. Previous studies from this laboratory have shown that this dose of lipopolysaccharide induces a reversible endotoxic shock. During reversible endotoxic shock there is an alteration in plasma cholesterol; plasma total-cholesterol levels increase mainly at 6-24 h post-lipopolysaccharide injection, whereas cholesterol in high-density lipoproteins shows no significant variations, except a slight but significant decrease at 24 h. The cholesterol content in adrenal gland is diminished in endotoxemic rat, this decrease is more important at 6-24 h after endotoxin injection. We have also measured the acyl-CoA:cholesterol O-acyltransferase (ACAT) and cholesterol-esterase (CEH) activity during endotoxic shock. ACAT activity decreases after lipopolysaccharide injection. ACAT activity in endotoxemic rats is approximately 35-40% of the activity in control rats. This decrease is due to a defect in the functional capacity of the enzyme, since with exogenous cholesterol there is no significant variation in the ACAT activity. CEH activity, in contrast, increases during endotoxic shock; it shows a maximum (twofold the activity seen in control rats) at 6 h after lipopolysaccharide injection. These results show that lipopolysaccharide injection modifies cholesterol metabolism in plasma and in the adrenal gland, either directly or by mediators.
 ...
PMID:Cholesterol metabolism in rat adrenal gland during reversible endotoxic shock. 843 39

Close similarities of various physiological parameters makes the pig one of the preferred animal models for the study of human diseases, especially those involving the cardiovascular system. Unfortunately, the use of pig models to study diseases such as viral hemorrhagic fevers and endotoxic shock syndrome have been hampered by the lack of the necessary immunological tools to measure important immunoregulatory cytokines such as tumor necrosis factor (TNF). Here we describe a TNF-bioassay which is based on the porcine kidney cell line PK(15). Compared to the widely used murine fibroblastoid cell line L929, the PK(15) cell line displays a 100-1000-fold higher sensitivity for porcine TNF-alpha, a higher sensitivity for human TNF-alpha, and a slightly lower sensitivity for murine TNF-alpha. Using a PK(15) bioassay we can detect recombinant TNF-alpha as well as cytotoxic activity in the supernatants of lipopolysaccharide (LPS)-activated porcine monocytes at high dilutions. This suggests that the sensitivity of the test should permit the detection of TNF in biological specimens such as pig serum.
 ...
PMID:Improved bioassay for the detection of porcine tumor necrosis factor using a homologous cell line: PK(15). 845 14


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