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)

Tumour necrosis factor-alpha (TNF-alpha), a cytokine derived from macrophages, is considered to be an important endogenous mediator of endotoxic shock. Patients with fulminant hepatic failure are particularly susceptible to infection and the development of multi-organ failure and similarities to endotoxic shock suggest a possible pathogenetic role for TNF in fulminant hepatic failure. In vitro TNF production was therefore investigated serially in 21 consecutive patients with fulminant hepatic failure and in 21 healthy controls. Spontaneous and lipopolysaccharide-stimulated TNF production were elevated in viral-induced fulminant hepatic failure, compared with healthy controls (P less than 0.05 and P less than 0.01, respectively). By contrast, patients with paracetamol-induced fulminant hepatic failure had normal spontaneous and lipopolysaccharide-stimulated TNF production, while those who died had significantly reduced spontaneous TNF production compared with survivors (P less than 0.02); this difference was present throughout admission. In this group elevations in TNF production above baseline were associated with Gram-positive bacterial or fungal infection but not Gram-negative bacterial infection. There was no correlation between any of the clinical complications of fulminant microbial stimuli in fulminant hepatic failure, but do not support a direct role for TNF in the evolution of the clinical complications of fulminant hepatic failure.
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PMID:Tumour necrosis factor production in fulminant hepatic failure: relation to aetiology and superimposed microbial infection. 212 56

Reversible endotoxic shock was induced in adult rats by intravenous injection of E. coli 0111:B4 lipopolysaccharide (LPS) and the progression of metabolic and morphological alterations was evaluated. Serum samples and biopsies from adrenal gland, liver and lung were studied at different times after LPS injection. Histological changes in these tissues were observed after endotoxin administration, coinciding with both the acute-phase and the recovery-phase of shock (24-72h after LPS injection). Signs of tissue regeneration can be correlated with the regression of some serum parameters to their normal values. All these results indicate that in this experimental model of endotoxic shock, a reversible status was established, which will allow further studies of the endotoxic pathophysiological mechanisms in vivo, avoiding the complexity of the non-reversible process.
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PMID:Morphological studies of cytotoxic lesions in reversible endotoxic shock. 213 55

Decreased responsiveness of the vasculature to vasoconstrictors has been implicated in the pathogenesis of endotoxic shock, yet the mechanism of diminished responsiveness has not been determined. In these studies, exposure of rat aortic rings to purified Escherichia coli lipopolysaccharide (endotoxin) in vitro inhibited subsequent contractions caused by vasoconstrictors. Contractions caused by the alpha-adrenoceptor agonist phenylephrine, as well as those induced by potassium depolarization, were depressed by endotoxin. The effect of endotoxin on vascular contractions was delayed. Phenylephrine-induced contractions were not decreased during a 1-h exposure to endotoxin (10 micrograms/ml), but they were markedly decreased when tested several hours after the exposure period. A large part of the inhibition caused by a 1-h exposure to endotoxin was endothelium dependent. In contrast, endotoxin inhibited contractions equally in rings with or without endothelium exposed to endotoxin for a longer period (3 h). The inhibitory effect of endotoxin was not affected by indomethacin, but it was eliminated in aortic rings treated with the protein synthesis inhibitor cycloheximide. These studies indicate that endotoxin potently inhibits vascular contraction in vitro. The effect of endotoxin is apparently independent of prostanoids but may involve protein synthesis and effects on both vascular smooth muscle and endothelial cells.
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PMID:Endotoxin inhibits contraction of vascular smooth muscle in vitro. 218 81

A rat anti-recombinant mouse tumour necrosis factor-alpha (rmTNF-alpha) monoclonal IgM antibody (1F3F3) with high specific binding activity for rmTNF-alpha was generated. The 1F3F3 monoclonal antibody (mAb) neutralizes the cytotoxic activity in vitro of rmTNF-alpha on L929 cells and inhibits the binding of radiolabelled rmTNF-alpha to its putative receptor on L929 cells. The 1F3F3 mAb binds to monomeric, dimeric and trimeric rmTNF-alpha and does not bind to reduced rmTNF-alpha, indicating that the recognized epitope is sensitive to denaturation. Using the 1F3F3 mAb as a capturing antibody and a biotinylated anti-rTNF-alpha as a detecting antibody, we have developed a sandwich ELISA that can specifically detect biologically active mTNF-alpha with a detection limit of 10 pg mTNF-alpha/well. This assay correlates well with the classical L929 cristal violet assay for the detection of bioactive rmTNF-alpha in biological fluids. The 1F3F3 mAb inhibits various in vitro biological activities of the rmTNF-alpha, such as the TNF-alpha-mediated tumoricidal activity of activated macrophages, the rmTNF-alpha-dependent stimulation of neutrophil degranulation and the growth-promoting effect of rmTNF-alpha. In vivo the 1F3F3 mAb inhibits lipopolysaccharide (LPS)-induced endotoxic shock. In conclusion, the 1F3F3 mAb is a useful tool to probe rmTNF-alpha activity both in vitro and in vivo.
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PMID:Generation and characterization of a neutralizing rat anti-rmTNF-alpha monoclonal antibody. 222 22

Gram negative sepsis/septic shock continues to be a major cause of morbidity and mortality in newborns. We studied the effects of anti-inflammatory drugs, indomethacin (IND) and dexamethasone (DX), on glucoregulation, body weight, and mortality in 10-day-old suckling rats administered Salmonella enteritidis lipopolysaccharide (LPS). IND (1.5 mg/kg) or DX (4 mg/kg) was intraperitoneally (ip) administered immediately after highly lethal LPS injection. Both IND and DX attenuated the LPS-induced hypoglycemia and lactacidemia, and decreased the mortality, IND did not alter body weight changes in rats with septic shock. DX continued a catabolic state and reduced their body weights. In rats fasted for 24 hr before LPS injection, DX, but not IND, increased the mortality. We concluded that IND and DX improved the LPS-induced glucose dyshomeostasis and decreased the mortality of endotoxic shock in 4-hr-fasted 10-day-old rats. Per contra, DX was detrimental in 24-hr-fasted 10-day-old endotoxic rats.
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PMID:Dexamethasone and indomethacin treatment during endotoxicosis in the suckling rat. 225 15

Heat-stable soluble products of rodent malarial parasites induce activated peritoneal macrophages to secrete tumour necrosis factor (TNF) in vitro. Since heat-stable parasite antigens are known to be present in the circulation of patients with malaria and it has been suggested that much of the pathology of malaria is due to TNF, we investigated the ability of such antigens to induce the production of TNF in vivo and to be toxic to mice. Injection of antigens obtained from Plasmodium yoelii or from P. berghei into mice which had previously received the macrophage-activating agent Propionibacterium acnes induced the release of TNF into the serum in amounts equivalent to the maximum release induced by bacterial lipopolysaccharide (LPS). Specific antiserum blocked the ability to the boiled soluble antigens, but not of LPS, to induce release of TNF. Similarly, vaccination specifically inhibited the release of TNF into the serum in response to subsequent stimulation with the antigens, but not with LPS. Mice made hypersensitive to the lethal action of TNF by pretreatment with D-galactosamine were killed in a dose-related fashion by administration of antigen preparations; addition of specific antiserum or prior vaccination with the antigens protected such mice, but not those given LPS, from death. We conclude that, in malaria, soluble antigens derived from the parasites may act like a toxin by stimulating the production of TNF, an important mediator of endotoxic shock, and that immunization with such antigens may diminish TNF secretion and consequently many of the clinical manifestations of the disease.
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PMID:Soluble malarial antigens are toxic and induce the production of tumour necrosis factor in vivo. 265 12

We tested the hypothesis that complement (C')-dependent release of prostaglandin (PG) I2 is an important factor contributing to the development of hypotension and low systemic vascular resistance index (SVRI) in endotoxic shock. Two groups (n = 7) of pentobarbital-anesthetized pigs (12-15 kg) were infused over 40 min with Escherichia coli lipopolysaccharide (LPS; 200 micrograms/kg) and continuously resuscitated with normal saline (1 ml/kg min): LPS-Control (no pretreatment) and LPS-Decomplemented (pretreatment 18 hr before study with 500-1,500 units of Naje haje cobra venom factor, CVF). Prior treatment with CVF: i) decreased the mean titer of total hemolytic C' to 15.9% of pretreatment levels; ii) significantly decreased post-LPS plasma concentrations of immunoreactive TxB2 (TxA2 metabolite) and 6-keto-PGF1 alpha (PGI2 metabolite); iii) abrogated the early transient decrease in cardiac index observed in the LPS-Control group; iv) tended to improve post-LPS visceral perfusion assessed using radioactive microspheres; and v) had no discernible effect on the late sustained decrease in SVRI observed following infusion of LPS. We conclude that C' activation is a major determinant of LPS-induced prostanoid release in vivo, although our results do not support the view that C'-dependent release of PGI2 is an important factor contributing to low SVRI in resuscitated endotoxic shock.
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PMID:Complement depletion with Naje haje cobra venom factor limits prostaglandin release and improves visceral perfusion in porcine endotoxic shock. 266 44

Thirty-two horses with clinicopathologic evidence of endotoxic shock were randomly selected for a double-blind trial of hyperimmune lipopolysaccharide (LPS) core antigen plasma. Horses were suffering from acute toxic enteritis (n = 15), 360 degrees volvulus of the large colon (n = 9), proximal jejunitis/duodenitis (n = 6), or strangulating obstruction of the small intestine (n = 2). Plasma was harvested from suitable equine plasma donors (preimmune plasma) and horses were immunized with a whole-cell bacterin of an Rc mutant E. coli (J5). Plasma was again harvested from these horses when IgG ELISA titers recognizing LPS core antigen were greater than 1:32,000. All horses included in the trial received either preimmune or hyperimmune plasma in addition to traditional therapy (fluids, antimicrobials, antiinflammatory agents, etc.) as dictated by the attending clinician. The mortality rate in the group of horses receiving hyperimmune plasma was 13%; in the control group receiving preimmune plasma, the mortality rate was 47% (P = .045). Horses receiving J5 hyperimmune plasma had a significantly improved clinical appearance 48 hours after plasma administration (P less than .05) and a shorter period to recovery than control horses (P = .069).
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PMID:Protection against clinical endotoxemia in horses by using plasma containing antibody to an Rc mutant E. coli (J5). 267 Mar 8

The kallikrein-kinin system is activated during endotoxic shock, suggesting that bradykinin plays a role in the pathology of this disease. To test this hypothesis, a bradykinin antagonist, D-Arg-Hyp3-D-Phe7-bradykinin (NPC 567), was studied in conscious, chronically catheterized rats undergoing lipopolysaccharide (LPS)-induced endotoxic shock. LPS treatment resulted in an increase in circulating bradykinin from less than 23 pg/ml to 144 +/- 18 pg/ml at 1 hr. Intravenous administration of LPS resulted in a 38% drop in mean arterial pressure at 1 hr which was partially reversed by NPC 567. NPC 567 did not affect the moderate tachycardia observed following LPS. NPC 567 infusion at 8 nmol/kg/min dramatically reduced mortality from 100% to 50% at 24 hr (P less than 0.01). In response to LPS, blood thromboxane B2 (TXB2) rose from less than 200 pg/ml to 2,298 +/- 64 pg/ml, while 6-keto-prostaglandin-F1 alpha (6kPGF1 alpha) rose from 289 +/- 23 pg/ml to 7,927 +/- 822 pg/ml. NPC 567 reduced the rise in 6kPGF1 alpha by 42% (P less than 0.05), without affecting TXB2. In summary, NPC 567 reduced mortality in rats treated with LPS, reduced the rise in 6kPGF1 alpha and partially reversed the hypotensive effects. These results suggest that bradykinin plays a significant role in the pathology of endotoxic shock.
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PMID:D-Arg-[Hyp3-D-Phe7]-bradykinin, a bradykinin antagonist, reduces mortality in a rat model of endotoxic shock. 270 51

An anti-lipopolysaccharide (LPS) preparation for the intravenous treatment of septic endotoxic shock was prepared by purifying immunoglobulin G (IgG) from pooled serum from Danish blood donors. The sera were selected by the use of an enzyme-linked immunosorbent assay (ELISA) to screen blood donors for high concentrations of antibodies to a mixture of LPS from 11 different Gram-negative bacteria. ELISA was also used for indirect quantification of IgG antibodies to lipid A, and to rough LPS from Escherichia coli Ra and Salmonella minnesota R60 (Ra). The concentration of human antibodies to the LPS mixture correlated with the concentration of antibodies to the E. coli and S. minnesota rough LPS and to lipid A. The specificity of sera with high concentrations of anti-LPS IgG was investigated by immunoblotting. Sera from individual donors reacted with LPS from different bacteria and recognized different sites on the LPS molecules. The range of specificities to different LPS was increased by the pooling of selected sera. The IgG fraction from the high titre donor pool neutralized biological activities of LPS such as activation of the Limulus amoebocyte lysate reaction and induction of tumour necrosis factor secretion from human monocytes.
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PMID:Immunochemical and biological reactivity of human anti-lipopolysaccharide IgG obtained by screening of blood donors. 271 79


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