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 role of neutrophils (PMN) in acute renal failure (ARF) is controversial. Although the development of acute renal failure (ARF) frequently occurs in situations where there is partial activation of PMN (primed PMN) and mild renal ischemia, the interaction between primed PMN and ischemic organs has not been studied in any biological system. To define the interaction between primed PMN and mild renal ischemia, kidneys were made ischemic for 10 minutes in situ and reperfused by the isolated kidney technique with untreated PMN or PMN primed with low concentrations of lipopolysaccharide (LPS) or phorbol myristate acetate (PMA). We found that primed PMN had no effect on control (non-ischemic) kidneys and that untreated PMN did not cause injury to kidneys previously subjected to mild ischemia. However, addition of primed PMN to mildly ischemic kidneys caused severe injury. To determine the nature of renal injury, ischemic kidneys were reperfused with primed PMN and catalase (CAT) or the elastase inhibitor, Eglin C. In ischemic kidneys reperfused with LPS-primed PMN, Eglin C (but not CAT) was partially protective while in ischemic kidneys reperfused with PMA-primed PMN, CAT (but not Eglin C) was partially protective. Reperfusion with both CAT and Eglin C completely prevented the damaging effects of either LPS- or PMA-primed PMN. In conclusion, addition of primed but not untreated PMN causes ARF in mildly ischemic kidneys by PMN oxidant- and/or protease-mediated mechanisms. This synergism could account for the high frequency of ARF in conditions associated with prerenal azotemia and primed PMN.
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PMID:Mild renal ischemia activates primed neutrophils to cause acute renal failure. 140 39

Hemolytic uremic syndrome (HUS) is characterized by hemolytic anemia, thrombocytopenia, and uremia; it is a common cause of acute renal failure in children. Although many microbial agents have been associated with HUS, only Escherichia coli O157: H7 has been clearly demonstrated to be a major cause of this illness. A case is presented of a healthy 4-year-old boy who had a recent varicella infection; when evaluated for HUS his blood and stool cultures both grew Salmonella montevideo and blood cultures grew group A beta-hemolytic streptococci. A stool cultured on MacConkey-sorbitol agar also grew E. coli O157: H7. An eightfold rise in serum antibodies to E. coli O157: H7 lipopolysaccharide was also demonstrated. The child recovered completely and was healthy 3 years later. Although this child had several infectious agents anecdotally associated with HUS, appropriate culture of stool showed that he also had E. coli O157: H7 infection. Previous cases thought to be due to other pathogens may similarly have been caused by co-infection with E. coli O157: H7.
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PMID:Hemolytic uremic syndrome due to Escherichia coli O157: H7 in a child with multiple infections. 161 38

Gram-negative bacterial sepsis is frequently associated with acute renal failure but the specific effects of lipopolysaccharide (LPS) and other bacterial products on kidney function are not known. Since either LPS or formyl-methionyl-leucyl-phenylalanine (FMLP)--a chemotactic peptide from bacterial cell walls--activate neutrophils (PMN) to release a number of potentially toxic factors in vitro, we determined the effect of adding PMN with LPS and/or FMLP to isolated perfused rat kidneys. Isolated rat kidneys perfused with LPS alone or LPS and normal PMN had normal glomerular filtration rates (GFR) and tubular Na reabsorption (TNa). Kidneys perfused with FMLP alone or FMLP and normal PMN also had normal GFR and TNa. In contrast, addition of PMN with both FMLP and LPS caused progressive renal dysfunction. For example, after 60 minutes of perfusion, GFR was reduced from 610 +/- 31 to 147 +/- 17 microliters/min/g and TNa from 97 +/- 1 to 72 +/- 2%, both P less than 0.01. Perfusion with the O2 metabolite scavengers catalase or dimethylthiourea afforded no protection while perfusion with the neutrophil elastase inhibitor Eglin C conferred substantial, but not complete, protection: GFR 492 +/- 34 microliters/min/g; TNa 91 +/- 3%. However, perfusion with both Eglin C and catalase completely prevented the toxic effects of LPS and FMLP-treated PMN on renal function. We conclude that in isolated kidneys, 1) the toxic effects of LPS requires FMLP-treated PMN and that 2) LPS and FMLP treated PMN cause progressive renal injury which is mediated by both O2 metabolites and neutrophil elastase.
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PMID:Role of neutrophil derived oxidants and elastase in lipopolysaccharide-mediated renal injury. 205 18

Platelet-activating factor (PAF), a potent vasoactive phospholipid, may contribute to acute renal failure and septic shock accompanying endotoxemia. Rat glomerular mesangial cells in culture synthesize PAF and contract after the addition of PAF. We thus investigated the potential of mesangial cells to respond to Escherichia coli lipopolysaccharide endotoxin with enhanced PAF synthesis in vitro. The mesangial cells were incubated with [3H]acetate, substrate for lyso-PAF: acetyl-CoA acetyltransferase, and endotoxin at different concentrations for various periods of time at 37 degrees C. Lipids were extracted and PAF was isolated by thin-layer chromatography. Endotoxin stimulated PAF generation in a time- and dose-related manner. Whereas most of the PAF was associated with the cells, endotoxin more than doubled the amount of PAF released into the extracellular medium as compared to control. Furthermore, the PAF-like material obtained from endotoxin-stimulated mesangial cells irreversibly aggregated washed rabbit platelets. This effect was lost after alkaline methanolysis and was totally blocked by L-652,731, a specific PAF-receptor antagonist. Finally, the PAF-like material exerted a hypotensive effect, which was abolished by L-652,731, when infused intravenously into healthy rats. These data indicate that rat glomerular mesangial cells have the ability to synthesize PAF in response to endotoxin. This suggests that PAF, so generated within the glomerulus, may contribute to acute decrements of glomerular filtration rate in endotoxemia.
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PMID:The effects of endotoxin on platelet-activating factor synthesis in cultured rat glomerular mesangial cells. 337 Feb 22

The acute renal failure complicating bacterial septicemia has multiple potential causes, prominent among which are endotoxemic and antibiotic nephrotoxic injury. Because the toxic interactions of endotoxin and antibiotics cannot be manipulated for study in human disease, we have developed a model of this interaction in the rabbit. Toxicity was assessed by quantification of tubular necrosis and serum creatinine concentrations 48 hr after single-dose i.v. endotoxin and/or antibiotic administration. A minimally nephrotoxic quantity of endotoxin (Escherichia coli lipopolysaccharide 0111:B4, 0.5 mg/kg b.w.) significantly increased the nephrotoxicity of the cephalosporins cephaloglycin (60 mg/kg) and cephaloridine (90 mg/kg) and the aminoglycoside neomycin (60 mg/kg), each of which was mildly-to-minimally damaging by itself. In studies of the acute functional effects of endotoxemia, the lipopolysaccharide had different effects on the renal handling of the two cephalosporins. Endotoxin increased the uptake of cephaloglycin, but decreased uptake of cephaloridine, in renal cortex in the first 0.5 hr after antibiotic administration. However, a prolonged elevation of serum levels of cephaloridine allowed later uptake of toxic amounts of this cephalosporin. Although these findings suggest a role of altered transport in the endotoxin-cephalosporin toxic synergy, the synergy was not reduced when cephaloglycin was given 1.5 hr before the endotoxin, a time which allows substantial elimination of antibiotic before the endotoxemic insult. Studies in another laboratory have demonstrated an endotoxin-induced increase of cortical concentrations of aminoglycosides, which could be a mechanism of the augmented toxicity seen in the present study. It is concluded that endotoxemia causes significant augmentation of the nephrotoxicity of cephalosporin and aminoglycoside antibiotics.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Augmentation of antibiotic nephrotoxicity by endotoxemia in the rabbit. 402 Jun 78

Acute renal failure (ARF) is a common manifestation of a septic condition which very often complicates surgical and traumatic events. The release of endotoxin, a lipopolysaccharide (LPS) from the cell wall of Gram-negative bacteria, and subsequently of numerous host mediators, is the initiating event of sepsis syndrome and eventually of septic shock. Particularly interesting is the observation that not only endotoxins but also Staphylococcus aureus which does not produce endotoxins induce the same cardiovascular changes of septic shock. The main aspect of septic shock is the inadequate oxygen supply to the body tissues. However, despite the documented myocardial depression in the course of septic shock, myocardial ischaemia is not to be considered a contributing factor, and the coronary blood flow is normal or even increased. Protein hypercatabolism can be at best only limited; in any case the optimal protein-sparing effect was observed with 1.5 g/kg proteins. Recently monoclonal antibodies to endotoxin core glycolipid have been developed; they are: (a) E5, a murine IgM anti-lipid A monoclonal antibody; (b) HA-1A, a human monoclonal antibody to endotoxin core glycolipid. In conclusion, hypercatabolic septic patients should be managed in an intensive care environment where a continuous monitoring of fluids, electrolytes, and acid-base disorders can be achieved. Surgical search of septic foci, and wide-spectrum antibiotic therapy are fundamental measures to combat cytokine and vasodilator production which impair tissue perfusion and create the premise of a shock status complicated by lactic acidosis. Dialysis treatment is a further complementary but fundamental approach that allows a large fluid and nutritional intake and a continuous correction of electrolyte and acid-base disorders.
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PMID:Basic therapeutic requirements in the treatment of sepsis in acute renal failure. 780 Feb 55

The haemolytic uraemic syndrome, first described in 1955 by Gasser, is the number one cause of acute renal failure in infants. There are three types of the haemolytic uraemic syndrome: the seasonal epidemic form with prodromic diarrhoea and generally favourable outcome which usually occurs in infants, a less typical form without signs of digestive tract involvement and no seasonal prevalence which occurs more readily in older children and sometimes in families has a less favourable prognosis, and finally drug- or disease-related forms. Currently, overall mortality due to haemolytic uraemic syndrome has been reduced to about 4%, usually as a result of damage to the central nervous system. Several microorganism, including Shigella dysenteriae, Salmonella typhi, Campylobacter jejuni, Streptococcus pneumoniae, Rickittsiae and certain viruses (Coksackiae, Influenzae, Epstein-Barr) have been identified as causative agents. In 1983, digestive tract infection due to an Escherichia coli strain producing verotoxin was identified as capable of producing haemolytic uraemic syndrome and more rarely thrombopenic thrombotic purpura. The germ produces two exotoxins (whose effect is accentuated by the E. coli lipopolysaccharide endotoxin) which lead to the glomerular microangiopathy causing haemolytic uraemic syndrome. Diagnosis is based on identification (monoclonal antibodies, ELISA, PCR) of the verotoxins themselves or the two encoding genes in stool samples. Symptomatic treatment is essential but the effectiveness of antibiotics is still debated. Theoretically, antibiotics could worsen the syndrome by increasing endotoxin release from lysed bacteria, but inversely they could also prevent the syndrome if given early enough. Further research is required to acquire precise epidemiological data and identify animal reservoirs of verotoxin producing E. coli.
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PMID:[Hemolytic-uremic syndrome after verotoxin-producing Escherichia coli infection]. 789 53

The mitogen-induced activation responses of rat splenic lymphocytes were determined for control and uremic rats. Lymphocyte activation was quantified by incorporation of [3H]thymidine. Glycerol-induced acute renal failure (ARF) inhibited the proliferation of both lipopolysaccharide (LPS)-induced B-lymphocytes and concanavalin A (Con A)-induced T-lymphocytes by 80% and 87%, respectively. The decrease in [3H]thymidine incorporation in both the LPS- and con A-activated cells significantly correlates with increases in plasma urea and creatinine concentrations (r = 0.83). Total glutathione (GSH) concentration in the splenocytes was not significantly different in terms of GSH per 10(7) cell, although the overall GSH and the number of viable splenocytes were generally lower in the uremic rats. Determination of GSH-related enzymes (GSH S-transferase, GSSG reductase and GSH peroxidase) in the spleen of control rats and rats with ARF showed little difference in the activities of these enzymes, although the GSSG/GSH ratio, which is an indication of oxidative stress, was significantly increased in the spleen of uremic rats. Incubation of normal splenocytes from control rats with uremic plasma obtained from rats with ARF also significantly decreased the proliferation responses. Metabolic inhibitors present in uremic plasma may contribute to the inhibitory action on mitogen-induced proliferation of B- and T-lymphocytes, although oxidative stress which occurs in ARF may itself be sufficient to affect the immune function.
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PMID:Effect of glycerol-induced acute renal failure on glutathione status and mitogen-induced proliferation of rat splenocytes. 825 21

Increasing evidence supports a role of cytokines, tumor necrosis factor alpha (TNF alpha), interleukin-1 (IL-1), and IL-6 in the development of endotoxin-induced acute renal failure. Several activities of these cytokines require a local rather than a systemic production and function. Thus, this study investigates the chronology of cytokine expression in glomeruli isolated from normal rats or rats given iv lipopolysaccharide injections. Detectable levels of TNF alpha could be found in glomeruli isolated from normal rats as assessed by L-929 fibroblast lytic assay and ELISA. Glomeruli isolated from rats given lipopolysaccharide transiently released increased amounts of TNF alpha in relation to the dose of lipopolysaccharide (10 to 500 micrograms/kg body wt) and the lag period between lipopolysaccharide injection and glomerular isolation (20 to 120 min). TNF alpha was released in similar amounts by glomeruli from normal rats that were exposed in vitro to lipopolysaccharide challenge (0.01 to 10 micrograms/mL), indicating that lipopolysaccharide had direct effects on the release of TNF alpha from glomerular cells. These cells consisted mainly of resident cells because reduction of glomerular infiltration by bone marrow-derived cells after the irradiation of normal rats did not affect TNF alpha release. Glomerular IL-1 and IL-6 production was evaluated by specific bioassays under identical conditions. No IL-1 activity could be detected in the medium or within the glomerular cells at any time within 120 min after lipopolysaccharide injection. By contrast, glomerular IL-6 production was induced after lipopolysaccharide challenge both in vivo and in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytokine formation within rat glomeruli during experimental endotoxemia. 832 73

It was found in acute experiments on white rats that injection of Salmonella typhimurium lipopolysaccharide activates renin-angiotensin-aldosterone system (RAAS) and causes oligohydruria form of acute renal failure (ARF). Enalapril, angiotensin-converting enzyme, being injected simultaneously with endotoxin, increases diuresis, glomerular filtration rate, electrolytes excretion and reabsorption by proximal tubules, decreases proteinuria and blood nitrogen-down to the normal. Thus, RAAS takes part in endotoxemia ARF induction and enalapril has protective effect.
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PMID:[The participation of the renin-angiotensin-aldosterone system in the pathogenesis of acute kidney failure in endotoxemia]. 881 32


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