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)

Nitric oxide is a potent endogenous vasodilator that regulates arterial tone. A family of nitric oxide synthases uses L-arginine and L-homoarginine stereospecifically as substrates for nitric oxide production in vivo. By preventing expression of inducible but not constitutive nitric oxide synthases, glucocorticoids differentiate which enzyme in this family is the predominant source of nitric oxide generation in a given situation. We proposed that defective production of nitric oxide produces salt-sensitive hypertension in the Dahl/Rapp rat. Plasma concentrations of L-arginine, citrulline, and ornithine of salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) rats on 8% sodium chloride chow for 1 week did not differ. However, intravenous infusion of L-arginine and L-homoarginine, but not D-arginine, increased urinary excretion of nitrate, the degradation product of nitric oxide, and simultaneously lowered blood pressure in hypertensive SS/Jr rats. Oral L-arginine also prevented development of hypertension and increased urinary excretion of cyclic GMP and nitrate in these rats. Dexamethasone, in a dose that prevented hypotension from parenteral injection of lipopolysaccharide, completely prevented the increase in excretion of cyclic GMP and nitrate, and hypertension resulted despite concomitant treatment with L-arginine. These studies supported an important role of dexamethasone-suppressible nitric oxide synthesis in the prevention of salt-sensitive hypertension in the Dahl/Rapp rat.
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PMID:Role of nitric oxide synthesis in salt-sensitive hypertension in Dahl/Rapp rats. 750 51

Recently, sepsis has been shown to impair intestinal amino acid absorption in addition to gut metabolic and barrier functions. We investigated intestinal proline absorption in a rabbit model of sepsis. Twelve hours after intraperitoneal injection of lipopolysaccharide, proline uptake by everted jejunal sacs prepared from septic animals (480.4 +/- 67.4 nmol per sac per hour) was significantly reduced compared with controls (846.8 +/- 73.5 nmol per sac per hour) (p < .001 by t test). We next investigated whether reduced expression of transporter proteins contributed to the impaired intestinal proline uptake during sepsis. The proline (imino) carrier of rabbit jejunum is covalently bound by fluorescein isothiocyanate (FITC) and/or phenylisothiocyanate with irreversible inhibition of proline uptake. This binding and inhibition is prevented by sodium chloride and L-proline. Single-cell suspensions of rabbit enterocytes were prepared 12 hours after intraperitoneal injection of lipopolysaccharide/saline or saline alone. Enterocytes were incubated for 30 minutes in tris(hydroxymethyl)aminomethane/ethylenediaminetetraacetate (Tris/EDTA) buffer; buffer with 1 mM phenylisothiocyanate; or buffer with 10 mM proline, 100 mM sodium chloride, and 1 mM phenylisothiocyanate. After incubation with 10 microM FITC in Tris/EDTA buffer for 15 minutes, the percent positivity and fluorescent intensity of FITC binding to enterocytes were determined by using flow cytometry. Sepsis significantly reduced the percentage of enterocytes binding FITC and the fluorescent intensity of FITC binding of proline/sodium chloride-pretreated or untreated cells. This suggests that sepsis depresses the expression of imino transporters by rabbit enterocytes, which may explain the reduced intestinal proline absorption.
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PMID:The role of the imino transporter protein in sepsis-impaired intestinal proline absorption. 830 2

Ibuprofen treatment was compared with saline solution treatment in an endotoxin-induced experimental model of bovine mastitis. Acute mastitis was induced in healthy lactating Holstein cows (n = 12) by intramammary inoculation of 1 mg of Escherichia coli 026:B6 lipopolysaccharide in a single quarter per cow. Cows were assigned at random to ibuprofen (25 mg/kg of body weight, IV, n = 6) or 0.9% sodium chloride solution control (1.25 ml/kg, IV, n = 6) treatment groups. Ibuprofen or saline solution was administered once, 2 hours after endotoxin administration. The clinical course of endotoxin-induced mastitis and hematologic, clinical biochemical, and plasma mineral changes were monitored and compared between ibuprofen-treated and control cows. Clinical monitoring and blood sample collection were performed at 0, 2, 4, 6, 8, 12, 24, 48, 96, and 192 hours after endotoxin challenge. Rectal temperature and heart and respiratory rates were significantly (P < or = 0.05) increased in saline treated cows, compared with cows treated with ibuprofen. Blood eosinophil count and serum phosphorus, sodium, and total carbon dioxide concentrations were significantly (P < or = 0.05) decreased in saline-treated cows, compared with cows treated with ibuprofen. Ibuprofen treatment did not significantly change ruminations per minute, electrical conductivity of milk, quarter size, or quarter inflammation. The remaining hematologic, serum biochemical, plasma mineral, and coagulation values also were not changed significantly in response to ibuprofen treatment. Untoward effects attributed to ibuprofen administration were not observed. These results indicate that ibuprofen may provide empiric relief of clinical signs of coliform-induced mastitis.
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PMID:Ibuprofen treatment of endotoxin-induced mastitis in cows. 836 9

The amounts of pertussis toxin (PT), filamentous haemagglutinin (FHA), 69 kDa outer membrane protein (69 kDa OMP) and agglutinogens (AGG) 2 and 3 in extracts from the Danish whole-cell pertussis vaccine were studied in quantitative capture ELISA. With the exception of PT, the most effective extraction of these antigens was by heating the bacteria at 60 degrees C for 30 min in 2 M urea followed by sonication for 45 s. Extraction by 1 M sodium chloride prior to sonication resulted in higher levels of antigenic and biologically active PT. On average, a single human dose of pertussis vaccine (approximately 16 opacity units) was found to contain 5520 ng FHA, 63 ng PT, 1061 ng 69 kDa OMP, 397 ng AGG 2, 534 ng AGG 3 and 4840 ng lipopolysaccharide (LPS). The antigen content of one dose of the Danish pertussis vaccine appears to be low compared with the amounts found in the acellular vaccines currently in use. These findings may have important implications for the evaluation of the protective substances and the immunogenicity of whole-cell as opposed to acellular pertussis vaccines.
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PMID:Quantification of pertussis toxin, filamentous haemagglutinin, 69 kDa outer membrane protein, agglutinogens 2 and 3 and lipopolysaccharide in the Danish whole-cell pertussis vaccine. 844 60

Bacterial peritonitis is the most important complication of peritoneal dialysis (PD), limiting its widespread application. Conventional glucose-based peritoneal dialysates (G-PDS) depress oxygen consumption, chemiluminescence, superoxide production, phagocytosis, bacterial killing and actin polymerization in neutrophils (PMN) in vitro. Expression of adhesion receptors is critical to leukocyte activation, adhesion, migration and phagocytosis. The effects of G-PDS on basal and stimulated leukocyte adhesion molecule expression and leukocyte adhering capacity is unknown. We examined the effect of a five minutes incubation of whole blood in either HEPES-buffered saline or G-PDS containing 1.5% (83 mM), 2.5% (139 mM) or 4.25% (236 mM) glucose, at pH = 5.2, and pH = 7.4. PMN intracellular pH was measured spectrofluorometrically. Leukocyte CD11b, CD18 and CD14 were measured by flow cytometry using monoclonal antibodies in otherwise unstimulated cells or 60 minutes after lipopolysaccharide (LPS) stimulation. In addition, leukocyte adhering capacity to nylon wool was tested. In an attempt to dissect the effect of high glucose concentrations from that of the attendant hyperosmolality, the experiments were repeated with dialysates in which glucose was substituted by sodium chloride (NaCl-PDS) to attain identical osmolalities. G-PDS, as well as the mixtures of spent and fresh G-PDS, significantly depressed the basal PMN expression of adhesion receptors CD11b and CD18 and monocyte expression of CD14, and substantially mitigated the LPS-mediated up-regulation of CD11b and CD18. Likewise, G-PDS significantly inhibited leukocyte adhering capacity without affecting cell viability. Similar results were observed with NaCl-PDS. The observed abnormalities were primarily osmolality-dependent, and largely intra- and extracellular pH-independent. Impaired adhesion receptor expression and cell adhesion capacity shown here reveal another dimension of the G-PDS-induced leukocyte abnormalities.
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PMID:Effects of conventional peritoneal dialysates on leukocyte adhesion and CD11b, CD18 and CD14 expression. 891 36

Endotoxin (lipopolysaccharide; LPS) and mercury are nephrotoxic compounds of food safety concern. Endotoxin is a product of cell walls of gram negative bacteria. Humans are constantly exposed to LPS through food, water and air. Food is the main source of mercury exposure for humans. Endotoxin potentiates the toxicity of a number of xenobiotics, but its interaction with nephrotoxic heavy metals has not been investigated. We tested the hypothesis that endotoxin enhances mercury-induced nephrotoxicity. Thirty-two, 41-43-day-old, male Sprague-Dawley rats were allocated randomly to four groups of eight rats each as follows: group I received 0.9% sodium chloride, group II received 2.0 mg of Escherichia coli 0128:B12 LPS kg(-1) once, group III received 0.5 mg mercuric chloride kg(-1) once, and group IV received 2.0 mg E. Coli 0128:B12 LPS kg(-1) once 4 h before receiving 0.5 mg mercury chloride kg(-1) once. Mercury, LPS and 0.9% sodium chloride were all injected IV through the tail vein. Rats were monitored for 48 h after mercury injection. Serum creatinine, urea nitrogen, and polyuria were significantly increased in rats given LPS plus mercury relative to those given either agent alone or saline (P</=0.05). The most severe morphologic lesions were found in rats given LPS plus mercury, which also had significantly greater renal mercury concentration than those given mercury alone (P < or = 0. 05). In conclusion, LPS potentiated mercury-induced nephrotoxicity.
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PMID:Potentiation of mercury-induced nephrotoxicity by endotoxin in the Sprague-Dawley rat. 1096 5

Endotoxin (lipopolysaccharide; LPS) and mercury are compounds of food safety concern. Endotoxin is a product of cell walls of gram negative bacteria. Humans are constantly exposed to LPS through infection plus translocation into circulation from the gastrointestinal tract. Food is the major source of mercury in humans. The toxic interaction between LPS and mercury has not been well investigated. In a previous study, we demonstrated that LPS potentiated mercury-induced nephrotoxicity in the rat. Whether this observation was species specific was not clear. In this study we tested the hypothesis that LPS enhances mercuric chloride (HgCl(2))-induced nephrotoxicity in mice. In a 2x2 factorial design, mice received either Escherichia coli 0128:B12 endotoxin (2.0 mg/kg body weight) or 200 microliter of 0.9% sodium chloride (saline), and this was followed 4 h later by either mercury (1.75 mg mercuric chloride per kg body weight) or 200 microliter of saline. Mice were monitored for 48 h. Monitored end-points included body and renal weights, urine volume, renal histology and ultrastructural pathology, serum urea nitrogen and creatinine, selected serum and urine cytokines, and renal mercury concentrations. Endotoxin by itself was not nephrotoxic at the dose used in this study. Overall, mice given LPS plus mercury were the most severely affected. Mice given LPS and mercury also had significantly greater renal mercury concentration than those given mercury alone (P</=0.05). In conclusion, LPS potentiates mercury-induced nephrotoxicity in the mouse.
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PMID:Augmentation of mercury-induced nephrotoxicity by endotoxin in the mouse. 1107 5

Midazolam, a benzodiazepine, has an hypnotic effect via benzodiazepine receptors and is widely used as an anaesthetic. Recently, it has been suggested that benzodiazepines modulate cytokine responses. The purpose of the present study was to evaluate the effect of midazolam on interleukin-6 (IL-6) response by observing mRNA expression levels in human peripheral blood mononuclear cells (PBMCs) in the absence of lipopolysaccharide (LPS). PBMCs were isolated from healthy volunteers in endotoxin-free 0.9% sodium chloride solution. The cells were incubated for 2 h at 37 degrees C immediately after isolation. IL-6 mRNA expression levels in the cells were quantified using reverse transcription and competitive polymerase chain reaction. It was found that midazolam time-dependently inhibited the IL-6 mRNA expression in PBMCs in the absence of LPS, and significantly inhibited the IL-6 mRNA expression at 1 microg/ml (P<0.05) or 10 microg/ml (P<0.01) in the absence of LPS. However, neither a specific agonist of peripheral-type benzodiazepine receptors, Ro5-4864, nor a specific agonist of central-type benzodiazepine receptors, clonazepam, inhibited IL-6 mRNA expression. These findings indicated a suppression of the IL-6 response in human PBMCs by midazolam in the absence of LPS, and suggests that midazolam has its effect not via benzodiazepine receptors, but by another mechanism.
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PMID:Effect of midazolam on interleukin-6 mRNA expression in human peripheral blood mononuclear cells in the absence of lipopolysaccharide. 1159 99

The therapeutic efficacies of buforin II, indolicidin, and KFFKFFKFF were investigated in three rat models of septic shock: (i) rats injected intraperitoneally with 10 microg of Escherichia coli O111:B4 lipopolysaccharide, (ii) rats given an intraperitoneal injection of 2 x 10(10) CFU of Escherichia coli ATCC 25922, and (iii) rats in which intra-abdominal sepsis was induced via cecal ligation and single puncture. All animals were randomized to receive parenterally isotonic sodium chloride solution, 1 mg of buforin II per kg of body weight, 1 mg of indolicidin per kg, 1 mg of KFFKFFKFF per kg, and 20 mg of imipenem per kg. The main outcome measures were bacterial growth in abdominal exudate and plasma, endotoxin and tumor necrosis factor alpha (TNF-alpha) concentrations in plasma, and lethality. Treatment with all peptides resulted in significant reductions in plasma endotoxin and TNF-alpha concentrations compared with those resulting from the imipenem and saline treatments. On the other hand, imipenem treatment significantly reduced the levels of bacterial growth compared with the reductions achieved with the peptide and saline treatments. All compounds reduced the rates of death compared to that for the controls. Although the peptides demonstrated lower levels of antimicrobial activity than imipenem, they exhibited the dual properties of antimicrobial and antiendotoxin agents.
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PMID:Potential therapeutic role of cationic peptides in three experimental models of septic shock. 1206 65

Bacteria and viruses are suspected to induce arteriosclerosis; however, most investigators have focused on coincidences rather than causal relationships. The aim of this work was to establish a rabbit model in which the vessel reaction to local perivascular injection of defined bacterial products can be analyzed. A total of 23 rabbits were randomized to four groups. Groups A and B were fed a normal diet, groups C and D were fed a cholesterol-enriched diet. Groups A and C were treated with a single perivascular injection of bacterial lipopolysaccharide (LPS, endotoxin) placed next to auricular, carotid and femoral arteries, and sodium chloride placed next to the contralateral arteries (control). Group B and D animals were treated with repeated perivascular injections over 90 days. Vascular tissues (n=116 treated segments of 23 rabbits) were analyzed using morphometry at histology, and using immunohistochemistry to detect macrophages, lymphocytes and vascular smooth muscle cells. LPS treatment resulted in transient focal intima thickening. After single LPS application, no increase in atheromatous lesion formation was observed in comparison with controls (group C, lesion area index 0.031+/-0.012 vs 0.015+/-0.006, P=1.0). Repeated LPS application resulted in significant atheromatous lesion formation compared with saline control (group D, lesion area index 0.148+/-0.049 vs 0.008+/-0.006, P=0.003) in hypercholesterolemic rabbits. Repeated LPS inflammation in normocholesterolemic did not lead to atheromatous lesion formation (intima media ratio 0.04+/-0.01 vs 0.04+/-0.007, P=1.0). Single perivascular administration of low-dose bacterial LPS resulted in transient focal intimal thickening, while significant increase in lesion formation occurred after repeated LPS application in cholesterol-fed animals. In conclusion, this animal model will allow the assessment of the impact of defined dosages of different bacterial pathogens onto the vascular wall in the context of atherogenesis. The atheromatous lesion-promoting effect of repeated perivascular administration of LPS supports the hypothesis that bacterial pathogens may be involved in atherogenesis.
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PMID:Recurrent perivascular inflammation induced by lipopolysaccharide (endotoxin) results in the formation of atheromatous lesions in vivo. 1496 25


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