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)

Newborns are susceptible to gram-negative sepsis/septic shock, but there is no established method of its treatment. This study was performed to evaluate the adjuvant effects of dopamine and dobutamine in the indomethacin treatment of newborn endotoxic shock. Endotoxic shock was induced in newborn dogs (2 to 10 days old; 300 to 800 g) by Escherichia coli lipopolysaccharide (LPS; 1.5 mg/kg, intravenously [IV]). Indomethacin (1.5 mg/kg, IV) was injected 5 minutes after LPS injection. Dopamine (5 micrograms/kg/min) or dobutamine (5 micrograms/mg/min) infusion started 5 minutes after LPS injection immediately following indomethacin injection. Hemodynamic parameters were monitored serially for 120 minutes. LPS induced bradycardia and hypotension, decreased the cardiac output and cardiac performance, and increased the total vascular resistance. When dopamine, dobutamine, or indomethacin were used alone, they attenuated the hemodynamic deterioration by LPS. Dopamine infusion following indomethacin administration improved the hemodynamics further, although dobutamine infusion did not. Therefore, we conclude that the adjuvant therapy of dopamine in the indomethacin treatment of newborn endotoxic shock is beneficial.
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PMID:Adjuvant effects of beta-adrenergic drugs on indomethacin treatment of newborn canine endotoxic shock. 177 23

Taurolidine (Geistlich Pharm, AG, Wolhusen, Switzerland), a derivative of the amino acid taurine, is commonly used in some parts of the world as an adjunctive therapy for various infections. Its mechanism of action is thought to be related to its antimicrobial properties, including its ability to interfere with some of the biological activities of endotoxin (lipopolysaccharide, LPS). For example, taurolidine has been shown to protect animals against endotoxic shock and death. In this study we examined the ability of taurolidine to block LPS-induced tumor necrosis factor (TNF) and interleukin 1 (IL-1) synthesis in human peripheral blood mononuclear cells (PBMC) from 27 donors. We observed a dose-dependent reduction in the synthesis of these two cytokines when taurolidine was preincubated with LPS before being added to PBMC. This reduction was independent of the molar ratio of taurolidine to LPS but was related to the concentration of taurolidine present in the PBMC cultures. There was a 80 to 90% reduction in total IL-1 and TNF synthesis induced by LPS at concentrations of taurolidine of 40 to 100 micrograms/mL; the vehicle was without effect. Following a 30-min preincubation with PBMC, taurolidine could be washed from the cells and still suppress cytokine synthesis induced by LPS. Using release of lactic acid dehydrogenase, 100 micrograms/mL of taurolidine was not toxic for PBMC. Taurolidine also reduced IL-1 and TNF synthesis induced by the Staphylococcus aureus-derived toxic shock syndrome toxin-1 as well as that induced by nontoxic heat-killed Staphylococcus epidermidis organisms.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Taurolidine, an analogue of the amino acid taurine, suppresses interleukin 1 and tumor necrosis factor synthesis in human peripheral blood mononuclear cells. 179 Mar 4

The biological stains, methylene blue and its metabolite azure B, were evaluated as anti-tumor and anti-inflammatory agents. Azur B, administered in drinking water to tumor-bearing mice, inhibited the growth of transplanted tumors and the growth of primary tumors induced by methylcholanthrene. Inhibition of growth of primary tumors was observed only in female mice. Azure B also reduced the wet weight of carrageenin-induced granulomas in rats. Azure B, given intravenously to BCG-sensitized mice 15 minutes prior to challenge with lipopolysaccharide, decreased TNF production (to 10% of control values) and prevented death from endotoxic shock. Methylene blue decreased TNF production (to 50% of control values) but did not protect the animals from endotoxic shock. Our results suggest that some of the effects previously ascribed to methylene blue are probably mediated via its metabolite, i.e. azure B. Low toxicity and easy administration of the dyes explain their use in clinical settings.
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PMID:Anti-tumoral and anti-inflammatory effects of biological stains. 181 Jan 51

We used a selective leukotriene (LT) D4/E4 receptor antagonist (LY 203647) to investigate the role of cysteinyl LTs as mediators of several important pathophysiological events in a porcine model of endotoxic shock. Pentobarbital-anesthetized pigs (11.8-17.5 kg) were mechanically ventilated with 100% O2. Pigs in groups I (n = 10), IIA (n = 10), and IIB (n = 5) were infused with Escherichia coli lipopolysaccharide (LPS; 250 micrograms/kg) from time (t) = 0-20 min. Pigs in group III (n = 3) were normal controls. All pigs were resuscitated from t = 0-240 min with Ringer lactate (0.8 ml.kg-1.min-1). Pigs in group I received no further treatment. At t = 30 min, groups IIA and IIB were injected with LY 203647 (30 mg/kg) and were started on an infusion of the compound at 10 (group IIA) or 30 mg.kg-1.h-1 (group IIB). Delayed treatment with LY 203647 significantly (P less than 0.05) and persistently ameliorated LPS-induced pulmonary hypertension. The compound also abrogated LPS-induced pulmonary edema, as assessed by gravimetrically determined lung extravascular wet-to-dry weight ratios. Despite its beneficial effect on pulmonary edema, delayed treatment with LY 203647 did not improve arterial oxygenation. Delayed treatment with LY 203647 transiently improved mesenteric perfusion. These data suggest that cysteinyl LTs are important mediators in porcine endotoxicosis.
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PMID:Delayed treatment with an LTD4/E4 antagonist limits pulmonary edema in endotoxic pigs. 185 25

Lipid A is the active moiety of lipopolysaccharide (LPS, also referred to as endotoxin), a surface component of Gram-negative bacteria that stimulates macrophage activation and causes endotoxic shock. Macrophages can bind, internalize and partially degrade LPS, lipid A and its bioactive precursor, lipid IVA. We report here that lipid IVA binding and subsequent metabolism to a less active form by macrophage-like RAW 264.7 cells is mediated by the macrophage scavenger receptor. Scavenger-receptor ligands inhibit lipid IVA binding to, and metabolism by, RAW cells, and lipid IVA binds to type I and type II bovine scavenger receptors on transfected Chinese hamster ovary cells. Although in vitro competition studies with RAW cells indicate that scavenger receptor binding is not involved in LPS or lipid IVA-induced stimulation of macrophages, in vivo studies show that scavenger-receptor ligands greatly inhibit hepatic uptake of lipid IVA in mice. Thus, scavenger receptors expressed on macrophages may have an important role in the clearance and detoxification of endotoxin in animals.
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PMID:Recognition and plasma clearance of endotoxin by scavenger receptors. 185 9

Prostaglandins have been reported to play an important role in endotoxic shock. However, the beneficial effects of prostaglandin synthesis inhibitors for the treatment of newborn endotoxic shock have been controversial. This study was performed to evaluate the effects of indomethacin on the hemodynamics during fulminant endotoxic shock in newborn dogs. After E. coli lipopolysaccharide (LPS) injection, mean arterial pressure was maintained for the first 60 min, and then declined from 53 +/- 2 to 27 +/- 2 mmHg at 120 min. Cardiac output dropped from 0.37 +/- 0.03 to 0.24 +/- 0.03 L/min/kg 5 min after LPS injection and continued to decline to 0.12 +/- 0.01 L/min/kg at 120 min. Indomethacin treatment 20 min prior to LPS injection attenuated the hypotension (50 +/- 3 mmHg at 120 min, p less than 0.05) and the decrease of cardiac output (0.18 +/- 0.02 L/min/kg at 120 min, p less than 0.05). Indomethacin treatment 5 min after LPS injection also attenuated the hypotension (55 +/- 4 mmHg at 120 min, p less than 0.05) and the decrease of cardiac output (0.21 +/- 0.02 L/min/kg at 120 min, p less than 0.05). Survival times were increased by the indomethacin treatments. Thus, indomethacin appears to be beneficial for the treatment of fulminant hemodynamic deterioration in newborn endotoxic shock.
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PMID:Indomethacin treatment in newborn canine endotoxic shock. 192 Aug 24

Superior mesenteric arterial perfusion (Q) decreases and gut intramucosal hydrogen ion concentration, [H+], increases in resuscitated normodynamic endotoxic pigs. The present study tested the hypothesis that these adverse phenomena can be prevented by pretreatment with LY171883, a specific leukotriene (LT) D4/E4 receptor antagonist. Pentobarbital-anesthetized pigs (14-18 kg) were instrumented to permit measurement of Q (ultrasonic flow probe) and [H+] (tonometer). Mesenteric O2 delivery (DO2) and consumption (VO2) were calculated from the O2 contents of arterial and superior mesenteric venous blood. At t = -20 min, groups (N = 6) of pigs were pretreated witH LY171883 (10 mg/kg) or vehicle. At t = 0 min, the pigs were infused over 20 min with lipopolysaccharide (LPS; 150 micrograms/kg) and resuscitated for 2 hr with saline (1.2 ml/kg min). Irrespective of treatment group, mean arterial pressure and systemic vascular resistance index decreased significantly after infusion of LPS. In general, cardiac index (CI) was well preserved, although in controls at t = 20, 100, and 120 min, CI decreased significantly with respect to the t = 0 min value. Normal mesenteric Q and DO2 were maintained in the LY171883 group, whereas, in controls, these parameters decreased significantly. Mesenteric VO2 increased transiently but significantly in controls; this phenomenon was abrograted by the LT receptor antagonist. In controls, intramucosal [H+] increased by almost threefold; this adverse effect was significantly ameliorated by LY171883. These data suggest that decreased mesenteric Q and increased intramucosal [H+] may be mediated by LT in this porcine endotoxic shock model.
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PMID:LY171883 preserves mesenteric perfusion in porcine endotoxic shock. 197 68

The mortality of septic shock remains high in newborns. Although the effectiveness of adrenergic drug therapy continues to be controversial, adrenergic drugs have been used for the treatment of newborn endotoxic shock. To elucidate the effects of beta-adrenergic drugs on the fulminant hemodynamic deterioration of newborn endotoxic shock, newborn dogs (2-10-day-old, 264-800 g) were given Escherichia coli lipopolysaccharide (LPS; 10 mg/kg iv) and treated with isoproterenol (0.1 micrograms/kg/min) or dopamine (5 micrograms/kg/min) infusion from 5 to 120 min after LPS injection. Isoproterenol attenuated the effects of LPS by increasing the mean arterial pressure (32 +/- 2 vs. 13 +/- 1 mmHg at 120 min), cardiac output (183 +/- 29 vs. 118 +/- 23 ml/min/kg at 120 min), and the survival time (5.3 vs 2.9 hr). However, dopamine did not improve the hemodynamic deterioration. As dopamine-beta-hydroxylase activity in the blood was significantly lower in newborn dogs than in adult dogs, inadequate response of newborn dogs to dopamine was thought to be in part due to enzymatic immaturity.
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PMID:Beta-adrenergic drug therapy in newborn canine endotoxic shock. 197 57

The present study was designed to define the potential of chlorpromazine (CPZ) as a protective agent against lipopolysaccharide (LPS) toxicity in comparison with glucocorticoids, and to obtain initial correlations with its effects on the levels of tumor necrosis factor (TNF), a pivotal mediator of endotoxic shock. It was found that CPZ protects mice, normal or adrenalectomized, and guinea pigs against lethality of LPS, and inhibited TNF serum levels, like dexamethasone (DEX), a well-known inhibitor of TNF synthesis. CPZ protected against LPS lethality when administered 30 minutes (min) before, simultaneously, or up to 10 min after LPS and was ineffective when given 30 min after LPS, paralleling the inhibitory effect on TNF production. In another experimental model, where mice were sensitized to LPS toxicity by actinomycin D, CPZ significantly inhibited LPS lethality and hepatotoxicity, whereas under these conditions DEX was inactive. These experiments indicate that CPZ has a protective action in both glucocorticoid-sensitive and -resistant models of endotoxic shock.
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PMID:Protective effect of chlorpromazine on endotoxin toxicity and TNF production in glucocorticoid-sensitive and glucocorticoid-resistant models of endotoxic shock. 203 66

The mortality of sepsis/septic shock continues to be high in newborns. However, there is no established method in its treatment. Although calcium channel blockers ameliorate the hemodynamic deterioration of adult circulatory shock, their effects on newborn endotoxic shock have not been elucidated. This study was performed in newborn dogs to investigate the effects of diltiazem on newborn endotoxic shock. Endotoxic shock was induced in newborn dogs (2-10 days old, 300-800 g) by an intravenous injection of E. coli lipopolysaccharide (LPS; 1.5 mg/kg), and diltiazem (DZ) at the dose of 300, 600 or 1200 micrograms/kg was administered intravenously 20 min prior to LPS injection. Hemodynamic changes were serially observed until 120 min after LPS injection. The heart rate, mean arterial pressure and cardiac output decreased after LPS injection, and systemic vascular resistance decreased. DZ at the dose of 600 micrograms/kg attenuated the decreases of MAP and cardiac output, but 300 and 1200 micrograms/kg of DZ exacerbated them. DZ at the dose of 1200 micrograms/kg decreased the heart rate, and DZ at all three doses attenuated the increase of systemic vascular resistance. Therefore, 600 micrograms/kg of DZ is beneficial in the treatment of endotoxic shock in newborn dogs.
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PMID:Diltiazem treatment in newborn canine endotoxic shock. 208 81


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