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 28,634 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcitonin gene-related peptide (CGRP), a potent vasodilator, and neuropeptide Y (NPY), a potent vasoconstrictor and potentiator of norepinephrine-induced vasoconstriction, were examined in an animal model of endotoxin shock. Gram-negative bacterial endotoxin (lipopolysaccharide B from Salmonella enteritidis) was administered as a bolus (16.7 mg/kg, i.v.) to conscious, unrestrained rats, previously cannulated for blood pressure measurements and blood withdrawal. At 30 min, endotoxin caused 35-40 mm Hg drop in mean arterial pressure and significant increases in heart rate and plasma levels of glucose and lactate. By 3 hr, blood pressure had returned to near normal levels and remained normal until cardiovascular collapse at 4-6 hr (approximately 70% of the rats). Endotoxin elevated plasma CGRP levels by fourfold at 30 min and 22-fold at 3 hr. Of the organs tested, only vena cava showed significant decreases in CGRP levels. Endotoxin also elevated plasma NPY levels by 67% and decreased NPY levels in adrenal gland and vena cava at 30 min and 3 hr. The data suggest that both CGRP and NPY are released into the circulation during development of endotoxin shock in the rat. NPY may contribute to the compensatory mechanism, tending to bring arterial pressure back to normal levels during intermediate stages of endotoxemia. CGRP, because of its extremely high potency as a hypotensive agent, may contribute to the hypotension at both early and late stages during pathogenesis of endotoxin shock.
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PMID:Calcitonin gene-related peptide (CGRP) and neuropeptide Y (NPY) levels are elevated in plasma and decreased in vena cava during endotoxin shock in the rat. 155 Nov 83

Endotoxins (lipopolysaccharides, LPS) are potent bacterial poisons always present within the intestines in considerable amounts. Several pathophysiological conditions such as hypovolaemia, hypoxia, intestinal ischaemia, burns and radiation lead to a breakdown in the barrier and depending upon the extent of the injury, endotoxins enter the systemic circulation in increasing amounts. Antibiotics do not inactivate the endotoxins which continue to exert their toxic effects leading to nausea, vomiting, diarrhoea, fever, disseminated intravascular coagulation, vascular collapse and organ failure. When nonabsorbable antibiotics are given prior to the insult, systemic endotoxaemia is prevented. Immunotherapy, using anti-lipopolysaccharide IgG, inactivates plasma endotoxins, destroys gram-negative bacteria and opsonises them and may become a major form of therapy. An outline of endotoxin and anti-lipopolysaccharide and its importance to the anaesthetist and intensive care specialist is presented.
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PMID:Endotoxins and anti-endotoxins (their relevance to the anaesthetist and the intensive care specialist). 265 93

Bacterial infection of the mammalian bloodstream can lead to overwhelming sepsis, a potentially fatal syndrome of irreversible cardiovascular collapse (shock) and critical organ failure. Cachectin, also known as tumour necrosis factor, is a macrophage-derived peptide hormone released in response to bacterial lipopolysaccharide, and it has been implicated as a principal mediator of endotoxic shock, although its function in bacterial sepsis is not known. Anaesthetized baboons were passively immunized against endogenous cachectin and subsequently infused with an LD100 dose of live Escherichia coli. Control animals (not immunized against cachectin) developed hypotension followed by lethal renal and pulmonary failure. Neutralizing monoclonal anti-cachectin antibody fragments (F(ab')2) administered to baboons only one hour before bacterial challenge protected against shock, but did not prevent critical organ failure. Complete protection against shock, vital organ dysfunction, persistent stress hormone release and death was conferred by administration of antibodies 2 h before bacterial infusion. These results indicate that cachectin is a mediator of fatal bacteraemic shock, and suggest that antibodies against cachectin offer a potential therapy of life-threatening infection.
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PMID:Anti-cachectin/TNF monoclonal antibodies prevent septic shock during lethal bacteraemia. 331 66

When Escherichia coli B6 lipopolysaccharide, 0.2 mg/kg of body weight, was infused into nonpregnant minipigs during a 5-hour period, the animals died after 12 to 16 hours as a result of endotoxic shock. When the same infusion was given to six pregnant minipigs at term, these animals died after only 3 1/2 hours. The decrease in the number of white blood cells, the number of platelets, hematocrit, and clotting factors was not significantly different between the two groups. The acid-base status, however, indicated a much more pronounced metabolic acidosis in the pregnant animals than in the nonpregnant controls. In the pregnant minipigs heart rate, cardiac output, mean arterial pressure, and total peripheral resistance indicated cardiovascular collapse, and the multiple wire, platinum surface electrode revealed a drastic reduction in uterine tissue oxygenation in the pregnant animals. The data support the hypothesis that pregnant animals at term are more susceptible to the harmful effects of lipopolysaccharide. Early death in the pregnant minipigs, however, was not associated with disseminated intravascular coagulation as it is in smaller animals (rat, rabbit, and hamster).
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PMID:Septicemia during pregnancy: a study in different species of experimental animals. 392 Sep 12

Treatment of gram-negative bacteria with lethal doses of polymyxin B and colistin resulted in the formation of projections of the outer layer of the cell wall. Phages T3, T4, and T7, which use wall lipopolysaccharide as receptors, were specifically prevented from adsorbing to Escherichia coli B cells treated with polymyxin, whereas phages T1, T2, T5, and T6 were not. In the systems of phage P22C-Salmonella typhimurium LT2 and phage C21-S. typhimurium variant SL1069, the phage were prevented from adsorbing to the host cell treated with the antibiotics. Electron microscopic observations show that phage T2 adsorbed irreversibly to the normal smooth surface between the projections on the outer layer caused by the drug treatment. These results indicate that lipopolysaccharide is affected by polymyxin functionally and morphologically, but lipoprotein is not. The purified lipopolysaccharide showed a ribbon-like structure when viewed face on and showed trilamellar structure when viewed edge on. The lipopolysaccharide from E. coli B was irreversibly adsorbed by phages T3, T4, and T7, but not phage T2. Often, phage T4 adsorbed to both sides of the lipopolysaccharide strand at comparable distances. Phage P22C adsorbed through the spikes of the tail-plates to the lipopolysaccharide from S. typhimurium LT2. Lipopolysaccharide which was treated with low doses of the drug (2.5 to 6.25 mug of polymyxin B per ml to 100 mug of lipopolysaccharide per ml) turned into the coiled form and was partially broken down into short segments with coiled form. The loosely coiled lipopolysaccharide retains both its function as the receptor and its trilamellar structure. Treatment with high doses of the drug (12.5 to 25 mug of polymyxin B per ml to 100 mug of lipopolysaccharide per ml) caused the collapse of the trilamellar structure of the strand. These collapsed lipopolysaccharides became flat and fused with each other, making an amorphous mass, and finally they were broken into small collapsed fragments.
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PMID:Effect of polymyxin on the bacteriophage receptors of the cell walls of gram-negative bacteria. 410 66

The effects of different serum components alone and in conjunction with each other on Escherichia coli B were investigated. In general, the viability, turbidity, and electron microscope results were compatible with the following conclusions. The most efficient killing and destruction of E. coli B occurred when beta-lysin, lysozyme, and the antibody-complement system functioned in cooperation with each other at the serum concentration in isotonic solutions. The addition of sucrose protected the bacteria from the lethal and lytic action of these agents. Elimination of lysozyme from serum had the least effect on bactericidal activity, even though lysozyme treatment caused the cell wall to separate from the cytoplasmic membrane and caused clear areas to appear in the inner granular layer of the cell wall. Beta-lysin removal had an intermediate effect on the serum bactericidal activity. Beta-lysin treatment caused cell walls to collapse, allowed cytoplasmic contents to leak out of the cells, and stopped the separation of cell wall and cytoplasmic membrane, which normally takes place in 0.5 M sucrose solution. Inactivation of the complement eliminated the serum bactericidal activity against E. coli B. After treatment with antibody and complement, the cell walls became thick and indistinct, a portion of the cytoplasmic contents escaped, and patches of the middle layer of the cell wall appeared in freeze-etch preparations. Beta-lysin damaged the cytoplasmic membrane, lysozyme damaged the inner peptidoglycan layer of the cell wall, and the antibody-complement system damaged both the middle lipopolysaccharide layer of the cell wall and the cytoplasmic membrane.
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PMID:Interrelationship between serum beta-lysin, lysozyme, and the antibody-complement system in killing Escherichia coli. 460 6

The lesions induced in man by Entamoeba histolytica are characterized by massive tissue injury in the absence of major local signs of a host immune response. The amoeba damages surrounding cells preferentially by contact-mediated cytolysis. Recently, a presumptive aetiological factor underlying this process has been identified. It is a protein, amoebapore, capable of spontaneous incorporation into host cell membranes. Therein it induces high conductance ion-channels which rapidly collapse the cellular transmembrane potential and lead to a prelytic state. Amoebapore is present within the amoeba in a highly aggregated state in a small, dense particle. It is shed into the medium in a particulate form by a stimulus-mediated process. Release is enhanced by addition of concanavalin A, lipopolysaccharide or the calcium ionophore A23187. Surface-labelling of intact amoeba, followed by fractionation of the homogenate in self-generating Percoll gradients, identified two labelled fractions, the plasma membrane and a particulate fraction sedimenting in the region of intracellular particulate amoebapore. This latter fraction appears to be material in the process of exocytosis. A highly immunogenic surface lipid has been identified and shown to be involved in the rapid surface redistribution of immune complexes, their shedding and endocytosis. The relevance of these findings to the immunoprophylaxis of amoebiasis is discussed.
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PMID:Cytopathogenicity of Entamoeba histolytica. 615 90

Cardiovascular collapse associated with Gram-negative septicemia is believed to result from the stimulation of phagocytes by bacterial lipopolysaccharide (endotoxin, LPS). It remains unclear how endotoxin activates phagocytes, but recent evidence suggests the involvement of the glycosyl phosphatidylinositol-linked myelocyte antigen, CD14. We report that transfection of human CD14 into Chinese hamster ovary fibroblasts transfers macrophage-like responsiveness to otherwise LPS-unresponsive cells. These data demonstrate that LPS-induced responsiveness can be transferred to a heterologous non-responder cell type by expression of a single leukocyte-specific gene product.
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PMID:Surface expression of human CD14 in Chinese hamster ovary fibroblasts imparts macrophage-like responsiveness to bacterial endotoxin. 769 22

Tumor necrosis factor-alpha (TNF-alpha), a central mediator in the hemodynamic response to injury and infection, is a primary mediator of endotoxin-induced hemodynamic instability. Two types of naturally occurring soluble TNF receptors circulate in human experimental endotoxemia and the recombinant proteins of both have been hypothesized as potential therapeutic agents antagonizing TNF-mediated effects of endotoxemia. The administration of recombinant sTNFr-I has been previously shown to attenuate the hemodynamic collapse of lethal bacteremia. In the current study, we investigated the role of recombinant sTNFR-II at low (0.5 mg/kg) and high (2.5 mg/kg) doses as a potential therapeutic agent for the inhibition of endotoxin lipopolysaccharide (LPS)-mediated hemodynamic instability. Eighteen male Sprague-Dawley rats were anesthetized and cannulated for continuous blood pressure monitoring and cardiac output measurement by thermodilution. Groups of animals received saline, LPS (1 mg/kg), or sTNFr-II (at 0.5 or 2.5 mg/kg) 15 min prior to LPS (1 mg/kg). Hemodynamic variables (blood pressure, cardiac output, heart rate) were monitored every 15 min for 2 hr. LPS caused a 30% decrease in mean arterial pressure by 60 min, which began to recover by 120 min. sTNFr-II was unable to prevent LPS-induced hypotension at low or high dose. Serum levels of immunoreactive TNF-alpha, undetectable in control animals, were significantly increased by sTNFr-II compared to LPS alone. Serum from animals treated with high-dose sTNFr-II showed significantly less TNF cytotoxicity than those treated with low-dose sTNFr-II, indicating that high doses of sTNFr-II are required for the inhibition of the bioactivity of TNF.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of soluble tumor necrosis factor receptor-II on endotoxin-mediated hemodynamic instability. 783 Apr 6

Nitric oxide (NO) formation via the expression of an endotoxin- and cytokine-inducible NO synthase (iNOS) within the vascular smooth muscle is thought to be responsible for the cardiovascular collapse that occurs during septic shock and antitumor therapy with cytokines. Because the molecular mechanisms that underlie induction of iNOS are still unclear and because tyrosine kinases are implicated in interleukin-1 beta (IL-1 beta)-induced prostaglandin synthesis in mesangial cells and in NO generation by an insulinoma cell line, we investigated the influence of tyrosine kinase inhibitors on iNOS induction in cultured rat aortic smooth muscle cells (RASMC). The production of biologically active NO was demonstrated by L-arginine-dependent guanosine 3',5'-cyclic monophosphate (cGMP) accumulation after a 3-h exposure to either IL-1 beta or lipopolysaccharide (LPS). Pretreatment of RASMC for 30 min with the tyrosine kinase inhibitor genistein prevented both IL-1 beta- and LPS-elicited cGMP accumulation in a concentration-dependent manner. Geldanamycin, a chemically different tyrosine kinase inhibitor, also blocked cGMP formation in response to both LPS and IL-1 beta at nanomolar concentrations. Genistein and geldanamycin inhibited cGMP accumulation even when added 90 min after LPS exposure, but no inhibition was observed when they were included at later time points (120-180 min), suggesting that the inhibitors had no direct effect on iNOS activity after its induction. Formation of cGMP in response to sodium nitroprusside and to NO released from bovine aortic endothelial cells remained virtually unaffected by genistein and geldanamycin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tyrosine kinase inhibitors suppress endotoxin- and IL-1 beta-induced NO synthesis in aortic smooth muscle cells. 821 7


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