Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although liposuction is considered to be a relatively safe procedure, several deaths and nonfatal serious complications such as sepsis, toxic shock syndrome, thromboembolic disease, fat emboli, and adult respiratory distress syndrome have been reported. In the present study, we have investigated a wide variety of components belonging to the coagulation, fibrinolytic, plasma kallikrein-kinin, and complement systems in 22 patients undergoing syringe-assisted liposuction using the superwet or tumescent technique. In spite of a relatively high mean aspirate volume (2,648 ml), only small changes over time well within the normal range were found for the different parameters. In nine randomly selected patients, we also measured interleukin 6 and tumor necrosis factor-alpha. The size of the interleukin-6 peaks was found to be of the same order of magnitude as those measured in patients undergoing hernia repair or percutaneous cholecystectomy but lower than those in patients undergoing open cholecystectomy, breast reduction, or breast reconstruction. Tumor necrosis factor-alpha was not detected in any sample in any of the patients. We conclude that syringe-assisted liposuction with the present aspirate volumes using the superwet or tumescent technique represents a small to moderate surgical trauma without clinical significant activation of the cascade systems.
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PMID:Effect of syringe-assisted liposuction on activation of cascade systems and circulating cells when using the superwet or tumescent technique. 750 16

Tumor necrosis factor-alpha (TNF-alpha) inhibits release of nitric oxide (NO) in vitro by stimulating the degradation of constitutive NO synthase (cNOS III) mRNA. However, TNF-alpha is believed to be the cytokine mediator of the hypotension and upregulation of inducible NO synthase (iNOS II) produced by gram-negative bacterial endotoxin (LPS). Some in vivo effects of TNF-alpha are opposite to those which occur in vitro. This study tested the hypothesis that in vivo administration of exogenous TNF-alpha and endogenously released TNF-alpha induce iNOS II activity and inhibit cNOS III activity, and thereby mediate the acute phase effects of LPS on blood pressure and the NO system in the rat. We show that LPS produces acute phase hypotension in ketamine anesthetized rats. The hypotension was associated with elevation of biologically active TNF-alpha in plasma, increased production of RNI (NO2- and NO3- anion) in rat neutrophils (PMN) and suppression of RNI production by A23187 (1 microM) stimulated thoracic aorta (RTA) ex vivo. TNA-alpha (10(6) U/ml, iv) did not produce acute phase hypotension but initially raised arterial blood pressure and heart rate (HR), did not increase RNI production by PMN, and inhibited RNI production by A23187 stimulated RTA ex vivo. Pretreatment of rats with the immunex monomeric soluble P75 receptor binding protein for TNF-alpha (TNFsr, 0.5 mg/kg, iv) 15 min prior to LPS administration decreased circulating TNF-alpha from 92,137 +/- 12,456 U/ml to undetectable levels as determined by the L929 bioassay. However, LPS-induced increases in RNI in PMN was enhanced and LPS-induced decreases in RNI production by RTA was inhibited by TNFsr. Thus, in vivo administration of TNF-alpha does not mimic the hemodynamic and NO-inducing effects of LPS. However, TNF-alpha mediates in part LPS-induced inhibition of RNI production by RTA. Thus, endogenous TNF-alpha is not required for LPS-induced acute phase hypotension or iNOS II activity. The importance of TNF-alpha in sepsis resides in systems other than iNOSII and blood pressure.
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PMID:In vivo administration of endotoxin and tumor necrosis factor-alpha produce different effects on constitutive and inducible nitric oxide synthase activity in rat neutrophils and aorta ex vivo. 753 Mar 65

Tumor necrosis factor-alpha (TNF alpha), a cytokine that is produced in a variety of inflammatory diseases associated with cholestasis, is believed to be the primary mediator of the systemic effects of endotoxin. Thus, we have investigated the role of TNF alpha in the pathogenesis of endotoxin-induced cholestasis in intact animals, and in the uptake of taurocholate by cultured hepatocytes. Male Sprague-Dawley rats received either intravenous (IV) endotoxin (7.5 mg/kg) or monoclonal anti-TNF alpha antibody followed by endotoxin. Basal bile flow and bile salt excretion were measured for a 2-hour period, after which all animals received an IV bolus of taurocholate (10 mumol/100 g body weight). Endotoxin decreased basal bile flow by 41% and bile salt stimulated bile flow by 38% (n = 12; P < .01). Basal bile salt excretion was decreased 86% after endotoxin administration. Passive immunization with anti-TNF alpha antibody blocked this endotoxin-associated cholestasis. In addition, rat hepatocytes were isolated and cultured in the presence of either endotoxin (10 micrograms/mL) or TNF alpha (100 ng/mL) for 24 hours. These primary hepatocyte cultures exhibited a dose- and time-dependent, noncompetitive, inhibition of taurocholate uptake. We postulate that TNF alpha is an important mediator of the cholestasis of sepsis.
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PMID:Tumor necrosis factor-alpha decreases hepatocyte bile salt uptake and mediates endotoxin-induced cholestasis. 755 81

Tumor necrosis factor-alpha (TNF-alpha), a monokine that contributes to vascular dysfunction accompanying the host response to gram-negative sepsis, has been shown to increase vascular permeability in vivo and to diminish the barrier function of cultured endothelial cell (EC) monolayers. The studies reported here indicate that a mechanism through which TNF alters EC barrier function involves a reduction in intracellular adenosine 3',5'-cyclic monophosphate (cAMP) content, due in part to increased cyclic nucleotide phosphodiesterase (CNPDE) activities. TNF increased the diffusional transit of [3H]sorbitol, [3H]inulin, and 125I-labeled albumin across confluent bovine aortic EC monolayers. This effect of TNF was both time and dose dependent and occurred in parallel with a fall in EC cAMP. cAMP analogues, such as dibutyryl cAMP (DBcAMP), prevented TNF-induced perturbation of EC barrier function. TNF also mediated another important alteration in the EC phenotype, in that both mRNA and activity of the anticoagulant cofactor thrombomodulin were reduced after exposure of EC to TNF and were normalized by the addition of DBcAMP. EC monolayers exposed to TNF-alpha showed increased cAMP levels when exposed to 3-isobutyl-1-methylxanthine, a nonspecific CNPDE inhibitor. Ion exchange chromatography of cytosol derived from TNF-treated EC consistently showed an approximately 245% increase in phosphodiesterase (PDE) IV (high-affinity, cAMP-specific PDE) activity as identified by rolipram inhibition. PDE II activity was increased by 150% after TNF-alpha treatment of early passage EC, which was identified by cGMP-activated hydrolysis of cAMP. Western and Northern analyses, as well as activity studies, revealed that TNF treatment did not change the amount of PDE IV protein or mRNA but rather increased the specific activity of the isozyme, suggesting that a posttranslational modification had occurred. These data indicate that activation of EC CNPDE activity and decreased intracellular cAMP may represent a mechanism by which TNF increases EC permeability and promotes a procoagulant EC phenotype.
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PMID:TNF modulates endothelial properties by decreasing cAMP. 776 2

Tumor necrosis factor-alpha (TNF alpha) is recognized as a principal mediator of a variety of inflammatory conditions. In animal models, pentoxifylline attenuates the morbidity and mortality of bacterial sepsis, an effect which has been attributed to its ability to suppress the induction of TNF alpha. To determine whether pentoxifylline also directly inhibits the effects of TNF alpha, the ability to inhibit cytotoxicity on the TNF alpha-sensitive murine fibrosarcoma cell line, L929, was examined. Cell viability was assessed by crystal violet staining and cell proliferation was assessed by [3H]-thymidine uptake assay. TNF alpha induced dose-dependent cytotoxicity. At concentrations of TNF alpha of 1000 U/ml, viability at 3 days was approximately 35% of control. When L929 cells were co-incubated with TNF alpha (1000 U/ml) and pentoxifylline (1 mM), cell viability increased to approximately 75% of control (P = 0.001). At concentrations of TNF alpha of 10,000 U/ml, cell viability which was 11% of control with TNF alpha alone increased to 53% in the presence of pentoxifylline (P = 0.002). TNF alpha at 1000 and 10,000 U/ml concentrations decreased [3H]-thymidine uptake to approximately 5% of control values. Co-incubation with pentoxifylline significantly increased uptake to 13% of control at both TNF alpha concentrations (P = 0.002). Pentoxifylline did not affect the level of type I TNF alpha receptor--ligand cross-link product. However, in TNF alpha receptor binding assays, incubation with pentoxifylline 1 mM for 4 h was associated with an increase in the receptor affinity (control: KD = 0.42 nM vs pentoxifylline-treated: KD = 0.21 nM, P = 0.006), without significant change in number of type I TNF alpha receptors, suggesting that pentoxifylline affects post-receptor signalling events. We have observed that pentoxifylline prevents the TNF alpha-mediated activation of sn-2 arachidonic acid-specific cytosolic phospholipase A2, an important component of the signal transduction pathway of TNF alpha cytotoxicity. Because pentoxifylline does not inhibit all activities mediated by the type I TNF alpha receptor, its selective inhibition of post-receptor signalling may facilitate further study into the mechanisms underlying the diverse effects of TNF alpha.
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PMID:Pentoxifylline inhibits tumor necrosis factor-alpha-mediated cytotoxicity and cytostasis in L929 murine fibrosarcoma cells. 780 30

Tumor necrosis factor-alpha (TNF) exerts numerous influences which, in association with severe infection, subserve both detrimental as well as beneficial host responses. The current review addresses recent insights into the structure and function of this pleiotropic cytokine, with a particular emphasis upon cellular and organ system consequences of sepsis-induced TNF activity. A comparison of responses elicited by endotoxin or TNF administration are discussed as are mechanisms of endogenous TNF regulation, such as soluble receptors, anti-inflammatory cytokines, and counter-regulatory responses. A review of past and future clinical strategies for altering TNF activity during sepsis is also provided.
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PMID:Tumor necrosis factor in sepsis: mediator of multiple organ failure or essential part of host defense? 785 May 74

Tumor necrosis factor-alpha (TNF-alpha) is an important mediator in sepsis and septic shock. Kupffer cells (KCs) are the resident macrophages of the liver and are potent producers of TNF-alpha in response to inflammatory stimuli such as bacterial endotoxin or lipopolysaccharide (LPS). Although the effects of exogenous cytokines such as interferon-gamma on TNF-alpha production by macrophages have been fairly well studied, the intracellular pathways regulating KC TNF-alpha synthesis are largely unknown. We investigated the role of guanylate cyclase and cGMP in LPS-induced KC TNF-alpha synthesis. Exogenous 8-BrcGMP and dbcGMP increased LPS-stimulated TNF-alpha synthesis but had no effect on KC TNF-alpha in the absence of LPS. Sodium nitroprusside (SNP), a nitric oxide-releasing substance that stimulates guanylate cyclase, increased TNF-alpha synthesis in response to LPS, whereas methylene blue and LY83583, guanylate cyclase inhibitors, decreased KC TNF-alpha synthesis. The inhibitory effect of methylene blue could be overcome with exogenous dbcGMP or SNP. Our results demonstrate that guanylate cyclase and cGMP mediate LPS-induced KC TNF-alpha synthesis and suggest that agents that alter cyclic nucleotide metabolism in KCs may affect the response of these cells to inflammation and inflammatory stimuli.
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PMID:Cyclic GMP and guanylate cyclase mediate lipopolysaccharide-induced Kupffer cell tumor necrosis factor-alpha synthesis. 785 45

The neutrophil is an important effector cell of the host response to sepsis. Tumor necrosis factor-alpha (TNF-alpha), a cytokine mediator of the septic response, is rapidly released following endotoxemia or gram-negative bacteremia. Interleukin-6 (IL-6) is another cytokine mediator of the host response to sepsis whose role is less well understood than that of TNF-alpha. It is known to be elevated in gram-negative sepsis, where peak levels have been correlated with mortality. This study examined the effect of IL-6 alone and in combination with TNF-alpha on three neutrophil functions--CD18 adhesion receptor expression, phagocytosis, and superoxide anion generation. Neutrophils from human volunteers were incubated with amounts of IL-6 ranging from 10 to 1000 ng/ml. At a concentration of 1000 ng/ml, IL-6 increased neutrophil phagocytosis of opsonized bacteria (826 +/- 255 x 10(3) MESF vs 552 +/- 103 MESF, P < 0.05) and also increased neutrophil superoxide anion generation (18.41 +/- 1.86 vs 12.6 nmol O2-/10(6) PMN/10 min, P < 0.05). Lesser amounts of IL-6 had no effect on phagocytosis or superoxide generation. IL-6 did not increase neutrophil CD18 adhesion receptor expression. Combining IL-6 with TNF-alpha at doses of 100 ng/ml and 100 U/ml, respectively, neutrophil phagocytosis (221 +/- 455 MESF vs 552 +/- 103 MESF) and superoxide generation (23.18 +/- 1.86 vs 12.6 nmol O2-/10(6) PMN/10 min) were significantly (P < 0.05) increased above control by an amount similar to that seen with 1000 U/ml TNF-alpha alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tumor necrosis factor-alpha and interleukin-6 selectively regulate neutrophil function in vitro. 786 62

The proinflammatory cytokines have been implicated in mediating myocardial dysfunction associated with myocardial infarction, severe congestive heart failure, and sepsis. We tested the hypothesis that cytokine levels are elevated after uncomplicated coronary artery bypass grafting and associated with episodes of postoperative myocardial ischemia and dysfunction. Coronary artery bypass grafting was performed under general anesthesia with moderate systemic hypothermia and cold-blood potassium cardioplegic solution. Tumor necrosis factor-alpha and interleukin-6 levels were determined by bioassays, and interleukin-8 levels were measured by a sandwich enzyme-linked immunosorbent assay. Myocardial function and ischemic episodes were assessed by intraoperative transesophageal echocardiography and perioperative 12-channel Holter monitoring. A total of 22 patients were studied, with no deaths or complications. Arterial tumor necrosis factor-alpha rose in a bimodal distribution, peaking at 2 and 18 to 24 hours after the operation (at 20.2 +/- 6.4 pg/ml, [mean +/- standard error of the mean]) and 5.8 +/- 1.6 pg/ml, respectively; before cardiopulmonary bypass: 0.90 +/- 0.20 pg/ml, p < 0.001 for both peaks) then progressively declined to levels before bypass. Arterial interleukin-6 was maximally elevated immediately on termination of cardiopulmonary bypass and peaked again 12 to 18 hours after cardiopulmonary bypass (at 7520 +/- 2439 pg/ml and 6216 +/- 1928 pg/ml, respectively; before bypass: 746 +/- 187 pg/ml, p < 0.0001 for both peaks). Arterial interleukin-8 levels were more variable but followed a similar pattern, peaking in the early period after cardiopulmonary bypass and again at 16 to 18 hours after the operation (at 4110 +/- 1403 pg/ml and 1760 +/- 1145 pg/ml, respectively; before bypass: 461 +/- 158, p < 0.05 for both peaks). By multivariate analysis, the aortic crossclamp time was independently predictive of postoperative cytokine levels. Left ventricular wall motion abnormalities were associated with both interleukin-6 and interleukin-8 levels, worsening scores being associated with increasing levels (for interleukin-6, p = 0.003; for interleukin-8, p = 0.05). Postoperative myocardial ischemic episodes were associated with interleukin-6 levels, six of seven (85%) patients with episodes of myocardial ischemia after a peak in interleukin-6 concentrations (p < 0.01). We conclude that proinflammatory cytokines are elevated after uncomplicated coronary revascularization and may contribute to postoperative myocardial ischemia and segmental wall motion abnormalities.
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PMID:Relationship of the proinflammatory cytokines to myocardial ischemia and dysfunction after uncomplicated coronary revascularization. 793 95

Vascular thrombosis and tissue infarction is a principal lesion in Haemophilus somnus septicemia known also as thrombotic meningoencephalitis. This study was undertaken to examine whether tumor necrosis factor-alpha (TNF-alpha) can influence the adherence of H. somnus to cultured bovine aortic endothelial cells (BAEC). Confluent BAEC were exposed to 0-100 nM of human recombinant TNF-alpha for 12-48 h. Suspensions of different strains of H. somnus (approximately 1.5-3 x 10(8) labelled with [methyl-3H]-thymidine, were added to BAEC and incubated for 1.5 h. Initial studies with one pathogenic (P) strain and one non-pathogenic (NP) strain revealed that both strains adhered to normal endothelial cells but minimally to subendothelial matrix remaining after removal of BAEC. Adherence to BAEC was reduced by an excess of unlabelled H. somnus of the same strain. Adherence was enhanced for both strains by exposure of BAEC to TNF-alpha in a manner that increased with TNF-alpha concentration and with duration of exposure to TNF-alpha prior to addition of bacteria. A survey of adherence of six live P strains and six NP strains demonstrated considerable variation but no difference in adherence between P and NP strains to normal or to TNF-alpha-stimulated BAEC. However, TNF-alpha consistently increased adhesion of each strain to BAEC. Both P and NP strains caused more severe cytotoxic changes in TNF-alpha-treated BAEC. Tumor necrosis factor-alpha also increased adhesion of formalin-killed bacteria of P and NP strains.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adherence of Haemophilus somnus to tumor necrosis factor-alpha-stimulated bovine endothelial cells in culture. 795 24


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