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)

Lipid profile is known to alter in patients with severe sepsis, but few studies regarding the status of lipid levels in enteric fever are available. Twenty patients with enteric fever, belonging to different age groups and both sexes, along with an equal number of matched patients with fever due to non-enteric causes, were studied with regard to alterations in lipid profile. We observed a severe and protracted hypertriglyceridaemia, decrease in HDL-cholesterol levels and increase in LDL-cholesterol levels in patients with enteric fever at the peak of fever. The values returned to normal on recovery and convalescence. This study serves to highlight the complexity of lipid variation during Salmonella typhi infection.
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PMID:Lipid profile in enteric fever. 188 95

Macrophages are induced by LPS to release a number of products that determine the host response during gram negative sepsis. To examine the role of one such substance, tumor necrosis factor (TNF), in mediating LPS-induced injury, we employed a rabbit model of endotoxic shock to (a) determine the kinetics and extent of release of TNF into plasma after injection of LPS, and (b) to evaluate the protective effect of in vivo neutralization of LPS-induced TNF by prior infusion of anti-TNF antibody. TNF was maximally induced 45-100 min after injection of 10 micrograms i.v. parent Salmonella minnesota Re595 LPS or 250 micrograms Re595 LPS-HDL complexes. Maximal induction of TNF by LPS was associated with development of hypotension, focal hepatic necrosis, intravascular fibrin deposition and lethality. Based on (a) the peak levels of TNF observed in serum, 2.5 X 10(3) U/ml, (b) the specific activity of purified rabbit macrophage-derived TNF, 1 X 10(8) U/mg, and (c) the biphasic disappearance of intravenously injected purified TNF (t1/2 = 0.5 min, 11 min) we constructed a kinetic model showing that at least 130 micrograms of TNF (1.3 X 10(7) U) was released into plasma 30-200 min postinjection of LPS. Prior infusion of anti-TNF antibody (30-45 min before LPS injection) resulted in neutralization of the LPS-induced serum TNF activity and provided significant protection from the development of hypotension, fibrin deposition, and lethality. Thus, these results provide further evidence that TNF plays a central role mediating the pathophysiologic changes that occur during gram negative endotoxic shock.
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PMID:Participation of tumor necrosis factor in the mediation of gram negative bacterial lipopolysaccharide-induced injury in rabbits. 338 55

Lipopolysaccharide (LPS) Binding Protein (LBP) is an acute phase protein with the ability to recognize bacterial LPS and transport it to the CD14 molecule or into HDL particles. It is synthesized in hepatocytes and secreted into the blood stream. LBP levels significantly rise during the acute phase response and levels of LBP may be important for an appropriate host reaction to bacterial challenge and for developing the sepsis syndrome. In order to elucidate the mechanisms of LBP regulation we investigated its transcription pattern and performed promoter studies under experimental conditions mimicking an acute phase scenario. In human hepatoma cell lines stimulation with IL-1 beta, IL-6, TNF-alpha and dexamethasone leads to strong transcriptional activation of the LBP gene in a dose- and time-dependent manner. IL-6 alone induces LBP significantly, whereas IL-1 beta mainly increases the IL-6 effect when applied in combination. Our results furthermore show that AP-1 and C/EBP beta are transcription factors involved in the activation of the LBP gene, as revealed by Luciferase reporter gene analysis and electromobility shift assays. Elucidating the mechanism of transcriptional activation of LBP potentially may help in understanding host-pathogen response patterns and mechanisms involved in the acute phase reaction and in the pathophysiology of sepsis.
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PMID:The transcriptional activation pattern of lipopolysaccharide binding protein (LBP) involving transcription factors AP-1 and C/EBP beta. 944 84

LPS-binding protein (LBP) recognizes bacterial LPS and transfers it to CD14, thereby enhancing host cell stimulation, eventually resulting in pathogenic states such as septic shock. Recently, LBP also was shown to detoxify LPS by transferring LPS into HDL particles in vitro. Thus, the predominant in vivo function of LBP has remained unclear. To investigate the biological activity of acute phase concentrations of recombinant murine LBP, high concentrations of LBP were investigated in vitro and in vivo. Although addition of low concentrations of LBP to a murine macrophage cell line enhanced LPS-induced TNF-alpha synthesis, acute phase concentrations of LBP blocked this effect in comparison to low-dose LBP. When injected into mice intraperitoneally, LBP inhibited LPS-mediated cytokine release and prevented hepatic failure resulting in a significantly decreased mortality rate in LPS-challenged and D-galactosamine-sensitized mice, as well as in a murine model of bacteremia. These results complement a recent study revealing LBP-deficient mice to be dramatically more susceptible to an intraperitoneal Salmonella infection as compared with normal mice. We conclude that acute phase LBP has a protective effect against LPS and bacterial infection and may represent a physiologic defense mechanism against infection. Despite the limitations of any murine sepsis model, the results shown may imply that LBP could have beneficial effects during gram-negative peritonitis in humans.
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PMID:LPS-binding protein protects mice from septic shock caused by LPS or gram-negative bacteria. 959 62

Lipoproteins are able to bind to lipopolysaccharide (LPS) and neutralize its deleterious effects. However, it is not clear why the LPS-binding capacity of circulating lipoproteins, which is 10- to 10 000-fold above the maximal LPS concentrations found in septic patients, is not sufficient to inhibit the effects of LPS during an infection, whereas infusion of exogenous lipoproteins has a potent inhibitory action. In this study, the kinetics of LPS-neutralization by VLDL, LDL, and HDL were investigated, at lipoprotein-to-LPS ratios found in severe Gram-negative sepsis. At least 4-8-h preincubation of LPS with either LDL or HDL were necessary to inhibit 50% of the LPS-induced TNF-alpha production by human peripheral blood mononuclear cells (PBMC), whereas after 24 h of preincubation LDL or HDL strongly inhibited the TNF-alpha synthesis (70-90%, P<0.01). VLDL was the least effective lipoprotein fraction. In contrast, FITC-LPS bound to PBMC much more rapidly, with 70% of the total binding after 30 min, and 90% after 1-h incubation. The increase of LDL or HDL concentrations up to 10-fold (as in experimental models of hyperlipoproteinaemia) was able not only to further decrease TNF-alpha production after long LPS-lipoproteins preincubation periods, but also to improve the kinetics of LPS neutralization. In conclusion, LPS binds and stimulates the mononuclear cells in circulation before neutralization by endogenous lipoproteins can occur. Additional increase in the lipoprotein-to-LPS molar ratio (e.g. by infusion of exogenous lipoproteins) accelerates the kinetics of LPS neutralization, and may be useful as adjunctive therapy in severe Gram-negative infections.
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PMID:Bacterial lipopolysaccharide binds and stimulates cytokine-producing cells before neutralization by endogenous lipoproteins can occur. 981 29

Sepsis-induced changes in human plasma decrease LPS association with monocytes by regulating dynamic interactions among LPS, monocytes, and plasma lipoproteins. In the physiological environment of undiluted human serum, we have found that: (i) LPS binds transiently to monocytes and is released into plasma lipoproteins; (ii) the release of LPS from monocytes is dependent upon lipoprotein acceptors and is enhanced by soluble CD14 (sCD14); and (iii) both lipoproteins and sCD14 can attenuate cytokine responses in monocytes that have already bound LPS. Whereas LPS binding protein (LBP) also inhibited LPS responses after LPS had bound to monocytes, this did not require extensive release of cell-bound LPS as was observed with sCD14. In the serum of septic patients, both free LPS and monocyte-bound LPS were usually transferred to lipoproteins at an accelerated rate. In spite of a sharp decline in HDL levels, HDL remained the dominant LPS acceptor in many severely septic patients, whereas in some cases LPS binding shifted largely to a non-HDL lipoprotein fraction that co-eluted according to size with very low-density lipoprotein (VLDL). Preliminary data suggest that these lipoproteins have a very low density, and they contain apolipoprotein E and higher than normal proportions of the total lipoprotein cholesterol, phospholipid, apolipoprotein B, and serum amyloid A. The data suggest that the VLDL fraction contains acute phase lipoproteins of significantly altered composition that can replace HDL as the dominant LPS acceptor during sepsis when HDL levels are low.
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PMID:Impact of sepsis-induced changes in plasma on LPS interactions with monocytes and plasma lipoproteins: roles of soluble CD14, LBP, and acute phase lipoproteins. 1280 85

There appear to be ethnic disparities in frequencies of diabetic complications in type 2 diabetic patients and such data from Asian countries are relatively few and limited. Thai type 2 diabetic patients who attended the diabetic clinic at Prince of Songkla University hospital during January-December 1997 and had no history of coronary heart disease (CHD) and stroke were studied to determine cause of death and to establish the incidence of and risk factors for cardiovascular disease (CVD). All patients were followed to death or to the end of year 2001. End-points included death from any cause, fatal and nonfatal CHD, fatal and nonfatal stroke and lower-extremity amputation. There were 229 patients who were followed for 4.2+/0.7 (S.D.) years (range: 0.6-5.0) with total follow-up period 958.2 patient-years. Twenty-nine patients died during follow-up; the total mortality rate was 30.3 (95%CI 20.2-43.4)/1000 patient-years. Of these, 9(9.4/1000 patient-years; 95%CI 4.3-17.8) died from sepsis, 7(7.3/1000 patient-years; 95%CI 2.9-15.0) from CVD, 5(5.2/1000 patient-years; 95%CI 2.7-12.2) from end-stage renal disease, 3(3.1/1000 patient-years; 95%CI 0.6-9.2) from malignancy and 1(1.0/1000 patient-years; 95%CI 0.03-5.8) from peripheral vascular disease. The incidences of fatal and nonfatal CHD as well as fatal and nonfatal stroke were 21.4(95%CI 13.0-33.0)/1000 and 12.8(95%CI 6.6-22.4)/1000 patient-years, respectively whereas the incidence of lower-extremity amputation was 4.3(95%CI 1.2-10.9)/1000 patient-years. Age, the presence of proteinuria and serum HDL-C < or = 0.9 mmol/l were independent risk factors of CHD with the respective Hazard ratios 1.09(95%CI: 1.02-1.17; P=0.016), 4.41(95%CI: 1.18-16.45; P=0.027) and 3.91(95%CI: 1.20-12.80; P=0.024). In conclusion, sepsis and CVD were the major causes of death accounting for approximately 50% of total mortality in Thai type 2 diabetic patients. Age, the presence of proteinuria and low HDL-C were independent risk factors for the development of CHD. The mortality from and the incidence of CHD in Thai type 2 diabetic patients are lower than those reported from Caucasian populations but the incidence of stroke appears to be higher. These findings need to be confirmed by a large-scale population-based study.
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PMID:Causes of death, incidence and risk factors of cardiovascular diseases in Thai type 2 diabetic patients: a 5 year follow-up study. 1282 63

The use of lipoproteins has been suggested as a treatment for Gram-negative sepsis because they inhibit lipopolysaccharide (LPS)-mediated cytokine production. However, little is known about the neutralizing effects of lipoproteins on cytokine production by meningococcal LPS or whole Gram-negative bacteria. We assessed the neutralizing effect of LDLs, HDLs, and VLDLs on LPS- or whole bacteria-induced cytokines in human mononuclear cells. A strong inhibition of Escherichia coli LPS-induced interleukin-1beta (IL-1beta), tumor necrosis factor-alpha, and IL-10 by LDL and HDL was seen, whereas VLDL had a less pronounced effect. In contrast, Neisseria meningitidis LPS, in similar concentrations, was neutralized much less effectively than E. coli LPS. Effective neutralization of meningococcal LPS required a longer interaction time, a lower concentration of LPS, or higher concentrations of lipoproteins. The difference in neutralization was independent of the saccharide tail, suggesting that the lipid A moiety accounted for the difference. Minimal neutralizing effects of the lipoproteins were observed on whole E. coli or N. meningitidis bacteria under all conditions tested. These results indicate that efficient neutralization of LPS depends on the type of LPS, but a sufficiently long interaction time, a low LPS concentration, or high lipoprotein concentration also inhibited cytokines by the less efficiently neutralized N. meningitidis LPS. Irrespective of these differences, whole bacteria showed no neutralization by lipoproteins.
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PMID:Human lipoproteins have divergent neutralizing effects on E. coli LPS, N. meningitidis LPS, and complete Gram-negative bacteria. 1475 10

An increasing body of evidence demonstrates a close interplay between lipoprotein metabolism and sepsis. Sepsis results in an increase of plasma triglycerides within VLDL as a consequence of an enhanced hepatic VLDL production and/or inhibited peripheral and hepatic VLDL clearance. In contrast, sepsis decreases plasma cholesterol within LDL and mainly HDL. The decrease in HDL is accompanied by a loss of mainly apoAI-containing particles, an almost total loss of apoCI, and an increase in apoE-containing HDL, as related to the effect of LPS on a wide range of apolipoproteins, plasma enzymes, lipid transfer factors, and receptors that are involved in HDL metabolism. Reciprocally, all lipoprotein classes have been shown to bind LPS and to attenuate the biological response to LPS in vitro and in rodents. Moreover, triglyceride-rich lipoproteins protect rodents against death from LPS and bacterial sepsis. Accumulating evidence indicates that apolipoproteins such as apoE and apoAI, and not the lipid moieties of the particles, may be responsible for these protective effects of lipoproteins. Therefore, to increase our understanding of the complex interaction between lipoprotein metabolism and sepsis, further studies that address the specific roles of apolipoproteins in sepsis are warranted.
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PMID:Apolipoproteins modulate the inflammatory response to lipopolysaccharide. 1594 36

Total and HDL cholesterol levels fall at the onset of acute illness and the cholesterol levels normalize as the patient recovers. Hypocholesterolemia may predispose the critically ill patient to sepsis and adrenal failure. Early enteral nutrition and tight glycemic control accelerate the recovery of the cholesterol levels.
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PMID:Dyslipidemia in the critically ill. 1639 25


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