Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hyperlipidemia is associated with gram-negative sepsis. In this study we characterized the plasma lipoproteins of fasted and fed septic and control rats with respect to their lipid and apolipoprotein composition. Sepsis was induced by i.v. injection of 8 x 10(7) live Escherichia coli colonies/100 g body wt. Food was removed from fasted control and fasted E. coli-treated rats after injection. Fed rats were infused intragastrically with a nutritionally complete diet for 5 days prior to E. coli treatment. 24 h after treatment with E. coli, lipid and protein concentrations of very-low-density lipoprotein (VLDL) were over 2-fold higher in the fasted E. coli-treated rats than those of the fasted control rats. This appears to be due to a decrease in the clearance of VLDL. The relative composition of apolipoprotein B-48 and apolipoprotein E were lower while that of apolipoprotein B-100 was higher in fasted E. coli-treated rats than in fasted controls. Low-density lipoprotein (LDL) and high-density lipoprotein lipids were also significantly elevated, indicating greater synthesis of these particles during sepsis and food deprivation. By contrast, VLDL-triacyglycerol from fed, E. coli-treated did not differ from that of their respective controls although the total cholesterol remained elevated. Percentages of apolipoprotein B-48 and apolipoprotein B-100 increased while apolipoprotein E contributed significantly less to the total protein of VLDL from the E. coli-treated rats compared with controls. LDL lipids were also increased. In conclusion, gram-negative sepsis leads to marked changes in the plasma lipoprotein composition which may be attributed to altered hepatic synthesis, peripheral metabolism or hepatic uptake of lipoproteins and their remnants. These in turn may be a function of the nutritional status.
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PMID:Disturbances in the composition of plasma lipoproteins during gram-negative sepsis in the rat. 157 63

In 10 patients with polytrauma and 2 patients with sepsis a relation of the severity of trauma and the change of lipoproteins has been found. Cholesterol and triglycerides as well as apolipoproteins A-I and B decrease significantly in the first days after the injury. During the following rise of cholesterol and triglycerides apolipoprotein A-I increases also to a concentration of lower normal range; apolipoprotein B remains lowered. Apolipoprotein C-III2 is determined in 3 patients and is increased. The concentration of apolipoprotein A-I decreases in three of five patients, who had parenteral fat administration. Apolipoprotein B increases during fat administration. The following fat free parenteral nutrition causes a decrease of apolipoprotein B again. The composition of lipoproteins is similarly changed in 2 patients with sepsis. The apolipoproteins as well as the lipids decrease more in patients who died later than in the case of reconvalescence, in which the increase of concentrations of lipids and apolipoprotein B may be accelerated with parenteral nutrition. Apolipoprotein A-I reacts variably, A-II is lowered.
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PMID:[Serum apolipoproteins and lipids in severe injury as influenced by nutrition. A pilot study]. 681 33

The etiology of hypertriglyceridemia associated with sepsis remains unclear, but we will attempt to elucidate its character by studying the hepatic production of apolipoproteins B and E. Male Lewis rats (260-330 g) were assigned to two groups, control (n = 5) and septic (n = 5). The septic group was injected with 2 x 10(8) live Escherichia coli colonies/100 g body wt. Food was removed from all rats after injections. Twenty-four hours later a recirculating in situ liver perfusion was performed for 120 min with KRB buffer, containing L-[35S]methionine. The production of apolipoprotein B (apo B), apolipoprotein E (apo E), albumin, and transferrin was determined by immunoprecipitation. The septic rats showed a protein-specific response to sepsis. The total protein secreted increased throughout each perfusion, septic greater than control. Apo B production was increased 2.6-fold in the septic versus control groups (P = 0.037), while apo E production was decreased by 2.9 times control (P = 0.036). Albumin production was decreased 2-fold in the septic group (P = 0.002). The increased hepatic production of apo B represents an increased number of very low density lipoprotein (VLDL) particles and contributes to the elevated VLDL triglyceride levels seen in sepsis. In contrast, decreased apo E production may result in a diminished ability for peripheral and/or hepatic receptor recognition of VLDL and VLDL remnants, respectively. Each of these changes are factors in the development of hypertriglyceridemia in sepsis.
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PMID:Altered hepatic production of apolipoproteins B and E in the fasted septic rat: factors in the development of hypertriglyceridemia. 823 Nov 64

Heparin induced extracorporeal lipoprotein fibrinogen precipitation (HELP) is an established procedure for removal of low-density lipoprotein (LDL) cholesterol, lipoprotein (a), and fibrinogen in patients with severe hypercholesterolemia. In vitro studies revealed that HELP also removes endotoxin, tumor necrosis factor alpha (TNF-alpha) and C-reactive protein (CRP). With the intention to treat, we applied this procedure to 4 patients with severe gram-negative sepsis with highly elevated endotoxin blood levels. Nine treatments were performed, 6 using the standard HELP precipitating buffer and 3 without addition of heparin to the precipitating buffer. Heparin was omitted from the precipitating buffer to avoid fibrinogen depletion in patients at risk (low fibrinogen, postoperative). The average processed plasma volume was 3,386 ml in the standard and 2,963 ml in the modified treatment. Mean reductions (%) in plasma solute concentrations were (standard/ modified procedure) as follows: endotoxin, 50/57; TNF-alpha, 25/5; CRP, 49/55; fibrinogen, 49/6; total cholesterol, 38/5; and apolipoprotein B (Apo B), 41/2. Both treatment modalities were equally effective in removing endotoxin and CRP. With the modified precipitation buffer, fibrinogen was not removed. To further simplify the extracorporeal treatment, we have designed a closed-loop circuit with 2 adsorbers in series, one for removal of TNF-alpha (dextran sulfate modified cellulose) and the other for removal of endotoxin (DEAE-cellulose). In vitro evaluation confirmed very efficient endotoxin and TNF-alpha removal from plasma. This system is very simple, operates at physiological pH, and uses adsorbers already in clinical use for other purposes.
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PMID:HELP apheresis in the treatment of sepsis. 945 25

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

Tumor necrosis factor-alpha (TNF-alpha) plays a pivotal role in the host response to infection. Rapidly liberated to the bloodstream, TNF-alpha triggers the production of other cytokines and the acute-phase response. Hypertriglyceridemia is a sepsis hallmark associated with high plasma levels of very low-density lipoprotein (VLDL) particles, partly ascribed to increased hepatic production. The kinetics of the hepatocyte response, the cytokine/s responsible, and the underlying mechanisms are not fully elucidated. VLDL biogenesis is a complex, time-consuming process that depends on lipid availability and microsomal triglyceride transfer protein (MTP) activity for correct apolipoprotein B (apoB) lipidation. Studies were performed to define the direct effect of TNF-alpha on VLDL secretion rate and composition in rat hepatocytes cultured in conditions resembling the fed situation. Increases of 17-24% in the number of VLDL particles secreted and of 44-88% in the cellular levels of apoB mRNA were caused by 5, 20, or 100 ng/mL TNF-alpha in 8 h. Lipoprotein secretion returned to baseline levels in 16 h, whereas TNF-alpha-treated cells continued to exhibit higher apoB transcript levels. The mass of each lipid class in secreted VLDL and of MTP mRNA in cells was not affected by any of the tested TNF-alpha doses or treatment periods. These findings indicate that over a wide range of concentrations, TNF-alpha was capable of inducing sustained upregulation of apoB mRNA expression and transient increase in secretion of its protein, but, apparently, VLDL triglyceride secretion was not a TNF-alpha target under conditions in which fatty acids were not extracellularly provided.
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PMID:Upregulation of apolipoprotein B secretion, but not lipid, by tumor necrosis factor-alpha in rat hepatocyte cultures in the absence of extracellular fatty acids. 1740 16

Liver dysfunction is an early event in sepsis-related multi-organ failure. We here report the establishment and characterization of a microfluidically supported in vitro organoid model of the human liver sinusoid. The liver organoid is composed of vascular and hepatocyte cell layers integrating non-parenchymal cells closely reflecting tissue architecture and enables physiological cross-communication in a bio-inspired fashion. Inflammation-associated liver dysfunction was mimicked by stimulation with various agonists of toll-like receptors. TLR-stimulation induced the release of pro- and anti-inflammatory cytokines and diminished expression of endothelial VE-cadherin, hepatic MRP-2 transporter and apolipoprotein B (ApoB), resulting in an inflammation-related endothelial barrier disruption and hepatocellular dysfunction in the liver organoid. However, interaction of the liver organoid with human monocytes attenuated inflammation-related cell responses and restored MRP-2 transporter activity, ApoB expression and albumin/urea production. The cellular events observed in the liver organoid closely resembled pathophysiological responses in the well-established sepsis model of peritoneal contamination and infection (PCI) in mice and clinical observations in human sepsis. We therefore conclude that this human liver organoid model is a valuable tool to investigate sepsis-related liver dysfunction and subsequent immune cell-related tissue repair/remodeling processes.
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PMID:Monocyte-induced recovery of inflammation-associated hepatocellular dysfunction in a biochip-based human liver model. 2975 6