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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To further understand the development of fatty liver during gram-negative sepsis, we measured fatty acid uptake in addition to esterification and secretion of lipids by freshly isolated hepatocytes from fasted and fed control and Escherichia coli-treated rats. Rats were made septic by intravenous (IV) injection of 8 x 10(7) live E coli colonies per 100 g body weight. For the fasted groups, food was removed after E coli injection. Fed rats received a nutritionally adequate diet intragastrically for 5 days before and 24 hours after inducing sepsis. Twenty-four hours after E coli injection, the esterification of newly synthesized fatty acids, as measured by 3H2O incorporation, and the esterification of exogenous fatty acids, measured from 14C-palmitate incorporation, into triglyceride (TG), total cholesterol, and total phospholipid phosphorus were significantly greater in hepatocytes from fasted septic rats compared with their control rats. In fed septic rats, esterification of 14C-palmitate into TG was fourfold greater than in the fed control rats. The increased rates of esterification in hepatocytes from fasted and fed septic rats were not accompanied by an increase in the labeled TG in the medium. This inability to secrete the additional TG that the hepatocytes produce resulted in a higher concentration of cellular TG in fasted and fed septic rats than in their controls. The enzymes glycerol-3-phosphate acyltransferase (GPAT) and phosphatidate phosphohydrolase (PPH) do not appear to be factors contributing to the increased TG synthesis, since the increase in enzyme activity was not accompanied by a similar increase in TG synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulatory factors in the development of fatty infiltration of the liver during gram-negative sepsis. 820 57

1. We investigated the relationship between circulating tumour necrosis factor-alpha concentrations, resting energy expenditure, cachexia and altered intermediary metabolism in patients with cystic fibrosis and chronic pulmonary infection. 2. Twenty adult patients with cystic fibrosis and chronic bronchial sepsis covering a spectrum of severity of lung disease (forced expiratory volume in 1 s 30-100% of predicted) were compared with 10 age matched, healthy, non-cystic fibrosis subjects. 3. Circulating tumour necrosis factor-alpha, C-reactive protein and neutrophil elastase-alpha 1-antiproteinase complex concentrations were determined simultaneously with glycerol, non-esterified fatty acids, catecholamines, anthropometric indices and resting energy expenditure (ventilated hood method). 4. Weight, body mass index and arm muscle mass were reduced in patients with cystic fibrosis compared with healthy control subjects (P < 0.01), whereas mean resting energy expenditure was increased [121 versus 101% predicted, mean difference 19.2% (95% confidence interval 11.0-27.4%), P < 0.001]. Circulating concentrations of glycerol (P < 0.01), non-esterified fatty acids (P < 0.01), adrenaline (P < 0.05), tumour necrosis factor-alpha, C-reactive protein and neutrophil elastase-alpha 1-antiproteinase complex (P < 0.01) were increased in patients compared with control subjects [tumour necrosis factor-alpha 96.9 versus 24.7 pg/ml, mean difference 72.2 pg/ml [95% confidence interval 27.7-116.7 pg/ml), P < 0.001]. Resting energy expenditure was significantly related to tumour necrosis factor-alpha levels and forced expiratory volume in 1 s. 5. In patients with cystic fibrosis and chronic pulmonary sepsis changes in resting energy expenditure, body composition and intermediary metabolism are consistent with the systemic effects of the host inflammatory response, which may be responsible for cachexia in adult patients. In particular these changes are consistent with the action of tumour necrosis factor-alpha, which was detected in the circulation during a period of apparent clinical stability.
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PMID:Tumour necrosis factor-alpha, resting energy expenditure and cachexia in cystic fibrosis. 828 44

We report a 70-year-old man who had a sudden onset of right hemiparesis and mutism. The lower extremity was more involved than the upper one. He had a long history of diabetes and chronic renal failure for which hemodialysis was necessary. On August 30, 1990, he had an sudden onset of right hemiparesis and mutism. Neurological examination revealed awake but mute in no acute distress. He could only respond to very simple commands such as opening his mouth or protruding his tongue. He did not appear to understand more difficult questions. In addition, he could not answer verbally. He was totally mute. Cranial nerves appeared intact except for slight right central facial paresis and severe diabetic retinopathy. He had complete paralysis of his right leg and a moderate weakness in his right upper extremity. Deep reflexes were diminished in both upper extremities and absent in the lower limbs. Frotal signs such as grasp and snout reflexes were present. Cranial CT scans revealed an ill-defined low density area in the left parasagittal subcortical area and a part of the anterior cerebral artery territory. The supplementary motor area appeared at least in part to be involved. He was treated with glycerol and other supportive cares, however, his clinical course was complicated by pneumonia, heart failure, septicemia, and he expired two months after his stroke. The patient was discussed in a neurological CPC, and the chief discussant arrived at a conclusion that he had an artery-to-artery embolism at the internal carotid bifurcation resulting in the cerebral infarction mainly in the territory of the anterior cerebral artery.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[A 70-year-old man with right hemiparesis and mutism]. 836 54

Sepsis or endotoxaemia inhibits gluconeogenesis from various substrates, the main effect being related to a change in the phosphoenolpyruvate carboxykinase transcription rate. In addition, sepsis has been reported to affect the oxidative phosphorylation pathway. We have studied glycerol metabolism in hepatocytes isolated from rats fasted and injected 16 h previously with lipopolysaccharide from Escherichia coli. Endotoxin inhibited glycerol metabolism and led to a very large accumulation of glycerol 3-phosphate; the cytosolic reducing state was increased. Furthermore glycerol kinase activity was increased by 33% (P<<0.01). The respiratory rate of intact cells was significantly decreased by sepsis, with glycerol or octanoate as exogenous substrates, whereas oxidative phosphorylation (ATP-to-O ratio or respirations in state 4, state 3 and the oligomycin-insensitive state as well as the uncoupled state) was unchanged in permeabilized hepatocytes. Hence the effect on energy metabolism seems to be present only in intact hepatocytes. An additional important feature was the observation of a significant increase in cellular volume in cells from endotoxic animals, which might account for the alterations induced by sepsis.
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PMID:Inhibition of glycerol metabolism in hepatocytes isolated from endotoxic rats. 923 Jan 36

Combined sepsis and rhabdomyolysis result in a mortality rate much higher than that caused by each process alone. An analogous rat model is obtained by simultaneous i.p. administration of a nonlethal dose of lipopolysaccharide (LPS 0.025 mg/100 g) and a nonlethal i.m. injection of glycerol (1 ml/100 g). The aim of this study was to determine the factors contributing to the high mortality rate in this rat model. The factors examined include: Dehydration, plasma volume expansion, 'immunization' to glycerol, induction of LPS tolerance and the effect of free radicals formed in this model. Neither dehydration nor volume expansion affected mortality. 'Immunization' with glycerol was also not effective. In contradistinction, tolerance to LPS achieved by a daily injection with gradual increasing doses of LPS (from 0.05 mg/100 g to 1 mg/100 g) for 6 days reduced the mortality rate by 60% (P < 0.001). Moreover, decreasing free radical activity using the natural antioxidant (NAO) (5 mg/100 g) reduced mortality rates by 50%. A different antioxidant, dimethylthiourea (DMTU) (50 mg/100 g) failed to reduce mortality rates. This study suggests that the synergism between glycerol and LPS is apparently due to an increase in the rats' sensitivity to endotoxin following glycerol injection. However, endotoxin apparently does not enhance sensitivity to glycerol in the rat. The new antioxidant NAO significantly reduced the high mortality rate.
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PMID:Glycerol-induced augmentation of sensitivity to endotoxin in rats. 923 33

Catabolism of lean body mass (particularly muscle) occurs in sepsis and other forms of critical illness despite apparently adequate nutritional support. The determination of the optimal balance of carbohydrate and fat intake in this circumstance should be based on the resulting effect on the maintenance of lean body mass, and the nature and extent of any side effects. The general stress response involves a disruption in normal glucoregulation, in that hepatic glucose production is accelerated and the normal blood glucose lowering action of insulin is diminished. Nonetheless, the capacity to oxidize glucose once inside the cells is not impaired. Lipolysis, or the breakdown of peripheral triglycerides to free fatty acids (FFA) and glycerol, is accelerated in critical illness, to a greater extent than fat oxidation. Provision of exogenous fat maintains fat stores, but has minimal effect on the direct oxidation of plasma FFA. From the results of oxidation studies, it seems that about 5 mg kg x min of glucose can be readily oxidized, and the balance of energy will be supplied by the oxidation of fat, either endogenous or exogenous. However, an additional consideration in determining the optimal caloric substrate is that insulin is a potent anabolic hormone and stimulates muscle protein synthesis. Consequently, provision of exogenous insulin enhances retention of muscle. This procedure dictates that almost all non-protein calories be provided as carbohydrate to avoid hypoglycemia. Preliminary studies suggest this may be the optimal approach in critically ill patients. Glucose and fatty acids are the major energy substrates in the body. The oxidative metabolism of these substrates provides the ATP needed for physiological function, including protein synthesis. Over the past 20 y, development of new techniques in nutritional support have made it possible to provide large amounts of carbohydrate and fat to critically-ill patients, along with protein or amino acids. However, despite providing such patients with what should be more than adequate caloric and protein intake, critically ill patients lose lean body mass (Streat et al, 1987), largely because of persistent muscle catabolism (Sakurai et al, 1995). The general relation between energy substrate metabolism and maintenance of lean body mass has been recognized for many years (Calloway & Spector, 1954), so it is important to examine the alterations in energy substrate metabolism that occur in response to critical illness that may play a role in causing the persistent catabolism of muscle protein.
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PMID:Sepsis as a modulator of adaptation to low and high carbohydrate and low and high fat intakes. 1036 91

Adipose tissue is a major source of metabolic fuel. This metabolic fuel is stored in the form of triacylglycerol. Lipolysis of triacylglycerol yields non-esterified fatty acids and glycerol. In human subjects in vivo studies of the regulation of lipid metabolism in adipose tissue have been difficult because of the heterogeneous nature of the tissue and lack of a vascular pedicle. In the last decade the methodology of study of adipose tissue has improved with the advent of the anterior abdominal wall adipose tissue preparation technique and microdialysis. These techniques have demonstrated that lipid metabolism in adipose tissue is finely coordinated during feeding and fasting cycles, in order to provide metabolic fuel when required. Lipolysis takes place both in extracellular and intracellular space. The extracellular lipolysis is regulated by lipoprotein lipase and the intracellular lipolysis is regulated by hormone-sensitive lipase. In pathophysiological conditions such as trauma, sepsis and starvation profound changes are induced in the regulation of lipid metabolism. The increased mobilization of lipid fuel is brought about by the differential actions of various counter-regulatory hormones on adipose tissue blood flow and adipose tissue lipolysis through lipoprotein lipase and hormone-sensitive lipase, resulting in increased availability of non-esterified fatty acids as a source of fuel. In recent years, it has been demonstrated that adipose tissue produces various cytokines and these cytokines can have paracrine and endocrine effects. It would appear that adipose tissue has the ability to regulate lipid metabolism locally as well as at distant sites such as liver, muscle and brain. In future, it is likely that the mechanisms that lead to the secondary effects of lipid metabolism on atheroma, immunity and carcinogenesis will be demonstrated.
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PMID:Sir David Cuthbertson Medal Lecture. Regulation of lipid metabolism in adipose tissue. 1099 71

Macrophage activation plays a central role in host defense against a variety of pathogens via inducible messengers. The transcription factor NF-kappaB controls the synthesis of cytokines involved in immune responses. In quiescent cells, NF-kappaB is located in the cytosol bound to an inhibitor IkappaB. Upon appropriate signal, NF-KB translocates to the nucleus and binds to DNA. The present study investigated the involvement of an immunomodulator, (diHDA-glycerol) on the NF-kappaB/IkappaB complex. Results were compared to those obtained with lipopolysaccharide (LPS) as a major virulence factor in bacterial sepsis. Data showed that exposure of J774.1 cells either to LPS or diHDA-glycerol substantially increased with time the nuclear levels of NF-kappaB complexes. Antibodies to various NF-kappaB proteins supershifted p50, p65 and to a lesser extent c-rel. Western blot analyses showed a rapid cytosolic IkappaB-alpha turn over following LPS exposure in contrast to diHDA-glycerol treatment. Further experiments investigated the involvement of protein kinase C (PKC) by using two inhibitors, staurosporine and H7. Pretreatment of J774.1 with either inhibitor prior to diHDA-glycerol or LPS exposure decreased NF-kappaB activation. Our results indicate that diHDA-glycerol was acting on NF-kappaB through IkappaB regulative mechanisms differing from those used by LPS. DiHDA-glycerol is likely acting on many other transcription factors targeting distinct genes implied in up regulation of the immune system.
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PMID:Effect of a synthetic lipid immunomodulator on the regulation of the transcription factor NF-kappaB. 1110 79

Gram-negative sepsis often produces endotoxin (LPS) which causes infection. Reduction in tissue perfusion due to microcirculatory failure may lead to septic shock. We studied the effect of LPS on lipid peroxidation of erythrocyte. In vitro studies using 50 microg to 250 microg LPS/ml blood showed increased lipid peroxidation of erythrocyte in a dose-dependent manner. The increased effect of lipid peroxidation does not occur with LPS when erythrocytes were washed to remove plasma and leukocytes. Mannitol and glycerol, known scavengers of hydroxyl radical, arrest the elevation in lipid peroxidation of erythrocytes after LPS treatment. Hemolysis of erythrocytes was reduced with low doses of LPS. Plasma lipid peroxidation was elevated after treatment of blood with LPS. From the results we suggest that the peroxidation of erythrocyte lipid caused by LPS may probably play a role in the production of septic shock.
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PMID:Studies on the effects of lipopolysaccharide on lipid peroxidation of erythrocyte and its reversal by mannitol and glycerol. 1132 8

In sepsis and endotoxemia, metabolism is characterized by accelerated catabolism. In the present study, lipolytic responsiveness of subcutaneous and mesenteric adipose tissue to the sub-lethal dose of endotoxin injection (5 mg/kg) was evaluated using microdialysis techniques in rats. All rats were urethane-anesthetized and implanted with microdialysis probes in their subcutaneous and mesenteric adipose tissue. Lipolysis in each adipose tissue was assessed by measuring the glycerol concentration (an index of lipolysis) in the dialysate from the microdialysis probe. Lipolysis was continuously monitored for 7-hours, prior to and following the injection of endotoxin. The control animals were injected with only saline. Lipolysis in subcutaneous adipose tissue began to increase by 1-hours after endotoxin injection, and reached a peak 60% higher than the basal level by 2-hours after injection. This activated lipolysis after endotoxin was markedly greater than that in the control animals and maintained for 5 hours. In mesenteric adipose tissue, lipolysis after endotoxin injection was greater than in the control animals, but not significant. The endotoxin-induced lipolysis in the subcutaneous adipose tissue was significantly greater than that in the mesenteric adipose tissue. We conclude that the sub-lethal dose of endotoxin injection cause active lipolysis in adipose tissues, and that the lipolytic responsiveness to endotoxin in subcutaneous adipose tissue is greater than in mesenteric adipose tissue.
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PMID:The lipolytic responsiveness to endotoxin in subcutaneous adipose tissue is greater than mesenteric adipose tissue. 1270 61


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