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

A model was developed in the rhesus monkey to determine if the marked wasting of body proteins associated with sepsis could be prevented by an intravenous supply of various nutritional substrates. All monkeys were given a basic infusion of 0.5 gm of amino acid nitrogen/kg body weight via an indwelling catheter in the jugular vein. Three groups were given diets with no added calories, 85 calories/kg from dextrose or 85 calories from lipid. In each group, six monkeys were inoculated with 3 x 10(8) Streptococcus pneumoniae and four with heatkilled organisms. In the monkeys infused with the amino acids alone, pneumococcal sepsis resulted in a fourfold increase in loss of body proteins compared with calorie-restricted controls. Addition of 85 calories/kg/day of either dextrose or lipid reduced body wasting associated with infectious disease. The calories from lipid were utilized bythe septic host as a source of energy, with a slightly reduced efficiency when compared with the isocaloric infusion of dextrose. The nitrogen sparing of the fat emulsion could not be accounted for by its glycerol content. Therefore, the septic monkey seemed to utilize fatty acids as an energy substrate. It appears that the carbohydrate calories tend to favor the synthesis of peripheral proteins (associated mainly with skeletal muscle), while lipid calories favor synthesis of visceral proteins such as plasma albumin and acute-phase proteins.
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PMID:Protein-sparing therapy during pneumococcal infection in rhesus monkeys. 10 60

The relationship of glucogenesis and other energy-requiring functions of the liver to the proteolysis which is characteristic of trauma and sepsis was studied in conscious pigs following laporotomy and after the induction of intraperitoneal sepsis. By means of appropriately placed thermal dilution catheters, portal and hepatic arterial blood flows, hepatic oxygen consumption, glucogenesis, and uptake of the fuel, substrates were measured. No animal was in shock. Despite significant increases of lactate and aminoacids delivered to the liver, the blood concentrations were maintained in the normal range. The rate of glucogenesis was proportional (r equals 0.71) to the sum of the glucogenic precursors (lactate, pyruvate, glycerol, and alanine) taken up by the liver. Higher rates of glucose production were accompanied by elevated blood insulin values. Hepatic oxygen consumption and the uptake of free fatty acids also were related directly to the glucogenic rate, the correlation coefficients being 0.69 and 0.74, respectively. In the absence of shock, the liver function and hepatic energy production remained normal in post-traumatic and septic states. Under the conditions insulin-resistant muscle in the presence of reduced free fatty acid availability mobilize protein to satisfy local energy requirements. Skeletal muscle can oxidize only branch chain aminoacids; other aminoacids, including alanine, are transported to the liver for glucogenesis or other purposed. This concept accounted for failure of glucose infusion to eliminate post-traumatic and septic proteolysis, since alanine is cleared only from blood by conversion in the liver to glucose. Thus it is concluded that in sepsis the release of glucogenic substrates because of altered metabolism in peripheral tissues determines the rate of hepatic glucogenesis. This relationship constitutes an important metabolic homeostatic mechanism.
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PMID:Liver metabolism and glucogenesis in trauma and sepsis. 114 47

1. Administration of tumour necrosis factor (cachectin) and of interleukin-1-alpha increased the plasma level of nonesterified fatty acids in fed rats, and in the case of interleukin-1-alpha the blood glycerol level was also increased, suggesting stimulation of adipose tissue lipolysis. There were parallel increases in the plasma level of triacylglycerols. Neither cytokine had significant effects on blood or liver total ketone body (acetoacetate plus 3-hydroxybutyrate) concentrations. 2. In starved rats, the higher plasma non-esterified fatty acid concentration was not increased further by the cytokines. The plasma triacylglycerol level was increased, although the absolute change was less than in fed rats. The ketonaemia associated with starvation tended to be increased by the cytokines, but this was only significant in the case of interleukin-1-alpha. Parallel changes occurred in hepatic ketone bodies. 3. It is concluded that tumour necrosis factor-alpha and interleukin-1-alpha are not responsible for the hypoketonaemia associated with sepsis or other inflammatory states.
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PMID:Acute administration of tumour necrosis factor-alpha or interleukin-1-alpha does not mimic the hypoketonaemia associated with sepsis and inflammatory stress in the rat. 131 59

The objective of this study was to evaluate the safety and the effect of recombinant exogenous growth hormone (GH) on nitrogen production in patients with severe sepsis. It was designed as a prospective, randomized, placebo-controlled trial, and performed in the medical intensive care unit of a university hospital. Twenty patients admitted with septic shock and receiving standard parenteral nutrition served as subjects. Treatment consisted of GH 0.1 mg/kg/day or placebo administered as continuous intravenous infusion on the second, third, and fourth days after admission. The study period was eight days. During GH administration, nitrogen production decreased significantly in the GH group and increased in controls (p < 0.01). Nitrogen balance became slightly positive in the GH group during treatment: 1.2 +/- 6.4 versus controls -3.7 +/- 3.8 g/day (day 3) (p < 0.05). Within 24 hours after cessation of treatment, differences between GH and controls disappeared. 3-Methylhistidine excretion as a measure of absolute muscle breakdown declined during the study period, but did not differ between groups. The levels of insulin, insulinlike growth factor 1, glycerol, free fatty acids, and beta-hydroxybutyrate increased during treatment. Despite continuous intravenous administration, GH levels gradually declined during the 3 treatment days, indicating increased metabolic clearance. Side effects other than insulin resistance were not observed. Growth hormone administration reduces nitrogen production and improves nitrogen balance in patients with severe sepsis. These effects are not sustained after cessation of treatment.
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PMID:Effects of recombinant human growth hormone in patients with severe sepsis. 146 18

Hypertriglyceridemia and fatty liver are common lipid abnormalities associated with Gram-negative sepsis. Fish oils have been shown to have beneficial effects in reducing plasma triglycerides (TG). This study was designed to investigate whether fish oils would prevent the elevation of plasma TG and the accumulation of liver lipids during sepsis. One group of rats was fed a 10% menhaden oil diet and the other group was fed a 10% corn oil diet for 14 days. On the 14th day, sepsis was induced by injecting the rats with 8 x 10(7) live Escherichia coli colonies/100 g of body weight and the rats were fasted for 22 hours. The liver composition of total lipids and TG in the septic rats prefed the fish oil was lower than in the septic rats prefed the corn oil. In the rats adapted to the corn oil diet, lipids accumulated in the livers of the septic rats in comparison with the control rats. Hepatocytes isolated from the septic rats adapted to the corn oil diet showed an increased esterification of [1-14C]palmitate into TG and phospholipids than hepatocytes from the control rats. Feeding the fish oil diet instead of the corn oil diet before inducing sepsis reduced TG, cholesterol, and phospholipid synthesis by 58%, 79%, and 71%, respectively. The rise in TG synthesis in the septic rats prefed the corn oil diet was associated with an 89% increase in the activity of phosphatidate phosphohydrolase. There was no significant difference in the activities of glycerol-3-phosphate acyltransferase and phosphatidate phosphohydrolase between control and septic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adaptation to a fish oil diet before inducing sepsis in rats prevents fatty infiltration of the liver. 164 Jun 34

The most appropriate nutriment for total parenteral feeding (TPF) must be nutritionally efficient, safe and easy to use. Glucose is the most used carbohydrate as it has most of these qualities, as well as a high rate of metabolism by all tissues. It has not been clearly demonstrated that the administration of exogenous insulin with glucose improves nitrogen retention. Substitutes for glucose, such as fructose, maltose, galactose or polyols (xylitol, surbitol, glycerol) are not really superior to glucose itself. On the other hand, they have major side-effects. Therefore, they are not much used as energy substrates for TPF, at least not for long term TPF. Intravenous fat emulsions have taken an important place as a source of energy during TPF. Fat emulsions containing long chain triglycerides (LCT) supply essential fatty acids (EFA) (linolenic and linoleic acids), thus preventing EFA deficiency. The metabolism of fat emulsions is influenced by various factors: age, metabolic and nutritional status, the amount of glucose intake, insulin deficiency, sepsis, heparin therapy. Recently, medium chain triglycerides (MCT) have been proposed as an alternative energy source. The latter are cleared more rapidly from the blood, and are therefore less liable to be deposited in the liver and adipose tissue; they are also oxidized more quickly and more completely. MCT are safe to use at a rate of less than 0.12 g.kg-1.h-1 and with a MCT/LCT ratio less than 3 to 1. The simultaneous administration of glucose prevents an acceleration of ketogenesis. MCT/LCT emulsions are a safe and effective source of calories. It is important that those patients for whom such nutriment may be of particular interest should be identified. Fat emulsions associated with glucose seem to be more efficient in terms of nitrogen sparing effect than glucose alone. They also avoid the problems due to the infusion of large amounts of glucose (excessive carbon dioxide production, fatty infiltration of the liver), while there is no EFA deficiency. If the infusion of TPF nutriment must be continuous in intensive care patients, or during the postoperative period, cyclic nocturnal parenteral nutrition over a 12 or 16 hour period may be used in patients who are not in a catabolic state, or only mildly so. This is a safe and efficient method of nutritional support, which reduces the incidence rate of TPF-induced cholestasis.
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PMID:[Energy substrates in parenteral nutrition]. 178 8

To evaluate the role of tumor necrosis factor (TNF) in the initiation of the metabolic response to acute infection, we performed a crossover saline-controlled study in six healthy postabsorptive men, investigating the metabolic effects of a bolus intravenous injection of recombinant human TNF (50 micrograms/m2). TNF induced a transient stress hormone response, associated with an early and sustained rise in plasma glucose concentrations (percentage increase at 2 h 23 +/- 7; P less than 0.05). Glucose turnover, measured 7.5 h postinjection, was 10 +/- 3% higher after TNF administration (P less than 0.05). Plasma free fatty acids (FFA) and glycerol concentrations increased transiently after TNF injection, peaking after 4 h (percentage increase 363 +/- 83 and 67 +/- 14, respectively; both P less than 0.05). FFA turnover, determined 6.5 h postinjection, increased in five subjects to a variable extent (percentage increase 126 +/- 55; P less than 0.05). Finally, resting energy expenditure showed a transient rise after TNF injection (34 +/- 2% at 4 h; P less than 0.05). We conclude that intravenous TNF reproduces many of the metabolic changes observed in septicemia, suggesting that TNF may be an initiating factor in the development of the metabolic response to acute infection.
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PMID:Tumor necrosis factor mimics the metabolic response to acute infection in healthy humans. 192 37

Clinical and experimental studies on the development of myoglobinuria-associated acute renal failure (ARF) were reviewed. ARF developed in 30% of the cases of rhabdomyolysis. Rhabdomyolysis-associated ARF accounted for 5-10% of all ARF. The presence of dehydration or hypotension at the presentation of rhabdomyolysis seems to be a risk factor in the development of rhabdomyolysis-associated ARF. ARF occurred more frequently in the rhabdomyolysis caused by sepsis or burns. Glycerol-induced ARF in rats or rabbits has been studied to investigate the pathogenesis of myoglobinuria-associated ARF. The early decrease in inulin clearance (Cin) in glycerol-induced ARF was dependent upon the decrease in renal blood flow, but the decrease in Cin in the late phase could not be attributed to the decrease in renal blood flow. Diminished glomerular permeability and cast formation might play important roles in the decrease in Cin in the late phase of glycerol-induced ARF.
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PMID:[Myoglobinuria and acute renal failure]. 204 Dec 8

1. The regulation of renal gluconeogenesis was studied in rats made septic by a caecal ligation and puncture technique. 2. Blood glucose concentrations were not markedly different in septic rats, but lactate, pyruvate and alanine concentrations were markedly increased, compared with sham-operated rats. Conversely, blood ketone body concentrations were significantly decreased in septic rats. Both plasma insulin and glucagon concentrations were markedly elevated in response to sepsis. 3. The maximal activities of glucose-6-phosphatase (EC 3.1.3.9), fructose-1,6-bisphosphatase (EC 3.1.3.11), pyruvate carboxylase (EC 6.4.1.1) and phosphoenolpyruvate carboxykinase (EC 4.1.1.49) were markedly decreased in kidneys obtained from septic rats, suggesting diminished renal gluconeogenesis. 4. Renal concentrations of lactate, pyruvate and other gluconeogenetic intermediates were markedly elevated in septic rats, whereas those of acetyl-CoA and fructose 2,6-bisphosphate were decreased and unchanged, respectively. 5. The rate of gluconeogenesis from added lactate, pyruvate and glycerol was decreased in isolated incubated renal tubules from septic rats. 6. Sepsis decreased the arteriovenous concentration difference for glucose, lactate, and alanine. Septic rats showed decreased net rates of glucose production and net rates of removal of lactate and alanine as compared with sham-operated controls. 7. It is concluded that the diminished capacity for renal gluconeogenesis in septic rats could be the result of changes in the maximal activities or regulation of key non-equilibrium gluconeogenic enzymes or both, but the effect of other factors (e.g. toxins) has not been excluded.
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PMID:Metabolic regulation of renal gluconeogenesis in response to sepsis in the rat. 217 16

The mechanism for the development of hypertriglyceridemia during gram-negative sepsis was studied by examining liver production and clearance of very-low-density lipoprotein (VLDL) triglyceride (TG). To assess liver output and peripheral clearance the kinetics of VLDL-TG were determined by a constant iv infusion of [2-3H]glycerol-labeled VLDL. Clearance of VLDL-TG was also evaluated by measuring activities of lipoprotein lipase (LPL) in heart, soleus muscle, and adipose tissue from fasted control, fasted E. coli-treated, fed control, and fed E. coli-treated rats. Lewis inbred rats, 275-300 g, were made septic with 8 x 10(7) live E. coli colonies per 100 g body wt. Twenty-four hours after E. coli injection, serum TG, free fatty acids (FFA), and cholesterol of fasted E. coli-treated rats were elevated by 170, 76, and 16%, respectively. The elevation of serum TG may be attributed to the 67% decrease in clearance rate of VLDL-TG in fasted E. coli-treated rats compared with their fasted controls. The suppressed activities of LPL in adipose tissue, skeletal muscle, and heart were consistent with reduced clearance of TG. Secretion of VLDL-TG declined by 31% in livers of fasted E. coli-treated rats, which was accompanied by a twofold increase in the composition of liver TG. Rates of in vivo TG synthesis in livers of the fasted E. coli-treated rats were twofold higher than in those of fasted control rats. Decreased rate of TG appearance along with the increase in liver synthesis of TG contributed to the elevation of liver lipids in the fasted E. coli-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Triglyceride kinetics, tissue lipoprotein lipase, and liver lipogenesis in septic rats. 218 49


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