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)

Interleukin-2 (IL-2) is secreted during the immune response to trauma, sepsis, and transplant rejection. Its role in the development of the metabolic abnormalities observed in these circumstances is not well defined. We studied the clinical, hormonal, and metabolic response to a 5-day IL-2 infusion (3 x 10(6) U/m2/day) of nine patients with metastatic renal carcinoma. IL-2 induced systemic manifestations after a latent period of 4 h (fever, tachycardia) or 8 h (hypotension). These manifestations persisted until the end of the infusion. Insulin levels were not modified. Among the stress hormones, cortisol increased at the onset of fever and tachycardia, whereas the rise in catecholamines occurred later (24 h) and appeared more as a response to the development of hypotension. The only metabolic effects observed were a late (third day) rise of lactate and a late and transient (third to fourth day) decrease of glycerol and nonesterified fatty acids. These metabolic modifications were temporally related to the development of hypotension and result more likely from low tissue perfusion rather than from a direct or hormone-mediated effect of IL-2.
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PMID:Hormonal and metabolic effects of chronic interleukin-2 infusion in cancer patients. 234 64

Fatty acid metabolism was studied in fasted control, fasted Escherichia coli-treated, fed control, and fed E. coli-treated rats to find out whether the reduction in myocardial carnitine was associated with changes in oxidation and esterification of long chain fatty acids. Rats were made septic by injecting i.v. 8 X 10(7) live colonies of E. coli per 100 g body weight. Fed rats were infused intragastrically with a nutritionally adequate diet containing glucose plus fat for five days before inducing sepsis. Food was removed from the fasted rats after E. coli injection. Twenty-four hours later, the production of CO2 from [1-14C]palmitate was not altered in heart homogenates from fasted or fed E. coli-treated rats. In comparison to control rats, heart homogenates from fasted E. coli-treated rats incorporated 32% more [1-14C]palmitate into triglycerides. The heart content of triglycerides was also increased threefold during sepsis. Rates of esterification and lipid composition were not altered in the hearts from fed E. coli-treated rats. The increased rate of triglyceride synthesis in the hearts from fasted E. coli-treated rats appears to be due to a 40% higher content of glycerol 3-phosphate and 55% more activity of glycerol 3-phosphate acyltransferase. These results also suggest that the reduced content of myocardial carnitine that occurs during E. coli sepsis does not limit the availability of fatty acids for oxidation.
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PMID:Fatty acid metabolism in the heart during Escherichia coli sepsis in the rat. 268 69

Although nutritional support is vital to treatment of severe sepsis, the septic patient does not respond normally to glucose infusion. We have used the hyperglycemic glucose clamp technique to investigate the initial hormonal and metabolic responses of the septic patient to glucose under controlled conditions. The plasma glucose concentration was raised to and maintained at 12 mmol/liter for 2 hr in 12 septic patients and 11 normal controls. Glucose utilization, assessed from the amount infused, was significantly depressed in the patients, despite similar plasma insulin concentrations in the two groups. Forearm glucose uptake was similarly impaired. Despite very similar plasma free fatty acid concentrations in the two groups, which were suppressed equally by the glucose infusion, whole-body fat oxidation was elevated in the patients compared with the controls, and suppressed to a lesser extent in response to glucose. Glycerol and ketone body concentrations were elevated in the patients in keeping with a picture of accelerated release, clearance, and oxidation of fatty acids. Plasma cortisol, epinephrine, and norepinephrine concentrations were elevated in the septic patients in a severity-related manner, but not to high levels compared with experimental work. Norepinephrine showed no response to the glucose infusion in either group. Plasma glucagon concentrations were not significantly elevated in the septic patients. We conclude that the hyperglycemic glucose clamp provides a useful model for studying glucose intolerance in sepsis. Impaired glucose utilization in septic patients is associated with increased fat oxidation, although the hormonal basis for these changes is still unclear.
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PMID:Hormonal and metabolic responses to glucose infusion in sepsis studied by the hyperglycemic glucose clamp technique. 311 25

Metabolic alterations related to resting energy expenditure (REE) and fat metabolism have been noted during sepsis, and often depend on the causative agent and the stage and severity of the illness. We studied the effect of IL-1, the protein mediator of the 'acute phase' response during infection, on REE, respiratory quotient (RQ), and fat metabolism in male rats (210 g), who were infused over an 8-h period with (1-14C)-palmitate (PALM), (2-3H)-glycerol (GLY) and either saline or interleukin-1 (IL-1). At 7-8 h post infusion, the IL-1 group showed a significant increase in REE but no change in RQ. The IL-1 group also exhibited a significant decrease in serum free fatty acid (FFA) and an increase in FFA clearance. Free fatty acid flux, %PALM oxidation, serum (GLY), glycerol clearance, and glycerol flux (a measure of lipolytic rate) were not significantly different between the two groups. We conclude that IL-1 can mimic the increase in REE seen during infection; the increase in REE is not due to a selective increase in fat oxidation only, although the unchanged RQ and increased REE suggest that there is a proportional increase in net FFA oxidation.
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PMID:Changes in energy expenditure and fat metabolism in rats infused with interleukin-1. 312 50

The effect of gram-negative sepsis on the kinetics and oxidation of very low-density lipoprotein (VLDL) fatty acids was assessed in conscious dogs in the normal state and 24 h after infusion of live Escherichia coli. VLDL, labeled with [2-3H]glycerol and [1-14C]palmitic acid, was used to trace VLDL kinetics and oxidation, and [1-13C]palmitic acid bound to albumin was infused simultaneously to quantify kinetics and oxidation of free fatty acid (FFA) in plasma. Sepsis caused a fivefold increase in the rate of VLDL production (RaVLDL). In the control dogs, the direct oxidation of VLDL-fatty acids was not an important contributor to their overall energy metabolism, but in dogs with sepsis, 17% of the total rate of CO2 production could be accounted for by VLDL-fatty acid oxidation. When glucose was infused into dogs with insulin and glucagon levels clamped at basal levels (by means of infusion of somatostatin and replacement of the hormones), RaVLDL increased significantly in the control dogs, but it did not increase further in dogs with sepsis. We conclude that the increase in triglyceride concentration in fasting dogs with gram-negative sepsis is the result of an increase in VLDL production and that the fatty acids in VLDL can serve as an important source of energy in sepsis.
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PMID:Effect of sepsis on VLDL kinetics: responses in basal state and during glucose infusion. 389 May 59

In the United States, glucose has been until recently the sole non-protein energy substrate utilized in total parenteral nutrition (TPN). However, recent reports show that the administration of massive glucose loads to surgical patients cause a high incidence of pulmonary and hepatic complications. Indirect calorimetry data indicate that these hypermetabolic patients seem to utilize endogenous fat preferentially to carbohydrate. Therefore, we have undertaken some studies on the metabolism of endogenous and exogenous fat. Peripheral lipolysis - as estimated by measurements of glycerol turnover - is increased after injury and during sepsis. There is not correlation between the turnover of glycerol and the plasma concentration in surgical patients. High glucose intake induces a marked decrease in the glycerol turnover of nutritionally depleted subjects but has only a slight effect on the lipolytic rate of injured and septic patients. The rates of free fatty acid turnover and oxidation are elevated in surgical patients. High carbohydrate loads reduce FFA oxidation rate less in hypermetabolic patients than in depleted subjects. The utilization of exogenous fat was studied by associating an estimation of the oxidation rate to the measure of the clearance after the injection of 14C -Intralipid in surgical patients. Both oxidation and clearance rates are increased in these patients in relation with the severity of the injury. A dissociation between the variations of the clearance and the oxidation rates was observed when TPN was given to surgical patients. In such conditions, the clearance rate does not indicate the further utilization of a fat emulsion. Administration of TPN containing exogenous fat seem to induce less pulmonary and hepatic complications than TPN with glucose alone. In conclusion, kinetic measurements are needed for studying the metabolism of endogenous fat in surgical patients. An increased utilization of endogenous and exogenous fat takes place in these patients. Including exogenous fat as part of their parenteral diet is indicated but the optimal proportion of glucose and fat has not been precisely determined yet.
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PMID:Glycerol turnover and kinetics of exogenous fat in surgical patients. 679 81

There seems little doubt that there are signals for the increased mobilization of fat in shock, trauma, and sepsis. Whether those signals are reflected by an actual increase in mobilization is dependent on many variables including cardiovascular status. A hypothetical scheme based on our own experiments in the hyperdynamics phases of response to burn injury and to sepsis is presented in Figure 8. According to this scheme, catecholamines stimulate lipolysis in the adipose tissue, resulting in the release of glycerol and FFA into the plasma at increased rates. The glycerol is cleared by the liver and converted into glucose--a process stimulated by, among other things, glucagon. Some of the increased flux of FFA is also cleared by the liver, whereupon the fatty acids are incorporated into VLDL and released again into the plasma. The increased FFA levels also exert a dampening effect on the factors stimulating hepatic glucose production. At the periphery, plasma FFA as well as VLDL fatty acids are taken up at an increased rate. The tissues are attuned to the oxidation of fat, and as a consequence most of the energy production is derived from fat oxidation. The increased fatty acids exert an inhibitory effect on the complete oxidation of glucose, so although glucose may be taken up at an accelerated rate, the relative contribution of glucose oxidation to total energy production may fall. Rather than being completely oxidized, pyruvate is reduced to lactate and released into the plasma at an accelerated rate. The lactate then contributes to the production of glucose in the liver, completing a cyclical process called the Cori Cycle. Although all aspects of this scheme are supported by data highlighted in this paper, it certainly must be an oversimplification of the overall response of substrate metabolism to trauma and sepsis. It is presented for the purpose of highlighting the potential role of fat as a controller of the metabolic response, and to suggest that the enhanced mobilization and oxidation of fat is one of the fundamental responses to stress.
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PMID:Energy metabolism in trauma and sepsis: the role of fat. 686 23

Abdominal surgery increases blood glucose concentration and peripheral release and splanchnic uptake of gluconeogenic substrates, including alanine. During trauma or sepsis, infusion of glucose fails to depress alanine conversion to glucose. The effect of intra-operative glucose infusion on splanchnic metabolism was examined in the present study. In eight patients undergoing elective cholecystectomy, splanchnic glucose metabolism was investigated before, during and immediately after surgery. Glucose was infused at a constant rate of 1 mmol/min. Splanchnic blood flow and arterio-hepatic venous differences of oxygen, glucose, lactate, glycerol, 3-hydroxybutyrate and alanine were measured. Eight other patients, who received saline instead of glucose, served as a control group. Infusion of glucose resulted in total inhibition of splanchnic glucose release before as well as during and immediately after surgery. This was observed, even before surgery, at an arterial glucose level which was lower than that in the control group at the end of and immediately after surgery, at which no decrease of the splanchnic glucose release was recorded. changes in neuronal and hormonal factors due to the surgical trauma are considered responsible for this difference in glucose homeostasis. Splanchnic alanine uptake increased during surgery in both groups, but tended to be somewhat lower in the glucose group. The arterial glycerol concentration and splanchnic uptake, as well as the arterial concentration and splanchnic release of 3-hydroxybutyrate, were reduced. It is concluded that an intravenous infusion of glucose at the rate of 1 mmol/min during abdominal surgery (a) increases the arterial blood glucose level and abolishes splanchnic glucose release, (b) reduces, but does not totally prevent the increase in splanchnic uptake of gluconeogenic substrates, and (c) diminishes lipolysis and the formation of 3-hydroxybutyrate.
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PMID:Influence of abdominal surgical trauma and intra-operative infusion of glucose on splanchnic glucose metabolism in man. 719 97

The effect of minimal changes in circulating plasma endothelin-1 (ET-1) was studied in 12 healthy subjects receiving either 60 min of ET-1 (0.2 pmol.kg-1.min-1) or physiological saline intravenously. Blood was drawn from arterial, renal, and central hepatic vein catheters. Arterial ET-1-like immunoreactivity (ET-1-LI) increased from 4.7 +/- 0.4 (SE) to 8.6 +/- 1.0 pmol/l during ET-1 infusion. After 10 min, plasma ET-1-LI had increased to 6.12 +/- 0.29 pmol/l. For comparison the plasma ET-1-LI level was 12.9 +/- 4.2 pmol/in five patients with sepsis syndrome. Mean arterial blood pressure rose from 92 +/- 3 to 99 +/- 4 mmHg. Estimated splanchnic and renal blood flows fell by 18 +/- 5 and 10 +/- 3%, respectively, and splanchnic glucose production fell by 42 +/- 6% within 10 min of the ET-1 infusion and differed compared with corresponding control values. Only estimated splanchnic blood flow had increased 60 min after the ET-1 infusion. No change in splanchnic uptake of lactate or glycerol was seen. In conclusion, we suggest that circulating ET-1 with small or no demonstrable change in plasma concentration interferes with vasoactivity and splanchnic glycogenolyses in health and possibly pathophysiological conditions.
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PMID:Circulating endothelin-1 reduces splanchnic and renal blood flow and splanchnic glucose production in humans. 755 11

Certain phosphatidic/plasmanic/plasmenic acid (PA) species function as lipid intermediates in cell activation and may function directly as intracellular signaling molecules. PA can also be dephosphorylated to 1,2-diradyl-sn-glycerol by phosphatidate phosphohydrolase. Treatment of various cell types, including murine P388 monocytic leukemia cells, with bacterial lipopolysaccharide rapidly stimulates large increases in PA and PA-derived diradylglycerol. Pentoxifylline, 1-(5-oxohexyl)-3,7-dimethylxanthine, inhibits lipopolysaccharide-stimulated formation of PA in P388 cells at high concentrations (IC50 = 500 microM). Lisofylline [1-(5R-hydroxyhexyl)-3,7-dimethylxanthine] is a unique metabolite of pentoxifylline in humans and is > 800-fold more active as an inhibitor of PA formation than pentoxifylline (IC50 = 0.6 microM). Lisofylline does not inhibit lipopolysaccharide-induced activation of phosphatidylinositol-specific phospholipase C and generation of phosphatidylinositol-derived diradylglycerol. Lisofylline but not pentoxifylline protects BALB/c mice from endotoxin lethality when administered 4 hr after lipopolysaccharide. This protective effect is independent of either agent's effect on suppression of plasma tumor necrosis factor alpha. These data suggest that inhibitors of PA formation may have significant clinical potential in the treatment of sepsis and septic shock.
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PMID:Protection from endotoxic shock in mice by pharmacologic inhibition of phosphatidic acid. 817 Oct 2


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