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)

To determine the mechanism for the reduced content of myocardial carnitine during gram-negative sepsis, carnitine transport was examined in isolated perfused hearts. Rats were injected i.v. with 8 x 10(7) live colonies of E. coli per 100 g body weight or physiological saline. All rats were fasted after injection for 22 hr to equalize the differences in food intake. Total carnitine uptake in the hearts from both groups was essentially linear between 10 and 20 min of perfusion with 40 microM of carnitine. However, total uptake was significantly reduced by approximately 30% in the hearts from the E. coli-treated rats. In addition to the significant reduction in total carnitine uptake at 40 microM, uptake was significantly lower at 100 microM perfusate carnitine in hearts from E. coli-treated rats. However, total uptake was not significantly different between the groups at 200 and 300 microM perfusate carnitine. Carnitine uptake in the presence of 0.05 M mersalyl acid was comparable in both groups of hearts at all perfusate carnitine concentrations indicating no change in the diffusion component of transport in the hearts from the fasted E. coli-treated rats. The reduction in total uptake at 40 microM and 100 microM of perfusate carnitine was due to a 42% and 26%, respectively, decrease in the carrier-mediated uptake. This data suggests that the reduced content of myocardial carnitine in fasted E. coli-treated rats is due to the decrease in the carrier-mediated component of transport.
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PMID:Impaired carnitine transport in the rat heart during E. coli sepsis. 177 54

Cytokines have been implicated in the modulation of fat metabolism after sepsis. Carnitine palmitoyltransferase (CPT), the regulatory enzyme of hepatic mitochondrial long-chain fatty-acid oxidation, is involved in the control of hepatic fat oxidation in sepsis. Using either H4IIe rat hepatoma cells or rat hepatocytes in primary culture, we tested the hypothesis that interleukin-1-alpha (IL-1 alpha) would modulate CPT transcription (CPT mRNA), CPT translation (35S-methionine CPT protein incorporation), and hepatic mitochondrial oxidation of 1-Carbon 14-labeled (14C) palmitate to ketone bodies (acid soluble products). We showed that IL-1 alpha significantly increased CPT mRNA, 35S-methionine incorporation CPT protein, and hepatic mitochondrial oxidation of 1-14C-palmitate to acid soluble products. We further hypothesized that the Ca2+ second messenger system may play a role in the IL-1 alpha induction of hepatic CPT gene transcription. We showed that either calcium ionophore (A23187) or phorbol myristate acetate increased CPT gene transcription and that either calcium chelation, protein kinase C inhibition (acridine orange), or chronic exposure to phorbol myristate acetate significantly inhibited IL-1 alpha induction of CPT mRNA. We conclude that the IL-1 alpha increases in hepatic mitochondrial fatty-acid oxidation may be, in part, secondary to increased CPT gene transcription and translation and that the Ca2+ second messenger system may play an important role in IL-1 alpha induction of CPT gene transcription.
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PMID:The Ca2+ second messenger system and interleukin-1-alpha modulation of hepatic gene transcription and mitochondrial fat oxidation. 185 38

Carnitine has been hypothesized to be a semi-essential nutrient in the nutrition of critically ill patients. The purpose of this study was to evaluate the effect of sepsis upon carnitine metabolism in the rat, using the model of cecal ligation and puncture. Three treatment groups, septic, sham, and non-operative controls, were used. The septic rats had significantly increased (p less than 0.05) excretion of acylcarnitine and over six-fold higher urinary acylcarnitine/free carnitine ratio, relative to the other two groups. The septic rats also had significantly higher liver and plasma free and total carnitine compared to the other two groups. A possible explanation for the increased urinary acylcarnitine excretion is that carnitine may be acting to remove toxic metabolites from the body. The septic model of cecal ligation and puncture was suitable for the study of carnitine metabolism during sepsis in the rat.
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PMID:Increased acylcarnitine clearance and excretion in septic rats. 185 90

Plasma concentrations of carnitine and carnitine esters were determined in patients with multiple forms of acute renal failure with and without sepsis, and also before and after haemodialysis therapy. Total carnitine, free carnitine, short-chain and long-chain acylcarnitine values of both groups of acute renal failure patients were markedly elevated compared with healthy subjects and chronically uraemic patients undergoing regular haemodialysis treatment. Carnitine and carnitine esters did not differ between septic and non-septic patients before and after haemodialysis with dialysers made of cuprophane or polysulphone. Animal experiments with acutely uraemic rats were performed in order to determine whether the liver or the kidney may be responsible for elevated carnitine and carnitine esters in acute renal failure. Plasma and liver total carnitine, free carnitine, short-chain acylcarnitine and long-chain acylcarnitine were significantly elevated in sham-operated animals, and further in ureter ligated and bilateral nephrectomised rats. Skeletal muscle and heart muscle carnitine and carnitine esters remained the same as in sham-operated controls. Our data demonstrate markedly increased liver carnitine synthesis and carnitine acylation in an acute uraemic rat model even after binephrectomy and 48-h food depletion and in the presence of elevated serum carnitine concentrations. Furthermore, from our clinical study we conclude that there is no need for carnitine supplementation in patients who developed acute renal failure in the postoperative and post-traumatic state under adequate nutrition even when requiring daily haemodialysis.
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PMID:Carnitine and carnitine esters in acute renal failure. 251 86

Carnitine performs a critically important role in energy metabolism and is synthesized in the healthy adult predominantly in the liver and kidney. The typical well balanced American diet contains significant amounts of carnitine as well as the essential amino acids and micronutrients needed for carnitine biosynthesis. Thus carnitine is an infrequent problem in the healthy, well nourished adult population in the United States. However, carnitine can be a conditionally essential nutrient for several different types of individuals. Preterm infants require carnitine for life-sustaining metabolic processes but have a carnitine biosynthetic capability that is not fully developed. There is an increasing number of documented problems with carnitine metabolism in preterm infants not receiving an exogenous source of carnitine indicating that endogenous biosynthesis of carnitine is not adequate to meet the infant's need. Children with different forms of organic aciduria appear to have a greatly increased need for carnitine to function in the excretion of the accumulating organic acids. This need exceeds their dietary carnitine intake and carnitine biosynthetic capability. Renal patients treated with chronic hemodialysis appear to lose carnitine via the hemodialysis treatment, and this loss cannot be repleted simply by endogenous biosynthesis and dietary intake. Treatment with drugs such as valproic acid and metabolic stresses such as trauma, sepsis, organ failure, etc, can also result in a requirement for exogenous carnitine. Accurate assessment of the carnitine status of patients at risk for carnitine deficiency is fundamental to the identification of those patients who require carnitine as the result of altered metabolism.
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PMID:Carnitine as an essential nutrient. 308 84

Carnitine metabolism was studied in rats that were injected i.v. with 8 X 10(7) live colonies of E. coli per 100 g body weight or physiological saline. All rats were fasted after injection to equalize differences in food intake. Twenty-two hours following E. coli injection serum total carnitine, free carnitine, and acyl carnitine of septic rats increased by 53%, 74%, and 40% respectively, compared with the levels of the control rats. The elevated serum carnitine does not appear to be due to increased mobilization from the skeletal muscle as there were no changes in the total carnitine content of the gastrocnemius muscle during sepsis. Urinary excretion of total carnitine decreased by 62% in the septic rats compared with their controls which may account, in part, for the high serum levels of carnitine in the septic rat. There were no significant differences in the carnitine content of the livers from the septic and control rats. The acid-soluble and acid-insoluble carnitine content of the hearts from the septic rats decreased by 35% and 27%, respectively compared with the hearts from the control rats. The reduced myocardial carnitine occurs in spite of the elevated levels of serum carnitine which suggests that the rates of carnitine transport may be altered in the hearts from septic rats.
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PMID:Changes in tissue levels of carnitine during E. coli sepsis in the rat. 327 15

Carnitine is an indispensable factor for the beta-oxidation of medium- and long-chain fatty acids, and it plays a possible role in the oxidation of branched-chain amino acids. Plasma and urinary levels of free carnitine and short-chain acyl-carnitines were studied in 67 surgical patients, after non-septic surgical procedures or during sepsis. The septic state was associated with increased urinary excretion of free carnitine (p less than 0.001), as well as with lower plasma levels of short-chain acyl-carnitines (p less than 0.001); the latter feature correlated with the level of hypermetabolism, as evaluated by the metabolic rate and by the arterial-mixed venous O2 difference. In 26 patients during total parenteral nutrition D, L-acetyl-carnitine was administered (100 mg/kg/24 hrs, in continuous iv infusion) and was associated, in septic patients only, with a significant decrease in the respiratory quotient, suggesting enhanced oxidation of low respiratory quotient substrates (fatty acids and/or branched-chain amino acids). Carnitine supplementation during total parenteral nutrition might be of theoretical benefit in some clinical conditions, such as sepsis, in which the following conditions coexist enhanced utilization of substrates whose oxidation is partially or totally carnitine dependent; prolonged absence of exogenous intake of carnitine (as in long-term total parenteral nutrition); eventual impairment of carnitine synthesis due to hepatic dysfunction; increased, massive urinary loss of carnitine.
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PMID:Plasma carnitine levels and urinary carnitine excretion during sepsis. 392 25

Inappropriate hepatic lipogenesis, hypertriglyceridaemia, decreased fatty acid oxidation and muscle protein wasting are common in patients with sepsis, cancer or AIDS. Given carnitine's role in the oxidation of fatty acids (FAs), we anticipated that carnitine might promote FA oxidation, thus ameliorating metabolic disturbances in lipopolysaccharide (LPS)- and methylcholanthrene-induced sarcoma models of wasting in rats. In the LPS model, rats were injected with LPS (24 mg kg-1 i.p.), and treated with carnitine (100 mg kg-1 i.p.) at -16, -8, 0 and 8 h post LPS. Rat health was observed, and plasma inflammatory cytokines and triglycerides (TG) were measured before and 3 h post LPS. In the sarcoma model, rats were implanted subcutaneously with tumour, and treated continuously with carnitine (200 mg kg-1 day-1 i.p.) via implanted osmotic pumps. Tumour burden, TG and cytokines were measured weekly for 4 weeks. Carnitine treatment significantly lowered the tumour-induced rise in TG (% rise) in the sarcoma model (700 +/- 204 vs 251 +/- 51, P < 0.03) in control and carnitine groups respectively. Levels of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) (pg ml-1) were also lowered by carnitine in both LPS (IL-1 beta: 536 +/- 65 vs 378 +/- 44: IL-6: 271 +/- 29 vs 222 +/- 32; TNF-alpha: 618 +/- 86 vs 367 +/- 54, P < or = 0.02) and sarcoma models (IL-1 beta: 423 +/- 33 vs 221 +/- 60; IL-6: 222 +/- 18 vs 139 +/- 38; TNF-alpha: 617 +/- 69 vs 280 +/- 77, P < or = 0.05) for control and carnitine groups respectively. We conclude that carnitine has a therapeutic effect on morbidity and lipid metabolism in these disease models, and that these effects could be the result of down-regulation of cytokine production and/or increased clearance of cytokines.
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PMID:Effects of L-carnitine on serum triglyceride and cytokine levels in rat models of cachexia and septic shock. 757 64

Carnitine CAR) plays an important role in the beta-oxidation of fatty acids. Less attention. however, has been paid to CAR compared to other nutrients even in total parenteral nutrition (TPN). To examine CAR metabolism during TPN and the effect of simultaneous oral L-CAR supplementation on CAR levels, the blood CAR level was measured in a 3-year-old boy receiving long-term TPN because of short bowel syndrome. Both the total and acyl CAR in the serum were evaluated under various nutritional conditions including oral supplementation of L-CAR. Low CAR concentrations were observed especially when lipid containing TPN regimens were in place. Oral L-CAR supplementation was not sufficient to restore the low CAR levels in the present index patient even when the dose was increased to 120 mg/kg in accordance with the result of the L-CAR absorption test that revealed poor intestinal absorption of this nutrient. Moreover, a markedly low CAR level was measured during the onset of sepsis in the patient, and the blood CAR was depleted when lipid metabolism was activated by lipid loading or sepsis. To date, the late effects of CAR depletion on child growth have not been well examined. It is recommended that the blood CAR level be maintained at normal levels before any prominent manifestations of the deficiency have developed. The intravenous administration of CAR appears to be necessary to supply a sufficient amount of CAR for patients with severe malabsorption.
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PMID:Carnitine depletion during total parenteral nutrition despite oral L-carnitine supplementation. 914 Dec 53

Carnitine and its congeners may regulate the immune networks, and their influence on functions of immune cells predominantly or exclusively relies on carnitine-dependent energy production from fatty acids. A reduced pool of carnitines has been demonstrated in either serum or tissues, or both, from patients with a wide spectrum of disorders characterized by unregulated or impaired immune responses ranging from sepsis syndrome to systemic sclerosis, infection with human immunodeficiency virus, and chronic fatigue syndrome. Furthermore, experimental studies have consistently reported that the deranged immune responses and the less efficient inflammation towards infectious organisms associated with aging may be enhanced or modulated by treatment with carnitines. There is also evidence that carnitine deprivation could adversely affect the course of the sepsis syndrome, at least in experimental models, and preliminary studies suggest that carnitine deficiency is ultimately implicated in the pathophysiology of endotoxin-mediated multiple organ failure. Several data indicate that carnitine deficiency is a contributing factor to the progression of infection with human immunodeficiency virus, and carnitine therapy in those patients could counteract the unregulated process of lymphocyte apoptosis and improve CD4 counts. Some case reports have suggested the use of carnitine for the treatment of the severe lactic acidosis that complicates in some patients the use of reverse transcriptase inhibitors.
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PMID:Carnitines and its congeners: a metabolic pathway to the regulation of immune response and inflammation. 1559 Oct 10


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