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

Blood concentrations of branched chain amino acids (BCAA; leucine, isoleucine, and valine) and glutamine (Gln) decrease markedly in sepsis. We investigated the effect of carnitine on serum concentrations of BCAA and Gln in fasted septic rats. Rats were made septic by cecal ligation and puncture. They developed extremely high blood concentrations of endotoxin, and serum concentrations of BCAA and Gln were markedly decreased 2 d after the operation. When L-carnitine was administered subcutaneously to the rats at 500 mg/kg body weight every 12 h for 2 d starting at the operation, no decrease in the serum concentrations of BCAA and Gln was observed. This indicates that the administration of carnitine can prevent the decrease of serum concentrations of BCAA and Gln in septic animals.
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PMID:Effect of carnitine on decrease of branched chain amino acids and glutamine in serum of septic rats. 882 Sep 32

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

Sepsis and endotoxemia are important stressors for the neonate. Newborn infants receiving total parenteral nutrition are routinely deprived of carnitine. To investigate whether carnitine deprivation affects the neonate's ability to respond to endotoxin, 19 newborn piglets received parenteral nutrition for 2-3 weeks that was either carnitine free (CARN-) or supplemented (CARN+) with L-carnitine (400 mg/L). Cardiovascular performance, i.e., heart rate; blood pressure (BP); cardiac output (CO); systemic vascular resistance (SVR), and metabolic response, i.e., plasma glucose; lactate; tumor necrosis factor alpha; tissue nitric oxide; and urinary nitrites, were studied serially in anesthetized piglets for 3 h after endotoxin (lipopolysaccharide (LPS), 250 microg/kg intravenous bolus) or vehicle administration. Plasma and tissue carnitine values were lower in CARN- than in CARN+ piglets. Prior to LPS, no differences were found for most parameters (excepting lower diastolic BP and SVR in CARN- animals). Systolic, diastolic, and mean BP fell after LPS but recovered by the end of the experiment. Nadirs were lower in CARN- than in CARN+ piglets. CO tended to be higher in CARN- than in CARN+ animals and fell after LPS. SVR fell after LPS and was lower in CARN- than in CARN+ piglets. LPS-treated animals transiently increased urinary flow. By all measures (plasma tumor necrosis factor alpha, glucose and lactate, tissue nitric oxide, and urinary nitrite excretion), LPS provocation was similar for both groups. Chronologically, BP changes were more closely related to SVR than to CO. Our findings suggest that carnitine deprivation diminishes tissue carnitine concentrations and adversely affects cardiovascular response to LPS, in part mediated by the peripheral vasculature.
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PMID:Carnitine deprivation adversely affects cardiovascular response to bacterial endotoxin (LPS) in the anesthetized neonatal pig. 984 Jun 55

Sepsis and hypoxia are important stressors for the neonate. Newborn infants receiving total parenteral nutrition are routinely deprived of carnitine and develop low carnitine plasma and tissue levels. Because of its high metabolic rate and dependence on fatty acids for energy, the newborn heart may be particularly vulnerable to stress in the face of an inadequate carnitine supply. To investigate whether carnitine deprivation affects cardiac performance under stress, 23 neonatal piglets received parenteral nutrition for 2-3 weeks that was either carnitine free (CARN -) or supplemented (CARN +) with L-carnitine (400 mg/L). Bacterial endotoxin (lipopolysaccharide (LPS), 250 microg/kg intravenous bolus) or saline vehicle was administered to anesthetized piglets 3 h prior to study of isolated perfused hearts. Left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure, and left ventricular developed pressure (LVDP) were measured in vitro under aerobic, hypoxic, and reoxygenation conditions in all animals. Plasma and tissue carnitine values were lower in CARN - than in CARN + piglets. In hearts from LPS-treated animals prior to hypoxia, there was no difference in ventricular compliance between CARN - and CARN + groups. LVSP and LVDP were lower in CARN - than CARN + hearts. During hypoxia, LVSP and LVDP fell, but left ventricular end diastolic pressure increased in hearts from both LPS- and saline- treated piglets. Reoxygenation led to poorer recovery in CARN - than CARN + hearts from LPS-treated animals, but not from saline controls. During hypoxia/reoxygenation, lactate efflux initially rose and then fell, while carnitine efflux increased continually. Acetyl- and medium-chain acylcarnitines were detected in the coronary effluent. Our findings suggest that carnitine deprivation diminishes heart carnitine concentrations and impairs cardiac recovery from combined endotoxic and hypoxic stress. Possible mechanisms include reduced acyl buffering and/or impaired transport of fatty acyl groups into mitochondria.
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PMID:Carnitine deprivation adversely affects cardiac performance in the lipopolysaccharide- and hypoxia/reoxygenation-stressed piglet heart. 1003 Jul 99

Despite the increased application of aseptic techniques for blood collection and the preparation of platelet concentrates, morbidity and mortality arising from the transfusion of bacterially contaminated allogeneic platelet products persist. This problem exists because stored platelet concentrates represent a nearly ideal growth medium for bacteria and because they are stored at temperatures (22 degrees +/- 2 degrees C) that facilitate bacterial growth. The presence of bacteria in blood components including platelets has been a problem for many decades and currently is the most common microbiological cause of transfusion-associated morbidity and mortality. A variety of strategies have been devised and/or proposed in an attempt to try to reduce the risk of transfusion-associated sepsis. These include pretransfusion bacterial detection, efforts to reduce the likelihood of bacterial contamination, the optimization of blood product processing and storage, reducing recipient exposure, and the introduction of pathogen inactivation methodology. With regard to doing bacterial detection, a number of automated detection systems have become available to test for contaminated platelet components, but their utility to some extent is restricted by the time they take to indicate the presence of bacteria and/or their lack of sensitivity to detect initially low bacterial loads. A variety of other approaches has been shown to reduce the risk of bacterial contamination and include filtration to remove leukocytes and bacteria, diversion of the initial aliquot of blood during donation, and improved donor skin disinfection. Platelet pathogen inactivation methods under investigation include the addition of L-carnitine, gamma-irradiation, riboflavin plus UVA irradiation, and amotosalen HCl plus UVA irradiation. The latter process is licensed for clinical use with platelets in some countries in Europe. All of these approaches, either collectively or individually, hold considerable promise that the prevalence of adverse events associated with bacteria in platelet products will decline significantly in the very foreseeable future.
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PMID:Improving the bacteriological safety of platelet transfusions. 1524 73

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

The distribution of carnitine was investigated in male Wistar rats with sepsis or acute liver failure. Sepsis was produced by cecal ligation and puncture, while acute liver failure was induced by intraperitoneal injection of carbon tetrachloride. Then 14C-carnitine or L-carnitine was injected intravenously. In healthy control rats and rats with sepsis, both 14C-radioactivity and carnitine were increased in the liver and kidneys. When the carnitine fractions were investigated, it was found that free carnitine and short-chain acylcarnitine were increased. In the rats with acute liver failure, 14C-radioactivity decreased in the liver, but carnitine increased, with free carnitine and short-chain acylcarnitine levels rising. These findings suggested that exogenous free carnitine accumulated directly in the organs with carnitine deficiency in rats with sepsis and acute liver failure. In addition, there was differential regulation of the fractions of both exogenous and endogenous carnitine (free carnitine, short-chain acylcarnitine, and long-chain acylcarnitine). Furthermore, the distribution of exogenous carnitine differed between sepsis and acute liver failure.
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PMID:Distribution of endogenous and exogenous carnitine in rats with sepsis and acute liver failure. 1684 93

The purpose of this study was to determine if free or esterified carnitine could alter fatty acid metabolism and ameliorate sepsis in lipopolysaccharide (LPS)-treated rats. Throughout a 96 h observation post-LPS, i.p. administration of both markedly reduced illness and accelerated recovery. Carnitine prevented the acute LPS-induced rise in serum triglycerides (45 +/- 6, 59 +/- 5 vs. 83 +/- 8 mg/ml, p < 0.001), respectively. This difference was accompanied by a significant increase in liver lipogenesis in LPS controls compared to both carnitines and normal rats (6.1 +/- 0.3 vs. 3.9 +/- 0.5, 4.3 +/- 0.5, and 1.8 +/- 0.4 mumol/h, respectively, p < 0.04). Compared to normal rats, total liver carnitine was significantly elevated in LPS controls and even higher in the carnitine groups (357 +/- 40 vs. 736 +/- 38, 796 +/- 79, and 1081 +/- 21 nmol/g). The data suggest that carnitines may be of therapeutic value in sepsis treatment and one action may be to partition fatty acids from esterification to oxidation.
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PMID:Amelioration of popolysaccharide-induced sepsis in rats by free and esterified carnitine. 1847 72

The testis is an immunologically privileged organ. Sertoli cells can form a blood-testis barrier and protect sperm cells from self-immune system attacks. Spermatogenesis may be inhibited by severe illness, bacterial infections and chronic inflammatory diseases but the mechanism(s) is poorly understood. Our objective is to help in understanding such mechanism(s) to develop protective agents against temporary or permanent testicular dysfunction. Lipopolysaccaride (LPS) is used as a model of animal sepsis while L-carnitine (LCR) is used as a protective agent. A total of 60 male Swiss albino rats were divided into four groups (15/group). The control group received Saline; the 2(nd) group was given LCR (500 mg/kg i.p, once). The third group was treated with LPS (5 mg/kg i.p once) and the fourth group received LCR then LPS after three hours. From each group, five rats were used for histopathological examination. Biochemical parameters were assessed in the remaining ten rats. At the end of the experiment, animals were lightly anaesthetized with ether where blood samples were collected and testes were dissected on ice. Sperm count and motility were evaluated from cauda epididymis in each animal. Also, oxidative stress was evaluated by measuring testicular contents of reduced glutathione (GSH), malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-HDG, the DNA adduct for oxidative damage) in testicular DNA. The pro-inflammatory mediator nitric oxide (NO) in addition to lactate dehydrogenase (LDHx) isoenzyme-x activity as an indicator for normal spermatozoal metabolism were assessed in testicular homogenate. Serum interlukin (IL)-2 level was also assessed as a marker for T-helper cell function. The obtained data revealed that LPS induced marked reductions in sperm's count and motility, obstruction in seminiferous tubules, hypospermia and dilated congested blood vessels in testicular sections concomitant with decreased testicular GSH content and LDHx activity. Moreover, the testicular levels of MDA, 8-HDG (in testicular DNA) and NO as well as serum IL-2 level were increased. Administration of LCR before LPS returned both sperm count and motility to normal levels. Also, contents of testicular GSH, MDA, 8-HDG and NO returned back to the corresponding control values. In addition, serum IL-2 level as well as histological abnormalities were markedly improved in LCR + LPS-treated rats. In conclusion, LPS increased proinflammatory and oxidative stress markers in the testis leading to a marked testicular dysfunction. L-carnitine administration ameliorates these effects by antioxidant and/or anti-inflammatory mechanisms suggesting a protective role against male infertility in severely infected or septic patients.
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PMID:Pro-inflammatory and oxidative stress pathways which compromise sperm motility and survival may be altered by L-carnitine. 2035 28

Carnitine is a conditionally essential nutrient that plays a vital role in energy production and fatty acid metabolism. Vegetarians possess a greater bioavailability than meat eaters. Distinct deficiencies arise either from genetic mutation of carnitine transporters or in association with other disorders such as liver or kidney disease. Carnitine deficiency occurs in aberrations of carnitine regulation in disorders such as diabetes, sepsis, cardiomyopathy, malnutrition, cirrhosis, endocrine disorders and with aging. Nutritional supplementation of L-carnitine, the biologically active form of carnitine, is ameliorative for uremic patients, and can improve nerve conduction, neuropathic pain and immune function in diabetes patients while it is life-saving for patients suffering primary carnitine deficiency. Clinical application of carnitine holds much promise in a range of neural disorders such as Alzheimer's disease, hepatic encephalopathy and other painful neuropathies. Topical application in dry eye offers osmoprotection and modulates immune and inflammatory responses. Carnitine has been recognized as a nutritional supplement in cardiovascular disease and there is increasing evidence that carnitine supplementation may be beneficial in treating obesity, improving glucose intolerance and total energy expenditure.
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PMID:Role of carnitine in disease. 2039 44


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