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 risk factors for the development and clinical characteristics of hypoglycemia in patients with sepsis, a case-control study was performed in 52 case-patients who developed spontaneous hypoglycemia (plasma glucose < 50 mg/dl) during episodes of sepsis compared with 49 nondiabetic, control-patients who had sepsis as an immediate cause of death and did not develop hypoglycemia. The presence or absence of potential risk factors for the development of hypoglycemia which consisted of the state of starvation, malnutrition, renal insufficiency, acute or chronic liver disease and malignancy were evaluated in both groups as well as the clinical characteristics of hypoglycemia. The mean of the lowest plasma glucose levels in hypoglycemic patients was 23.4 +/- 14.9 (SD) mg/dl (range 3-47). One-third of patients were found having hypoglycemia since the time of arrival to the hospital. About 90 per cent had septic shock at the time of hypoglycemia. The mortality rate was 90 per cent; 80 per cent died within 48 hours after the first episode of hypoglycemia. Among those risk factors, starvation and liver disease were independently associated with the development of hypoglycemia with odd ratios of 6.38 (95% confidence interval 1.95-20.86; P = 0.002), and 3.59 (95% confidence interval 1.09-11.81; P = 0.035), respectively. In conclusion, hypoglycemia in patients with sepsis was associated with a grave prognosis. The risk of developing hypoglycemia increased significantly in patients who had been fasted for more than 24 hours or had acute or chronic liver disease at the time of sepsis.
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PMID:Hypoglycemia in sepsis: risk factors and clinical characteristics. 947 Mar 28

Loss of lean body mass is common in patients with acute or chronic renal failure but the mechanisms causing this loss are only beginning to be understood. One mechanism involves an inability of uremic patients to activate the critical metabolic responses that maintain protein balance when dietary protein is limited. Metabolic responses to dietary protein restriction include a sharp reduction in the degradation of essential amino acids and protein; changes in protein synthesis are less reliable. If uremia prevents suppression of essential amino acid or protein degradation when dietary protein is reduced by anorexia, negative nitrogen balance and loss of lean body mass will ensue. One complication of uremia, metabolic acidosis, stimulates the degradation of branched-chain amino acids and proteins and therefore blocks the ability of the patient to respond to a low-protein diet. The mechanisms require glucocorticoids and involve increased activity of branched-chain keto acid dehydrogenase and the ubiquitin-proteasome proteolytic pathway; there also is increased transcription of genes encoding components of enzymes involved in the pathways. Besides acidosis, a low insulin concentration and cytokines activate the ubiquitin-proteasome proteolytic pathway. Understanding how proteolysis is activated, including how these genes are stimulated, is important because the same pathways are activated in diabetes, cancer, sepsis, burns, starvation, and muscle denervation. Activation of the ubiquitin-proteasome pathway leads to reduced lean body mass.
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PMID:Robert H Herman Memorial Award in Clinical Nutrition Lecture, 1997. Mechanisms causing loss of lean body mass in kidney disease. 949 77

The ubiquitin-proteasome proteolytic system is stimulated in conditions causing muscle atrophy. Signals initiating this response in these conditions are unknown, although glucocorticoids are required but insufficient to stimulate muscle proteolysis in starvation, acidosis, and sepsis. To identify signals that activate this system, we studied acutely diabetic rats that had metabolic acidosis and increased corticosterone production. Protein degradation was increased 52% (P < 0.05), and mRNA levels encoding ubiquitin-proteasome system components, including the ubiquitin-conjugating enzyme E214k, were higher (transcription of the ubiquitin and proteasome subunit C3 genes in muscle was increased by nuclear run-off assay). In diabetic rats, prevention of acidemia by oral NaHCO3 did not eliminate muscle proteolysis. Adrenalectomy blocked accelerated proteolysis and the rise in pathway mRNAs; both responses were restored by administration of a physiological dose of glucocorticoids to adrenalectomized, diabetic rats. Finally, treating diabetic rats with insulin for >/=24 h reversed muscle proteolysis and returned pathway mRNAs to control levels. Thus acidification is not necessary for these responses, but glucocorticoids and a low insulin level in tandem activate the ubiquitin-proteasome proteolytic system.
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PMID:Evaluation of signals activating ubiquitin-proteasome proteolysis in a model of muscle wasting. 1032 62

Both starvation and sepsis are characterized by growth hormone (GH) insensitivity, which leads to a reduction in circulating insulin-like growth factor (IGF)-I. Because of the anabolic properties of this growth factor, its decline may contribute to the growth arrest and the catabolic reaction observed in starvation and sepsis. This review focuses on the mechanisms responsible for the reduction in circulating IGF-I and impairment of GH responsiveness that occur during starvation and sepsis. A clearer understanding of the complex nature of GH resistance should lead to the development of new therapeutic strategies aimed at restoring the beneficial effects of anabolic agents such as GH and IGF-I.
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PMID:Regulation of insulin-like growth factor-I in starvation and injury. 1043 29

Tissue carnitine levels have been measured in man and the dog. Skeletal muscle carnitine levels rise in the dog with starvation to roughly twice the normal level. An equal degree of starvation plus peritonitis is associated with unchanged skeletal muscle carnitine levels. In the presence of peritonitis, sequential skeletal muscle biopsies show a progressive fall in the tissue carnitine levels with a subsequent rise in those animals which survive and clear their peritonitis. Normal human skeletal muscle levels are essentially the same as in the dog. A combination of sepsis and starvation in man is associated with essentially unchanged skeletal muscle carnitine levels, whereas pure sepsis without starvation is associated with decreased skeletal muscle carnitine levels. It is suggested that these changes are in the direction expected for a limitation of fat catabolism and, in the presence of a limited exogenous source of glucose, that this would result secondarily in a protein catabolic state to supply glucose for the body's energy needs.
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PMID:Carnitine levels in severe infection and starvation: a possible key to the prolonged catabolic state. 1048 66

We analyzed clinical, biochemical, and histo- logic parameters of ten infants with parenteral nutrition-induced hepatobiliary dysfunction. The data were compared with the results of a rabbit model. All infants were born prematurely with low birth weight. Their clinical diagnoses were necrotizing enterocolitis (6), gastroschisis (1), intrauterine volvulus (1), and lung hypoplasia (2). All required total (TPN) or partial parenteral nutrition for at least 8 weeks. All had repeated episodes of infections or sepsis. A rise in bilirubin and aminotransferase levels occurred after a minimum of 5 weeks; peak bilirubin levels ranged from 4 to 14 mg% and aminotransferases from 40 to 140 IU/l. One child later developed gallstones. Liver biopsies after 1 to 24 months showed fibrosis, bile-duct proliferation, cholestasis, and hydropic degeneration. All of the above-mentioned clinical factors have been accused of causing the observed biochemical and histologic changes. In our rabbit model we were able to produce almost identical symptoms by TPN alone: gallbladder distension, sludge, and stones developed after 1-4 weeks of TPN as well as uncharacteristic changes in aminotransferases and bilirubin after 4 weeks. Liver histology revealed severe hydropic degeneration of zone 3 as early as 1 week after beginning TPN. A rise of fibrosis and bile-duct proliferation after 1 to 4 weeks of infusion was statistically significant. Cholestasis, as was observed in the infants, could not be detected. In our model, all alterations observed could be attributed exclusively to TPN. We therefore assume that TPN was the true cause of the dysfunction. In a second experimental series infusions were reduced to 80% PN and free access to lab chow. These animals produced normal feces, indicating physiologic enteral stimulation. They developed the same degenerative and proliferative histologic changes, whereas gallbladder distension, sludge, and stones were not noted. We conclude that: (1) The TPN solution itself is responsible for the histologic changes in the liver, which is supported by the fact that hydropic degeneration of zone 3 is typical of a direct toxic effect; and (2) Complete enteral starvation with an absence of enteral stimulation causes disease of the lower biliary tract.
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PMID:Parenteral nutrition-induced hepatobiliary dysfunction in infants and prepubertal rabbits. 1052 3

The liver shows net glutamine uptake after a protein-containing meal, during uncontrolled diabetes, sepsis and short-term starvation, but changes to net release during long-term starvation and metabolic acidosis. Some studies report a small net release of glutamate by the liver. The differential expression of glutamine synthetase (perivenous) and glutaminase (periportal) within the liver indicates that glutamine is used for urea synthesis in periportal cells, whereas glutamine synthesis serves to detoxify any residual ammonia in perivenous cells. Experiments in vivo suggest that changes in net hepatic glutamine balance are due predominantly to regulation of glutaminase activity, with the flux through glutamine synthetase being relatively constant.
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PMID:Glutamine and glutamate metabolism across the liver sinusoid. 1073 66

Data collected on 3256 lambs born to Horro and Menz breed ewes single-sire mated to 71 rams at the International Livestock Research Institute (ILRI) Debre Berhan station between September 1992 and June 1996 were analysed for rates of survival and growth from birth to weaning. A significantly lower proportion of Menz lambs died before 1 year of age (28%) than the Horro lambs (59%). Least squares means for pre- and post-weaning mortality were 8.8 and 19.3%, respectively in Menz, and 25.3 and 34.2% for Horro sheep. Major causes of death were similar in Horro versus Menz lambs and were pneumonia (53 vs. 54%, respectively), digestive problems (14 vs. 12%), endoparasite infections (9 vs. 13%), starvation-mismothering-exposure (SME) complex (10 vs. 7%) and septicemia (3 vs. 2%). Relationships among causes of mortality with breed, birth weight (BWT), season of birth, parity, litter size and lamb health category (number of times a lamb was sick between birth and 1 year of age) were determined. The impact of these factors on mortality varied with lamb age. Lambs that were born with <2kg BWT had a greater risk of dying from any cause except pneumonia. But, even though Horro lambs were heavier than Menz at birth (2.4 vs. 2.1kg, respectively), twice as many died before 1 year of age. The cause of mortality was further influenced by season of birth, lamb sex and health category. In addition, sires were a significant source of variation for progeny survival at 6, 9 and 12 months of age, but not at the younger ages. The best and worst Horro ram sired progeny groups that had mortality rates up to 1 year of age of 22 vs. 80%, respectively. The same estimates in Menz rams were 11 and 48%, respectively. Reduced mortality rate would significantly increase lamb output. However, isolated efforts to solve this problem are likely to have limited impact. Instead, an integrated approach to minimise the impact of underlying factors is advocated. Farm (animal) management routines that could be introduced in the short or longer term are discussed.
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PMID:Between and within breed variation in lamb survival and the risk factors associated with major causes of mortality in indigenous Horro and Menz sheep in Ethiopia. 1081 97

Loss of muscle mass usually characterizes different pathologies (sepsis, cancer, trauma) and also occurs during normal aging. One reason for muscle wasting relates to a decrease in food intake. This study addressed the role of leucine as a regulator of protein breakdown in mouse C2C12 myotubes and aimed to determine which cellular responses regulate the process. Determination of the rate of protein breakdown indicated that leucine is one key regulator of this process in myotubes because starvation for this amino acid is responsible for 30-40% of the total increase generated by total amino acid starvation. Leucine restriction rapidly accelerates the rate of protein breakdown (+11 to 15% (p < 0.001) after 1 h of starvation) in a dose-dependent manner. By using various inhibitors, evidence is provided that acceleration of protein catabolism results mainly from an induction of autophagy, activation of lysosome-dependent proteolysis, without modification of mRNA levels encoding the lysosomal cathepsins B, L, or D. Those results suggest that autophagy is an essential cellular response for increasing protein breakdown in muscle following food deprivation. Induction of autophagy precedes a decrease in global protein synthesis (-20% to -30% (p < 0.001)) that occurs after 3 h of leucine starvation. Inhibition of the mammalian target of rapamycin (mTOR) activity does not abolish the effect of leucine starvation and the level of phosphorylated ribosomal S6 protein is not affected by leucine withdrawal. These latter data provide clear evidence that the mTOR signaling pathway is not involved in the mediation of leucine effects on both protein synthesis and degradation in C2C12 myotubes.
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PMID:Leucine limitation induces autophagy and activation of lysosome-dependent proteolysis in C2C12 myotubes through a mammalian target of rapamycin-independent signaling pathway. 1089 13

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


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