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)

Hepatobiliary dysfunctions (TPN-HBD) occur during parenteral nutrition. In older children these are usually reversible whereas in newborns and infants these hepatobiliary abnormalities play a significant role in the morbidity. Cholestasis is a commonly occurring TPN-HBD. It correlates directly with the decreasing gestational age, low birth weight and increasing duration of TPN therapy. The pathogenesis of cholestasis of TPN is multifactorial and predisposed by necrotising enterocolitis, sepsis, cardiac failure, shock, and hypotension. Diagnosis is made with exclusion of other causes of direct hyperbilirubinemia. Most TPN-HBD appear within 4 weeks of starting of TPN but severe complications manifest usually after the 16th week. Histologically there is intralobular cholestasis. In few cases there may be severe portal fibrosis followed by development of micronodular biliary cirrhosis. Enteral starvation, defective bile acid carriers, hypercaloric TPN are the major factors responsible for TPN-HBD, including cholestasis. Biliary complications of TPN-HBD are acalculous, cholecystitis, and cholelithiasis. Bile stasis is a major pathological factor for these. If the calories are provided only by glucose or glucose-containing electrolyte solutions it may lead to cholestasis and other TPN-HBD. Even small oral alimentation (continuous or bolus) during TPN, prevent TPN-HBD. Choleretic agents have been useful in the prevention and management of cholestasis and other parenteral nutrition induced hepatobiliary abnormalities.
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PMID:Hepatobiliary abnormalities and parenteral nutrition. 1102 27

Refeeding syndrome encompasses fluid and electrolyte imbalances and metabolic, intestinal, and cardiorespiratory derangements associated with appreciable morbidity and mortality. Although refeeding syndrome has been well documented in concentration-camp subjects, and more recently during parenteral therapy of critically ill patients, little is known about the importance of refeeding syndrome during recovery from a hunger strike. Thus, we studied the response to a four-step dietary replenishment routine in eight hunger strikers who refused food for 43 d. In this retrospective, observational study, we assessed the safety and efficacy of the refeeding procedure and analyzed the clinical and nutritional course of the cohort during both starvation and refeeding, mainly on the basis of clinical as well as a few biochemical determinations. During starvation, average weight loss was about 18% and, with the exception of occasional oral vitamins and electrolytes, the subjects consumed only water. Available body-composition and biochemical profiles showed no clinically significant changes during starvation, but one-half of the group displayed spontaneous diarrhea at some time before refeeding. Stepwise nutritional replenishment lasted for 9 d, after which all patients tolerated a full, unrestricted diet. Only one episode of diarrhea occurred during this phase, and both clinical and biochemical indexes confirmed a favorable clinical course, without any manifestation of refeeding syndrome. In conclusion, we observed the following: 1) Hypophosphatemia and other micronutrient imbalances did not occur, nor was macronutrient intolerance detected. 2) Despite some episodes of diarrhea, nutritional replenishment was not associated with significant enteral dysfunction. 3) There was some fluid retention, but this was mild. 4) Acute-phase markers were abnormally elevated during the refeeding phase, without associated sepsis or inflammation.
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PMID:Refeeding procedures after 43 days of total fasting. 1124 Mar 36

We have investigated sequential changes in skeletal muscle and hepatic protein synthesis following sepsis, and their relationship to changes in circulating and tissue glutamine concentrations. Male Wistar rats underwent caecal ligation and puncture (CLP) or sham operation, with starvation, and were killed 24, 72 or 96 h later. A group of non-operated animals were killed at the time of surgery. Protein synthesis was determined using a flooding dose of L-[4-(3)H] phenylalanine, and glutamine concentrations were measured by an enzymic fluorimetric assay. Protein synthesis in gastrocnemius muscle fell in all groups. Gastrocnemius total protein content was reduced after CLP and at 72 and 96 h after sham operation. After CLP, protein synthesis was lower at 24 h, and total protein content was lower at 72 and 96 h, than in sham-operated animals. CLP was associated with increased liver protein synthesis at all time points, whereas there was no change after sham operation. Liver protein content did not change after CLP, but was lower at 72 and 96 h after sham operation than in non-operated animals. Plasma glutamine concentrations were reduced at 24 h after sham operation, and at 72 and 96 h after CLP. Muscle glutamine concentrations were reduced in all groups, with the decrease being greater following CLP than after sham operation. In the liver, glutamine concentrations were unchanged after CLP, but increased after sham operation. In rats with sepsis, decreases in muscle protein synthesis and content are associated with markedly reduced muscle glutamine concentrations. Plasma glutamine concentrations are initially maintained, but fall later. In liver, protein synthesis is increased, while glutamine concentrations are preserved. These results support a peripheral-to-splanchnic glutamine flux in sepsis.
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PMID:Sequential changes in in vivo muscle and liver protein synthesis and plasma and tissue glutamine levels in sepsis in the rat. 1152 47

During sepsis and major trauma the blood glutamine (Gln) level is reduced. The administration of Gln can improve the outcome of these patients. However, the mechanism of this beneficial effect of Gln is poorly understood. In the course of critical illness leucocytes are confronted with cytotoxic inflammatory mediators. To protect themselves against these factors, cells express heat shock proteins (HSP). Previous studies have shown that the expression of the major inducible HSP (HSP70) is improved by high Gln concentrations above 4 mM. In this study we investigated whether Gln depletion, such as observed during critical illness, has an effect on HSP70 expression. Human lymphocytes exposed for 2 h to 42 degrees C showed a 3-fold increase in HSP70 expression (P<0.01). A preceding Gln starvation period over 3 days had no influence on this increase. However, when Gln is reduced during the stress response, HSP70 expression is impaired. A reduction of Gln from 0.5 mM (physiological) to 0.125 mM (pathological) led to a 40% lower HSP70 level (P<0.002). In contrast, increasing Gln concentrations (up to 2 mM) had only minor stimulatory effects (about 15%). This Gln-dependency of heat mediated HSP70 expression was observed in resting as well as proliferating lymphocytes. Our data indicate that during periods of reduced plasma Gln levels the stress response of human lymphocytes is impaired. Thus, Gln may be essential to minimize the susceptibility of leucocytes to cytotoxic inflammatory mediators. This is a new aspect of the protective effect of Gln supplementation in critically ill patients.
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PMID:Glutamine depletion impairs cellular stress response in human leucocytes. 1189 51

Skeletal muscle proteins are constantly being synthesized and degraded, and the net balance between synthesis and degradation determines the resultant muscle mass. Biochemical pathways that control protein synthesis are complex, and the following must be considered: gene transcription, mRNA splicing, and transport to the cytoplasm; specific amino acyl-tRNA, messenger (mRNA), ribosomal (rRNA) availability; amino acid availability within the cell; the hormonal milieu; rates of mRNA translation; packaging in vesicles for some types of proteins; and post-translational processing such as glycation and phosphorylation/dephosphorylation. Each of these processes is responsive to the need for greater or lesser production of new proteins, and many states such as sepsis, uncontrolled diabetes, prolonged bed-rest, aging, chronic alcohol treatment, and starvation cause marked reductions in rates of skeletal muscle protein synthesis. In contrast, acute and chronic resistance exercise cause elevations in rates of muscle protein synthesis above rates found in non-diseased rested organisms, which are normally fed. Resistance exercise may be unique in this capacity. This chapter focuses on studies that have used exercise to elucidate mechanisms that explain elevations in rates of protein synthesis. Very few studies have investigated the effects of aging on these mechanisms; however, the literature that is available is reviewed.
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PMID:Protein metabolism and age: influence of insulin and resistance exercise. 1191 14

Expression of high activities of both glutamine synthetase and glutaminase allows the liver to play a major role in the regulation of glutamine homeostasis. The liver shows net glutamine output in metabolic acidosis, in prolonged starvation and animals bearing tumors, net glutamine uptake in the postabsorptive state, on consuming high protein diets, and in uncontrolled diabetes or sepsis. Liver glutamine synthetase is expressed only in a small population of perivenous cells that allows it to salvage any ammonia not incorporated into urea in periportal cells. Hepatic glutaminase is a unique isozyme found only in periportal liver parenchymal cells where it provides glutamate and ammonia for the urea cycle. Control of hepatic glutamine metabolism occurs almost exclusively through changes in the activity of glutaminase, with no change in glutamine synthetase flux.
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PMID:Hepatic glutamine metabolism. 1193 40

The effect of sepsis on the rate of protein synthesis in the heart is poorly described. We have investigated changes in protein synthesis in the ventricles of the heart over time after cecal ligation and puncture (CLP) in rats in comparison with sham-operated and unoperated animals (ad libitum). All operated animals were starved from the time of surgery to the time of sacrifice. When operated animals were compared with ad libitum animals, ventricular weight and ventricular protein, and DNA and RNA contents were unchanged at 24 h, but were invariably reduced at 72 and 96 h. Fractional rate of protein synthesis (FSR), RNA activity, and cellular efficiency were reduced at 24 h and further reduced at 72 and 96 h. There were no differences, however, between septic and sham-operated animals. Eighteen hours after CLP, additional groups of rats were infused intravenously with 0.9% sodium chloride, parenteral nutrition (PN), or PN with glutamine, and were given a single dose of 400 microg recombinant human growth hormone (rhGH) or an equal volume of 0.9% sodium chloride. FSR was higher in animals given PN when compared with those given 0.9% sodium chloride only, and did not differ from FSR measured in unoperated animals. There was no additional benefit from the acute administration of either glutamine-enriched PN or rhGH. These results indicate that ventricular protein synthesis is markedly reduced by surgery and starvation, but that superimposed sepsis does not further influence these changes. PN can prevent the fall in cardiac protein synthesis associated with starvation, surgery, and sepsis, but neither glutamine nor rhGH produced any additional benefit.
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PMID:Influence of starvation, surgery, and sepsis on cardiac protein synthesis in rats: effects of parenteral nutrition, glutamine, and growth hormone. 1235 29

Altered pyruvate dehydrogenase (PDH) functioning occurs in primary PDH deficiencies and in diabetes, starvation, sepsis, and possibly Alzheimer's disease. Currently, the activity of the enzyme complex is difficult to measure in a rapid high-throughput format. Here we describe the use of a monoclonal antibody raised against the E2 subunit to immunocapture the intact PDH complex still active when bound to 96-well plates. Enzyme turnover was measured by following NADH production spectrophotometrically or by a fluorescence assay on mitochondrial protein preparations in the range of 0.4 to 5.0 micro g per well. Activity is sensitive to known PDH inhibitors and remains regulated by phosphorylation and dephosphorylation after immunopurification because of the presence of bound PDH kinase(s) and phosphatase(s). It is shown that the immunocapture assay can be used to detect PDH deficiency in cell extracts of cultured fibroblasts from patients, making it useful in patient screens, as well as in the high-throughput format for discovery of new modulators of PDH functioning.
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PMID:Immunocapture and microplate-based activity measurement of mammalian pyruvate dehydrogenase complex. 1263 10

The population decline of the nominate lesser black-backed gull Larus fuscus fuscus in the Gulf of Finland (northern Baltic) is caused by an exceedingly high chick mortality due to diseases. The chick diseases include degeneration in various internal organs (primarily liver), inflammations (mainly intestinal), and sepsis, the final cause of death. The hypothesis of starvation causing intestinal inflammations (leading to sepsis) was tested by attempting to reproduce lesions in apparently healthy herring gull L. argentatus chicks in captivity. The herring gull chicks were provided a similar low food-intake frequency as observed for the diseased chicks in the wild. However, empty alimentary tract per se did not induce the intestinal inflammations and therefore, inflammations seem to be innate or caused by other environmental factors in the diseased lesser black-backed chicks. They had very high concentrations of PCB in their liver; but the concentrations were not significantly higher than those of the healthy herring gull chicks, indicating a common exposure area for both species (i.e. the Baltic Sea). When compared to NOEL and LOEL values for TEQs in bird eggs our TEQ levels clearly exceed most or all of the values associated with effects. Compared with published data on fish-eating waterbirds, the DDE concentrations in the diseased lesser black-backed chicks were well above the levels previously correlated with decreased reproduction, while the residues in apparently healthy herring gulls were below those levels. The DDE/PCB ratio in lesser black-backs was significantly elevated, indicating an increased exposure to DDTs as compared with most other Baltic and circumpolar seabirds. The possible exposure areas of DDT in relation to differential migration habits of the two gull species are discussed.
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PMID:Organochlorine concentrations in diseased vs. healthy gull chicks from the northern Baltic. 1463 2

Hunger strike is described as voluntary refusal of food and/or fluids. Prolonged starvation may produce many adverse events including even death in rare circumstances. Here, we present three fatal cases (all males, 25-38 years) died from hunger strike. In all corpses, obvious muscle wasting with reduced subcutaneous and internal fat deposits, and atrophy in some organs were demonstrated at autopsy. The extraordinary long starvation period before death could presumably be linked to the thiamine uptake in this period, which had been discontinued by all subjects before the death occurred. Prolonged caloric deficiency with subsequent complications such as multiple organ failure, severe sepsis and ventricular fibrillation could account as major causes of death in these subjects. The competence of the physicians working with hunger strikers about the processes and potential problems is of great importance since they have to acknowledge about them to their patients.
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PMID:Deaths due to hunger strike: post-mortem findings. 1548 19


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