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)

Because high calcium concentration in vitro stimulates muscle proteolysis, calcium has been implicated in the pathogenesis of increased muscle breakdown in different catabolic conditions. Protein breakdown in skeletal muscle is increased during sepsis, but the effect of sepsis on muscle calcium uptake and content is not known. In this study the influence of sepsis, induced in rats by cecal ligation and puncture, on muscle calcium uptake and content was studied. Sixteen hours after cecal ligation and puncture or sham operation, calcium content of the extensor digitorum longus (EDL) and soleus (SOL) muscles was determined with an atomic absorption spectrometer. Calcium uptake was measured in intact SOL muscles incubated in the presence of calcium 45 (45Ca) for between 1 and 120 minutes. Total and myofibrillar protein breakdown was determined in SOL muscles, incubated in the presence of different calcium concentrations (0; 2.5; 5.0 mmol/L), and measured as release into the incubation medium of tyrosine and 3-methylhistidine (3-MH), respectively. Calcium content was increased by 51% (p less than 0.001) during sepsis in SOL and by 10% (p less than 0.05) in EDL muscle. There was no difference in 45Ca uptake between control and septic muscles during the early phase (1 to 5 minutes) of incubation. During more extended incubation (30 to 120 minutes), muscles from septic rats took up significantly more 45Ca than control muscles (p less than 0.05). Tyrosine release by incubated SOL muscles from control and septic rats was increased when calcium was added to the incubation medium, and at a calcium concentration of 2.5 mmol/L, the increase in tyrosine release was greater in septic than in control muscle. Addition of calcium to the incubation medium did not affect 3-MH release in control or septic muscle. The results suggest that calcium uptake and content in skeletal muscle are increased during sepsis and that high calcium concentrations in vitro stimulate nonmyofibrillar protein breakdown. Muscles from septic animals may be more sensitive to the effect of calcium in vitro than muscles from nonseptic rats. Whether increased calcium uptake and content in skeletal muscle is partly responsible for accelerated muscle proteolysis during sepsis remains to be determined.
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PMID:Effect of sepsis on calcium uptake and content in skeletal muscle and regulation in vitro by calcium of total and myofibrillar protein breakdown in control and septic muscle: results from a preliminary study. 274 Sep 90

The effect of major trauma and sepsis on skeletal muscle, central tissue and whole body nitrogen (N) metabolism was investigated in 5 patients before and during TPN (30 kcal, 0.30 g N kg-1 day-1). Fasting 3-methylhistidine (MEH) urinary excretion was elevated (407.9 +/- 67.6 mumol m-2 day-1), muscle and body N balances (NB) were markedly negative (-28.2 +/- 4.6 g m-2 day-1 and -15.7 +/- 3.1 g m-2 day-1), while central tissue NB was positive (13.0 +/- 2.4 g m-2 day-1). TPN effected a reduction in MEH excretion (261.8 +/- 27.5 mmol m-2 day-1 - p less than 0.05) and decreased the release of almost all amino acids from muscle tissue, some of them acting as catabolic markers. Muscle (-7.2 +/- 1.2 g m-2 day-1 - p less than 0.01) as well as body NB (-4.8 +/- 1.4 g m-2 day-1 - p less than 0.01) improved, whilst central tissue NB worsened, even though still positive (3.1 +/- 1.6 g m-2 day-1 - p less than 0.05). Gathering fasting and TPN data MEH excretion was significantly related to both body (r = 0.89) and muscle (r = 0.73) NB, that were highly related to each other (r = 0.93), being muscle always worse than body NB. In conclusion, the anticatabolic activity of TPN is confirmed, although our setting did not achieve muscle NB, it was consistently improved and seems to be the major determinant of body NB, in contrast central NB and central N utilization (46.4% +/- 5.4 vs 15.8% +/- 8.4 - p less than 0.05) worsened.
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PMID:Peripheral, visceral and body nitrogen balance of catabolic patients, without and with parenteral nutrition. 313 91

We measured amino acid concentrations in plasma and skeletal muscle of three groups of patients with acute hemorrhagic pancreatitis: (a) patients without secondary organ lesions, (b) patients also suffering from kidney damage, and (c) patients in whom the pancreatitis was accompanied by sepsis and multiple organ failure. In all three groups, especially the third group, the amino acid concentrations in both plasma and muscle were below normal. Glutamine was only 14% of normal in muscle tissue of the third group. Onset of renal insufficiency was indicated by increasing values for 3-methylhistidine and cystathionine; multiple organ failure, by increased concentrations of methionine and phenylalanine in plasma. The low amino acid concentrations of patients with acute pancreatitis can be explained as a combined effect of semistarvation and hypercatabolism. Changes in the plasma concentrations of amino acids did not reflect necessarily the concentrations in muscle tissue.
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PMID:Amino acid concentrations in plasma and skeletal muscle of patients with acute hemorrhagic necrotizing pancreatitis. 401 35

The severely burned patient responds differently to starvation ketosis in the early stage of injury as compared to the normal individual. A similar response has been observed in the patient after skeletal trauma and sepsis. In order to determine the extent of muscle protein contribution and the mechanism(s) involved, 11 burn patients with 35% to 80% BSA burn were resuscitated using carbohydrate-free solutions for 3 days followed by unrestricted intake. Blood was drawn daily and 24-hour urinary nitrogens were determined. Controls consisted of 10 preoperative elective surgical patients and two normal volunteers. The burned patients lost a mean +/- SEM of 17.1 +/- 1.72 g nitrogen per day on the third day. The mean +/- SEM ketone body response on the third day for burned patients was 385 +/- 77 mumol/l compared to 727 +/- 81 mumol/l for control patients. The mean +/- SEM 3-methylhistidine loss for burned patients on the third day was 9.83 +/- 0.82 mumol/kg compared to 3.6 mol/kg for control patients. Insulin levels on the third day of fast were three times the normal group. This insulin increase may be the modulating factor that suppresses excessive fat mobilization. This metabolic response causes a lower plasma ketone level, which may then necessitate the need for continued protein catabolism for glucose production for certain tissues. The protein contribution to the hypercatabolic response as assessed by increased urinary nitrogen losses is in part supported by an increased muscle protein breakdown as indicated by increased 3-methylhistidine excretion.
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PMID:The effect of major thermal injury and carbohydrate-free intake on serum triglycerides, insulin, and 3-methylhistidine excretion. 638 84

The effects of adequate total parenteral nutrition (TPN) on nitrogen excretion, urea N percentage, 3-methylhistidine excretion, and leg amino acid output, were studied during the ten-day period following abdominal surgery for generalized peritonitis in nine patients. The first two postoperative days were without nutritional intake, TPN was started on the third postoperative day (57 cal/KgBW--40% as Intralipid--0.30 g of N/KgBW). Leg amino acid outputs were done before TPN (DO), then two days (D2) and eight days (D8) after TPN. Total nitrogen and urea N percentage did not significantly differ before and after TPN. Between DO and D2 there was a significant reduction of urinary 3-methylhistidine (467 +/- 37 to 280 +/- 29 mumol/24 h-P less than 0.001) and leg amino acid release (604 +/- 103 to 254 +/- 87 nmol/mn/100 g of calf muscle--P less than 0.01) reflecting reduction in muscle hypercatabolism despite the persistence of the septic state. Between D2 and D8, 3-methylhistidine remained stable while leg amino acid release continued to decrease (254 +/- 87 to 68 +/- 40 nmol/mn/100 g--P less than 0.05). This association suggests an increased muscle protein synthesis. A closer examination of the clinical evolution of these patients, especially concerning their septic evolution, shows that only improved patients with recovery from sepsis increased their muscle protein synthesis. Thus, in septic hypercatabolic patients TPN seems to be able to reduce muscle catabolism while the increase in protein synthesis is mainly the consequence of recovery from the septic state. In such patients TPN should be used as a preventive therapeutic measure.
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PMID:Effect of parenteral nutrition on muscle amino acid output and 3-methylhistidine excretion in septic patients. 642 10

The daily urinary excretion of 3,methylhistidine (3,MeHis) was measured in eight severely injured patients for periods of at least two weeks to at most one month after the trauma. The patients were fed with 0.20 +/- 0.05 g X kg-1 X 24 h-1 of nitrogen and 25 +/- 5 kcal X kg-1 X 24 h-1 given as glucose. The pattern of 3,MeHis and creatinine excretion as well as the weight loss suggested the following: 1) the muscle protein breakdown in these patients was approximately twice the normal value (the mean 3,MeHis excretions were respectively 7.98, 7.21, 6.26 and 5.14 mumol X kg-1 X 24 h-1 for the four week study period, compared with the normal value of 3.73); 2) the creatinine excretion decreased slowly. This showed the magnitude of muscle wasting in these patients who, in one month, could lose up to 20% of their initial weight. Various factors could be responsible for increasing and extending the muscle protein catabolism: the importance of muscle damage, the metabolic response to neurotrauma, sepsis and prolonged immobilization. In these conditions, it would seem useless and even harmful to try, at all costs, to obtain a positive nitrogen balance. The authors suggest therefore an average intake of 0.2 g X kg-1 X 24 h-1 of nitrogen, which should be sufficient to meet the requirements for protein synthesis.
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PMID:[Urinary excretion of creatinine and 3-methylhistidine in multiply injured patients]. 651 97

Management of protein-calorie malnutrition found in 32 patients with severe liver diseases such as fulminant hepatitis and cirrhosis of the liver was carried out using 2 types of synthetic amino acid solution (Hep-OU and Fischer solution) for intravenous and enteral alimentations with rapid monitoring of serum aminogram. Intravenous hyperalimentation of these cases resulted in maintenance of nutritional status with improvement of nitrogen balance and normalization of impaired serum aminogram. During this study, however, nutritional support was initiated only when intractable ascites, upper gastrointestinal bleeding and hepatic encephalopathy were observed. In 2 cases of fulminant hepatitis with sepsis and 3 hepatoma patients with ascites, elemental diet containing maltose and amino acids was used to supply sufficient amounts of nutrients in a minimum volume of water. These techniques with simultaneous monitoring of urinary excretion of 3-methylhistidine and creatinine height index as nutritional parameters make nutritional management easy for patients with liver disease.
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PMID:Nutritional management of patients with severe liver disease by using intravenous hyperalimentation and elemental diet. 676 41

The urinary 3-methylhistidine (3-MH) and creatine excretion were measured serially in two patients on total parenteral nutrition for 201 and 225 days, respectively. Variations in excretion were related to clinical events, such as sepsis; 3-MH excretion and the 3-MH:creatinine ratio were raised in association with some episodes of infection, but not all. It is concluded that, although infection is often associated with increased myofibrillar protein breakdown, this is not always the case. It is suggested that in susceptible patients a high 3-MH:creatine ratio may indicate occult infection not detectable by other means.
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PMID:Urinary 3-methylhistidine:creatinine ratio in patients on long-term parenteral nutrition. 677 9

The urinary excretion of 3-methylhistidine (3 MEH) has been shown to be a reliable index of muscle protein breakdown. It is decreased in protein-calorie malnutrition and increased during the hypercatabolic phase of sepsis and thermal trauma. Losses of 3 MEH after moderate to severe skeletal trauma in man and animals are reported as increased or unchanged. To clarify this response, 24 male and 6 female skeletal trauma patients were evaluated for 24 hr urinary losses of 3 MEH, nitrogen and creatinine. Eight of the 24 males also received a catabolic steroid for treatment of a head injury. In addition, 3 male and 1 female septic patients were similarly evaluated. Controls consisted of 10 volunteers on a meat free diet for 4 days and of 8 volunteers who were given only intravenous 5% dextrose in water for 3 days. The 3 MEH excretion for all control males was 3.6 mumole/Kg/day and for females was 2.8 Skeletal trauma produced a 280% increase for the males and a 225% increase for the females. Trauma with steroids caused a 325% increase. Sepsis induced a 227% increase in 3 MEH losses for males and 292% for females during the febrile episode. Creatinine excretion also increased significantly in response to trauma and sepsis but the magnitude of the increase was less than for 3 MEH. This was reflected in the 3 MEH to creatinine molar ratio increase from 0.018 for controls to 0.030-0.040 in sepsis and trauma. Patients with extensive body weight loss showed decreases in 3 MEH and creatinine excretion and a molar ratio similar to controls. The calculated contribution of muscle protein to whole body protein breakdown in the trauma and septic groups showed a twofold increase compared to the control group. The data indicate that the increased muscle protein catabolic response following stress of skeletal trauma and sepsis provides an insight on the origin of the large urinary nitrogen losses following such insults.
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PMID:Urinary excretion of 3-methylhistidine: an assessment of muscle protein catabolism in adult normal subjects and during malnutrition, sepsis, and skeletal trauma. 679 Sep 1

Branched-chain amino acids (BCAAs) may regulate muscle amino acid flux. Metabolic studies of both experimental animals and humans utilizing comparatively large amounts of BCAAs infused with hypocaloric glucose have shown that catabolism and proteolysis can be blunted. These studies suggested that the nitrogen-sparing properties of amino acid solutions used in postoperative trauma or sepsis might be improved by increasing the amount of BCAAs. This hypothesis was tested on ten patients undergoing operations of moderate severity utilizing a peripheral amino acid mixture with a branched-chain:non-branched-chain ratio of 45:55% given in 5% dextrose. The patients received 1.7 gm of protein equivalent/kg of ideal body weight in 5% dextrose-crystalloid solution with a concentration of 3.5% amino acids for the first 5 postoperative days. Nitrogen balance, 3-methylhistidine excretion, blood chemistries, and plasma amino acid profile tests were done daily. The results showed that nitrogen equilibrium was maintained for 5 postoperative days without any untoward effects on patients, their surgical wounds, or hepatic function. Plasma amino acids showed no significant changes from baseline with the exception of elevations of the BCAAs. We conclude that this 45% BCAA-enriched solution may be safely administered to patients with postoperative traumatic injury and results in nitrogen equilibrium over a 5-day period.
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PMID:The effect of a new branched chain--enriched amino acid solution on postoperative catabolism. 681 32


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