Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of urinary trypsin inhibitor (UTI) on the number, morphology and function of platelets under septic state were studied in rat models of cecal ligation and puncture (CLP). At formation of CLP, 5,000 U/kg/h of UTI was serially administered intraperitoneally and blood was sampled after 16 hours. Comparative study among sham-operation group, CLP group, and CLP + UTI group revealed: 1) inhibition of the platelets of platelet counts and appearance of large-sized, active platelets by UTI in the CLP + UTI group, 2) increase of platelet maximum aggregation rate (MAR) by ADP and increase of collagen in the CLP group, while inhibition in the CLP + UTI group and 3) by HPLC evaluation of adenine nucleotide in the platelet, increased levels of total ATP and ADP in the CLP group, particularly, increases of ATP in the metabolic pool and ADP in the granular pool. CLP + UTI group did not show these changes in the adenylate pool. UTI was thus considered to stabilize the platelet cycle in sepsis. Platelets under septic state might be hyperactive, and thrombosis is easy to occur. UTI administration might work for maintaining constancy of the platelet internal environment and improve septic state because adenine nucleotide level in the platelet did not change in the CLP + UTI group through changed in the CLP group.
 ...
PMID:[Effects of the administration of urinary trypsin inhibitor on the morphology and function of platelets in the rat septic models]. 232 1

In pursuing the mechanism of endotoxin action, we examined the effect of lipopolysaccharide (LPS) and its chemically defined components, lipid A and lipid X on cultured bovine endothelial cells. We report that LPS and lipid A caused detachment and altered morphology of endothelial cells while lipid X did not. Phorbol myristate acetate, a compound known to activate protein kinase C, also caused endothelial cell detachment. Morphologic changes were readily apparent in the endothelial cells after 6 hours of exposure to lipopolysaccharide (1 microgram/ml); at that time many of the cells had contracted and formed bleblike structures on the surface. Large vacuoles, dense bodies, and pyknotic nuclei were found in the detaching cells, indicating necrosis or cell death. Preceding the morphologic changes and actual detachment, endothelial cell DNA and RNA synthesis was impaired by LPS. The changes in DNA and RNA synthesis occurred within 4 hours of exposure to 1 microgram/ml of LPS when the cells were still able to maintain normal levels of ATP. In addition to the inhibition of nucleic acid synthesis, protein synthesis was inhibited after 6 and 8 hours of LPS exposure. DNA, RNA, and protein synthesis returned to control levels after 24 hours of exposure. Investigation on the cultured bovine endothelial cells as a model for LPS action was useful in that these cells are sensitive to relatively low levels of LPS and the endothelium may be an important target in sepsis.
 ...
PMID:Effects of lipopolysaccharide, lipid A, lipid X, and phorbol ester on cultured bovine endothelial cells. 245 32

An infant with the acute neonatal form of pyruvate carboxylase deficiency (cross-reacting material negative) presented with severe intractable lactic acidosis within 4 h after birth. He also had hyperammonemia, hypercitrullinemia, and hyperlysinemia. Plasma glutamine was not elevated. He had a rapidly deteriorating clinical course with severe liver dysfunction, repeated septicemia and seizures; he was comatose and was on a ventilator throughout; death occurred at 8 wk of age. Skin fibroblast study confirmed the enzyme deficiency. Detailed biochemical parameters and histopathology of the brain and liver are presented. The evidence from this infant suggests that disturbances of intracellular oxaloacetate levels as a result of the primary enzyme defect might also contribute to deficiency in ATP generation which may explain the various other biochemical changes and liver pathology.
 ...
PMID:Biochemical and histologic pathology in an infant with cross-reacting material (negative) pyruvate carboxylase deficiency. 308 60

We investigated the relationship of systemic blood flow to skeletal muscle tissue oxygenation, lactate production, and energy production during rat peritonitis established by cecal ligation and perforation. The study included five sham rats, five septic rats, and five septic rats infused with 5% albumin. Thermodilution cardiac output and skeletal muscle tissue oxygen tension were sequentially measured over a 6 hr interval. At 6 hr the rectus femoris was biopsied. In sham rats, there was no change in cardiac output or tissue oxygen tension. Skeletal muscle lactate/pyruvate ratio was 10.4 +/- 0.6, ATP was 5.39 +/- 0.23 mumol/g and total tissue adenine nucleotides were 6.41 +/- 0.21 mumol/g. In septic rats, significant decreases in cardiac output and tissue oxygen tension were associated with a lactate/pyruvate ratio of 25.7 +/- 3.7, an ATP level of 4.38 +/- 0.08 mumol/g and tissue adenine nucleotides of 5.59 +/- 0.08 mumol/g (P less than 0.01 vs. sham). In albumin infused septic rats, cardiac output and tissue oxygen tension were maintained at control levels. Skeletal muscle lactate/pyruvate ratio was 14.8 +/- 1.0, ATP was 4.70 +/- 0.12 mumol/g and tissue adenine nucleotides were 5.80 +/- 0.12 mumol/g (P less than 0.05 vs. sham). Despite the maintenance of systemic blood flow and tissue oxygenation in albumin infused septic rats, the increase in lactate/pyruvate ratio and decrease in high energy phosphates suggest impaired oxidative metabolism and energy production early in the course of severe sepsis.
 ...
PMID:Early impairment of oxidative metabolism and energy production in severe sepsis. 320 24

In healthy tissues, decreases in oxygen delivery (QO2 = cardiac output X arterial O2 content) do not lower oxygen consumption (VO2) because tissue O2 extraction increases proportionately. When delivery is reduced below a critical threshold, VO2 falls because tissue extraction exceeds a critical threshold, and cannot compensate for the reduction in delivery. In the adult respiratory distress syndrome and perhaps in septicemia, tissue extraction capacity is impaired, leading to O2 supply dependency despite normal or increased overall delivery. This pathologic supply dependency could be caused by a loss in autoregulatory capacity, by disrupted blood flow distribution secondary to peripheral microembolization, or to other factors interfering with efficient tissue distribution of QO2 with respect to VO2. Alternatively, the increased VO2 may be consumed in biochemical pathways not associated with ATP production, or in the production of oxygen radicals or hydrogen peroxide. To the extent this abnormal dependence of VO2 on QO2 reflects tissue hypoxia, clinical interventions which decrease systemic delivery should be evaluated with regard to possible deleterious effects on organ system function.
 ...
PMID:The concept of a critical oxygen delivery. 330 69

Recent experimental studies have demonstrated that gastric mucosal blood flow is an essential factor in mucosal defense against acute ulceration. Clinically, most patients who develop stress ulcers have experienced an episode of shock from hemorrhage, sepsis, or cardiac dysfunction. Diminished mucosal blood flow is also a common denominator in animal experiments that employ restraint, hemorrhage, or endotoxemia for the production of acute lesions. The mechanisms by which ischemia produces ulceration have been examined extensively. The leading hypothesis is that gastric mucosal blood flow plays an important role in the disposal, or buffering, of the H+ entering the tissue. Ischemia reduces the capacity of the gastric mucosa to neutralize acid that enters the tissue. This, in turn, leads to accumulation of H+ within the tissue, mucosal acidification, and ulceration. Ischemia may also render the stomach more susceptible to acute ulceration by a severe energy deficit of the gastric mucosa. Using a rat hemorrhagic shock model, a series of experiments demonstrated a profound reduction in mucosal ATP and other high-energy phosphate intermediates that coincided with the development of epithelial cell necrosis. In recent years, many of these experimental observations have been applied clinically in the management of critically ill patients at high risk for development of stress lesions. These include the correction of abnormalities in cardiac output and intravascular volume, careful attention to systemic acid-base balance, adequate nutritional support, and the use of antacids or antisecretory agents. As a result of these preventive measurements, the incidence and prevalence of stress ulcers have decreased significantly in recent years.
 ...
PMID:Gastric blood flow and mucosal defense mechanisms. 330 51

Protein synthesis and degradation are particularly sensitive to malnutrition and catabolic states. Intracellular protein degradation is determined by the conformation, molecular weight, isoelectric point, and carbohydrate content of the proteins. ATP-stimulated endoproteases appear to catalyse the rate-limiting steps. In the liver, proteolysis is reduced by amino acids and/or insulin, whereas glucagon stimulates protein degradation, probably due to depletion of intracellular gluconeogenic amino acids. In the muscle, protein degradation is promoted by interleukin-1 and inhibited by Ep-475, which specifically inactivates cathepsin B,H, and L. Myofibrillar alkaline proteinase activity increases postoperatively and in patients suffering from malignant tumors, whereas normal proteinase values were observed in these patients following total parenteral nutrition. Increased alkaline proteinase activity is also observed in diabetes mellitus and is normalized by insulin. Extracellular proteolysis has been reported in patients with hypercatabolic acute renal failure and in patients with sepsis or acute pancreatitis. Plasma fractions obtained from hypercatabolic patients with postoperative acute renal failure were proteolytic. Plasma proteinase activity decreases during hemodialysis due to elimination of a metallo-proteinase. Plasma alpha 2-macroglobulin decreases in patients with acute renal failure and also during acute pancreatitis. Proteolytic degradation of parathyroid hormone by sera obtained from patients with acute pancreatitis has been observed. Also, there is a decrease of high molecular weight kininogen during experimental acute pancreatitis. Granulocyte elastase increases postoperatively, mainly in patients with sepsis. Sepsis also causes increased proteolytic activity in the urine. In conclusion, intracellular protein degradation can supply important precursors for hepatic and renal gluconeogenesis during malnutrition.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Proteinases in catabolism and malnutrition. 331

Chronic sepsis is always associated with profound wasting leading to increased release of amino acids from skeletal muscle. Net protein catabolism may be due to decreased rate of synthesis, increased rate of degradation, or both. To determine whether protein synthesis is altered in chronic sepsis, the rate of protein synthesis in vivo was estimated by measuring the incorporation of [3H]-phenylalanine in skeletal muscle protein in a chronic (5-day) septic rat model induced by creation of a stable intra-abdominal abscess using an E. coli + B. fragilis-infected sterile fecal-agar pellet as foreign body nidus. Septic rats failed to gain weight at rates similar to control animals, therefore control animals were weight matched to the septic animals. The skeletal muscle protein content in septic animals was significantly reduced relative to control animals (0.18 +/- 0.01 vs. 0.21 +/- 0.01 mg protein/gm wet wt; p less than 0.02). The rate of incorporation of [3H]-phenylalanine into skeletal muscle protein from control animals was 39 +/- 4 nmole/gm wet wt/hr or a fractional synthetic rate of 5.2 +/- 0.5%/day. In contrast to control animals, the fractional synthetic rate in septic animals (2.6 +/- 0.2%/day) was reduced by 50% compared to control animals (p less than 0.005). The decreased rate of protein synthesis in sepsis was not due to an energy deficit, as high-energy phosphates and ATP/ADP ratio were not altered. This decrease in protein synthesis occurred even though septic animals consumed as much food as control animals.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Inhibition of skeletal muscle protein synthesis in septic intra-abdominal abscess. 339 97

The effect of chronic sepsis on the concentration of active pyruvate dehydrogenase complex has been investigated in liver and skeletal muscle of normal, sterile inflammatory, and chronic septic (small and large abscess) animals. Hyperdynamic sepsis was induced by the intraperitoneal introduction of a rat fecal-agar pellet of known size and bacterial composition (Escherichia coli + Bacteroides fragilis). Total pyruvate dehydrogenase complex activity was not altered in either liver or skeletal muscle in any of the conditions studied. In hepatic tissue, sterile inflammation increased the proportion of active complex 2.5-fold compared with control. The same increase in the concentration of active complex was observed in animals with a small abscess. When the abscess size was increased (large abscess), the concentration of active complex was decreased relative to sterile inflammatory or small abscess septic animals. In contrast to liver, sterile inflammation did not alter the proportion of active complex in skeletal muscle. Sepsis (either small or large septic abscess) resulted in threefold decrease in the concentration of active complex relative to control or sterile inflammatory animals. Changes in the concentration of active complex did not appear to be dependent on the ATP/ADP concentration ratio or tissue pyruvate levels but were consistent with changes in the acetyl-coenzyme A-to-coenzyme A concentration ratio. The mechanism responsible for altered concentration of active complex may be mediated through changes in the activity of the pyruvate dehydrogenase kinase, secondary to alterations in the effector concentration ratios.
 ...
PMID:Effect of sepsis on activity of pyruvate dehydrogenase complex in skeletal muscle and liver. 352 10

In the present study protein synthesis and energy level in liver tissue were studied in bacteremic rats following intravenous infusion of 8 +/- 4 X 10(9) live E. coli bacteria and in control animals receiving a corresponding infusion of sterile saline. For the study of protein synthesis, liver slices were incubated in a medium containing 14C-leucine and incorporation rate of amino acid into protein was determined. Hepatic concentrations of ATP, ADP, and AMP were measured and energy charge (EC) was calculated. Twenty-four hours after infusion of E. coli, hepatic protein synthesis rate was 55% higher than in control animals. Liver weight and hepatic protein content were also increased in bacteremic animals. There were no significant differences in adenine nucleotide levels or EC in liver tissue between control and bacteremic animals. Since impairment of various other liver functions has been reported during sepsis, the present results suggest that hepatic protein synthesis has high priority in this condition.
 ...
PMID:Protein and energy metabolism in liver tissue following intravenous infusion of live E. coli bacteria in rats. 354 30


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>