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)

Peritonitis in rats was produced by cecal ligation and puncture. Sixteen hours following cecal ligation and puncture, the gangrenous cecum was removed and the animals received either 4 ml saline (nontreated), 0.75 ATP-MgCl2 (100 mumoles ATP plus 50 mumoles MgCl2), and 2.0 ml of 50% glucose or 2.0 ml of 50% mannitol and 1.25 ml saline. Two hours after the removal of the cecum, RES function was evaluated by measuring the intravascular clearance of a 131 I triolein-labeled gelatinized test lipid emulsion. The intravascular half-time (t1/2) in the nontreated animals was double that of sham-operated animals, suggesting that significant depression in RES function occurred during sepsis. Administration of ATP-MgCl2 plus glucose following sepsis resulted in t1/2 values similar to those of sham-operated animals, indicating that the impairment of pagocytic activity of the RES was reversed with treatment. The beneficial effect of treatment following sepsis does not appear to be due to hypertonicity, since administration of 50% mannitol failed to decrease the t1/2. The precise mechanism of the beneficial effect of ATP-MgCl2 + glucose on restoration of RES function is not known.
 ...
PMID:Impairment of reticuloendothelial system function with sepsis and its improvement with ATP-MgCl2 plus glucose administration. 26

The effects of sepsis on the ATP-dependent Ca2+ transport in rat liver plasma membranes were investigated. Sepsis was induced by cecal ligation and puncture (CLP). Control rats were sham-operated. The results show that the ATP-dependent Ca2+ transport by liver plasma membranes was not affected during early sepsis (9 hr after CLP) but was decreased by 30-50% (P < 0.05) during late sepsis (18 hr after CLP). Kinetic analysis of the data indicates that during late sepsis, the Vmax values for ATP and for Ca2+ were decreased by 38.5% (P < 0.05) and 41.8% (P < 0.05), respectively, while the Km values for ATP and Ca2+ remained unchanged. Mg2+ stimulated ATP-dependent Ca2+ transport. The Mg(2+)-stimulated activity was unaffected during early sepsis but was decreased by 34-63% (P < 0.05) during late sepsis. These data demonstrate that ATP-dependent Ca2+ transport in rat liver plasma membranes was impaired during late sepsis and that the impairment is associated with a mechanism not affecting the affinity of the Ca2+ transporter for ATP and Ca2+. Since plasma membrane ATP-dependent Ca2+ transport plays an important role in the regulation of intracellular Ca2+ homeostasis in hepatocytes, an impairment in the ATP-dependent Ca2+ transport by liver plasma membranes during late sepsis may have a pathophysiological significance in contributing to the development of altered hepatic metabolism during septic shock.
 ...
PMID:Calcium transport by rat liver plasma membranes during sepsis. 129 87

The covalent modification of receptor proteins via phosphorylation and dephosphorylation is one of the principal mechanisms controlling carbohydrate metabolism and is known to be regulated by various protein kinases. Recent studies indicated that many hormones may exert their effects on cellular metabolism by regulating intracellular c-AMP levels and by activating a c-AMP dependent protein kinase, i.e., protein kinase A. The metabolic disturbances during sepsis are characterized by an initial hyperglycemia followed by a progressive hypoglycemia and a depletion of hepatic glycogen content. The latter is coupled with a slowdown in glycogenesis, an accelerated glycogenolysis, and a depression in gluconeogenesis in the liver. Since the liver is the major organ that regulates the homeostatic level of blood glucose, it is conceivable that the sepsis-induced glucose dyshomeostasis might be mediated by changes in protein kinase activity and the kinetic characteristics of enzymes. The present experiment was designed to study the correlation between protein kinase A and the pathophysiology of hepatic glucose dyshomeostasis during sepsis. Sepsis was induced in rats by cecal ligation and puncture (CLP). Late sepsis occurred 18 hours after CLP. Protein kinase A was extracted from the rat livers by acid precipitation and ammonium sulfate fractionation, and then partially purified by DEAE-cellulose. The results show that in the late sepsis, type-I protein kinase A (eluted at low ionic strength) activity was significantly decreased by 34-52% (P < 0.01). The kinetic parameters such as Vmax's for ATP, histone, and c-AMP were also significantly decreased from the control values of 6.1 +/- 0.9, 5.4 +/- 0.8, and 5.1 +/- 1.9 nmoles/mg.min. to 3.6 +/- 0.5, 2.8 +/- 0.3, and 2.5 +/- 0.5 nmoles/mg.min., respectively. Analysis using Hill's equation indicates that the S0.5 and n (Hill coefficient) values of the various substrates and activators for type-I protein kinase A remained unchanged. In the case of type-II protein kinase A (eluted at high ionic strength), the Vmax, S0.5, and n values for ATP, histone, and c-AMP were unchanged during late sepsis. The results of the present study indicate that the activities and kinetic characteristics of type I protein kinase A in rat liver are modified during late sepsis. Since protein kinase A is known to regulate glucose metabolism through adrenergic receptor mediation, these findings may have a pathophysiological significance in the understanding of hepatic glucose dyshomeostasis during sepsis.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:[Kinetic studies of protein kinase A in rat liver during late sepsis]. 129 61

Recent investigations from our and other laboratories indicate that glycogen is a carbon-chain precursor in muscle for the synthesis of TCA cycle intermediates and glutamine. During intense exercise and in conditions of a relative lack of energy (hypoxia, trauma, sepsis) the metabolism of branched-chain amino acids (BCAA) is accelerated in muscle. In the primary BCAA aminotransferase reaction 2-oxoglutarate is used as amino-group acceptor (putting a carbon-drain on the TCA cycle) under formation of glutamate. Glutamate will subsequently react with ammonia, generated in the AMP deaminase reaction or by deamination of amino acids, under formation of glutamine in a reaction catalysed by glutamine synthetase (glutamate + ammonia + ATP--> glutamine + ADP). Muscle glycogen stores may be smaller or less available at high altitude. It is hypothesized that this will lead to premature fatigue (due to both a lack of fuel and of TCA cycle carbon-precursor) and to a reduction in the synthesis rate of glutamine. A chronic reduction in the synthesis rate of glutamine during a long term stay at high altitude on its turn may lead to gut atrophy, bacterial translocation, endotoxemia, muscle protein catabolism and a weakened immune status.
 ...
PMID:Amino acid metabolism, muscular fatigue and muscle wasting. Speculations on adaptations at high altitude. 148 45

In the conclusion of this series of reports, the application of 31P/2H NMR to investigate the pathophysiology of sepsis in rat hindlimb muscle is demonstrated. Sepsis decreased muscle [PCr] by 18%, 18 +/- 4 SD vs 22 +/- 4 SD mmol/kg tissue wet wt (P = 0.01) in control rats but [ATP] was unchanged, 6 mmol/kg tissue wet wt (P = 0.2). The derived free cytosolic [ADP] in the two groups was similar, [ADP]septic = 0.023 +/- 0.004 SD and [ADP]control = 0.021 +/- 0.003 SD mmol/kg tissue wet wt, and not statistically different (P = 0.14). Likewise [Pi] in the septic and control groups was not statistically different, [Pi]septic = 1.1 +/- 0.5 SD and [Pi]control = 1.2 +/- 0.4 SD mmol/kg tissue wet wt (P = 0.2). Septic rats presented the symptom of respiratory alkalosis evidenced by elevated blood pH. Sepsis decreased muscle blood flow by 33%, P = 0.003, but examination of individual subjects did not demonstrate a correlation with the reduction in [PCr]. Thus, a metabolic energy deficit caused by cellular ischemia/hypoxia is not a likely cause of cellular abnormality in rat hindlimb muscle during sepsis.
 ...
PMID:Concurrent quantification of tissue metabolism and blood flow via 2H/31P NMR in vivo. III. Alterations of muscle blood flow and metabolism during sepsis. 159 58

Hepatocellular dysfunction, as a result of sepsis or endotoxemia, plays a critical role in the pathogenesis of multiple systems organ failure. Conventional methods to assay hepatic ATP require large tissue samples, making repeat measurements in the same animal impossible, and are unable to detect the minimal changes in metabolism consistent with early or reversible cellular injury. 31P NMR is a modality available for the in vivo measurement of high energy phosphates. Inorganic phosphate (Pi) and phosphomonoester (PME) ratios (markers of cellular metabolism and viability) as well as fractionated ATP may be repeatedly quantitated. To assess the early effects of endotoxemia on hepatic function, phosphorus spectra of the liver were obtained using a 1.7-cm surface coil in six rats after the ip administration of 4 mg/kg Escherichia coli lipopolysaccharide. Conventional assay was performed on 24 matched controls. Pi, PME, alpha-, beta-, and gamma-ATP peaks (expressed as percentage total signal area) were collected over 20 min, integrated, and analyzed. Pi/beta-ATP decreased over time until 6 hr reflecting ongoing uptake of inorganic phosphate and continued cellular metabolism. PME/beta-ATP ratios, which indicate cellular viability, became significantly elevated at 6 hr. Using 31P NMR, beta-ATP best reflected the early subtle energy changes present prior to cell death and subsequent organ failure with significant decreases at 2, 4, and 6 hr. Conventional assay for ATP confirmed similar trends. We conclude that 31P NMR is a valuable tool for the study of reversible hepatic energy changes during early endotoxemia.
 ...
PMID:In vivo [31P]NMR assessment of early hepatocellular dysfunction during endotoxemia. 161 20

The polysialic acid capsule of Escherichia coli K1, a causative agent of neonatal septicemia and meningitis, is an essential virulence determinant. The 17-kb kps gene cluster, which is divided into three functionally distinct regions, encodes proteins necessary for polymer synthesis and expression at the cell surface. The central region, 2, encodes products required for synthesis, activation, and polymerization of sialic acid, while flanking regions, 1 and 3, are thought to be involved in polymer assembly and transport. In this study, we identified two genes in region 3, kpsM and kpsT, which encode proteins with predicted sizes of 29.6 and 24.9 kDa, respectively. The hydrophobicity profile of KpsM suggests that it is an integral membrane protein, while KpsT contains a consensus ATP-binding domain. KpsM and KpsT belong to a family of prokaryotic and eukaryotic proteins involved with a variety of biological processes, including membrane transport. A previously described kpsT chromosomal mutant that accumulates intracellular polysialic acid was characterized and could be complemented in trans. Results of site-directed mutagenesis of the putative ATP-binding domain of KpsT are consistent with the view that KpsT is a nucleotide-binding protein. KpsM and KpsT have significant similarity to BexB and BexA, two proteins that are essential for polysaccharide capsule expression in Haemophilus influenzae type b. We propose that KpsM and KpsT constitute a system for transport of polysialic acid across the cytoplasmic membrane.
 ...
PMID:Identification of two genes, kpsM and kpsT, in region 3 of the polysialic acid gene cluster of Escherichia coli K1. 185 62

Our previous experimental studies showed that the liver is firstly and most severely involved in metabolic damage among various organs after hypoperfusion and sepsis. Changes of metabolites in liver and other organs as well as the function of circulating leukocytes were measured in three rat models with liver ischemia, or systemic hypoperfusion and sepsis. Partial liver ischemia 120 minutes after reperfusion not only resulted in significant decline of ATP and GSH levels in ischemic liver lobes but also in metabolic disorders in non-ischemic liver lobes, kidney, and small intestine. The amount of circulating white blood cells and zymosan stimulated chemoluminescence was increased. The findings showed that ischemic injury in partial liver may accelerate the whole liver damage and aggravate the metabolic disorders in other organs as well as the deterioration of homeostasis. Changes of liver sulfhydryl group levels and related metabolism were estimated. Significant decrease in liver sulfhydryl group levels during hypoperfusion and sepsis may contribute to various cellular metabolic disorders and destruction in early liver damage.
 ...
PMID:[The liver in the pathogenesis of multiple organ failure]. 191 99

The effect of sterile inflammation and sepsis on the proportion of active pyruvate dehydrogenase complex (PDH) in mitochondria isolated from skeletal muscle has been investigated. The proportion of active PDH in mitochondria isolated from septic animals was significantly reduced compared with control under all incubation conditions examined, even in the presence of inhibitors of the PDH kinase. There was no significant difference between control and sterile inflammation in any of the incubations examined. The rate constant for ATP-dependent inactivation of the PDH complex in mitochondrial extracts from control animals was -0.42 min-1 (r = 0.993; P less than 0.001) and was not altered in mitochondrial extracts from sterile inflammatory animals (-0.43 min-1; r = 0.999; P less than 0.001). However, rate constants for inactivation in septic animals was significantly increased over twofold to -1.08 min-1 (r = 0.987; P less than 0.001) (P less than 0.001 vs. control or sterile inflammation). In the presence of inhibitors of the PDH kinase reaction (2.5 mM pyruvate or 1 mM dichloroacetate), inactivation of PDH after addition of ATP was significantly greater in mitochondrial extracts from septic than either control or sterile inflammatory animals. These results suggest that sepsis, but not sterile inflammation, induces a stable factor in skeletal muscle mitochondria that increased PDH kinase activity.
 ...
PMID:Increased pyruvate dehydrogenase kinase activity in response to sepsis. 203 22

Cecal ligation and puncture (CLP) were performed in rats. After 4 hr (early sepsis) and 16 hr (late sepsis), platelet morphology and function were studied. At 16 hr, platelet counts for the CLP group were significantly lower than for the sham-operated control group. Low maximum aggregation rates (MAR) and decreased platelet counts were elicited in platelet-rich plasma with 4 M ADP and 2 micrograms/ml collagen. However, with platelet counts equalized, MAR for the CLP group increased significantly, especially after 16 hr. The platelet-large cell rate and platelet distribution width decreased temporarily at 4 hr, then rose significantly at 16 hr. No significant changes were observed in the mean platelet volume after 4 hr, but there were significant increases after 16 hr. Total adenine nucleotide (TAN) levels within the platelets rose significantly in the CLP group, suggesting the appearance during the late sepsis of large, heavy platelets or adenine nucleotide-rich platelets. The platelet adenylate pool was divided into granular and cytoplasmic fractions, respectively characterized by ADP and ATP increases. However, no septicemia-related differences were noted in the degree of binding between goat antirat fibrinogen and platelet surface glycoprotein IIb/IIIa complex. Internal environment changes in the platelets indicated that during septicemia hyperfunctional or hypersensitive platelets with a latent capacity for active aggregation and release appeared in the circulation. Hypercoagulability in septicemia involves activation of coagulation factors, stimulation of the coagulation cascade, volume changes accompanying increased platelet TAN content, and changes in AN distribution in the two pools. These findings significantly increase our understanding of the transition from the prethrombotic state to thrombosis in septicemia.
 ...
PMID:Platelet size and function in septic rats: changes in the adenylate pool. 217 92


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