Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0243026 (sepsis)
 52,417 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in protein kinase A (PKA, or cAMP-dependent protein kinase) activity in the rat liver during different metabolic phases of sepsis were investigated. Sepsis was induced by cecal ligation and puncture (CLP). Experiments were divided into 3 groups: control, early sepsis, and late sepsis. Early and late sepsis refer to those animals killed at 9 and 18 h, respectively, after CLP. Hepatic PKA was extracted and partially purified by acid precipitation, ammonium sulfate fractionation, and diethylaminoethyl (DEAE)-cellulose chromatography. PKA was eluted from DEAE-cellulose column with a linear NaCl gradient. Two peaks of PKA, type I (eluted at low ionic strength) and type II (eluted at high ionic strength), were collected and their activities were determined on the basis of the rate of incorporation of [gamma-32-P]ATP into histone. The results show that during early sepsis, both type I and type II PKA activities remained unchanged. During late sepsis, type I PKA activity was decreased by 40.7-53.6%, whereas type II PKA activity was unaffected. Kinetic analysis of the data on type I PKA during the late phase of sepsis reveals that the Vmax (maximal velocity) values for ATP, cAMP, and histone were decreased by 40.7, 53.6, and 47.3%, respectively whereas the Km (substrate concentration required for half-maximal enzymatic activity) values for ATP, cAMP, and histone were unaltered. These data indicate that type I PKA was inactivated during the late hypoglycemic phase of sepsis in the rat liver. Because PKA-mediated phosphorylation plays an important role in the regulation of hepatic glucose metabolism, an inactivation of PKA may contribute to the development of hypoglycemia during the late phase of sepsis.
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PMID:Liver protein kinase A activity is decreased during the late hypoglycemic phase of sepsis. 1050 29

Acrodermatitis enteropathica is characterized by eczematous and scaly plaques on the face, scalp, acral, and anogenital regions. In addition to typical lesions, unusual prominent vesiculobullous lesions are also described. We report a full-term, 9-month-old boy who has acrodermatitis enteropathica and Pseudomonas sepsis. In this patient there were clinical findings of sepsis and eczematous vesiculobullous lesions on the periorificial and acral areas. Serum zinc level was extremely low. Pseudomonas aeruginosa was identified in cultures of blood and fluid which was aspirated from the bullous lesions. After oral zinc sulfate and intravenous antibiotic treatment his condition improved within 2 weeks.
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PMID:Acrodermatitis enteropathica with Pseudomonas aeruginosa sepsis. 1063 41

Inter-alpha-inhibitor (IalphaI) is a human plasma serine proteinase inhibitor. It contains one light peptide chain called bikunin that exerts antiproteinase activity and other antiinflammatory functions. Bikunin is covalently linked to two heavy chains that, after tissular diffusion, stabilize the extracellular matrix. Owing to its negative acute-phase reactant character and its susceptibility to proteolysis, IalphaI has been implicated in the pathophysiology of sepsis. Moreover, IalphaI has been shown to exert a protective effect on a pig model of endotoxic shock. Twenty patients admitted to the intensive care unit (ICU) for a septic syndrome were included in the present study. IalphaI and antithrombin III (ATIII) levels were measured on admission. Sequential measurements of IalphaI could be done in 4 patients. We demonstrate that IalphaI levels are significantly decreased in plasma samples collected on admission from patients with sepsis (59 +/- 32 mg/L vs 241 +/- 70 mg/L; P < .0001). This decrease was greater in severe sepsis and septic shock than in sepsis. Death was not predictable from initiol IalphaI levels. In 2 patients with a favorable course, IalphaI values regularly increased during the ICU stay. By sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by immunoblot analysis and microsequencing, we characterized IalphaI-related components in plasma from several patients; they obviously arise from IalphaI through proteolytic cleavage. Thus, systemic proteolysis and decreased biosynthesis both contribute to the fall in the plasma level of IalphaI. Because IalphaI is very sensitive to proteolysis by polymorphonuclear granulocytes (PMNs) that are stimulated during sepsis, we suggest that IalphaI plasma level would be a useful marker for neutrophil proteinase activity. ATIII, as well as IalphaI, is considered a negative acute phase protein. Because in vitro ATIII is less susceptible than IalphaI to proteolysis by PMNs and because their relative levels weakly correlated, we suggest that an unspecific systemic proteolysis is not significantly involved in the ATIII deficiency occurring in sepsis.
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PMID:Inflammation-induced systemic proteolysis of inter-alpha-inhibitor in plasma from patients with sepsis. 1069 65

Impaired vascular responsiveness in sepsis may lead to maldistribution of blood flow in organs. We hypothesized that increased production of nitric oxide (NO) via inducible nitric oxide synthase (iNOS) mediates the impaired dilation to ACh in sepsis. Using a 24-h cecal ligation and perforation (CLP) model of sepsis, we measured changes in arteriolar diameter and in red blood cell velocity (V(RBC)) in a capillary fed by the arteriole, following application of ACh to terminal arterioles of rat hindlimb muscle. Sepsis attenuated both ACh-stimulated dilation and V(RBC) increase. In control rats, arteriolar pretreatment with the NO donors S-nitroso-N-acetylpenicillamine or sodium nitroprusside reduced diameter and V(RBC) responses to a level that mimicked sepsis. In septic rats, arteriolar pretreatment with the "selective" iNOS blockers aminoguanidine (AG) or S-methylisothiourea sulfate (SMT) restored the responses to the control level. The putative neuronal NOS (nNOS) inhibitor 7-nitroindazole also restored the response toward control. At 24-h post-CLP, muscles showed no reduction of endothelial NOS (eNOS), elevation of nNOS, and, surprisingly, no induction of iNOS protein; calcium-dependent constitutive NOS (eNOS+nNOS) enzyme activity was increased whereas calcium-independent iNOS activity was negligible. We conclude that 1) AG and SMT inhibit nNOS activity in septic skeletal muscle, 2) NO could impair vasodilative responses in control and septic rats, and 3) the source of increased endogenous NO in septic muscle is likely upregulated nNOS rather than iNOS. Thus agents released from the blood vessel milieu (e.g., NO produced by skeletal muscle nNOS) could affect vascular responsiveness.
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PMID:Nitric oxide produced via neuronal NOS may impair vasodilatation in septic rat skeletal muscle. 1077 25

Endothelial cells have two important anticoagulant systems, heparan sulfate-antithrombin system and thrombomodulin-protein C system. Under physiological conditions, these two systems inhibit activation of coagulation on endothelial cells. However, under inflammatory conditions, tumor necrosis factor(TNF)-alpha or other cytokines produced by monocytes reduce the anticoagulant properties of endothelial cell by downregulating expression of heparan sulfate and thrombomodulin on endothelial cells. Antithrombin stimulates prostacyclin generation from endothelial cells by interacting with heparan sulfate of endothelial cells and generated prostacyclin inhibits TNF-alpha production by monocytes. Activated protein C inhibits TNF-alpha production by monocyte dependent of its protease activity. Thus, antithrombin and activated protein C might inhibit the endothelial perturbation induced by cytokines. Antithrombin regulates TNF-alpha induced tissue factor expression on endothelial cells by an unknown mechanism. Thus, antithrombin and activated protein C might be useful agents for treating coagulation abnormalities associated with sepsis or other inflammation because these agents inhibit not only coagulation but also downregulation of anticoagulant activities of endothelial cells.
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PMID:[Endothelial cells and coagulation abnormalities]. 1081 Aug 75

In this study, 72 newborn infants who were followed with the diagnosis of poisoning in Erciyes University Faculty of Medicine, Department of Pediatrics, Division of Neonatology, between 1975 and 1997 were evaluated retrospectively. Our purpose was to emphasize the importance of newborn poisoning among general poisoning in childhood. The age of infants ranged from 10 min to 25 days (0.82 +/- 2.81 days). Forty-seven (65.2%) infants were poisoned before or during delivery. Of the 47 infants' mothers, 46 had preeclampsia or eclampsia, and 27 received only magnesium sulfate; nine magnesium sulfate + diazepam; four magnesium sulfate + nifedipine; and the others received various drug combinations. Aside from these, one mother had Addison's disease and she used long-term dexamethasone during her pregnancy. In the newborn period, five (6.9%) infants inhaled organophosphate insecticides; eight (11.1%) ingested corrosive agents (four benzalkonium chloride; three chlorhexidine gluconate + cetrimide and an infant ammonium); four (5.5%) were poisoned by overdose of digoxin; three (4.1%) ingested overdose of phenobarbital; and two (2.7%) received acepromazine maleate. In addition, each infant ingested diphenoxilate HCL + atropine sulfate, pipenzolate bromid and tizanidine HCL. Follow-up period of the infants ranged from 24 hr to 26 days (0.82 +/- 2.81 days). The mortality rate was 17% (12/72). Death was not noted in the infants who were followed with poisoning after delivery. The causes of death were as follows: sepsis in four infants, meningitis, respiratory distress syndrome and necrotizing enterocolitis in two infants each, and the effects of overdose of magnesium sulfate and diazepam in two infants, respectively. In conclusion, we would like to stress that newborn infants whose mothers received magnesium sulfate or another drug during pregnancy or delivery should be closely monitored, and calculation of drug doses should be carefully taught to hospital nurses. When baby-rooms are disinfected with organophosphate insecticides in a hospital or house, infants should be removed from the room for at least 24 hr, and use of drugs should be explained in detail to the mothers.
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PMID:Neonatal poisonings in middle Anatolia of Turkey: an analysis of 72 cases. 1084 89

Escherichia coli is a gram-negative bacterium that causes sepsis and infections of the nervous system, and the digestive and urinary tracts. The availability of the complete nucleotide sequence encoding the E. coli K-12 genome has made this organism an excellent model for proteomic studies. Semi-preparative two-dimensional electrophoresis, including liquid phase isoelectric focusing (IEF), one-dimensional sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) and gel elution, have for the first time been used in combination with matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOFMS), electrospray tandem mass spectrometry and database searching for rapid separation of proteins from a uropathogenic strain of E. coli. The identity of 30 proteins, including the membrane protein nmpC, was obtained using this approach.
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PMID:Identification of proteins from Escherichia coli using two-dimensional semi-preparative electrophoresis and mass spectrometry. 1129 Nov 21

We evaluated the efficacy of combination therapy with sulbactam/cefoperazone (SBT/CPZ) and amikacin sulfate (AMK) in eligible patients with hematological disorders of neutrophil count less than 1,000/microliter. The clinical efficacy rate in 157 evaluated patients was 65.6%. The clinical efficacy rates were related to neutrophil counts and serum albumin levels at the 1 week later. The clinical efficacy rates were 87.1% in patients with neutrophil counts over 500/microliter and 34.8% in patients with serum albumin levels under 3 g/dl after 1 week. G-CSF treatment were not significant but tended to be more effective in patients with sepsis, and the neutrophil counts increased significantly. The group using G-CSF before the antibiotic treatment had a high clinical efficacy rate. It is suggested that G-CSF is effective in patients with neutropenia with the high risk to infection and in those who already have severe infections.
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PMID:[Clinical analysis of neutropenic fever associated with hematological disorders]. 1132 78

This is a report of a 54-year-old schizophrenic patient with a 15-year history of ingesting metal objects (pica). He presented with severe anemia (hemoglobin of 3 g/dl and hematocrit of 8.3%) and leukopenia (white blood count of 1,300/mm3). Work-up revealed copper deficiency (copper level of <0.05 microg/ml) and elevated zinc levels (280 microg/ml). The zinc toxicity was produced by the zinc content in the coins ingested by the patient over a period of many years. He was initially treated with -acetylcysteine and sodium bicarbonate followed by intravenous copper sulfate. He was also placed on Adolph's meat tenderizer and pancreatin thrice a day orally to loosen the massive amount of metallic objects including coins in his bowel and allow them to pass out in his feces. He was also continued on oral copper sulfate. His copper levels began to rise and reached a maximum of 0.72 microg/ml, and his zinc level fell to 153 microg/ml. However, as he refused surgery to remove the metal objects from his bowel and continued to ingest more coins, there was continued absorption of zinc, which later overcame the efforts to reduce the zinc level and increase copper levels in his blood. He finally succumbed to sepsis and multiorgan failure. Autopsy revealed a coin mass in the stomach weighing 1,870 grams in addition to a sigmoid volvulus caused by another coin bezoar in the colon.
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PMID:Case report of sideroblastic anemia caused by ingestion of coins. 1142 Dec 92

To determine the relative contribution of lipopolysaccharide (LPS) and non-LPS components of Neisseria meningitidis to the pathogenesis of meningococcal sepsis, this study quantitatively compared cytokine induction by isolated LPS, wild-type serogroup B meningococci (strain H44/76), and LPS-deficient mutant meningococci (strain H44/76[pLAK33]). Stimulation of human peripheral-blood mononuclear cells with wild-type and LPS-deficient meningococci showed that non-LPS components of meningococci are responsible for a substantial part of tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta production and virtually all interferon (IFN)-gamma production. Based on tricine sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of LPS in proteinase K-treated lysates of N. meningitidis H44/76, a quantitative comparison was made between the cytokine-inducing capacity of isolated and purified LPS and LPS-containing meningococci. At concentrations of >10(7) bacteria/mL, intact bacteria were more potent cytokine inductors than equivalent amounts of isolated LPS, and cytokine induction by non-LPS components was additive to that by LPS. Experiments with mice showed that non-LPS components of meningococci were able to induce cytokine production and mortality. The principal conclusion is that non-LPS parts of N. meningitidis may play a role in the pathogenesis of meningococcal sepsis by inducing substantial TNF-alpha, IL-1beta, and IFN-gamma production.
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PMID:Contributions of Neisseria meningitidis LPS and non-LPS to proinflammatory cytokine response. 1149 21


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