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)

A right-sided renal mass in an 11-month-old girl was diagnosed by percutaneous needle biopsy as Wilms tumor, which on histologic examination was found to be predominantly rhabdomyomatous. As part of the examination, serum creatine kinase (CK) and CK-MB levels were measured and were significantly elevated at 994 U/L (reference range, 42-180 U/L) and 40 U/L (reference range, 0-3 U/L), respectively. Subsequently, an 8-month-old girl was admitted to the hospital with septicemia and was found to have an abdominal mass. A diagnosis of bilateral Wilms tumor was made following percutaneous biopsy of both kidneys; histologic examination confirmed that the tumor was predominantly rhabdomyomatous. Serum CK and CK-MB levels also were measured and were significantly elevated at 685 U/L and 84.4 U/L, respectively. In both cases, the serum CK and CK-MB levels reflected the clinical course; elevation in serum levels was associated with tumor recurrence, infarction, or chemotherapy-related necrosis. We conclude that these enzymes have clinical usefulness as markers for Wilms tumor showing rhabdomyomatous morphologic features.
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PMID:Serum creatine kinase levels parallel the clinical course for rhabdomyomatous Wilms tumor. 1155 63

The present study was designed to test the hypothesis that induction of chronic peritoneal sepsis in rats would produce a more severe calcium paradox-mediated myocardial injury in isolated heart preparation than is seen in normal hearts, and that this would be inhibited by sucrose as in normal hearts. Male Sprague-Dawley rats were made septic using 200 mg of cecal material (obtained from a donor rat) suspended in 5 mL of 5% dextrose in sterile water D5 W/kg. In septic animals, the cecal material was injected in the peritoneum, while sham-septic animals received only D5 W/kg (5 mL/kg). A third group consisting of normal rats (no surgery) group was also included. Hearts were harvested from all three groups and were subjected to a calcium paradox-mediated injury in an isolated heart preparation. Hearts were perfused with Krebs-Henseleit (KH) medium and were allowed to stabilize, followed by a perfusion with Ca2+-free KH for 10 min. After this 10-min Ca2+-free KH perfusion, rats were reperfused with KH medium for 60 min. Ca2+-free KH medium was used in control experiments, while sucrose experiments were conducted with the same medium except that 150 mM sucrose replaced 75 mM NaCl. A marked decrease in ATP and phosphocreatine occurred during Ca2+ reperfusion in all hearts in absence of sucrose. In the presence of the disaccharide, no change in high-energy phosphate (HEP) levels was observed in normal hearts, while lower ATP concentrations were seen in sham and septic hearts. Thus, sucrose did not inhibit cellular injury in sham and septic hearts as it did in normal hearts, and this might be due to a smaller HEP availability. Control studies with normal, sham, and septic hearts exhibited cessation of contractions in the absence of Ca2+, and appearance of large amounts of cytosolic protein in the effluent perfusate during Ca2+ reperfusion. With normal hearts, perfusion with sucrose caused a 96% inhibition of the total creatine kinase (CK) release observed in control experiments. With sham hearts, 32% of CK release was inhibited by sucrose, while 68% of the CK release was attributed to stress associated with surgery performed in the sham-septic group. In septic hearts, only 8% of the CK release was inhibited by sucrose, suggesting that more severe myocardial injury occurs when septic hearts are subjected to a calcium paradox as compared to other groups. It is evident that sucrose can inhibit a small fraction of the CK release from septic hearts during the calcium paradox as compared to the large CK loss associated with sham sepsis. We have concluded that induction of sepsis made the heart more susceptible to a calcium paradox-mediated myocardial injury.
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PMID:Induction of peritoneal sepsis increases the susceptibility of isolated hearts to a calcium paradox-mediated injury. 1190 Mar 37

Although numerous studies have provided evidence that the inflammatory cytokines TNF-alpha and IL-1beta have significant negative inotropic effects, the role of the interleukins in burn-mediated cardiac dysfunction has not been defined. Furthermore, most studies examining the cardiotoxic effects of inflammatory cytokines have ignored the complex inflammatory milieu that occurs in the intact subject with trauma, sepsis, or ischemic heart disease. Therefore, this study examined the time course of IL-1beta and IL-6 secretion by cardiomyocytes after burn trauma, and additional studies examined the effects of these cytokines alone or in combination with TNF-alpha on cardiac contractile performance (Langendorff). Sprague-Dawley rats were given a full thickness burn injury over 40% of the total body surface area; fluid resuscitation was lactated Ringers solution, 4 mL/kg per burn percentage of burn area. Sham burn animals received identical anesthesia and handling, but no burn injury. Rats were sacrificed at several different times postburn, and isolated hearts (n = 4-5 rats/group/time period) were perfused with collagenase-containing buffer to prepare cardiomyocytes or were perfused in vitro to examine cardiac contractile function (n = 5-6 rats/group/time period). Additional naive control rats (n = 10) were included to prepare cardiomyocytes that, in turn, were challenged with different concentrations of either IL-1beta, IL-6, or TNF-alpha alone or in combination for several time periods (CO2 incubator at 37 degrees C for 1-3 h). Finally, inflammatory cytokines alone or in combination were added to the perfusate of hearts isolated from additional control rats (n = 6-7/group) to assess the cardiac contraction and relaxation effects of cytokine challenge. Despite aggressive fluid resuscitation, burn trauma produced a time-related increase in cardiomyocyte secretion of IL-1beta, IL-6, and TNF-alpha. Exposure of naive cardiomyocytes prepared from control rats to each cytokine alone or combined cytokine challenge produced a time-dependent and concentration-dependent decrease in cell viability and an increase in supernatant creatine kinase levels. Either IL-1beta or TNF-alpha produced greater cardiac defects than IL-6 when added separately to Langendorff-perfused hearts; dysfunction was maximal with combined cytokine challenge (IL-1beta plus TNF-alpha plus IL-6). The data confirm that burn trauma upregulates inflammatory cytokine secretion by cardiomyocytes and suggest that these inflammatory cytokines act in concert to produce burn-mediated cardiac contractile dysfunction.
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PMID:IL-1beta and IL-6 act synergistically with TNF-alpha to alter cardiac contractile function after burn trauma. 1239 81

It has been demonstrated that biopterin, an essential cofactor of nitric oxide synthase (NOS), plays an important role in the pathogenesis of endotoxin-induced shock, yet its biological significance in gram-positive sepsis remains unclear. In this study, we adopted a rat model of postburn Staphylococcus aureus sepsis to investigate the potential role of biopterin in the pathogenesis of gram-positive sepsis. Wistar rats were inflicted with a 20% total body surface area (TBSA) full-thickness scald injury followed by S. aureus challenge, and then guanosine triphosphate-cyclohydrolase I (GTP-CHI) mRNA expression and biopterin levels in liver, kidneys, lungs, and heart were determined. We found that after S. aureus challenge, GTP-CHI gene expressions and biopterin levels were markedly upregulated in various tissues. Meanwhile, multiple organ dysfunction was induced by S. aureus challenge. It was shown that cardiac GTP-CHI mRNA expression and renal BH(4) levels were positively correlated with MB isoenzyme of creatine kinase (CK-MB) and creatinine (r = 0.892, P = 0.0012 and r = 0.9423, P = 0.0015, respectively). These results suggested that thermal injury combined with S. aureus challenge could induce de novo biosynthesis of biopterin, which might play a role in the development of multiple organ dysfunction syndrome secondary to postburn sepsis.
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PMID:Significance of biopterin induction in rats with postburn Staphylococcus aureus sepsis. 1286 61

The role of endothelin ETA receptors in sepsis-induced mortality and edema formation was evaluated with a selective antagonist ABT-627 [2-(4-methoxyphenyl)-4-(1,3-benzodioxol-5-yl)-1-(N,N-di(n-butyl)amino carbonylmethyl)-pyrrolidine-3-carboxylic acid]. Sprague-Dawley rats received saline (control group), Escherichia coli endotoxin (10 mg/kg, sepsis group) or infusion of ABT-627 prior and immediately after saline and endotoxin injection. Mortality, edema formation (wet/dry ratios), and multiple tissue injury (indicated by serum concentrations of creatinine, urea, bilirubin, creatine kinase, lactate dehydrogenase, and aspartate aminotransferase) were monitored within 5 h. Endotoxin injection elicited 64% mortality, significantly augmented edema formation in liver, heart, lung, and kidney, and raised serum levels of tissue injury markers. Pretreatment with ABT-627 completely reversed endotoxin-induced mortality, significantly attenuated wet/dry ratios of the heart, liver, and kidney, but not lungs, and reduced serum levels of creatine kinase, creatinine, aspartate aminotransferase, and lactate dehydrogenase, but not that of urea and bilirubin. These results suggest that endothelin ETA receptors play a significant role in promoting mortality, edema formation (except in the lungs), and tissue injury in animals with severe sepsis.
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PMID:Role of endothelin ETA receptors in sepsis-induced mortality, vascular leakage, and tissue injury in rats. 1290 4

Neuroleptic malignant syndrome (NMS) is the most dangerous side effect of phenothiazines therapy. In the period of time from 1995 to 2002 in the Intensive Toxicological Unit there were five patients, 3 men and 2 women, aged from 25 to 62 (average 44.2) years-old, admitted from the regional inpatients psychiatric units with the diagnosis of pneumonia and/or sepsis. The patients about 48-72 hours before admittance were given some phenotiazine derivatives (promazine, perphenazine, clozapine, pipamperon) and/or buthyrophenone (haloperidol) because of psychotic state. Altered consciousness, muscle rigidity, hyperpyrexia (39.0-41.0 degrees C), sweating, tachycardia (120-150/min.), tachypnoea (respiratory rate more than 25/min.) and high level of creatine kinase activity (23,751-112,288 U/l) dominated. Only one patient had clinical picture of pneumonia. Because of the rapid development of acute respiratory failure, respirathorotherapy was initiated and continued for 8 and 10 days in two patients respectively. Transient thrombocytopenia (26,000/microliter) in one subject was observed. The neuroleptic drug was withdrawn and intensive supportive care with administration of bromocriptine (15-20 mg/24 h) was provided. None one of the doctors told the patients about the possibility of NMS during phenothiazines therapy.
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PMID:[Neuroleptic malignant syndrome]. 1456 9

Although protein carbonyl formation is an index of oxidative stress in skeletal muscles, the exact proteins, which undergo oxidation in these muscles, remain unknown. We used 2D electrophoresis, immunoblotting, and mass spectrometry to identify carbonylated proteins in the diaphragm in septic animals. Rats were injected with saline (control) or Escherichia coli lipopolysaccharides (LPS) and killed after various intervals. Diaphragm protein carbonylation increased significantly and peaked 12 h after LPS injection, and it was localized both inside muscle fibers and in blood vessels supplying muscle fibers. Aldolase A, glyceraldehyde 3-phosphate dehydrogenase, enolase 3beta, mitochondrial and cytosolic creatine kinases, alpha-actin, carbonic anyhdrase III, and ubiquinol-cytochrome c reductase were all carbonylated in septic rat diaphragms. In addition, we found significant negative correlations between the intensity of carbonylation and creatine kinase and aldolase activities. We conclude that glycolysis, ATP production, CO2 hydration, and contractile proteins are targeted by oxygen radicals inside the diaphragm during sepsis.
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PMID:Protein carbonyl formation in the diaphragm. 1547 39

The cardiac biomarkers cardiac troponin T (cTnT) and I (cTnI) and the cardiac isoenzyme of creatine kinase (CKMB) are used extensively in human medicine to diagnose and provide valuable prognostic information in patients with ischemic, traumatic, and septic myocardial injury. We designed a study to establish normal values for these markers in healthy, neonatal foals and to compare them with values obtained from septic neonates in a referral hospital population. The 25th, 50th, 75th, and 95th percentiles for cTnI and CKMB in the healthy-foal population were 0.08, 0.14, 0.25, 0.49 ng/mL and 1.4, 2.3, 4.0, 7.4 ng/mL, respectively. The values obtained for cTnT were frequently (43/52 foals; 83%) below the lower limit of detection of the assay (0.009 ng/mL), but the median and range were 0.009 and 0.009-0.041 ng/mL, respectively. In the septic foal population, the 25th, 50th, 75th, and 95th percentile values for cTnI and CKMB were 0.05, 0.12, 0.22, and 1.10 ng/mL and 2.0, 4.4, 7.8, and 24 ng/mL, respectively. The values obtained for cTnT were less frequently below the lower limit of detection (23/38 foals; 60%) compared with the healthy foal population, and the median and range were 0.009 and 0.009-0.20 ng/mL, respectively. Significantly higher values were observed for cTnT and CKMB in septic foals compared with the healthy neonatal foal population, but there were no differences among septic foals in survivors compared with nonsurvivors. These findings suggest that myocardial injury occurs during septicemia in neonatal foals but that the injury is not associated with survival among septic foals.
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PMID:Biochemical markers of cardiac injury in normal, surviving septic, or nonsurviving septic neonatal foals. 1609 77

Hydrogen sulfide (H2S) is a naturally occurring gaseous transmitter, which may play important roles in normal physiology and disease. Here, we investigated the role of H2S in the organ injury caused by severe endotoxemia in the rat. Male Wistar rats were subjected to acute endotoxemia (Escherichia coli lipopolysaccharide (LPS) 6 mg kg(-1) intravenously (i.v.) for 6 h) and treated with vehicle (saline, 1 ml kg(-1) i.v.) or DL-propargylglycine (PAG, 10-100 mg kg(-1) i.v.), an inhibitor of the H2S-synthesizing enzyme cystathionine-gamma-lyase (CSE). PAG was administered either 30 min prior to or 60 min after the induction of endotoxemia. Endotoxemia resulted in circulatory failure (hypotension and tachycardia) and an increase in serum levels of alanine aminotransferase and aspartate aminotransferase (markers for hepatic injury), lipase (indicator of pancreatic injury) and creatine kinase (indicator of neuromuscular injury). In the liver, endotoxemia induced a significant increase in the myeloperoxidase (MPO) activity, and in the expression and activity of the H2S-synthesizing enzymes CSE and cystathionine-beta-synthase. Administration of PAG either prior to or after the injection of LPS dose-dependently reduced the hepatocellular, pancreatic and neuromuscular injury caused by endotoxemia, but not the circulatory failure. Pretreatment of rats with PAG abolished the LPS-induced increase in the MPO activity and in the formation of H2S and in the liver. These findings support the view that an enhanced formation of H2S contributes to the pathophysiology of the organ injury in endotoxemia. We propose that inhibition of H2S synthesis may be a useful therapeutic strategy against the organ injury associated with sepsis and shock.
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PMID:Inhibition of endogenous hydrogen sulfide formation reduces the organ injury caused by endotoxemia. 1610 May 27

An ideal cardiac biochemical marker should have not only high sensitivity but also high specificity to myocardial infarction. The creatine kinase-MB, a relatively specific cardiac marker, could be elevated in situations other than acute myocardial infarction, such as renal failure, muscular injury, and myopathy. Although these are more specific than creatine kinase-MB, cardiac troponins have also been reported to be elevated in conditions other than acute myocardial infarction, such as chronic renal failure, acute myocarditis, cardiomyopathy, congestive heart failure, pulmonary embolism, rhabdomyolysis, sepsis, and left ventricular hypertrophy. With the ongoing research in this field, future holds hopes of finding an ideally specific marker of myocardial infarction, but until then biochemical markers should be used in conjunction with clinical assessment and electrocardiography in making the diagnosis of myocardial infarction, and the patients should not be treated merely on the basis of elevated serum levels of cardiac biochemical markers.
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PMID:Role of biochemical markers in diagnosis of myocardial infarction. 1616 23


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