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)

Purpose. The purpose of this study was to investigate the relationship between hepatic energy status and liver injury during sepsis, using transgenic mice which express creatine kinase in the liver catalyzing the phosphocreatine/creatine system. Methods. Creatine kinase transgenic mice were fed with normal rodent chow or chow containing 10% creatine for 5 days. Lipopolysaccharide (0.2 mg/kg) combined with d-galactosamine (600 mg/kg) was administered intraperitoneally. Results. Eighty percent of the creatine-fed transgenic mice had survived at 48 h post-d-galactosamine and lipopolysaccharide administration, compared with none of the normally fed transgenic mice. Hepatic phosphocreatine and ATP levels in the normally fed transgenic mice were significantly lower than those in the creatine-fed transgenic mice before and after lipopolysaccharide combined with d-galactosamine was administered. Massive hepatic hemorrhagic necrosis with apoptosis was seen in response to d-galactosamine and lipopolysaccharide in normally fed transgenic mice. These results are consistent with a significant increase in serum aminotransferase at 8 h. In contrast, there were faint necrotic changes in the liver with minimal cellular infiltration in creatine-fed transgenic mice. Conclusions. Maintenance of hepatic ATP levels protects from sepsis-induced liver injury and mortality.
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PMID:The beneficial effect of phosphocreatine accumulation in the creatine kinase transgenic mouse liver in endotoxin-induced hepatic cell death. 987 18

Patients with methamphetamine toxicity are presenting in greater numbers each year to emergency departments (ED) in the US. These patients are frequently agitated, violent, and often require physical and chemical restraint. The incidence and risk of rhabdomyolysis in this subpopulation is unknown. We conducted a 5-year retrospective review of all ED patients who received the final diagnosis of rhabdomyolysis. Patients with toxicology screens positive for methamphetamine were identified, and demographics, laboratory results, resource utilization, disposition, and outcome were compared to the remaining patients. Of the total 367 patients identified, 166 (43%) were toxicology positive for methamphetamine. Methamphetamine patients differed significantly from nonmethamphetamine patients with regard to demographics and hospital utilization. Methamphetamine patients had significantly higher mean initial creatine phosphokinase (CK), 12,439 U/L versus 5,678 U/L (P = 0.02), and lower mean peak CK, 16,827 U/L versus 19,426 U/L (P = 0.03). The development of acute renal failure was not significantly different between the 2 groups. There were 16 total deaths in the study population, 11 from concomitant infection/sepsis. An association between methamphetamine abuse and rhabdomyolysis may exist, and CK should be measured in the ED as a screen for potential muscle injury in this subpopulation. Patients with rhabdomyolysis with an unclear cause should be screened for methamphetamine or other illicit drugs.
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PMID:Methamphetamine abuse and rhabdomyolysis in the ED: a 5-year study. 1059 89

Septicaemia is a major threat to survival during the early stages of life. There are several reports that suggest that reactive oxygen species (ROs) play a role in a wide variety of diseases. We estimated the activity of xanthine oxidase (XO), malondialdehyde (MDA) content, creatine phosphokinase (CPK) activity, activities of key enzymatic antioxidants, such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and peroxidase (PO), and non-enzymatic antioxidants, viz. uric acid (UA) and albumin (ALB), in 30 neonates with sepsis and 20 age-matched controls. The babies were categorized as preterm/term, early onset/late onset, and shock/without shock, as per clinical and laboratory investigations. The study was carried out to evaluate the status of antioxidant enzymes and non-enzymatic antioxidants with a view to suggesting the introduction of antioxidant therapy in neonatal sepsis. The activities of serum XO, CPK, SOD and GPx, and the content of MDA were found to be significantly elevated in the neonates with sepsis when compared with controls. Conversely, the activity of PO and the levels of UA and ALB were decreased. The septic, full-term neonates registered significantly higher CPK activity (70%) than the preterm septic neonates. However, infants with late-onset and shock sepsis had a significant decrease in CPK activity (p < 0.05) compared with their corresponding sub-groups. Likewise, UA levels were found to be 28% depressed (p < 0.05) in the babies with late-onset sepsis and 51% increased (p < 0.001) in babies with shock compared with their respective sub-groups. Neonates with septic shock also registered a significant elevation in GPx activity (28%) compared with those without shock. This study suggests increased production of ROs in neonates with sepsis, as evidenced by the positive regulation of XO, SOD and GPx activity. The elevation of antioxidant enzymes, however, was not so effective as to protect from cellular damage and thereby result in higher MDA production. It is evident that antioxidant therapy might be useful in the management of neonates with sepsis but further detailed clinico-biochemical investigations are required to define effective antioxidant therapy.
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PMID:Alterations in antioxidant status during neonatal sepsis. 1082 10

A 22-year-old man developed unconsciousness, severe quadriplegia and muscle atrophy, and had markedly elevated serum creatine kinase levels after using the high-dose steroid and nondepolarizing neuromuscular blocking agents during the course of sepsis and DIC. On neurological examination, he was lethargic. The patient had generalized muscle weakness and wasting, and diminished deep tendon reflexes. He weakly responsed to painful stimuli on the legs. The motor nerve conduction study demonstrated decreased CMAP (compound muscle action potential) amplitudes. Motor and sensory nerve conduction velocities and their distal latencies were normal. Muscle biopsy revealed marked muscle fiber atrophy predominantly in type 2 fibers and numerous basophilic and a few necrotic fibers. Some atrophic fibers had decreased to absent myosin adenosine triphosphatase activity in their center. Accordingly, he was diagnosed as having acute quadriplegic myopathy (AQM), which has been reported mainly in Western countries. The mechanism of muscle fiber degradation in this myopathy is still unknown. On immunohistochemical analysis to our patient, enzyme activities of various proteases such as calpain, cathepsin B, and proteasomes were increased in the sarcoplasm, especially in the atrophic fibers. We suggest that lysosomal cathepsin, nonlysosomal calpain, and ATP-ubiquitin-proteasome proteolytic pathways participate in muscle fiber degradation in AQM.
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PMID:[A case of acute quadriplegic myopathy]. 1108 98

Inflammatory cytokines have been implicated in myocardial function, severe congestive heart failure and sepsis. The present study tested the hypothesis that cytokine levels are elevated after low-risk coronary artery bypass surgery (CABG), and that they may be associated with postoperative cardiac dysfunction. Twenty male patients undergoing elective CABG in cardiopulmonary bypass (CPB) were studied. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, IL-8, and IL-10 were measured before anesthesia induction, 5 minutes after, and 1, 4, and 20 hours after reperfusion to the myocardium. Levels of the MB isoenzyme of creatine kinase (CK-MB) were measured postoperatively. Hemodynamic data were also recorded. Myocardial ischemia was followed by an increase in the plasma levels of IL-6, IL-8, and IL-10. The duration of IL-6 response lasted throughout the postoperative period studied. Plasma cytokine levels at 1 hour after reperfusion correlated with the maximum CK-MB value (IL-6, r = 0.587, p < 0.01; IL-8, r = 0.460, p < 0.05; IL-10, r = 0.570, p < 0.05). Higher plasma IL-6 and IL-8 levels after reperfusion tended to be linked with lower cardiac index. The present results confirm that the levels of inflammatory cytokines IL-6, IL-8, and IL-10 are elevated after CABG. Increased systemic pro-inflammatory cytokine levels were partially associated with postoperative myocardial dysfunction. </hea
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PMID:Cytokine Responses in Low-Risk Coronary Artery Bypass Surgery. 1117 83

The subcellular mechanisms responsible for myocardial depression during sepsis remain unclear. Recent data suggest a role for impaired energy generation and utilization, resulting in altered contractile function. Here, we studied the energetic and mechanical properties of skinned fibers isolated from rabbit ventricle in a nonlethal but hypotensive model of endotoxemia. Thirty-six hours after lipopolysaccharide (LPS) injection (in the presence of altered myocardial contractility), mitochondrial respiration, coupling between oxidation and phosphorylation, and creatine kinase function were similar in preparations from endotoxemic (LPS) and control animals. The maximal Ca2+-activated force was similar in LPS and control preparations. However, the Ca2+ concentration corresponding to half-maximal force (pCa50, where pCa = -log10[Ca2+]) was 5.55 +/- 0.01 (n = 11) in LPS fibers versus 5.61 +/- 0.01 (n = 10) in control fibers (p < 0.01). Both protein kinase A (PKA) and alkaline phosphatase treatment led to the disappearance in the difference between control and LPS pCa50 values. Incubation of control fibers with the nitric oxide donor S-nitroso-N-acetylpenicillamine (SNAP) did not change the Ca2+ sensitivity after subsequent skinning, whereas isoproterenol decreased pCa50 from 5.62 +/- 0.01 to 5.55 +/- 0.01 (p < 0.01). These data suggest that during sepsis, cardiac mitochondrial and creatine kinase systems remain unaltered, whereas protein phosphorylation decreases myofibrillar Ca2+ sensitivity and may contribute to the depression of cardiac contractility.
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PMID:Phosphorylation-dependent alteration in myofilament ca2+ sensitivity but normal mitochondrial function in septic heart. 1117 7

Ten pigeons were crop inoculated with 1 x 10(9) colony-forming units of Salmonella typhimurium var. Copenhagen and observed during 28 days. Ten sham-inoculated pigeons served as noninfected controls. Clinical signs after Salmonella infection consisted of polydipsia, polyuria, and diarrhea. Morbidity was 90%, but there was no mortality. All inoculated pigeons showed fecal excretion of Salmonella for at least 7 days. Biochemical analysis of plasma samples taken at 3-day intervals indicated decreased concentrations of creatine kinase (CK)-MM and CK-MB isoenzymes and elevated total protein and alpha- and gamma-globulin values. No consistent changes in the level of 17 other blood parameters were observed. After 28 days, all pigeons were necropsied. Gross lesions and bacteriologic and histologic examination indicated septicemia in all Salmonella-inoculated pigeons. Results indicate that Salmonella septicemia in pigeons induces only limited changes in biochemical blood parameters. Decreased CK concentration was a consistent finding, however, and may therefore be a useful aid in the diagnosis of salmonellosis in pigeons.
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PMID:Plasma biochemistry in pigeons experimentally infected with Salmonella. 1141 30

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


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