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)

To assess the role of combined immunomodulator and antibiotic therapy in sepsis, glucan--a beta 1,3 polyglucose--and gentamicin were administered in a model of murine peritonitis. ICR/HSD mice received one of four treatment regimens: 5% dextrose; gentamicin 0.02 mg intramuscularly (sub-MIC) 2 hours before peritonitis; glucan 0.1 mg intraperitoneally 24 hours before peritonitis; combined glucan-gentamicin treatment. All animals were challenged with 1 X 10(8) Escherichia coli intraperitoneally. Long-term survival was significantly enhanced in the combined therapy group (56%, p less than 0.05) when compared with D5W (0%), gentamicin alone (0%), or glucan alone (9%). Macrophage secretory activity, as assayed by interleukin-1 (IL-1) production, was significantly enhanced by combined therapy when compared with the other three treatment groups. Combined therapy significantly reduced E. coli bacteremia at 8 hours after inoculation, when compared with the other three groups. Availability of host neutrophils was assessed by peripheral counts and bone marrow proliferation assay. Combined glucan-gentamicin significantly enhanced bone marrow proliferation when compared with the other three groups and this enhancement correlated with increased circulating neutrophils. Combined immunomodulator and antibiotic therapy had synergistic effects on survival in E. coli peritonitis. This combined therapy enhanced macrophage secretory activity and bone marrow proliferation. Clinical use of immunomodulators may alter conventional use and dosage of antibiotics.
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PMID:Synergistic effect of nonspecific immunostimulation and antibiotics in experimental peritonitis. 330 98

Haemolysin production (HLY), mannose resistant haemagglutinating activity (MRA), presence of antigens K1 and K5 and colicinogenicity (Col) were compared with LD50 for mice in 663 Escherichia coli strains, including 281 faecal, 129 urinary and 253 other extraintestinal isolates. Those isolates that LD50 value fell into less than or equal to 10(6) LD50 category were arbitrarily termed highly virulent (HV) and those which belonged to greater than or equal to 10(7) LD50 category were considered avirulent (AV). HV isolates occurred significantly more frequently (58%) among strains from different extraintestinal samples than from faeces (14%) or urine (16%). The incidence of HV strains was significantly higher in patients with sepsis (43%) or meningitis (100%) than in patients with enteritis (20%), urinary tract infections (UTI, 16%) or in healthy subjects (28%). The incidence of HV strains in the most frequent (O1, O2, O4, O6, O7, O18, O75) serogroups was significantly higher (60%) than in others (10%). Strains with different virulence markers (HLY, MRA, K1, K5, Col) belonged significantly more frequently to the HV group than those which failed to have these markers (44 vs 27%, 51 vs 25%, 83 vs 17%, 78 vs 27%, 52 vs 16%, respectively). Important role of antigen K1 playing in pathomechanism of meningitis was confirmed by data of analysis according to which significant difference was revealed in the incidence of HV strains between groups of isolates with MRA+K1+ (71%) and MRA+K1- (44%, p less than 0.02), or between groups of isolates with MRA+K1- and MRA-K1+ (91%, p less than 0.001). Moreover there were significant differences in the incidences of HV strains in K1+Col- (73%) and K1-Col+ (29%, p less than 0.001), and in K1+Col+ (86%) and K1-Col+ (29%, p less than 0.001) groups. Further evidence was given by those data that there were no significant differences between groups of HV strains with MRA+K1+ and MRA-K1+ (p greater than 0.05) or with K1+Col+ and K1+Col- (p greater than 0.1) properties. Isolates that possessed simultaneously two of MRA, HLY, Col markers were more pathogenic in LD50 assay than those that had one or the other of these markers alone. Strains in serogroup O18 killed mice significantly more frequently than those of other serogroups independently of having any virulence factor, suggesting that bacteria in serogroups O18 must have some special virulence other than K1, Col, MRA or K5. MRA+HLY+ HV strains occurred frequently in extraintestinal diseases (42%) supporting the preconception that these properties play an important role also in the pathomechanism of extraintestinal infections other than UTI.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Virulence factors of Escherichia coli. IV. Association in Escherichia coli of LD50 with haemolysin production, haemagglutinating capacity, antigens K1, K5 colicinogenicity and pathogenicity. 330 77

To determine whether hepatic dysfunction in sepsis results from hypoperfusion or direct cellular injury, Sprague-Dawley rats underwent either cecal ligation and puncture or sham operation. After either two or six hours, effective hepatic blood flow was measured using the galactose clearance method. Hepatocytes were isolated and intracellular sodium and potassium and glucose production were measured. Hepatic blood flow in septic rats decreased as early as two hours after sepsis when compared with sham-operated rats (3.8 +/- 1.4 vs 8.7 +/- 3.1 mL/min/100 g body weight). Intracellular sodium and potassium levels and glucose production in septic rats were not significantly different when compared with controls at two hours. After six hours, hepatic blood flow remained depressed and intracellular sodium level was increased compared with sham-operated rats (41.7 +/- 10.4 vs 31.4 +/- 5.9 mmol/L [41.7 +/- 10.4 vs 31.4 +/- 5.9 mEq/L]) and potassium decreased compared with controls (90.7 +/- 7.9 vs 111.5 +/- 6.7 mmol/L [90.7 +/- 7.9 vs 111.5 +/- 6.7 mEq/L]). Glucose production was decreased in septic rats after six hours when compared with controls (4.7 +/- 1.5 vs 15.4 +/- 6.4 mumol/g hepatocytes). These data suggest that hepatic blood flow is decreased before alterations in intracellular sodium and potassium as well as glucose production.
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PMID:Temporal relationship of hepatocellular dysfunction and ischemia in sepsis. 334 33

Sepsis was induced by cecal ligation and puncture in male Sprague-Dawley rats weighing approximately 70 g and the animals were intravenously infused with one of four isocaloric solutions: group I (N = 16), 8.5% dextrose solution; group II (N = 16), alpha-ketoisocaproic acid (KIA, 5.1 mg/ml) in 8.5% dextrose; group III (N = 16), FreAmine HBC (containing 45% branched-chain amino acids) in 2.5% dextrose; and group IV (N = 17), FreAmine HBC in 2.5% dextrose + KIA (5.1 mg/ml). Eighteen hr after induction of sepsis, extensor digitorum longus (EDL) and soleus (SOL) muscles were dissected with intact tendons and incubated for the study of protein synthesis and degradation, which were measured as incorporation of 14C-phenylalanine into protein and release of tyrosine into incubation medium, respectively. Urine was collected for determination of nitrogen balance. Nitrogen balance, which was equally negative in groups I and II, was significantly improved in groups III and IV and became equally positive in these groups. Protein synthesis and degradation rates in incubated EDL and SOL muscles were similar to those which we have reported previously in septic rats. Except for a higher synthetic rate in SOL in group II, no other differences in protein synthesis or degradation rates between the four experimental groups were found. Thus, the present study showed that infusion of a branched-chain amino acid-enriched solution improved nitrogen balance in septic rats. KIA alone or administered with the amino acid solution did not affect nitrogen balance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Infusion of a branched-chain amino acid-enriched solution and alpha-ketoisocaproic acid in septic rats: effects on nitrogen balance and skeletal muscle protein turnover. 339 21

The authors have shown that systemic activation of the complement system with either zymosan or cobra venom factor produces some of the hemodynamic changes characteristic of sepsis, specifically, a reduction in hepatic perfusion despite a normal or hyperdynamic systemic circulation. This study was undertaken to determine whether complement activation accompanied reductions in effective hepatic and renal blood flow (EHBF and ERBF, respectively) in a septic murine model previously demonstrated to be associated with flow redistribution. Rats underwent either cecal ligation and puncture (CLP) or sham laparotomy after a baseline blood sample was collected for complement assay. Eighteen hours later, thermodilution cardiac output, mean arterial pressure, heart rate, hematocrit, EHBF by galactose clearance, and ERBF by p-aminohippurate (PAH) clearance were determined. A second blood sample was collected for measurement of total hemolytic complement (CH50) by immune hemolysis of sheep erythrocytes and was compared to the t = 0 sample for calculation of per cent change in CH50. The cardiac output and hematocrit were normal in the CLP group relative to sham. The septic animals were tachycardic and slightly hypotensive, suggesting a diminished systemic vascular resistance. EHBF and ERBF fell dramatically in the septic group despite the normal cardiac output. Residual hemolytic complement activity was reduced to less than 40% of preseptic levels in the CLP group while sham values were no different than baseline, indicating massive complement activation in the septic animals. This study demonstrates an association between complement activation and hepatic and renal perfusion abnormalities in murine peritonitis. Work is underway to establish the temporal relationship between complement activation and visceral flow changes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Complement activation in peritonitis. Association with hepatic and renal perfusion abnormalities. First place winner: Conrad Jobst award. 342 93

Visceral hypoperfusion with local accumulation of lactate in the ischemic tissues has been reported in a septic rat model despite a hyperdynamic systemic circulation. This visceral ischemia is felt to contribute to the multiple system organ failure (MSOF) syndrome associated with sepsis. The purpose of this study was to determine whether a similar redistribution of blood flow existed in rats after a severe thermal injury as it too is associated with MSOF. Twenty-four hours after animals were subjected to either a resuscitated 50% scald burn (BURN) or sham treatment (SHAM), thermodilution cardiac output (CO), effective hepatic blood flow (EHBF) by galactose clearance at low concentrations, effective renal plasma flow (ERPF) by para-aminohippurate clearance, and blood, liver, and skeletal muscle pyruvate (P), and lactate (L) concentrations were determined. CO increased 52% in BURN (46.5 +/- 2.8 ml/min/100 g, n = 21) versus SHAM (30.7 +/- 1.0 ml/min/100 g, n = 22; P less than 0.001) while EHBF increased only 18% (BURN: 6.81 +/- 0.36 ml/min/100 g, n = 8 vs SHAM: 5.77 +/- 0.29 ml/min/100 g, n = 8; P less than 0.025) and ERPF showed an insignificant 24% increase (BURN: 2.98 +/- 0.32 ml/min/100 g, n = 6 vs SHAM: 2.40 +/- 0.40 ml/min/100 g, n = 6; P less than 0.10), demonstrating a redistribution of flow. There was no local accumulation of lactate in blood, liver, or skeletal muscle and no derangement in P/L ratios. This study when compared to previous observations in sepsis suggests that (1) the flow redistribution of sepsis has features differentiating it from solely a "stress response".(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Flow redistribution in a hyperdynamic small animal burn: comparison to patterns in sepsis. 359 83

Selected hemodynamic, pulmonary, acid-base, metabolic, hematological, and serum chemistry parameters were monitored for 6 hr in two groups of anesthetized dogs given an intravenous injection of Escherichia coli endotoxin. One group of animals was pretreated with purified human plasma fibronectin, and the other group received an equal volume of saline or dextrose. Between-group analysis showed that the fibronectin-treated group had significantly higher arterial blood pressure and glucose levels, and lower hemoglobin levels, at 4, 5, and 6 hr postendotoxin administration. This group also had higher arterial pH and base excess values at 5 and 6 hr postendotoxin administration. This study, along with others from our laboratory, suggests that exogenous administration of purified plasma fibronectin can be beneficial in the prophylactic treatment of impending sepsis or endotoxemia. However, the amount of benefit appears to be moderate. Whether combining fibronectin with other therapeutic modalities would be additive or synergistic cannot be ruled out and merits investigation.
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PMID:Effects of fibronectin pretreatment on cardiovascular, acid-base, metabolic, and organ function indices during endotoxin shock in the dog. 371 17

Whether organ dysfunction frequently encountered in overwhelming bacterial sepsis is a result of a direct cellular "toxic" effect or diminished cellular perfusion remains controversial. To assess the effects of peritonitis on cellular energy status and visceral blood flow, peritonitis was induced in rats by means of cecal ligation and perforation. Five, 10, or 20 hours after cecal ligation and perforation, cardiac outputs were determined by thermodilution, effective hepatic blood flow was determined by low-dose galactose clearance, and effective renal plasma flow was determined by paraminohippuric acid clearance. In similar groups of rats with peritonitis or sham controls, tissue samples of liver, kidney, and skeletal muscle were obtained by freeze-clamp technique for analysis of adenine nucleotides, energy charge, pyruvate, lactate, and pyruvate/lactate ratios (P/L). Despite an increase in cardiac output (p less than 0.05), results indicated in this model that effective hepatic blood flow and effective renal plasma flow were significantly reduced (p less than 0.05). The energy charge and P/L ratios of hepatic (p less than 0.01) and renal (p less than 0.05) tissues were also decreased. In contrast, skeletal muscle energy charge and P/L ratio were unchanged by 20 hours duration. These data support the hypothesis of diminished visceral perfusion as contributory to the cellular dysfunction observed in sepsis. Skeletal muscle appears either nonischemic or more tolerant of ischemia in sepsis.
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PMID:Effective organ blood flow and bioenergy status in murine peritonitis. 373 52

To study hepatic blood flow with clearance techniques during sepsis, it is essential to work within the limitations of the test being applied. Based on galactose elimination kinetics, this study validates galactose clearance at low concentrations as an estimate of effective hepatic blood flow in a rat peritonitis model of cecal ligation and puncture. Hepatic function as determined by galactose elimination capacity fell 25% at ten hours after induction of peritonitis, which correlated closely with the 20% reduction in effective hepatic blood flow at the same time point despite a normal cardiac output. The pattern of reduced flow and reduced function is consistent with intrahepatic flow redistribution. Inadequate flow at the microvascular level with secondary cellular injury may explain the liver dysfunction observed during sepsis.
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PMID:Galactose elimination kinetics in sepsis. Correlations of hepatic blood blow with function. 382 77

Diminished effective hepatic blood flow (EHBF) has been postulated as contributory to hepatocellular dysfunction in sepsis. In addition, dopamine has been demonstrated to increase perfusion to selective viscera. In order to examine the effects of peritonitis upon hepatic perfusion and its response to dopamine infusion, peritonitis was induced in rats via cecal ligation and perforation (CLP). Sixteen to 20 hours following insult, cardiac outputs were determined by thermodilution, and effective hepatic blood flow was determined by low-dose galactose clearance. Studies were performed in peritonitis-induced rats (CLP) and sham-operated controls with and without dopamine infusion for 30 minutes (0.5 microgram/100 g/min). Peritonitis resulted in a significant reduction in effective hepatic blood flow (p less than 0.01) despite a maintained cardiac output. Low-dose dopamine infusion resulted in a significant restoration of effective hepatic blood flow in CLP rats without altering cardiac output or hemodynamic status significantly. Dopamine may be beneficial in the maintenance of effective hepatic perfusion in peritonitis.
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PMID:Low-dose dopamine improves effective hepatic blood flow in murine peritonitis. 382 29


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