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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with end-stage liver disease have significant mortality often associated with intercurrent episodes of bleeding or sepsis. Intact adrenal function is essential in such situations. In order to test the hypothesis that adrenal insufficiency might be present in severe liver disease, hypothalamic-pituitary adrenal function was evaluated in patients with end-stage liver disease awaiting transplantation. The study had a prospective, open comparative design with patients restricted to those having non-alcoholic liver disease in order to avoid the confounding direct effects of alcohol on adrenocortical function. Fifty-one consecutive patients with end-stage, non-alcoholic liver disease undergoing evaluation for liver transplantation and 40 healthy controls were studied. Patients who had used corticosteroids (n = 8) or who were unable to complete the investigations (n = 5) were excluded leaving 38 patients eligible for analysis. Adrenal function was evaluated under basal conditions by single morning measurements of plasma total and free cortisol, corticosteroid-binding globulin, dehydroepiandrosterone sulfate and by adrenal stimulation indirectly using insulin-induced (0.1 U/kg, i.v.) hypoglycaemia and/or directly by adrenocorticotrophic hormone (ACTH); 250 micrograms tetracosactrin, i.v.) stimulation. Compared with healthy controls, patients with liver disease had a 64% reduction in maximal increments of plasma cortisol to indirect adrenal stimulation via insulin-induced hypoglycaemia and a 39% reduction to direct adrenal stimulation by ACTH (all P < 0.001). There was a significant negative correlation between the severity of underlying liver disease as assessed by Child-Pugh scores and peak control responses to ACTH (r = -0.647, P < 0.0001) and insulin-induced hypoglycaemia (r = -0.597, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hypothalamic-pituitary adrenal function in end-stage non-alcoholic liver disease. 839 Aug 70

Changes in the distribution of alpha 1-adrenergic receptors in two subcellular fractions, the plasma membrane and the light vesicle, of rat liver during sepsis were studied using [3H]prazosin binding and photoaffinity labeling with [125I]arylazidoprazosin in combination with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Sepsis was induced by cecal ligation and puncture (CLP). Septic rats exhibit two metabolically distinct phases: an initial hypermetabolic (hyperglycemic) phase (9 h after CLP; early sepsis) followed by a hypometabolic (hypoglycemic) phase (18 h after CLP; late sepsis). [3H]prazosin binding studies show that during early sepsis, the maximal binding capacity (Bmax) was increased by 35% in plasma membranes but was decreased by 28% in light vesicles; while during late sepsis, the Bmax was decreased by 30% in plasma membranes but was increased by 33% in light vesicles. The photoaffinity labeling studies revealed two major binding peptides with M(r) of 77,000 and 68,000 Da and one minor binding protein with M(r) of 39,000 Da. The total binding for the three labeled peptides during early sepsis was increased by 26% in plasma membranes but was decreased by 33% in light vesicles, while during late sepsis the total binding was decreased by 19% in plasma membranes but was increased by 35% in light vesicles. These data indicate that alpha 1-adrenergic receptors in the rat liver were externalized from light vesicles to plasma membranes during the hyperglycemic phase while they were internalized from surface membranes to intracellular sites during the hypoglycemic phase of sepsis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biphasic intracellular redistribution of alpha 1-adrenergic receptors in rat liver during sepsis. 839 54

Cyclophosphamide-induced neutropenia exacerbates septic shock and multiple organ injury in conscious rats during Escherichia coli (EC) bacteremia despite antibiotics and fluid administration. We hypothesized that such shock and inflammatory organ injury would be mitigated by rBPI23's microbicidal activity and/or binding of EC endotoxins. Four days after 100 mg cyclophosphamide/kg, catheterized rats with < 300 PMNs/microL were pretreated with rBPI23 or the irrelevant 22 kDa protein thaumatin [3.3-6.6 mg/kg, i.v. in 0.9% NaCl (NS)] 5 min before graded i.v. infection with 5 x 10(9) or 1 x 10(10) cfu of EC serotype 055:B5 ending at t = 0. Posttreatment with each protein continued (3.3-6.6 mg/kg in 1 mL NS/h) through 8 h, in addition to penicillin plus amikacin sulfate at t = 1.5 and 8 h. Arterial samples were obtained before pretreatment and at t = 1.5, 4.5, 8, and 24 h when animals were necropsied. One of eight thaumatin + 5 x 10(9) EC rats and none of six thaumatin + 10(10) EC rats survived 24 h. In contrast, rBPI23 significantly reduced mortality after either inoculum, improved bacterial clearance, and led to renormalization of early EC-induced hypotension, hypothermia, tachypnea, hyperoxemia, and hypocarbia. Compared with thaumatin, however, rBPI23 did not reduce circulating endotoxin or bioactive and antigenic tumor necrosis factor-alpha. Sepsis-induced severe neutropenia (< 50 PMNs/microL) evident in all EC rats by t = 1.5 h was reversed with rBPI23 by t = 8 h, but thrombocytopenia (< 5 x 10(4) platelets/microL) evident in all groups by t = 4.5 h was not altered.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The recombinant 23-kDa N-terminal fragment of bactericidal/permeability-increasing protein (rBPI23) decreases Escherichia coli-induced mortality and organ injury during immunosuppression-related neutropenia. 856 60

We evaluated the effects on survival of three different strategies for blocking the actions of nitric oxide (NO) during Gram-negative sepsis in rats. Male Sprague-Dawley rats underwent placement of a jugular vein catheter and i.p. implantation of a gelatin capsule containing a paste (.11 +/- 0.1 g final weight) consisting of sterile rat feces mixed with a suspension (.2 mL) of viable Escherichia coli (strain sm 18; 5.7 x 10(5) colony-forming units) in saline. Beginning at T = 6h, all animals received i.v. ampicillin (85 mg/kg every 12 h) until death or the administration of five doses. At the same time points, pairs of animals received an i.v. dose of either an experimental treatment agent or an appropriate control substance. The following experimental regimens were tested: 5 mg/kg per dose of S-methylisothiourea sulfate (SMT), a selective inhibitor of the inducible isoform of nitric oxide synthase (NOS); 10 mg/kg per dose or 25 mg/kg per dose of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of the inducible and constitutive isoforms of NOS; 200 mg/kg per dose of cross-linked human hemoglobin (HGB), an NO scavenger. SMT significantly prolonged survival in septic rats, although cumulative survival at T = 168 h was approximately equivalent in SMT- or saline-treated animals. In contrast, HGB and the higher dose of L-NAME significantly shortened survival times. At T = 20 h, arterial PO2 was significantly lower in rats treated with HGB as compared to time-matched controls. We conclude that SMT, a compound with reported activity as a selective inhibitor of the inducible isoform of NOS, prolongs survival in a rat model of antibiotic-treated Gram-negative sepsis.
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PMID:A selective inhibitor of inducible in nitric oxide synthase prolongs survival in a rat model of bacterial peritonitis: comparison with two nonselective strategies. 870 88

Brainstem auditory evoked potential (BAEP) recording was used to screen presymptomatically the hearing of 200 neonates treated with ampicillin (100 mg/kg daily) and gentamicin sulfate (5 mg/kg daily). The study included 130 male and 70 female neonates; post-conceptional age ranged from 34 to 57 weeks (mean 42.36 weeks). We divided neonates into 2 groups according to duration of antibiotic treatment; group 1 consisted of 179 patients who were treated with antibiotic agents for < or = 7 days. Although 15 (8.4%) in this group initially manifested abnormal BAEP recordings, only 8 of these brain-damaged neonates (4.5%) (6 with peripheral and 2 with central dysfunction) later manifested abnormal recordings. Group 2 consisted of 21 neonates who were treated for 10 to 30 days; BAEP recordings were abnormal in 7 patients (33.3%) (4 with peripheral and 3 with central dysfunction). We conclude that BAEP is indicated only for neonates treated with gentamicin sulfate for > 10 days. In this group, infants so treated usually have underlying disease or severe infection, including birth asphyxia, hypoxia, sepsis, and meningoencephalitis, all of which are clinically significant indicators of high risk for auditory pathway dysfunction.
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PMID:Recording of brainstem evoked potentials and their association with gentamicin in neonates. 880 69

Fifteen Bacteroides forsythus strains freshly isolated from patients with periodontitis were used together with three collection strains and one type strain for characterization of growth on various media; determination of enzymatic profiles, antibiotic susceptibility profiles, 16S rRNA ribotypes, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) outer membrane protein profiles, and pathogenicity; and gas chromatography analysis by using a wound chamber model in rabbits. All strains were stimulated by N-acetylmuramic acid, while one strain needed a further supplement such as yeast extract for optimal growth. All strains showed trypsin-like activity. While 10 different ribotypes were found, the SDS-PAGE profiles revealed similar patterns for all strains. All strains were sensitive to penicillin G (MICs, <0.5 microg/ml), ampicillin (MICs, <1.0 microg/ml), amoxicillin (MICs, <0.38 microg/ml), metronidazole (MICs, <0.005 microg/ml), tetracycline (MICs, <0.19 microg/ml), doxycycline (MICs, 0.05 microg/ml), erythromycin (MICs, <0.4 microg/ml), and clindamycin (MICs, <0.016 microg/ml), while they were less sensitive to ciprofloxacin (MICs, <4 microg/ml). B. forsythus did not cause abscess formation by monoinoculation. B. forsythus coinoculated with Fusobacterium nucleatum ATCC 10953 caused abscess formation in 75% of rabbits, while it caused abscess formation in 100% of rabbits when it was coinoculated with Porphyromonas gingivalis FDC 381. In the case of the latter combination, four of six rabbits died of sepsis after 6 to 7 days, and P. gingivalis and B. forsythus were recovered from the heart blood at a proportion of 10:1. B. forsythus strains were highly virulent and invasive in combination with P. gingivalis.
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PMID:Characterization of Bacteroides forsythus isolates. 916 47

Increased production of interleukin-1 and tumor necrosis factor-alpha (TNF-alpha) have been implicated in the pathophysiology of a variety of diseases including circulatory shock. The present study evaluated the efficacy of FR167653 (1-[7-(4-fluorophenyl)-1,2,3,4-tetrahydro-8-pyridylpyrazolo[5,1-c] [1,2,4]triazin-2-yl]-2-phenylethanedione sulfate monohydrate), a dual inhibitor of interleukin-1 and TNF-alpha production, to protect rabbits from the shock and lethality induced by lipopolysaccharide. In this sepsis model, FR167653 at a dose of 0.32 mg/kg per h ameliorated the 7-day mortality from 93% in the placebo group to 47% in the FR167653-treated group and, at doses of 0.10-0.32 mg/kg per h, attenuated the hypotensive response to lipopolysaccharide challenge and returned mean arterial blood pressure to almost normal levels. The increases in plasma interleukin-1 and TNF-alpha levels evoked by lipopolysaccharide administration were also inhibited by treatment with FR167653, which was efficacious at doses of 0.1-0.32 mg/kg per h. In addition, FR167653 treatment attenuated the increases in plasma creatinine concentrations consistent with renal damage in a dose-dependent manner. These findings suggested that FR 167653 has a beneficial potential as a drug for septic shock or multiple organ dysfunction syndrome.
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PMID:FR167653, a dual inhibitor of interleukin-1 and tumor necrosis factor-alpha, ameliorates endotoxin-induced shock. 920 May 56

Changes in the activities of protein kinase A (PKA, or cAMP-dependent protein kinase) in rat heart during different cardiodynamic phases of sepsis were investigated. Sepsis was induced by cecal ligation and puncture. Experiments were divided into three groups: control, early sepsis, and late sepsis. Early and late sepsis refers to those animals killed at 9 and 18 h, respectively, after cecal ligation and puncture. Cardiac PKA was extracted and partially purified by acid precipitation, ammonium sulfate fractionation, and 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 based on the rate of incorporation of [gamma-32P]ATP into histone. Results obtained show that during early sepsis, both type I and type II PKA activities were unaffected. During late sepsis, type I PKA activities were stimulated by 66.7-97.7%, while type II PKA activities remained constant. Kinetic analysis of the data on type I PKA during late sepsis reveals that the Vmax values for ATP, cAMP, and histone were increased by 84.7, 66.7, and 97.7%, respectively; while the Km values for ATP, cAMP, and histone were unaltered. These data indicate that type I PKA is activated in rat heart during late hypodynamic phase of sepsis. Since kinase-mediated phosphorylation plays an important role in regulating myocardial function and metabolism, an activation of type I PKA during late sepsis may contribute to the development of altered myocardial function during hypodynamic phase of sepsis.
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PMID:Protein kinase a activity is increased in rat heart during late hypodynamic phase of sepsis. 924 15

Changes in the activities of protein kinase A (PKA) (cAMP-dependent protein kinase) in various regions of rat myocardium during different cardiodynamic phases of sepsis were studied in an attempt to understand the pathophysiology of cardiac dysfunction during sepsis. Sepsis was induced by cecal ligation and puncture (CLP). Experiments were divided into three groups: control, early sepsis, and late sepsis. Early and late sepsis refers to those animals sacrificed at 9 and 18 hr, respectively, after CLP. Cardiac PKA was extracted and partially purified by acid precipitation, ammonium sulfate fractionation, and DEAE-cellulose chromatography. PKA was eluted from DEAE-cellulose column with a linear NaCl gradient. Two types of PKA, Type I (eluted at low ionic strength) and Type II (eluted at high ionic strength), were collected, and their activities were determined based on the rate of incorporation of [gamma-32P]ATP into histone. Under physiological conditions, Type I PKA activities were unevenly distributed (left atrium > right atrium > pacemaker region > left ventricle > right ventricle > ventricular septum) while Type II PKA activities were evenly distributed among different regions of myocardium. During early sepsis, Type I PKA activities remained unchanged while Type II PKA activities were activated by 32 and 70% in right atrium and pacemaker regions, respectively. During late sepsis, Type I PKA activities were stimulated by 228% in ventricular septum while Type II PKA activities were not affected. These data demonstrate that different PKA activities exist in various regions of the myocardium and that PKA activities were preferentially activated in certain areas during the progression of sepsis. Since PKA plays an important role in the regulation of myocardial function and metabolism, the activation of PKA in different regions of myocardial during different stages of sepsis may contribute to the altered cardiac function during the progression of sepsis.
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PMID:Differential activation of protein kinase A in various regions of myocardium during sepsis. 929 85

Enterobacter cloacae has been implicated as one of the causative agents in neonatal infection and causes a septicemia thought to be initiated via the gastrointestinal tract. The adhesion of radiolabeled E. cloacae to HT-29 cells was concentration and temperature dependent and was effectively blocked by unlabeled bacteria or by millimolar concentrations of alpha-mannosides and micromolar concentrations of high-mannose oligosaccharides. A variety of well-characterized mannose oligosaccharides were tested as inhibitors of adhesion. The best inhibitor was the Man9(GlcNAc)2-tyrosinamide, which was considerably better than other tyrosinamide-linked oligosaccharides such as Man7(GlcNAc)2, Man6(GlcNAc)2 or Man5(GlcNAc)2. Further evidence that the bacteria preferred Man9(GlcNAc)2 structures was obtained by growing HT-29 cells in the presence of glycoprotein processing inhibitors that block mannosidase I and increase the amount of protein-bound Man9(GlcNAc)2 at the cell surface. Such cells bound 1.5- to 2-fold more bacteria than did control cells. The adhesin involved in binding to high-mannose structures was purified from isolated pili. On sodium dodecyl sulfate-gels, a 35-kDa protein was identified by its specific binding to a mannose-containing biotinylated albumin. The amino acid sequences of several peptides from the 35-kDa subunit showed over 85% identity to FimH, the mannose-specific adhesin of Salmonella typhimurium. Pili were labeled with 125I and examined for the ability to bind to HT-29 cells. Binding showed saturation kinetics and was inhibited by the addition of Man9(GlcNAc)2-tyrosinamide but not by oligosaccharides with fewer mannose residues. Polyclonal antibody against this 35-kDa protein also effectively blocked adhesion of pili or E. cloacae, but no effect was observed with nonspecific antibody. These studies demonstrate that the 35-kDa pilus subunit is a lectin whose specificity is directed toward Man, (GlcNAc)2 oligosaccharides.
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PMID:Specificity of the high-mannose recognition site between Enterobacter cloacae pili adhesin and HT-29 cell membranes. 931 27


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