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)

Recent investigations from our and other laboratories indicate that glycogen is a carbon-chain precursor in muscle for the synthesis of TCA cycle intermediates and glutamine. During intense exercise and in conditions of a relative lack of energy (hypoxia, trauma, sepsis) the metabolism of branched-chain amino acids (BCAA) is accelerated in muscle. In the primary BCAA aminotransferase reaction 2-oxoglutarate is used as amino-group acceptor (putting a carbon-drain on the TCA cycle) under formation of glutamate. Glutamate will subsequently react with ammonia, generated in the AMP deaminase reaction or by deamination of amino acids, under formation of glutamine in a reaction catalysed by glutamine synthetase (glutamate + ammonia + ATP--> glutamine + ADP). Muscle glycogen stores may be smaller or less available at high altitude. It is hypothesized that this will lead to premature fatigue (due to both a lack of fuel and of TCA cycle carbon-precursor) and to a reduction in the synthesis rate of glutamine. A chronic reduction in the synthesis rate of glutamine during a long term stay at high altitude on its turn may lead to gut atrophy, bacterial translocation, endotoxemia, muscle protein catabolism and a weakened immune status.
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PMID:Amino acid metabolism, muscular fatigue and muscle wasting. Speculations on adaptations at high altitude. 148 45

Rabbits reconvalescent from experimental septicemia due to serologically defined strains of Serratia marcescens were examined for the diversity of their humoral antibody response with traditional serological procedures and the Western blot (immunoblotting) technique. Trichloracetic acid (TCA)-whole cell extracts of the homologous and heterologous O-antigen reference strains served as the antigen for the latter procedure. Reconvalescent rabbit sera contained antibodies against the homologous lipopolysaccharide (LPS) moiety (molecular weight (MW) range = 45-31 kilodaltons (= k] and antibodies against numerous heat-modifiable, cross-reactive proteins, in particular 7 proteins characterized by MWs of 117 k, 95 k, 91 k, 71 k, 68 k, 38 k, and 33 k in TCA-whole cell extracts from the homologous as well as from 11 heterologous S. marcescens O-antigen reference strains. Rabbits, which had been actively immunized with TCA-whole cell extracts from representative S. marcescens strains, mounted a humoral antibody response remarkably similar to that of rabbits which had recovered from septicemia, except that the sera from the actively immunized animals interacted somewhat more strongly with an additional cross-reactive protein (MW = 47 k). Conversely, conventional anti-O and anti-H rabbit immune sera revealed antibodies directed predominantly against the homologous LPS moiety (MW range = greater than or equal to 200 k - less than or equal to 15 k). It was concluded that numerous proteinaceous cellular constituents of S. marcescens accounted for immunoblot cross-reactivity.
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PMID:Humoral antibody response of rabbits against experimental Serratia marcescens septicemia. 224 83

The possibility that group B streptococci (GBS) may induce neonatal neutropenia by promoting neutrophil aggregation and the entrapment of aggregates in the lung was studied in vivo and in vitro utilizing a cell free GBS extract [(GBS)-trichloroacetic acid (TCA)]. The intravenous infusion of the extract into neonatal lambs induced reductions of circulating white blood cells (0 time, 3.1 X 10(3)/mm3 +/- 0.5 versus 2.2 X 10(3)/mm3 +/- 0.7) 5 min after infusion (p less than 0.01). At necropsy these lambs had prominent accumulation of polymorphonuclear leukocytes in their pulmonary interstitium. Subsequently, neutrophil aggregation was studied by incubating GBS-TCA in human serum or phosphate-buffered saline with subsequent addition to human polymorphonuclear leukocytes in an aggregometer. GBS-TCA incubated in human serum induced prompt polymorphonuclear leukocyte aggregation (mean delta T 12.3% +/- 2.8 in human serum versus delta T 2.5% +/- 2.1 in phosphate-buffered saline, p less than 0.001). Preincubation of GBS-TCA followed by incubation in human serum with human GBS hyperimmune IgG significantly reduced aggregation (GBS-TCA in serum mean delta T 14.9 +/- 2.44 versus 5.42 +/- 1.80, p = 0.002). Cell-free GBS products may induce polymorphonuclear leukocyte aggregation in the presence of whole serum. This phenomenon might contribute to the pulmonary injury experienced by infants with GBS pneumonia and sepsis.
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PMID:A group B streptococcal extract reduces neutrophil counts and induces neutrophil aggregation. 355 23

Protein synthesis and degradation in liver tissue were studied in rats following induction of septic peritonitis by ligation and puncture of the cecum. Protein synthesis was studied by determining the rate of leucine incorporation into protein in incubated liver slices. Protein degradation was measured in vitro as release of trichloroacetic acid soluble radioactivity from protein prelabelled with 14C-leucine and in vivo from decay of radioactivity in hepatic protein labelled with 14C-sodium bicarbonate. Measurements 24 hours after induction of septic peritonitis showed increase in liver weight and total hepatic protein content. Protein synthesis was higher in rats with septic peritonitis than in control rats 12 and 24 hours after cecal ligation and puncture. Protein degradation was unchanged. The results support the concept that net production of hepatic protein is increased in septic peritonitis, due to accelerated synthesis and unchanged degradation. Since other hepatocellular functions were previously reported to be depressed in the same experimental model, the present results indicate that hepatic protein synthesis has high priority during sepsis.
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PMID:Protein synthesis and degradation in liver tissue following induction of septic peritonitis in rats. 395 15

To evaluate the morbidity and mortality of corrosive esophageal injuries (CEI) in the neonatal period, the records of 184 children hospitalized following caustic ingestion over a 10-year period from January 1987 to November 1997 were reviewed. Eight (4.3%) were newborns (5 boys and 3 girls). The mean age of the newborns was 12 days (range 1-28). The ingested caustic materials were benzalkonium chloride in six patients and trichloroacetic acid in two. Oropharyngeal examination and esophagoscopy were performed for diagnosis. Hyperemia and fibrin plaques were present in the oropharynx in all patients. The management consisted of endotracheal intubation, antibiotics, corticosteroids, and total parenteral nutrition. Pneumonia and sepsis developed in three patients and one died of sepsis. Stenosis developed in two patients, who were treated three times with antegrade dilatations. The morbidity was 62.5% (five patients) and the mortality was 12.5% (one) in newborns with CEI. These results indicate that ingestion of a caustic substance results in high morbidity and mortality in newborns. Parents and nurses should be warned about this risk.
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PMID:Corrosive injuries of the esophagus in newborns. 1105 46

During the period from 1974 to June 2000 we used the straight ileo-anal Soave pull-through to treat 42 patients (24 affected by total colonic aganglionosis [TCA], 10 with ulcerative colitis and 8 with familial polyposis). The aim of this paper is to show that this operation, associated with total colectomy, is highly recommended, causing a lower number of complications when compared to the various "reservoir" techniques. The mean age of the 24 patients with TCA at the time of the pull-through was 2.8 years; in the ulcerative colitis group, it was 14.3 years and in the familial polyposis group 27.2 years. We always used an ileo-anal deferred anastomosis and never performed temporary loop-diverting ileostomy at the time of the pull-through. In the TCA patients we had no immediate or long-term serious post-operative complications: ileal adaptation, after a frequency of 10 - 12 liquid stools a day, showed a gradual, constant and in some cases amazing improvement in all children. Two years after surgery, the mean stool frequency was 3.6 per 24 hours with no significant differences between the 3 main groups; only 4 children still presented with occasional soiling. After pull-through, all children showed normal growth curves in the long term. There was no malabsorption, no serious electrolyte imbalance, no perianal excoriation, no strictures or intestinal obstruction; their quality of life was considered more than satisfactory by the children's families. We have no direct experience with the various ileal "reservoir" techniques for ulcerative colitis and ileal polyposis nor with colon-sparing operations for TCA; as reported in the literature, all these surgical procedures seem to have a higher number of complications such as pelvic sepsis, pouchitis, enterocolitis, etc. compared with our series; we therefore confirm that total colectomy with the straight ileo-anal Soave pull-through is our treatment of choice, as it is simpler to perform and has fewer short- and long-term complications.
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PMID:Total colectomy and straight ileo-anal soave endorectal pull-through: personal experience with 42 cases. 1171 70

Measurement of plasma neopterin by HPLC with fluorescence detection is used clinically as a marker of immune cell activation in the management of a number of disease pathologies. HPLC analysis of neopterin requires the acidic removal of plasma proteins but we have found that 7,8-dihydroneopterin is oxidised to neopterin with varying yield. Using acetonitrile as the precipitant, we have measured substantially higher quantities of both total neopterin (7,8-dihydroneopterin and neopterin) and neopterin from plasma of healthy and septicemia patient's. Total neopterin concentrations were on average 50% and 200% greater in healthy and septicemia subjects, respectively, when measured after acetonitrile precipitation compared to trichloroacetic acid. Our data suggests that some pterin co-precipitates with proteins during acid treatment.
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PMID:Dissociation of neopterin and 7,8-dihydroneopterin from plasma components before HPLC analysis. 1823 68

The present study reports comparative genomics and proteomics of Staphylococcus epidermidis (SE) strains isolated from bovine intramammary infection (PM221) and human hosts (ATCC12228 and RP62A). Genome-level profiling and protein expression analyses revealed that the bovine strain and the mildly infectious ATCC12228 strain are highly similar. Their genomes share high sequence identity and synteny, and both were predicted to encode the commensal-associated fdr marker gene. In contrast, PM221 was judged to differ from the sepsis-associated virulent human RP62A strain on the basis of distinct protein expression patterns and overall lack of genome synteny. The 2D DIGE and phenotypic analyses suggest that PM221 and ATCC12228 coordinate the TCA cycle activity and the formation of small colony variants in a way that could result in increased viability. Pilot experimental infection studies indicated that although ATCC12228 was able to infect a bovine host, the PM221 strain caused more severe clinical signs. Further investigation revealed strain- and condition-specific differences among surface bound proteins with likely roles in adhesion, biofilm formation, and immunomodulatory functions. Thus, our findings revealed a close link between the bovine and commensal-type human strains and suggest that humans could act as a reservoir of bovine mastitis-causing SE strains.
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PMID:Genomics and Proteomics Provide New Insight into the Commensal and Pathogenic Lifestyles of Bovine- and Human-Associated Staphylococcus epidermidis Strains. 2501 94

The human genitourinary tract is a common anatomical niche for polymicrobial infection and a leading site for the development of bacteremia and sepsis. Most uncomplicated, community-acquired urinary tract infections (UTI) are caused by Escherichia coli, while another bacterium, Proteus mirabilis, is more often associated with complicated UTI. Here, we report that uropathogenic E. coli and P. mirabilis have divergent requirements for specific central pathways in vivo despite colonizing and occupying the same host environment. Using mutants of specific central metabolism enzymes, we determined glycolysis mutants lacking pgi, tpiA, pfkA, or pykA all have fitness defects in vivo for P. mirabilis but do not affect colonization of E. coli during UTI. Similarly, the oxidative pentose phosphate pathway is required only for P. mirabilis in vivo. In contrast, gluconeogenesis is required only for E. coli fitness in vivo. The remarkable difference in central pathway utilization between E. coli and P. mirabilis during experimental UTI was also observed for TCA cycle mutants in sdhB, fumC, and frdA. The distinct in vivo requirements between these pathogens suggest E. coli and P. mirabilis are not direct competitors within host urinary tract nutritional niche. In support of this, we found that co-infection with E. coli and P. mirabilis wild-type strains enhanced bacterial colonization and persistence of both pathogens during UTI. Our results reveal that complementary utilization of central carbon metabolism facilitates polymicrobial disease and suggests microbial activity in vivo alters the host urinary tract nutritional niche.
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PMID:Preferential use of central metabolism in vivo reveals a nutritional basis for polymicrobial infection. 2556 46

Ionizing radiation exposure combined with wound injury increases animal mortalities than ionizing radiation exposure alone. Ciprofloxacin (CIP) is in the fluroquinolone family of synthetic antibiotic that are available from the strategic national stockpile for emergency use and is known to inhibit bacterial sepsis. The purpose of this study was to evaluate the efficacy of ciprofloxacin as a countermeasure to combined injury mortality and determine the signaling proteins involved in energy machinery. B6D2F1/J female mice were randomly assigned to receive either 9.75 Gy irradiation with Co-60 gamma rays followed by skin wounding (combined injury; CI) or sham procedure (sham). Either ciprofloxacin (90 mg/kg/day) or vehicle (VEH) (water) was administered orally to these mice 2 h after wounding and thereafter daily for 10 days. Determination of tissue adenosine triphosphate (ATP) was conducted, and immunoblotting for signaling proteins involved in ATP machinery was performed. Combined injury resulted in 60% survival after 10 days compared to 100% survival in the sham group. Furthermore, combined injury caused significant reductions of ATP concentrations in ileum, pancreas, brain, spleen, kidney and lung (-25% to -95%) compared to the sham group. Ciprofloxacin administration after combined injury resulted in 100% survival and inhibited reductions in ileum and kidney ATP production. Ileum protein levels of heat-shock protein 70 kDa (HSP-70, a chaperone protein involved in ATP synthesis) and pyruvate dehydrogenase (PDH, an enzyme complex crucial to conversion of pyruvate to acetyl CoA for entrance into TCA cycle) were significantly lower in the CI group (vs. sham group). Using immunoprecipitation and immunoblotting, HSP-70-PDH complex was found to be present in the ileum tissue of CI mice treated with ciprofloxacin. Furthermore, phosphorylation of serine residues of PDH resulting in inactivating PDH enzymatic activity, which occurred after combined injury, was inhibited with ciprofloxacin treatment, thus enabling PDH to increase ATP production. Increased ileum levels of pyruvate dehydrogenase kinase 1 protein (PDK1, an enzyme responsible for PDH phosphorylation) after combined injury were also prevented by ciprofloxacin treatment. Taken together, these data suggest that ciprofloxacin oral administration after combined injury had a role in sustained ileum ATP levels, and may have acted through preservation of PDH by HSP-70 and inhibition of PDK1. These molecular changes in the ileum are simply one of a host of mechanisms working in concert with one another by which ciprofloxacin treatment mitigates body weight loss and drastically enhances subsequent survival after combined injury. To this end, our findings indicate that oral treatment of ciprofloxacin is a valuable therapeutic treatment after irradiation with combined injury and warrants further analyses to elucidate the precise mechanisms involved.
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PMID:Ciprofloxacin Therapy Results in Mitigation of ATP Loss after Irradiation Combined with Wound Trauma: Preservation of Pyruvate Dehydrogenase and Inhibition of Pyruvate Dehydrogenase Kinase 1. 2601 Jul 14


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