Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004610 (bacteremia)
 13,199 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Markedly increased synthesis of alpha(2) and beta globulins and alpha(1), alpha(2), and beta glycoglobulins occurs during pneumococcal sepsis in the rat simultaneously with decreased albumin formation, diminished tritiated leucine incorporation into muscle protein, and enhanced excretion of nitrogen. This augmented synthesis of specific serum proteins does not become evident until fever and bacteremia develop, and it appears to be a fundamental aspect of host response to a proliferating bacterial infection in that it occurs even in rats fed a protein-deficient (6% protein) diet after weaning and before exposure to Diplococcus pneumoniae. Although amino acid catabolism, in general, appears to be increased during infection, tryptophan degradation via the kynurenine pathway, as assessed by measuring diazotizable urinary metabolites, changes little or is, at times, significantly less than in control animals. Coincidentally, functional tryptophan oxygenase activity decreases at 16 hr after exposure. Total tryptophan oxygenase activity, however, is unchanged.
 ...
PMID:Nitrogen metabolism and protein synthesis during pneumococcal sepsis in rats. 440 82

Indoleamine 2,3-dioxygenase (IDO), which is the rate-limiting enzyme for tryptophan (trp) catabolism, may play a critical role in various inflammatory disorders. Recent studies on trauma patients have suggested that the degradation of trp is associated with the development of sepsis. The role of IDO activity in bacteremic patients is unclear. We studied IDO activity in 132 patients with bacteremia caused by Staphylococcus aureus, Streptococcus pneumoniae, beta-hemolytic streptococcae, or Eschericia coli. The serum concentrations of trp and its metabolite kynurenine (kyn) were measured by reverse-phase high-performance liquid chromatography 1 to 4 days after the positive blood culture and on recovery. The kyn-to-trp ratio (kyn/trp), reflecting the activity of the IDO enzyme, was calculated. The maximum value in the ratio for every patient during 1 to 4 days after positive blood culture was used in analysis. The maximum kyn/trp ratio was significantly higher in nonsurvivors versus those who survived (193.7 vs. 82.4 micromol/mmol; P = 0.001). The AUC(ROC) of maximal kyn/trp in the prediction of case fatality was 0.75 (95% confidence interval, 0.64-0.87), and the kyn/trp ratio at a cutoff level of 120 micromol/mmol showed 83% sensitivity and 69% specificity for fatal disease. A kyn/trp ratio greater than 120 micromol/mmol was associated with increased risk of death versus low (<or=120 micromol/mmol) ratios (odds ratio, 10.8; confidence interval, 3.0-39.8). High IDO activity also remained an independent risk factor for case fatality in a multivariate model adjusted for potential confounders. The data in this report demonstrate that IDO activity is markedly increased in bacteremia patients, constituting an independent predictor of severe disease and case fatality.
 ...
PMID:High activity of indoleamine 2,3 dioxygenase enzyme predicts disease severity and case fatality in bacteremic patients. 1948 73

Tuberculosis (TB) continues to be a major health problem, and there are few biomarkers for predicting prognosis. Indoleamine 2,3-dioxygenase (IDO), a potent immunoregulatory molecule, catalyzes the rate-limiting step of tryptophan (Trp) degradation in the kynurenine (Kyn) pathway. An increase in IDO activity determined by the serum Trp/Kyn ratio has been shown to be associated with poor prognosis in cancers and bacteremia. In TB, however, there are no studies measuring serum IDO activity to determine its clinical significance. We evaluated serum IDO activity with 174 pulmonary TB (PTB) patients and 85 controls, using liquid chromatography/electrospray ionization tandem mass spectrometry. IDO activity was estimated by calculating the serum Kyn-to-Trp ratio. PTB patients had significantly higher Kyn concentrations and IDO activity and significantly lower Trp concentrations (P < 0.0001, P < 0.0001, and P < 0.0001, respectively) than the controls. Of 174 PTB patients, 39 (22.4%) died. The patients who died had significantly higher concentrations of Kyn and significantly lower Trp concentrations, resulting in significantly higher IDO activity (P < 0.0001, P < 0.0001, and P < 0.0001, respectively). In a receiver operating characteristic (ROC) analysis, serum IDO activity had the highest area under the curve (0.850), and this activity was an independent prognostic factor in multivariate analysis. These results suggest that serum IDO activity can be used as a novel prognostic marker in PTB.
 ...
PMID:Serum indoleamine 2,3-dioxygenase activity predicts prognosis of pulmonary tuberculosis. 2221 12

Delftia acidovorans (earlier known as Comamonas acidovorans) is an aerobic, non-fermentative, Gram negative rod, classified in the Pseudomonas rRNA homology Group III. Reports of isolation of the organism from serious infections like central venous catheter associated bacteremia, corneal ulcers, otitis media exist. The microbiologists can identify this organism based on an orange indole reaction. This reaction demonstrates the organism's ability to produce anthranilic acid from tryptophan on addition of Kovac's reagent; which gives the media its characteristic "pumpkin orange" colour. Here we report the isolation of this organism from the Endotracheal tube aspirate of a 4 year old child. With the increasing use of invasive devices, it has become important to recognize these non fermentative gram negative bacilli as emerging source of infection even in immunocompetent individuals.
 ...
PMID:Fatal Delftia acidovorans infection in an immunocompetent patient with empyema. 2356 72

Enteric fever, caused by Salmonella enterica serovar Typhi, is an important public health problem in resource-limited settings and, despite decades of research, human responses to the infection are poorly understood. In 41 healthy adults experimentally infected with wild-type S. Typhi, we detected significant cytokine responses within 12 h of bacterial ingestion. These early responses did not correlate with subsequent clinical disease outcomes and likely indicate initial host-pathogen interactions in the gut mucosa. In participants developing enteric fever after oral infection, marked transcriptional and cytokine responses during acute disease reflected dominant type I/II interferon signatures, which were significantly associated with bacteremia. Using a murine and macrophage infection model, we validated the pivotal role of this response in the expression of proteins of the host tryptophan metabolism during Salmonella infection. Corresponding alterations in tryptophan catabolites with immunomodulatory properties in serum of participants with typhoid fever confirmed the activity of this pathway, and implicate a central role of host tryptophan metabolism in the pathogenesis of typhoid fever.
 ...
PMID:Interferon-driven alterations of the host's amino acid metabolism in the pathogenesis of typhoid fever. 2721 37