Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018099 (gout)
 5,192 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Elevated serum uric acid (SUA) or urate is associated with inflammation and gout. Recent evidence has linked urate to cancers, but little is known about urate effects in prostate cancer. Activins are inflammatory cytokines and negative growth regulators in the prostate. A hallmark of prostate cancer progression is activin insensitivity; however, mechanisms underlying this are unclear. We propose that elevated SUA is associated with prostate cancer counteracting the growth inhibitory effects of activins. The expression of activins A and B, urate transporter GLUT9 and tissue urate levels were examined in human prostate disease. Intracellular and secreted urate and GLUT9 expression were assessed in human prostate cancer cell lines. Furthermore, the effects of urate and probenecid, a known urate transport inhibitor, were determined in combination with activin A. Activin A expression was increased in low-grade prostate cancer, whereas activin B expression was reduced in high-grade prostate cancer. Intracellular urate levels decreased in all prostate pathologies, while GLUT9 expression decreased in benign prostatic hyperplasia, prostatitis and high-grade prostate cancer. Activin responsive LNCaP cells had higher intracellular and lower secreted urate levels than activin-insensitive PC3 cells. GLUT9 expression in prostate cancer cells was progressively lower than in prostate epithelial cells. Elevated extracellular urate was growth promoting in vitro, which was abolished by the gout medication probenecid, and it antagonized the growth inhibitory effects of activins. This study shows for the first time that a change in plasma or intracellular urate levels, possibly involving GLUT9 and a urate efflux transporter, has an impact on prostate cancer cell growth, and that lowering SUA levels in prostate cancer is likely to be therapeutically beneficial.
 ...
PMID:Uric acid: a modulator of prostate cells and activin sensitivity. 2691 Jul 79

Erectile dysfunction (ED) affects millions of men worldwide. Men with ED generally complain failure to attain or maintain an adequate erection during sexual activity. The prevalence of ED is strongly correlated with age, affecting about 40% of men at age 40 and nearly 70% at age 70. A variety of chronic diseases, including diabetes, ischemic heart disease, congestive heart failure, hypertension, depression, chronic renal failure, obstructive sleep apnea, prostate disease, gout, and sleep disorder, were reported to be associated with ED. In this study, data retrieved from a subset of the National Health Insurance Research Database of Taiwan were used for designing the clinical decision support system (CDSS) for predicting ED incidences in men. The positive cases were male patients aged 20-65 who were diagnosed with ED between January 2000 and December 2010 confirmed by at least three outpatient visits or at least one inpatient visit, while the negative cases were randomly selected from the database without a history of ED and were frequency (1:1), age, and index year matched with the ED patients. Data of a total of 2832 ED patients and 2832 non-ED patients, each consisting of 41 features including index age, 10 comorbidities, and 30 other comorbidity-related variables, were retrieved for designing the predictive models. Integrated genetic algorithm and support vector machine was adopted to design the CDSSs with two experiments of independent training and testing (ITT) conducted to verify their effectiveness. In the 1st ITT experiment, data extracted from January 2000 till December 2005 (61.51%, 1742 positive cases and 1742 negative cases) were used for training and validating and the data retrieved from January 2006 till December 2010 were used for testing (38.49%), whereas in the 2nd ITT experiment, data in the training set (77.78%) were extracted from January 2000 till Deceber 2007 and those in the testing set (22.22%) were retrieved afterward. Tenfold cross validation and three different objective functions were adopted for obtaining the optimal models with best predictive performance in the training phase. The testing results show that the CDSSs achieved a predictive performance with accuracy, sensitivity, specificity, g-mean, and area under ROC curve of 74.72%-76.65%, 72.33%-83.76%, 69.54%-77.10%, 0.7468-0.7632, and 0.766-0.817, respectively. In conclusion, the CDSSs designed based on cost-sensitive objective functions as well as salient comorbidity-related features achieve satisfactory predictive performance for predicting ED incidences.
 ...
PMID:Design of a Clinical Decision Support System for Predicting Erectile Dysfunction in Men Using NHIRD Dataset. 3036 56