The urinary excretion of leukotriene E4 (LTE4) was measured in subjects presenting for emergency treatment of airway obstruction. A total of 72 subjects presenting with airway obstruction performed peak flow determinations before and after three treatments with nebulized albuterol given at 20-min intervals. Of these subjects, 22 more than doubled their peak flow rates, while 19 failed to increase their peak flow rates more than 25% during the treatment period. These groups were designated "responders" and "nonresponders," respectively. Urinary LTE4 excretion was determined in 16 of the 22 responders and 12 of the 19 nonresponders as well as 13 normal subjects by precolumn extraction, analytic reversed-phase high-performance liquid chromatography, and enzyme immunoassay. In the normal subjects the urinary LTE4 excretion was significantly (p less than 0.0001) less than the urinary LTE4 measured in the responder subjects, but not less than the urinary LTE4 excretion in the nonresponder group (p = 0.071). The enhanced recovery of LTE4 from the urine of subjects with acutely reversible airway narrowing is consistent with a bronchoconstrictor role for the cysteinyl leukotrienes in spontaneous acute asthma.

Epidemiological studies showed that women have a lower bladder cancer (BCa) incidence, yet higher muscle-invasive rates than men, suggesting that estrogen and the estrogen receptors, estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ), may play critical roles in BCa progression. Using in vitro cell lines and an in vivo carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced mouse BCa model, we found that ERβ plays a positive role in promoting BCa progression. Knockdown of ERβ with ERβ-shRNA in ERβ-positive human BCa J82, 647v and T24 cell lines led to suppressed cell growth and invasion. Mice lacking ERβ have less cancer incidence with reduced expression of the proliferation marker Ki67 in BBN-induced BCa. Consistently, our results show that non-malignant urothelial cells with ERβ knockdown are more resistant to carcinogen-induced malignant transformation. Mechanism dissection found that targeting ERβ suppressed the expression of minichromosome maintenance complex component 5 (MCM5), a DNA replication licensing factor that is involved in tumor cell growth. Restoring MCM5 expression can partially reverse ERβ knockdown-mediated growth reduction. Supportively, treating cells with the ERβ-specific antagonist, 4-[2-Phenyl-5,7-bis(trifluoromethyl) pyrazolo[1,5-a]pyrimidin-3-yl]phenol (PHTPP), reduced BCa cell growth and invasion, as well as MCM5 expression. Furthermore, we provide the first evidence that BCa burden and mortality can be controlled by PHTPP treatment in the carcinogen-induced BCa model. Together, these results demonstrate that ERβ could play positive roles in promoting BCa progression via MCM5 regulation. Targeting ERβ through ERβ-shRNA, PHTPP or via downstream targets, such as MCM5, could serve as potential therapeutic approaches to battle BCa.

Andropause symptoms and erectile dysfunction are common among infertile men, affecting approximately 38% of this population. This finding suggests that the population of infertile men should be carefully screened to identify and treat those with erectile dysfunction.

Microsurgical varicocelectomy with intentional preservation of the testicular artery(ies) is regarded as the gold standard approach to varicocele repair. We sought to determine whether the number of testicular arteries preserved at the time of micro-surgical varicocelectomy predicts improvement in postoperative semen parameters. We analyzed the records of 334 infertile men who underwent varicocelectomy performed by a single surgeon using a subinguinal microsurgical technique between July 1996 and January 2003. We examined the association between the number of testicular arteries preserved at the time of varicocelectomy and serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), varicocele grade, testicular volume, and postoperative improvement in semen parameters. Unilateral, left-sided varicocelectomy was performed in 194 men, while bilateral varicocelectomy was performed in 140 men. Mean (+/-SE) sperm concentration (20.1 +/- 1.5 x 10(6)/mL to 26.7 +/- 1.9 x 10(6)/mL, P =.001), percent motility (24.7 +/- 1.0% to 30.9 +/- 1.2%, P =.001), and percent normal morphology (35.8 +/- 1.4% to 37.7 +/- 1.5%, P =.046) improved significantly following varicocelectomy. The mean number of preserved testicular arteries was 1.5 on the left (range, 1-4) and 1.5 on the right (range, 1-4). The number of testicular arteries preserved at the time of varicocelectomy did not correlate significantly with preoperative assessment of serum FSH, LH, varicocele grade, and testicular volume or with postoperative improvement in semen parameters. Our data indicate that preoperative parameters are not predictive of the number of testicular arteries identified at the time of microsurgery. These data also suggest that the number of arteries identified and preserved with meticulous spermatic cord dissection does not correlate with improvement in semen parameters.