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The levels of reactive oxygen species were compared in semen specimens from suspected subfertile men and from normal volunteers, and correlated with other semen parameters. Reactive oxygen species formation was measured in semen samples that had no white blood cells by a chemiluminescence assay with a Luminometer. The relationship of seminal reactive oxygen species to several sperm parameters was evaluated. A total of 84 specimens from 69 suspected subfertile men and 15 normal volunteers was tested for reactive oxygen species production. Comparison of reactive oxygen species levels in white blood cell-negative patient and donor specimens showed significantly higher values (p < 0.005) in the patient group. Similarly, levels in patient and donor specimens with normal sperm motility were significantly lower (p < 0.005) than those in specimens showing poor motility. The seminal reactive oxygen species levels of white blood cell-negative patients with abnormal morphology were significantly higher (p < 0.005) than those in white blood cell-negative patients with normal morphology. Our results show that seminal reactive oxygen species levels in suspected subfertile men are significantly higher than in normal men, and that the presence of excess reactive oxygen species in semen is positively correlated with low sperm concentration, poor motility and poor morphology. In conclusion, the evaluation of reactive oxygen species levels in cases of idiopathic male infertility could serve as an important marker of sperm dysfunction.

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Background : The aim of the study presented here was to stratify drug therapy for patients with benign prostatic hyperplasia (BPH) displaying various voiding symptoms. Methods : Two different a 1-adrenoceptor antagonists; tamsulosin hydrochloride (Tam) and naftopidil (Naf ), were administered to 96 patients with BPH for 8 weeks in a crossover study.Results : With the administration of both drugs, the International Prostate Symptom Score (I-PSS) significantly decreased and the maximum urinary flow significantly increased. Whereas Naf monotherapy decreased the I-PSS for storage symptoms, Tam monotherapy decreased the I-PSS for voiding symptoms. In both the Naf-to-Tam and Tam-to-Naf groups, crossover was effective when the initial drug was judged subjectively and objectively to have been ineffective. Compliance was acceptable with both drugs. Conclusion : Our results show that either Naf or Tam can be used to treat patients on the basis of objective and subjective assessment of voiding symptoms. Our findings should be helpful for patient guidance and treatment of BPH.

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The HPC2/ELAC2 gene may be associated with hereditary/ familial prostate cancer (PCa). Two common missense variants (Ser217Leu and Ala541Thr) have been reported in the gene. We performed mutational, allelotyping and expression analyses and a molecular epidemiological study to clarify the relations between this gene and prostatic diseases, including PCa and benign prostatic hyperplasia (BPH) in Japanese men. We screened for mutations in 109 patients with PCa including 11 patients from 1 hereditary and 9 familial PCa. Loss of heterozygosity and expression were analyzed. An epidemiological study was done in sporadic PCa (n‫)89؍‬ and BPH (n‫)341؍‬ using 1 novel (Ser627Leu) and 2 previously described polymorphisms of the HPC2/ELAC2 gene. Somatic or germline mutations were not confirmed in any cases of PCa. Loss of heterozygosity at 2 microsatellites, D17S1289 and D17S520, was detected in 1 of 38 and 1 of 35 cases, respectively. Expression analysis revealed decreased or absent mRNA expression in 6 of 38 tumors. Epidemiologic analysis showed that a Leu allele at codon 217 was significantly more frequent in patients with PCa than in controls (10.2% vs. 3.5%, odds ratio ‫؍‬ 3.11; 95% confidence interval, 1.22-7.90). At codon 541, all patients with PCa or BPH and all control subjects had the Ala/Ala genotype. At codon 627, the incidence of the Leu variant was slightly, but not significantly, higher in patients with BPH than in controls (7.0% vs. 2.8%, odds ratio ‫؍‬ 2.59, 95% confidence interval, 0.94 -7.13, not statistically significant). We concluded that germline/somatic mutations of HPC2/ELAC2 are uncommon in PCa. Similarly, allelic imbalances at the gene locus and changes in expression are rare. Although no difference in allele frequency at Ser217Leu between patients with PCa and controls has been reported in a Western population, this polymorphism is a potential indicator of PCa risk in Japanese men and it should be examined in other ethnic groups.

The frequency, severity, and outcome of flutamide-induced hepatic injury were prospectively evaluated in 55 patients with prostate cancer who received 125 mg of flutamide 3 times a day (daily dose: 375 mg) combined with an agonistic analogue of luteinizing hormone-releasing hormone. In addition, we examined plasma and urine concentrations of flutamide and its major metabolites 4 weeks after the beginning of flutamide therapy, and evaluated their significance in predicting flutamide-induced hepatic dysfunction. Hepatic function could be assessed in 50 patients and hepatic dysfunction during therapy was observed in 9 patients (18%); 3 patients (6%) were classified as having moderate liver dysfunction and 6 (12%) were classified as having mild liver dysfunction. The steady-state plasma levels of flutamide and its biologic active metabolite, hydroxyflutamide (OH-Flu), were not related to hepatic dysfunction. However, the concentration of another major metabolite, 4-nitro-3-(trifluoromethyl)phenylamine (FLU-1) was considerably higher in 2 patients who developed clinically significant hepatic dysfunction. These findings suggest that clinically significant hepatic dysfunction could be induced in patients with compromised flutamide metabolism, which leads to a high concentration of FLU-1. Based on results of this study, we propose that plasma FLU-1 levels are one of the predictive factors for flutamide-induced hepatic dysfunction. This hypothesis will be confirmed in a large-scale study.