Koh Takeyama

Membrane-Anchored CD14 Is Important for Induction of Interleukin-8 by Lipopolysaccharide and Peptidoglycan in Uroepithelial Cells

ABSTRACT We investigated the induction of interleukin-8 (IL-8) by bacterial lipopolysaccharide (LPS) and peptidoglycan (PGN) in the bladder cancer cell lines T24, 5637, UM-UC-3, and HT1197. T24 and 5637 cells strongly induced IL-8 after stimulation with LPS or PGN in a dose- and time-dependent manner, whereas UM-UC-3 and HT1197 cells did so very weakly. The expression of CD14 at the mRNA, total cellular protein, and cell surface protein levels differed among these cell lines, but the expression levels of Toll-like receptors 2 and 4 (TLR2 and TLR4) were not significantly different. The CD14 expression levels were found to correlate with the inducibility of IL-8 by LPS or PGN. Treatment of T24 and 5637 cells with phosphatidylinositol-specific phospholipase C to eliminate CD14 from the cell surface dramatically suppressed the induction of IL-8. On the other hand, UM-UC-3 cells transfected with CD14 cDNA expressed membrane-anchored CD14 and showed more efficent induction of IL-8 by LPS stimulation than untransfected controls. These results suggest that the presence of the membrane-anchored, but not the soluble, form of CD14 is a strong factor in IL-8 induction in bladder epithelial cells in response to bacterial components. The presence of the membrane-anchored form of CD14 may thus be a determinant for the inflammatory response of uroepithelial cells.

Clinical efficacy of azithromycin for male nongonococcal urethritis

The aim of this study was to confirm the clinical efficacy of a single-dose azithromycin (AZM) regimen (1000 mg) for patients with nongonococcal urethritis in real-life practice. The study finally evaluated 55 patients, 42 who were symptomatic and 13 who were asymptomatic, after excluding 40 who visited clinics only once. Sixteen of the symptomatic patients were diagnosed as having nongonococcal chlamydial urethritis, 7 as having nongonococcal nonchlamydial urethritis, and 19 as having urethritis without any microbial detection. Chlamydia trachomatis was detected in 11 asymptomatic patients, Mycoplasma genitalium in 1, and Ureaplasma urealyticum in 1. Of the patients who were microbiologically evaluated before and after single-dose AZM, microbiological cure was achieved in 87% (20/23) of those with symptomatic nongonococcal urethritis and in 100% (13/13) of those with asymptomatic nongonococcal urethritis. The clinical cure rate was 86% for the 42 symptomatic patients with detectable and undetectable pathogens. There were adverse events in 5 (9%) patients but they were commonly mild and self-limited. In conclusion, the single-dose AZM regimen was well tolerated and eradicated the estimated and potential pathogens of nongonococcal urethritis.

α1-blocker tamsulosin as initial treatment for patients with benign prostatic hyperplasia: 5-year outcome analysis of a prospective multicenter study.

To comprehensively analyze the 5‐year outcomes of tamsulosin treatment for patients with benign prostatic hyperplasia.

Efficacy of treatment with carbapenems and third-generation cephalosporins for patients with febrile complicated pyelonephritis.

The purpose of this study was to clarify the clinical relevance of carbapenem and third-generation cephalosporin treatment for febrile complicated pyelonephritis, which often leads to urosepsis. Parenteral antimicrobial treatment with a carbapenem or third-generation cephalosporin was administered to febrile patients and the treatment was switched to oral antimicrobial agents after they became afebrile. In principle, the duration of the course of antimicrobial chemotherapy was limited to a total of 14 days. Clinically, the success rates were 97.3% in the carbapenem group and 96.0% in the third-generation cephalosporin group. For microbiological efficacy, the success rates were 89.2% in the carbapenem group and 92.0% in the third-generation cephalosporin group. There were no serious adverse events in the course of the study. The treatment regimen with a carbapenem or a third-generation cephalosporin was highly effective for patients with febrile complicated pyelonephritis and was well tolerated. Either of these regimens could become one of the standard treatments for patients with febrile complicated pyelonephritis.

Chlamydial seminal vesiculitis without symptomatic urethritis and epididymitis

Abstract  We previously reported that seminal vesiculitis was associated with acute epididymitis, and that Chlamydia trachomatis was the major causative pathogen for infection of the seminal vesicle, suggesting that seminal vesiculitis was a discrete disease entity. In this paper, we report two patients with bacteriologically and cytologically proven seminal vesiculitis who had asymptomatic urethritis but not epididymitis. The clinical courses of these patients suggest that chlamydial seminal vesiculitis may be a cause of asymptomatic infection of the urethra or subsequent development of acute epididymitis.

Pharyngeal Neisseria gonorrhoeae detection in oral-throat wash specimens of male patients with urethritis

Detection of Neisseria gonorrhoeae and Chlamydia trachomatis in the pharynx has been highlighted in the prevention of the unexpected spread of sexually transmitted diseases. We tried to clarify the detection rate of Neisseria gonorrhoeae in the pharynx and the clinical relevance of oral-throat wash specimens to detect the organism in heterosexual men with gonococcal and nongonococcal urethritis. In our cohort of 79 male patients with urethritis, oral throat wash specimens were collected after they had gargled with normal saline for approximately 30 to 60 s. Positive pharyngeal N. gonorrhoeae was defined as a positive result on the strand displacement amplification test for the specimen from the oral-throat wash. N. gonorrhoeae was detected in the oral-throat wash specimens of 13 (31.7%) of the 41 male patients with gonococcal urethritis. Oral-throat wash with a nucleic acid amplification test can detect pharyngeal N. gonorrhoeae easily and efficiently.

The 6-Fluoro-8-Methoxy Quinolone Gatifloxacin Down-Regulates Interleukin-8 Production in Prostate Cell Line PC-3

ABSTRACT Fluoroquinolones exhibit immunomodulatory effects on monocytes and macrophages, in addition to their bactericidal activities. It remains unknown even whether the quinolones act directly on the prostate. This study was based on the understanding of the molecular mechanisms of the actions of the fluoroquinolones that can be used for the treatment of chronic prostatitis/chronic pelvic pain syndrome. We investigated whether the 6-fluroro-8-methoxy quinolone gatifloxacin (GFLX) affected the production and secretion of interleukin-8 (IL-8) in the prostate cell line PC-3. GFLX decreased the level of IL-8 release from unstimulated PC-3 cells. GFLX also attenuated IL-8 secretion from PC-3 cells stimulated with peptidoglycan, Mycoplasma hominis, phorbol ester, and tumor necrosis factor alpha (TNF-α), indicating that GFLX exhibits an anti-inflammatory effect on the prostate cell line. However, GFLX failed to alter activation of the NF-κB and AP-1 elicited by these stimulants. GFLX significantly attenuated the expression of IL-8 mRNA in TNF-α-stimulated PC-3 cells and down-regulated the transcriptional activity of the 5′-flanking region of the IL-8 gene from −1481 to +44 bp. The deletion construct without the 5′-flanking region from −1481 to −170 bp but not the construct without the region from −1481 to −188 bp reversed the suppressive effect of GFLX on IL-8 promoter activity. These results demonstrate that GFLX suppresses IL-8 expression in the prostate cell line by decreasing the promoter activity of the IL-8 gene.

Gatifloxacin treatment for chronic prostatitis: a prospective multicenter clinical trial

Antimicrobial treatment is usually used for chronic prostatitis. However, the efficacy of such treatment has not been fully evaluated. We conducted a study to evaluate the efficacy of gatifloxacin for patients with chronic prostatitis using the Japanese version of the National Institutes of Health Chronic Prostatitis Symptom Index (JPN-NIH CPSI). The study included 46 patients for final analysis. Patients who were younger than 65 years of age were treated with 200 mg gatifloxacin twice daily, and those who were 65 years and older were treated with 100 mg gatifloxacin twice daily, for 4–8 weeks. The study consisted of 10 patients in category II, 13 in category IIIA, 11 in category IIIB, and 12 who were unclassified. The gatifloxacin treatment resulted in significant reductions in the scores on the JPN-NIH CPSI. Of the total number of patients, 58.1% and 27.9% were 25% and 50% responders, respectively, 4 weeks after treatment, and these figures improved to 66.7% and 33.3%, respectively, 8 weeks after treatment. No significant difference was found in the changes in symptom scores between Category II and Category IIIA/IIIB groups. In conclusion, gatifloxacin treatment improved the symptoms in patients with chronic bacterial and nonbacterial prostatitis. This study is the first in this country to evaluate the efficacy of antimicrobial treatment for chronic prostatitis by using the NIH CPSI.

Clinical relevance of single administration of prophylactic antimicrobial agents against febrile events after removal of ureteral stents for patients with urinary diversion or reconstruction.

Objective:  To assess the efficacy of antimicrobial prophylaxis when removing ureteral stents after urinary diversion or reconstruction and to establish the most appropriate prophylactic protocol to prevent febrile events.

Does Baseline Prostate Volume Affect the Short‐Term Outcome of Tamsulosin?

To investigate the short‐term efficacy of tamsulosin treatment for patients with lower urinary tract symptoms (LUTS) suggestive of benign prostatic hyperplasia (BPH) according to baseline prostate volume (PV).