In Silico and In Vitro Study: COX-2 Inhibition by Ethanol Extract of Dayak Onion Bulb (Eleutherine Americana Merr) as Treatment Innovation of Benign Prostatic Hyperplasia (BPH).

INTRODUCTION: Benign Prostatic Hyperplasia (BPH) is a benign tumor in males, which is histopathologically known with an increase of epithelial cells and prostatic stroma. Androgens, estrogens, stroma-epithelial interactions, growth factors, and chronic inflammation play a key role in the occurrence of BPH. Chronic inflammation in BPH is characterized by excessive expression of COX-2, which will trigger the expression of Bcl-2 anti-apoptotic protein. Dayak onion (Eleutherine Americana Merr) is a typical Kalimantan plant that is known as the treatment for prostate disease. This plant contains flavonoids which can inhibit the COX-2 enzyme thus causing a reduction in the production of prostaglandin E2. METHODS: This research was experimental research computationally and in vitro laboratory experimental research to determine COX-2 inhibitory activity by ethanol extracts of Dayak onion. RESULTS AND DISCUSSION: In in silico flavonoid, it was strongly related to COX-2 receptor on the active side of TYR371. Thus, it had the potential to inhibit COX-2. COX-2 inhibitor would cause BCL-2 to be inactive so that apoptosis occurr in BPH. In the in vitro research using human whole blood assay, the Dayak Onion bulb ethanol extract had IC50 COX-2 of 40.57 ng/ml and IC50 COX-1 of 364.89 ng/ml. Therefore, the ratio of IC50 COX-2 to IC50 COX-1 was 0.11. CONCLUSION: Ethanol extract of Dayak onion bulb has an inhibitory activity against COX-2. Thus, it has a potential of being an innovation for BPH treatment. Patient Summary: A healthy male, age 25-35 years old (history taking, physical and laboratory examination), and not using NSAIDs for the past 2 weeks.

High-frequency micro-ultrasound: a novel method to assess external urethral sphincter function in rats following simulated birth injury.

AIMS: We evaluated external urethral sphincter (EUS) function using high-frequency micro-ultrasound (US) in rats that were either uninjured (Control, C) or underwent vaginal distension (VD) as a substitute for vaginal birth injury induced stress urinary incontinence (SUI). METHODS: Thirteen female nulliparous Sprague-Dawley rats of 12 weeks were divided into two groups, either C (n = 6) or VD (n = 7). Vaginal balloon distension was performed under pentobarbital anesthesia for 4 hours. Five days after the injury, all animals underwent US assessment of the urethra during high-rate bladder filling and urine leakage/voiding. Urinary leakage, the presence, absence, and pattern of EUS bursting during the voiding phase were registered, and pre-determined parameters of intercontraction interval (ICI), length of contraction (LOC), and rate of contraction (ROC) were registered. RESULTS: Our ultrasound findings consistently showed the presence of rhythmic EUS bursting in all of the C rats (6/6), which were absent in all VD rats (0/7). The mean of ROC, ICI, and LOC in C group were 3.02 ± 0.12 contractions/sec, 471.43 ± 17.9 msec, and 103.41 ± 3.28 msec, respectively. CONCLUSIONS: Pre-determined parameters of LOC, ICI, and ROC during US provide objective and measurable data on EUS function. US showed the total disappearance of EUS bursting in the VD group as compared to the C group. These results indicate that ultrasound testing may become a valuable non-invasive tool in future translational studies to investigate SUI/urethral function in rat models.

Prostate-specific antigen and prostate-specific antigen density cutoff points among Indonesian population suspected for prostate cancer.

PURPOSE: Racial differences exist in the incidence of prostate cancer (PCa). Although many studies have looked at the performance of prostate-specific antigen (PSA) and PSA density (PSAD) in the detection of PCa, only a few have looked at it in relation to Indonesian men. The objective of this study is to find out better PSA and PSAD cutoff point in the detection of PCa in Indonesian men. METHODS: A total of 404 consecutive Indonesian men underwent prostate biopsy for suspicion of PCa from 2008 to 2011. The biopsy criteria include one or more of the following: serum PSA more than 10 ng/mL, PSAD more than 0.15 if PSA 4-10 ng/mL, hypoechoic lesion during transrectal sonography and/or abnormal digital rectal examination. RESULTS: Forty five out of 404 (11.1%) had positive biopsies. The mean age, prostate volume, PSA and PSAD were respectively 64.06 years, 43.03 mL, 45.59 ng/mL and 1.15. Of the 404, 131 cases (32.4%) were confirmed to be urinary retention. Positive urine culture found in 182 cases (45%). The cutoff point to detect PCa as estimated by the receiver operating characteristics was 6.95 ng/mL for PSA (sensitivity 97.8%, specificity 19.6%) and 0.7072 for PSAD (sensitivity 62.2%, specificity 78.7%). Positive predictive value for this PSA and PSAD cutoff point were 11.6% and 27.5% respectively (P=0.004 and P=0.000). There was a significant correlation between hypoechoic lesion and positive biopsy results (P =0.000). Urinary retention elevates PSA cutoff point to 14.55 (sensitivity 90.9%, specificity 50%), while positive urine culture alters almost no PSA cutoff elevation. CONCLUSIONS: PSA and PSAD cutoff point for Indonesian men in this series is relatively different from international consensus. Furthermore, these data show that PSA and PSAD cutoff point must be adjusted to racial variation to discriminate between malignant and benign disease. Urinary retention is a significant factor for PSA cutoff increase.

Efficacy and safety of tamsulosin hydrochloride compared to doxazosin in the treatment of Indonesian patients with lower urinary tract symptoms due to benign prostatic hyperplasia.

AIM: The objective of the study was to compare the efficacy and safety of tamsulosin hydrochloride and doxazosin in patients with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). METHODS: The safety and efficacy of tamsulosin (0.2 mg) and doxazosin (2 mg) was determined after once daily administration for 6 weeks in an open-label, randomized, multicenter study of 101 men with BPH. The International Prostatic Symptom Score (IPSS), maximal urinary flow rates (Qmax), average urinary flow rates (Qave) and residual urine were determined at baseline and again at 6 weeks as efficacy parameters. The primary parameters used for safety evaluation were vital signs (blood pressure and heart rate) and adverse events. The number of patients with a clinically significant response to treatment with tamsulosin or doxazosin was determined and defined as those with >20% improvement from the baseline Qmax or >20% decrease in total IPSS. RESULTS: The total IPSS decreased significantly in both the tamsulosin and doxazosin groups compared to baseline. There was a significant difference in the decrease in total IPSS between two groups. Qmax, Qave and residual urine significantly improved only in the tamsulosin group. There were no significant differences in systolic blood pressure, diastolic blood pressure or heart rate profile in the tamsulosin group; however, doxazosin resulted in a significant difference in systolic and diastolic blood pressure. Tamsulosin was well tolerated; only three patients (6%) in the tamsulosin group reported an adverse event (dizziness) while 11 patients (22%) in the doxazosin group reported an adverse event (dizziness), one of whom withdrew from the study. CONCLUSIONS: Tamsulosin was shown to be more effective than doxazosin in the treatment of LUTS due to BPH.

The 3rd Conference on Asian Trends in Prostate Cancer Hormone Therapy.

From its inception in 2001, the Conference on Asian Trends in Prostate Cancer Hormone Therapy has served as an annual forum for Asian urologists to compare data on prostate cancer and to discuss issues regarding the use of hormone therapy. The 3rd conference, held in Tokyo in December 2003, began with participants from China, Indonesia, Japan, Korea, Singapore, and Taiwan presenting QOL data deriving from a survey of patients with prostate cancer. For this purpose, each country translated the Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire into its own language. Although the surveys conducted in each country included a heterogeneous cohort of patients and gave very mixed results, the trial of FACT-P in Asian countries seemed propitious and in future may provide insights that could prove beneficial to patients. Day 2 of the conference included 2 discussions, focusing on the most appropriate number of biopsy cores and the implementation of prospective trials involving the collaboration of Asian countries, respectively. In the latter discussion, although a varied assortment of proposals were put forth, the participants generally agreed that any collaborative study must be a prospective outcome study conducted in a relatively short time not exceeding 2-3 years, and that patient registration should be done using the Internet.

The 2nd conference on Asian trends in prostate cancer hormone therapy.

Among the aims of the 2nd Conference on Asian Trends in Prostate Cancer Hormone Therapy, Hong Kong, December 7-8, 2002, was to lay the groundwork for eventually having cooperative or collaborative studies of prostate cancer specifically in Asian patients. The conference was divided into 2 sessions. In the first session, entitled "Current Status of Therapy for Prostate Cancer in Asian Countries," the results of analysis of 100 patients with prostate cancer enrolled in the Patients Registration System is each of the 6 participating Asian countries were discussed. The Patients Registration System is a database template established by the Japanese Urological Association that allows physicians to compare prostate cancer therapy in the different Asian countries. Session 2 was devoted to a "Roundtable Discussion on the Establishment of Asian Guidelines for Prostate Cancer." This session included 2 lively discussions, on whether Asian physicians can apply Western clinical data to Asian patients, and the need for Asian clinical data and developing clinical trials in the region, respectively.

Asian trends in prostate cancer hormone therapy.

The first Conference on Asian Trends in Prostate Cancer Hormone Therapy was held in September 2001 to serve as a forum for Asian urologists to compare data on prostate cancer and discuss issues regarding the use of hormone therapy. The conference revealed that due to various cultural and philosophical factors, differences exist in prostate cancer management among the Asian countries. In addition, a lack of databases on hormone therapy was exposed in some countries. It was noted that many decisions in the treatment of prostate cancer are influenced by the strategies adopted in Western countries, and that attempts to formulate uniform guidelines for the Asian region have hitherto been unsuccessful. The main findings of the conference are reported in this review.