The association between body mass index and testosterone deficiency in aging Chinese men with benign prostatic hyperplasia: results from a cross-sectional study.

BACKGROUND AND OBJECTIVES: Evidence has supported obesity as a risk factor for both benign prostate hyperplasia (BPH) and hypogonadism. In this paper, we performed a retrospective study and discussed the prevalence of testosterone deficiency (TD) and its relationship to body mass index (BMI) in aging Chinese men with BPH who have surgical intervention. MATERIAL AND METHODS: We reviewed the clinical data by age, BMI, medical history, serum prostate-specific antigen (PSA) levels, serum total testosterone (TT) levels, biochemical analysis, and transrectal ultrasound. BMI and other variables were considered to be independent variables in an effort to evaluate any potential associations between these factors and TD status using non-adjusted and multivariate-adjusted regression models. RESULTS: Of the 795 BPH participants, 27.2% (216) patients had TD. After adjusting for all potential covariates, there was a similar J-shaped relationship between BMI and TD, with an inflection point of 19.2 kg/m2. The effect sizes and the confidence intervals on the left and right sides of this inflection point were 0.6 (0.4-1.0) (p = .043) and 1.2 (1.1-1.3) (p < .001), respectively. CONCLUSION: Nearly one-third of the aging Chinese BPH patients had TD in this study. The association between BMI and TD is not simple. A J-shaped curve correlation was detected. BMI was positively correlated with TD when it was over 19.2 kg/m2 and inversely correlated with TD when it was below 19.2 kg/m2. Long-term prospective studies are needed to confirm these findings.

The possible association between serum interleukin 8 and acute urinary retention in Chinese patients with benign prostatic hyperplasia.

Acute urinary retention (AUR) is one of the progressive manifestations of benign prostatic hyperplasia (BPH). This cross-sectional study was conducted to analyse the possible association between serum interleukin 8 (sIL-8) and AUR in BPH patients to provide evidence of sIL-8 as a potential biomarker for the prediction of AUR. The relationship between sIL-8 levels and AUR was evaluated by logistic regressions in 245 ageing Chinese men with BPH. The discriminant validity of sIL-8 and the optimal cut-off value were determined by a receiver operating characteristic curve. The levels of sIL-8 increased significantly in BPH patients with AUR (p < 0.001). The sIL-8 concentration was positively correlated with AUR in BPH patients (OR = 1.024, 95% CI: 1.009-1.040, p = 0.002). The correlation with AUR in the group with a high sIL-8 level (≥43.05 pg/ml) was significantly enhanced (OR = 8.853, 95% CI: 2.433-32.205, p = 0.001). The sIL-8 level correlated with AUR in Chinese BPH patients independently. As a possible predictor, sIL-8 may contribute to the screening of high-risk populations for AUR to create opportunities for the early effective interventions to improve prognosis and enhance the quality of life. Prospective studies are needed to support all these results.

Down-regulation of spinal D-amino acid oxidase expression blocks formalin-induced tonic pain.

A series of inhibitors of d-amino acid oxidase (DAAO) are specific in blocking chronic pain, including formalin-induced tonic pain, neuropathic pain and bone cancer pain. This study used RNA interference technology to further validate the notion that spinal DAAO mediates formalin-induced pain. To target DAAO, a siRNA/DAAO formulated in polyetherimide (PEI) complexation and a shRNA/DAAO (shDAAO, with the same sequence as siRNA/DAAO after intracellular processing) expressed in recombinant adenoviral vectors were designed. The siRNA/DAAO was effective in blocking DAAO expression in NRK-52E rat kidney tubule epithelial cells, compared to the nonspecific oligonucleotides. Furthermore, multiple-daily intrathecal injections of both siRNA/DAAO and Ad-shDAAO for 7 days significantly inhibited spinal DAAO expression by 50-80% as measured by real-time quantitative PCR and Western blot, and blocked spinal DAAO enzymatic activity by approximately 60%. Meanwhile, both siRNA/DAAO and Ad-shDAAO prevented formalin-induced tonic phase pain by approximately 60%. Multiple-daily intrathecal injections of siRNA/DAAO and Ad-shDAAO also blocked more than 30% spinal expression of GFAP, a biomarker for the activation of astrocytes. These results further suggest that down-regulation of spinal DAAO expression and enzymatic activity leads to analgesia with its mechanism potentially related to activation of astrocytes in the spinal cord.

Serum interleukin 6 and acute urinary retention in elderly men with benign prostatic hyperplasia in China: a cross-sectional study.

BACKGROUND: While acute urinary retention (AUR) is a severe complication of benign prostatic hyperplasia (BPH), it can also indicate the progression of this common disease in aging men. This study aimed at exploring the possible relationship between serum interleukin 6 (sIL-6) and AUR in BPH patients. METHODS: A cross-sectional study was conducted based on 256 elderly men with BPH in China. The association between the sIL-6 level and the occurrence of AUR was evaluated by univariate and multivariable logistic regressions. The receiver operating characteristic (ROC) curve was utilized to determine the discriminant validity of the sIL-6 level and the optimal cut-off value. RESULTS: The concentration of sIL-6 was significantly elevated in the AUR group (P<0.001). A positive correlation was observed between the sIL-6 level and AUR in BPH patients [odds ratio (OR) =1.365, 95% confidence interval (CI): 1.174-1.586, P<0.001]. Based on the ROC curve analysis for sIL-6, the optimal cut-off point of 4.475 pg/mL was set to identify the occurrence of AUR in these patients [area under the curve (AUC) =0.7596, 95% CI: 0.6976-0.8216, P<0.001]. A high sIL-6 level (≥4.475 pg/mL) had a significantly stronger correlation with AUR (OR =9.666, 95% CI: 4.347-21.491, P<0.001). CONCLUSIONS: There was a positive correlation between the sIL-6 level and the occurrence of AUR in elderly Chinese patients with BPH. This study provides potential strategies for the screening of BPH individuals with a possible risk of AUR, which may contribute to the early implementation of effective interventions to improve the quality of life and prognosis. Long-term prospective studies are still required to further illustrate the causal relationship.

Bicalutamide 150 mg as secondary hormonal therapy for castration-resistant prostate cancer.

PURPOSE: This study was aimed to evaluate the effect and tolerability of bicalutamide 150 mg therapy in patients with castration-resistant prostate cancer (CRPC). METHODS: A total of 48 patients with histologically confirmed prostate cancer were included. They had been treated with continuous maximal androgen blockade therapy, but their serum prostate-specific antigen (PSA) increased after initial hormonal therapy. Patients were given bicalutamide (150 mg per day). Serum PSA testing was performed every 3 months. The response was defined according to PSA decline from baseline: PSA decline ≥85% as complete response, ≥50 % but <85% as partial response, and <50 % as failure. Response duration was defined as the time from PSA response until PSA increased ≥25 % or ≥2 ng/mL from the nadir. The potential predictive factors (Gleason score, clinical stage and serum PSA) were investigated. RESULTS: The time of follow-up was 3-30 months. A PSA decline ≥50% was observed in 37 of 48 patients including 18 ≥ 50% but <85% and 19 ≥ 85% responders. The median response duration was 12 months for partial responders and 20 months for complete responders. Patients with lower Gleason score, lower serum PSA and using flutamide as first-line nonsteroidal antiandrogen achieved more benefits. Moreover, bicalutamide 150 mg therapy was well tolerated. CONCLUSIONS: Bicalutamide 150 mg therapy was an appropriate therapeutic method for patients of CRPC, especially for those with lower Gleason score, lower serum PSA and using flutamide as first-line nonsteroidal antiandrogen.

TRPM2 mediates histone deacetylase inhibition-induced apoptosis in bladder cancer cells.

PURPOSE: Inhibition of histone deacetylase (HDAC) activity results in growth arrest and apoptosis in multiple types of cancer cells. It has been well established that p21 is responsible for HDAC inhibitor (HDACi)-induced growth inhibition, while the mechanism underlying HDACi-elicited apoptosis in bladder cancer cells remains largely unknown. METHODS: In this study, the apoptotic response to HDACi (trichostatin A and sodium butyrate) with different concentrations was determined by flow cytometry analysis and real-time polymerase chain reaction was conducted to examine the TRPM2 (Transient receptor potential cation channel, subfamily M, member 2) expression change on HDACi treatment. TRPM2 knockdown and overexpression were performed to investigate the role of TRPM2 in HDACi-induced apoptosis. The mechanism of HDACi-elicited upregulation of TRPM2 was studied by chromatin-immunoprecipitation. RESULTS: HDACi efficiently induced cell apoptosis and TRPM2 upregulation in a time- and dose-dependent manner in T24 bladder cancer cells. Functional analysis revealed that TRPM2 overexpression promotes apoptosis of T24 cells. Conversely, TRPM2 depletion remarkably antagonized HDACi-induced apoptosis. Furthermore, HDAC inhibition-elicited TRPM2 upregulation is caused by the increase of acetylated H3K9 (H3K9Ac) enrichment in TRPM2 promoter. CONCLUSIONS: These data suggest that the HDACi-elicited upregulation of TRPM2 expression is required for HDACi-induced apoptosis in bladder cancer cells and that HDACi activated the enrichment of H3K9Ac-represented permissive chromatin in TRPM2 promoter.