Imidazole propionate ameliorates atopic dermatitis-like skin lesions by inhibiting mitochondrial ROS and mTORC2.

Background: Imidazole propionate (IMP) is a histidine metabolite produced by some gut microorganisms in the human colon. Increased levels of IMP are associated with intestinal inflammation and the development and progression of cardiovascular disease and diabetes. However, the anti-inflammatory activity of IMP has not been investigated. This study aimed to elucidate the role of IMP in treating atopic dermatitis (AD). Methods: To understand how IMP mediates immunosuppression in AD, IMP was intraperitoneally injected into a Dermatophagoides farinae extract (DFE)/1-chloro-2,4 dinitrochlorobenzene (DNCB)-induced AD-like skin lesions mouse model. We also characterized the anti-inflammatory mechanism of IMP by inducing an AD response in keratinocytes through TNF-α/IFN-γ or IL-4 stimulation. Results: Contrary to the prevailing view that IMP is an unhealthy microbial metabolite, we found that IMP-treated AD-like skin lesions mice showed significant improvement in their clinical symptoms, including ear thickness, epidermal and dermal thickness, and IgE levels. Furthermore, IMP antagonized the expansion of myeloid (neutrophils, macrophages, eosinophils, and mast cells) and Th cells (Th1, Th2, and Th17) in mouse skin and prevented mitochondrial reactive oxygen species production by inhibiting mitochondrial energy production. Interestingly, we found that IMP inhibited AD by reducing glucose uptake in cells to suppress proinflammatory cytokines and chemokines in an AD-like in vitro model, sequentially downregulating the PI3K and mTORC2 signaling pathways centered on Akt, and upregulating DDIT4 and AMPK. Discussion: Our results suggest that IMP exerts anti-inflammatory effects through the metabolic reprogramming of skin inflammation, making it a promising therapeutic candidate for AD and related skin diseases.

Therapeutic efficacy of bipolar radiofrequency thermotherapy for patients with chronic prostatitis: a retrospective analysis of 26 cases.

PURPOSE: Chronic prostatitis (CP) does not yet have a universally successful therapy. Alternative treatments including thermotherapy have been adopted in the multimodal management of pain and voiding dysfunction. We retrospectively analyzed the therapeutic efficacy of bipolar radiofrequency thermotherapy for patients who were unsatisfied with conventional medication for CP. MATERIALS AND METHODS: A retrospective study between October 2009 and September 2010 of 26 patients who were under 50 years old and diagnosed with CP (National Institutes of Health [NIH]-category III) was performed. Twenty patients were diagnosed with inflammatory CP (NIH-category IIIa) and the rest with noninflammatory CP (NIH-category IIIb). We used the Tempro system at an intraprostatic temperature of 55℃ for 50 minutes with a medium heating rate. All patients also completed the NIH-Chronic Prostatitis Symptom Index (CPSI) before and after treatment. RESULTS: In the patients diagnosed with CP, the mean serum prostate-specific antigen (PSA) level was 0.9±0.3 ng/ml, the prostate volume was 27.1±5.5 g, and the average score for all 3 domains on the NIH-CPSI significantly decreased. The total scores decreased from 19.8±7.1 to 11.1±7.0, the pain domain decreased from 8.6±3.1 to 4.8±3.1, the voiding symptom domain decreased from 5.1±1.8 to 2.9±1.8, and the effect on the quality of life decreased from 6.1±2.2 to 3.4±2.2 (p<0.05). CONCLUSIONS: Bipolar radiofrequency thermotherapy for patients with CP intractable to conventional medication can provide significant improvement in the NIH-CPSI. Large, randomized controlled trials will also be required to confirm the efficacy of this therapy.

Comparison of ketoconazole and estramustine for treating patients with castration-resistant prostate cancer.

PURPOSE: We investigated the efficacy of ketoconazole and estramustine before chemotherapy for treating patients with progressive castration-resistant prostate cancer (CRPC) after anti-androgen withdrawal syndrome. MATERIALS AND METHODS: Eighty-four patients who were diagnosed with CRPC and were treated between 2005 and 2009 were included. Thirty-nine patients were treated with 600 mg of ketoconazole and 10 mg of prednisolone per day (group I), and 45 patients were treated with 560 mg of estramustine per day (group II). The prostate-specific antigen (PSA) response, progression-free survival, and side effects were compared. RESULTS: The median age of the patients, PSA level, and follow-up period were 72 years, 48.5 ng/ml, and 4 months (range, 1 to 29 months), respectively. The overall PSA response rate was 35.7%, and the PSA response rates were 33.3% for group I and 37.8% for group II (p=0.672). The median progression-free survival times were 8 months (95% confidence interval [CI] 5.9-10.1) overall, 5 months (95% CI 1.6-8.3) in group I, and 8 months (95% CI 5.9-10.0) in group II (p=0.282). The most common complications in groups I and II were nausea and vomiting (51.3%) and anemia (77.8%), respectively. Nausea and vomiting and hepatotoxicity were observed more often in group I, and gynecomastia, neutropenia, and anemia were observed more often in group II. The toxicities of each adverse effect were ≤grade 2. CONCLUSIONS: With a resultant PSA decline and mild adverse effects, both ketoconazole and estramustine are worth consideration as treatment options for progressive CRPC patients after primary hormonal therapy.

Prevalence of and Risk Factors for Levofloxacin-Resistant E. coli Isolated from Outpatients with Urinary Tract Infection.

PURPOSE: Levofloxacin has been widely used because of its broad spectrum and excellent penetration of the prostate. But levofloxacin-resistant Escherichia coli (E.coli) has been reported all over the world. We analyzed the annual levofloxacin resistance of E. coli and its risk factors. MATERIALS AND METHODS: From 2005 to 2009, we retrospectively analyzed patients who had undergone a urine analysis and a urine culture at the Outpatient Section of the Department of Urology of Kwangju Christian Hospital. Among them, we chose 509 patients infected by E. coli and evaluated the resistance rate to levofloxacin and its risk factors. RESULTS: The annual rates of levofloxacin resistance of E. coli were 29.49% in 2005, 26.51% in 2006, 40.21% in 2007, 43.20% in 2008, and 31.75% in 2009. A close correlation with the resistance rate was shown in cases that had underlying neurogenic bladder (p=0.002, odds ratio [OR]=4.236), a history of ciprofloxacin (p<0.001, OR=3.753) and levofloxacin (p<0.001, OR=2.996) administration for at least 48 hours in the past year, urolithiasis (p=0.003, OR=3.317), and older age (p<0.001, OR=1.027). CONCLUSIONS: This study from 2005 to 2009 showed that the levofloxacin resistance rates of E. coli were high at over 25%. The risk factors that affected the levofloxacin resistance rates of E. coli were underlying neurogenic bladder, ciprofloxacin administration history, urolithiasis, levofloxacin administration history, and older age. Levofloxacin should be prescribed cautiously in patients with these risk factors until the pathogen is identified.

Clinical factors associated with low valsalva leak point pressure among women with stress urinary incontinence.

PURPOSE: The purpose of this study is to determine the predictive factors that are associated with stress urinary incontinence (SUI) due to intrinsic sphincter deficiency (ISD) in women. METHODS: Between January 2008 and December 2009, 185 women with urodynamically proven SUI were included in this study and retrospectively reviewed the medical record. Preoperative SUI symptoms were classified by Stamey grade. Valsalva leak point pressure (VLPP) determination series was repeated two times in each subject after finishing one series of VLPP measurement. The patients were classified into three groups according to VLPP; 1) ISD: VLPP≤60 cm H(2)O, 2) equivocal: 6090 cm H(2)O. Chi-square test and multivariate (logistic regression test) analyses were performed to determine the factors associated with ISD. RESULTS: The mean patient age was 54.2 years (range, 44.5 to 68.4 years). Seventy-one women (38.3%) were in the ISD group and 70 (37.8%) in the AI group. The results of univariate and multivariate analyses found that women with ISD had a higher symptom grade than women with AI (P=0.001 and 0.0001, respectively). The number of patients in the ISD and AI group in accordance with the symptom grade were 7 (10%) and 44 (62%) in grade I, 50 (54%) and 23 (25%) in grade II, and 14 (63%) and 3 (14%) in grade III respectively. There was no correlation between VLPP and other clinical factors. CONCLUSIONS: High symptom grade was the only independent clinical factor that predicted the presence of ISD. This should be considered when counseling the patients with SUI.

Readjustable sling procedure for the treatment of female stress urinary incontinence with intrinsic sphincter deficiency: preliminary report.

PURPOSE: The Remeex (Mechanical External Regulation) sling is a mid-urethral sling that allows adjustment of the sling tension in the postoperative period. We evaluated the early outcomes of the procedure in patients in whom the success rate of tension-free slings is low, such as with intrinsic sphincter deficiency (ISD). MATERIALS AND METHODS: We included 17 women with urodynamically proven stress urinary incontinence (SUI) who underwent the Remeex procedure and were followed for at least 12 months. The patients were considered to have ISD on the basis of a Valsalva leak point pressure (VLPP) <60 cmH(2)O or a maximum urethral closure pressure (MUCP) <20 cmH(2)O. We analyzed parameters including history taking, urodynamic study (UDS), and postoperative clinical outcomes. Patient's success and satisfaction rates were evaluated after the procedure. Also, we asked about lower urinary tract symptoms (LUTSs) with a questionnaire, and the severity of LUTSs was assessed with the Visual Analog Scale (VAS) before and 12 months after the operation. RESULTS: The patients' mean age was 55.6+/-9.58 years. Four (23.5%) patients had mixed incontinence. Five patients (29.4%) had undergone previous surgery for SUI. At a mean follow-up of 13.3 months (range, 12-16 months), 14 patients (82.3%) were cured and 3 patients (17.6%) were improved. Four patients (23.5%) answered very satisfied and 13 patients (76.4%) answered satisfied on the satisfaction questionnaire. Also, LUTSs were improved except voiding pain (p<0.05). CONCLUSIONS: This procedure provides high cure and satisfaction rates. Our results demonstrate that the Remeex procedure is suitable for women with SUI with ISD.