A pilot study of brain morphometry following donepezil treatment in mild cognitive impairment: volume changes of cortical/subcortical regions and hippocampal subfields.

The efficacy of donepezil is well known for improving the cognitive performance in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Most of the recent neuroimaging studies focusing on the brain morphometry have dealt with the targeted brain structures, and thus it remains unknown how donepezil treatment influences the volume change over the whole brain areas including the cortical and subcortical regions and hippocampal subfields in particular. This study aimed to evaluate overall gray matter (GM) volume changes after donepezil treatment in MCI, which is a prodromal phase of AD, using voxel-based morphometry. Patients with MCI underwent the magnetic resonance imaging (MRI) before and after 6-month donepezil treatment. The cognitive function for MCI was evaluated using the questionnaires of the Korean version of the mini-mental state examination (K-MMSE) and Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog). Compared with healthy controls, patients with MCI showed significantly lower GM volumes in the hippocampus and its subfields, specifically in the right subiculum and left cornu ammonis (CA3). The average scores of K-MMSE in patients with MCI improved by 8% after donepezil treatment. Treated patients showed significantly higher GM volumes in the putamen, globus pailldus, and inferior frontal gyrus after donepezil treatment (p < 0.001). However, whole hippocampal volume in the patients decreased by 0.6% after 6-month treatment, and the rate of volume change in the left hippocampus was negatively correlated with the period of treatment. These findings will be useful for screening and tracking MCI, as well as understanding of the pathogenesis of MCI in connection with brain morphometric change.

Complications of glans penis augmentation.

Despite the controversy regarding penile augmentation (PA), glans penis augmentation (GPA) is used in penile reconstructive surgery in selected patients with small glans penis. Since 2003, injectable hyaluronic acid (HA) gel has been used for GPA. The attractiveness of HA gel fillers and interest in this technique have led to the use of other fillers for GPA, particularly irreversible fillers that improve the longevity of HA gels. Conversely, indirect glans augmentation via implantation of dermofat grafts or scaffolds between the corpus spongiosum and the distal tip of the corpus cavernosum is used to overcome poor longevity of the gel and glans surface undulation, which are the primary limitations of GPA using HA gel. Unfortunately, these implants form hard painful lumps over time in most patients and are difficult to remove. Blunt dissection is an invasive procedure that may cause vascular compromise and consequent glans necrosis in a few patients. We present our review regarding the current status of GPA for a more comprehensive understanding of this subject. Additionally, we have discussed a few complicated cases that were referred to us.

Prevalence of symptoms and associated comorbidities of testosterone deficiency syndrome in the Korean general population.

INTRODUCTION: Testosterone deficiency syndrome (TDS) is a prevalent disease of the aging male with much confusion to its associated presentation, diagnosis, and comorbidities. AIM: We investigated the overall prevalence of TDS and its putative symptoms and associated diseases in a nationwide study on participants recruited from routine checkup. METHODS: One thousand eight hundred seventy-five participants seeking biennial health checkup were enrolled from a nationwide distribution of randomly selected registry of primary clinics. Putative symptoms and comorbidities were assessed for serum testosterone-dependent prevalence change, independent of age. The identified symptoms were then assessed by multivariate backward stepwise binominal regression to determine the optimal reference level of testosterone and the strength of the associated comorbidities. MAIN OUTCOME MEASURES: TDS was assessed by serum testosterone, the Aging Males' Symptom scale, and the Androgen Deficiency in Aging Male questionnaire. Patient body habitus measurements and history of associated comorbidities were also described. The dependent variables included the age-specific prevalence of decreased testosterone and the probability of TDS-specific symptoms. RESULTS: Grossly 10.2% of the participants fell into the criteria for TDS. Testosterone was highly age dependent, and most putative symptoms of TDS showed significant age dependence but was not affected by serum testosterone levels. However, the symptoms of decreased libido and erectile dysfunction, and comorbidities such as hypertension, type 2 diabetes, and obesity showed relevant dependence on serum testosterone levels as well as age above 50 years of age. Furthermore, these symptoms were also affected at different serum testosterone thresholds. Decreased libido increased significantly at serum testosterone levels of 550 ng/dL (odds ratio [OR] = 1.295, 95% confidence interval [CI] = 1.047-1.601), and erectile dysfunction was affected by serum testosterone levels at 250 ng/dL (OR = 1.369, 95% CI = 1.005-1.866). CONCLUSIONS: Most symptoms and diseases thought to be associated with TDS are primarily age dependent. Few sexual symptoms and diseases such as hypertension, diabetes, and obesity show testosterone dependence only at older ages.

Survey on benign prostatic hyperplasia distribution and treatment patterns for men with lower urinary tract symptoms visiting urologists at general hospitals in Korea: a prospective, noncontrolled, observational cohort study.

OBJECTIVE: To survey cases of benign prostatic hyperplasia (BPH) among patients visiting urologists with lower urinary tract symptoms (LUTS) at general hospitals in Korea and to investigate treatment outcomes in current clinical practice. METHODS: This was a multicenter, prospective study conducted in 18 urology centers in Korea. The symptoms of BPH were observed via the International Prostate Symptoms Score (IPSS), transrectal ultrasonography, uroflometry, prostate, specific, antigen, PSA) and postvoid residual volume at the baseline, 1 week, 4 weeks, 12 weeks, 24 weeks, and 52 weeks after initial evaluation. The patients were divided into three groups according to age (group I: 50-59; group II: 60-69; group III: 70 years or older). RESULTS: Of the 1054 screened men, 966 were enrolled and 917 were diagnosed with BPH. Total IPSS and storage subscores were significantly higher in group III than in group II or I. By month 12, significant improvements on total IPSS and voiding subscores were demonstrated in group I over groups II and III (P = .02. 03, respectively). The incidence of dual combination therapy was significantly higher in the patients whose prostate volume was ≥30 mL and whose PSA was ≥1.5. CONCLUSION: At the initial visit, patients with LUTS/BPH, especially those who were relatively young, visited urologic centers because of to voiding symptoms rather than storage symptoms. In contrast, elderly men who visited the urologic centers complained not only of voiding symptoms but also storage symptoms. However, at 12 months' follow up, all of the age groups showed improvement in both storage and voiding symptoms.

The Expression of AQP1 and eNOS in Menopausal Rat Urinary Bladder.

PURPOSE: Aquaporins (AQPs) have been reported to be expressed in rat and human urothelium. Nitric oxide (NO) is thought to play an important role in the bladder overactivity related to menopause. The purpose of this study was to investigate the effect of hormonal alteration on the expression of AQP1 and eNOS in menopausal rat urinary bladder. MATERIALS AND METHODS: Female Sprague-Dawley rats (230-240 g, N=30) were divided into three groups: control (N=10), bilateral ovariectomy (Ovx, N=10), and bilateral ovariectomy followed by subcutaneous injections of 17ß-estradiol (50 mg/kg/day, Ovx+Est, N=10). After 4 weeks, urodynamic studies measuring the contraction interval and contraction pressure were done. The expression and cellular localization of AQP1 and eNOS were determined by performing Western blotting and immunohistochemistry on the rat urinary bladder. RESULTS: The approximate contraction interval (min) was significantly decreased in the Ovx group (3.9±0.25) compared to the control group (6.7±0.15), and was increased after estrogen treatment (9.7±0.22) (p<0.05). The AQP1 and eNOS immunoreactivities were localized in the same areas: capillaries, arterioles, and venules of the lamina propria. The protein expression of AQP1 was not changed significantly, whereas eNOS expression was significantly decreased in the Ovx group and restored to the control value in the Ovx+Est group. CONCLUSIONS: This study showed that ovariectomy causes a significant change in e-NOS expression without a change in AQP1 in menopausal rat urinary bladder. This may imply that e-NOS has a functional role in the bladder overactivity that occurs in association with menopause.

Prostate calculi in cancer and BPH in a cohort of Korean men: Presence of calculi did not correlate with cancer risk.

Prostatic calculi are common and are associated with inflammation of the prostate. Recently, it has been suggested that this inflammation may be associated with prostate carcinogenesis. The aim of this study was to investigate the relationship between prostatic calculi and prostate cancer (PCa) in prostate biopsy specimens. We retrospectively analyzed 417 consecutive patients who underwent transrectal ultrasonography (TRUS) and prostate biopsies between January 2005 and January 2008. Based on the biopsy findings, patients were divided into benign prostatic hyperplasia and PCa groups. TRUS was used to detect prostatic calculi and to measure prostate volume. The correlations between PCa risk and age, serum total PSA levels, prostate volume, and prostatic calculi were analyzed. Patient age and PSA, as well as the frequency of prostatic calculi in the biopsy specimens, differed significantly between both the groups (P < 0.05). In the PCa group, the Gleason scores (GSs) were higher in patients with prostatic calculi than in patients without prostatic calculi (P = 0.023). Using multivariate logistic regression analysis, we found that patient age, serum total PSA and prostate volume were risk factors for PCa (P = 0.001), but that the presence of prostatic calculi was not associated with an increased risk of PCa (P = 0.13). In conclusion, although the presence of prostatic calculi was not shown to be a risk factor for PCa, prostatic calculi were more common in patients with PCa and were associated with a higher GS among these men.

Reduced testicular steroidogenesis in tumor necrosis factor-alpha knockout mice.

We previously demonstrated that the expression of Mullerian inhibiting substance (MIS) in Sertoli cells is downregulated by tumor necrosis factor alpha (TNF-alpha), which is secreted by meiotic germ cells, in mouse testes. Several studies have reported that MIS that is secreted by Sertoli cells inhibits steroidogenesis and, thus, the synthesis of testosterone in testicular Leydig cells. Here, we demonstrate that in TNF-alpha knockout testes, which show high levels of MIS, steroidogenesis is decreased compared to that in wild-type testes. The levels of testosterone and the mRNA levels of steroidogenesis-related genes were significantly lower after puberty in TNF-alpha knockout testes than in wild-type testes. Furthermore, the number of sperm was reduced in TNF-alpha knockout mice. Histological analysis revealed that spermatogenesis is also delayed in TNF-alpha knockout testes. In conclusion, TNF-alpha knockout mice show reduced testicular steroidogenesis, which is likely due to the high level of testicular MIS compared to that seen in wild-type mice.

Efficacy and safety of oral SK3530 for the treatment of erectile dysfunction in Korean men: a multicenter, randomized, double-blind, placebo-controlled, fixed dose, parallel group clinical trial.

AIM: To evaluate the efficacy and safety of SK3530, a newly developed type 5 phosphodiesterase inhibitor (PDE5I), in Korean men with erectile dysfunction (ED). METHODS: A total of 119 patients were randomized at 10 centers in Korea to receive either SK3530 (50, 100, or 150 mg; n = 89) or placebo (n = 30) taken l h before anticipated sexual activity for an 8-week period. The patients were evaluated at baseline and 4 and 8 weeks after beginning therapy. Efficacy was assessed using the International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP), and the Global Assessment Question (GAQ). Safety was analyzed by adverse events, laboratory values and vital signs. RESULTS: At the end of the study, all the primary and secondary efficacy end-points were statistically significantly improved by SK3530 compared with placebo (P<0.05). Of the 89 patients in the treatment arm, 36 (42.3%) achieved normal erectile function after treatment, including six patients with severe ED. Treatment-related adverse events occurred in 32 patients. The most common adverse events were flushing, headache, dizziness and eye redness (10.9%, 7.6%, 2.5% and 2.5%, respectively), and most were mild. Only two patients discontinued treatment during the study period because of adverse events. CONCLUSION: The results of our phase II study have confirmed the efficacy and safety of SK3530 in a broad population of men with ED of various etiologies and severity. The optimal doses in terms of efficacy and safety were determined to be 50 mg and 100 mg, respectively.

Three cases of xanthogranulomatous epididymitis caused by E. coli.

Xanthogranulomatous epididymitis is an uncommon but benign process, characterized by tissue destruction and the accumulation of abundant foamy macrophages mixed with lymphocytes and plasma cells. The pathogens generally found to cause xanthogranulomatous inflammation have been Proteus and E. coli. We identified such a pathogen by sequencing divergent regions of 16S rRNA, followed by pathogen-specific-PCR using alr, ipaH, ial, and iuc primer pairs in DNA microdissected from an H&E stained slide. We report here three cases of xanthogranulomatous epididymitis caused by E. coli.

High glucose-induced inhibition of 2-deoxyglucose uptake is mediated by cAMP, protein kinase C, oxidative stress and mitogen-activated protein kinases in mouse embryonic stem cells.

Abnormally high glucose levels may play an important role in early embryo development and function. In the present study, we investigated the effect of high glucose on 2-deoxyglucose (2-DG) uptake and its related signalling pathway in mouse embryonic stem (ES) cells. 2. 2-Deoxyglucose uptake was maximally inhibited by 25 mmol/L glucose after 24 h treatment. However, 25 mmol/L mannitol and dextran did not affect 2-DG uptake. Indeed, 25 mmol/L glucose decreased GLUT-1 mRNA and protein levels. The glucose (25 mmol/L)-induced inhibition of 2-DG uptake was blocked by pertussis toxin (a G(i)-protein inhibitor; 2 ng/mL), SQ 22,536 (an adenylate cyclase inhibitor; 10(-6) mol/L) and the protein kinase (PK) A inhibitor myristoylated PKI amide-(14-22) (10(-6) mol/L). Indeed, 25 mmol/L glucose increased intracellular cAMP content. 3. Furthermore, 25 mmol/L glucose-induced inhibition of 2-DG uptake was prevented by 10(-4) mol/L neomycin or 10(-6) mol/L U 73,122 (phospholipase C (PLC) inhibitors) and staurosporine or bisindolylmaleimide I (protein kinase (PK) C inhibitors). At 25 mmol/L, glucose increased translocation of PKC from the cytoplasmic fraction to the membrane fraction. The 25 mmol/L glucose-induced inhibition of 2-DG uptake and GLUT-1 protein levels was blocked by SQ 22,536, bisindolylmaleimide I or combined treatment. In addition, 25 mmol/L glucose increased cellular reactive oxygen species and the glucose-induced inhibition of 2-DG uptake were blocked by the anti-oxidants N-acetylcysteine (NAC; 10(-5) mol/L) or taurine (2 yen 10(-3) mol/L). 4. Glucose (25 mmol/L) activated p38 mitogen-activated protein kinase (MAPK) and p44/42 MAPK. Staurosporine (10(-6) mol/L), NAC (10(-5) mol/L) and PD 98059 (10(-7) mol/L) attenuated the phosphorylation of p44/42 MAPK. Both SB 203580 (a p38 MAPK inhibitor; 10(-7) mol/L) and PD 98059 (a p44/42 MAPK inhibitor; 10(-7) mol/L) blocked 25 mmol/L glucose-induced inhibition of 2-DG uptake. 5. In conclusion, high glucose inhibits 2-DG uptake through cAMP, PLC/PKC, oxidative stress or MAPK in mouse ES cells.