Serum Testosterone Levels Are Negatively Correlated with International Prostate Symptom Score and Transitional Prostate Volume.

OBJECTIVES: To investigate the correlation of serum total testosterone levels with International Prostate Symptom Score and prostate volume in aging men. METHODS: A cross-sectional study was conducted in 50 men who had participated in a medical examination. Prostate specific antigen levels, International Prostate Symptom Score, total/transitional prostate volume, body mass index, maximal flow rate, and serum total testosterone levels were evaluated. The correlation between serum total testosterone levels and additional parameters was statistically analyzed. RESULTS: The median age and total testosterone levels were 60.4 years (interquartile range: 55.0-68.0 years) and 4.3 ng/mL (interquartile range: 3.6-5.1 ng/mL), respectively. Total testosterone levels showed a significant negative correlation with body mass index, transitional prostate volume, International Prostate Symptom Score (including voiding/storage sub scores). On multivariate linear regression models, the total testosterone level was associated with body mass index and total International Prostate Symptom Score. CONCLUSIONS: As total testosterone levels decrease, both International Prostate Symptom Score and transitional prostate volume increase significantly. These findings provide evidence of the presence of more severe lower urinary tract symptoms and larger transitional prostate volume in aging men.

Effect of Preoperative Low Maximal Flow Rate on Postoperative Voiding Trials after the Midurethral Sling Procedure in Women with Stress Urinary Incontinence.

OBJECTIVES: To evaluate the effects of preoperative low maximal flow rate (Qmax) on voiding trials after the midurethral sling (MUS) procedure in women with stress urinary incontinence (SUI). METHODS: One hundred and sixty-eight women who underwent MUS procedure were enrolled. Preoperative free uroflowmetry was performed and patients were divided by Qmax. Low Qmax was defined as a Qmax under 15 mL/sec with voided volume at least 150 mL. Surgical results, failure of voiding trial, and postoperative uroflowmetry parameters were compared between the groups. Failure of voiding trial was defined by a PVR more than 100 mL on postoperative uroflowmetry. RESULTS: At the discharge day, there were 42 cases showing failure of voiding trial and 33 cases requiring CIC, but only one patient showed failure of voiding trial at 12 months postoperatively. Overall, 48 patients had preoperative low Qmax. Low Qmax group showed lower Qmax in all of postoperative uroflowmetry, but there were no significant differences in the rate of postoperative voiding trial failure or CIC. The low Qmax group was then divided into two groups according to the preoperative detrusor pressure at Qmax over and under 20 cmH2 O in pressure flow study. Comparing the two groups, no significant differences were observed in the cure rate, voiding trial failure or CIC. CONCLUSIONS: Our results suggest that women with preoperative low Qmax experienced no definite unfavorable voiding problem from the MUS procedure compared to those with normal voiding function. MUS procedure may be regarded as a safe and successful procedure in SUI women with low Qmax.

Discovery of novel fibroblast growth factor receptor 1 kinase inhibitors by structure-based virtual screening.

Fibroblast growth factors (FGFs) play important roles in embryonic development, angiogenesis, wound healing, and cell proliferation and differentiation. In search of inhibitors of FGFR1 kinase, 2.2 million compounds were docked into the ATP binding site of the protein. A co-crystal structure, which shows two alternative conformations for the nucleotide binding loop, is reported. Docking was performed on both conformations and, ultimately, 23 diverse compounds were purchased and assayed. Following hit validation, two compounds 10 and 16, a benzylidene derivative of pseudothiohydantoin and a thienopyrimidinone derivative, respectively, were discovered that inhibit FGFR1 kinase with IC(50) values of 23 and 50 microM. Initial optimization of 16 led to the more unsaturated 40, which has significantly enhanced potency, 1.9 microM. The core structures represent new structural motifs for FGFR1 kinase inhibitors. The study also illustrates complexities associated with the choice of protein structures for docking, possible use of multiple kinase structures to seek selectivity, and hit identification.

Seborrheic keratosis in the Korean males: causative role of sunlight.

BACKGROUND/PURPOSE: Seborrheic keratoses (SKs) are common epidermal tumors in the white population over 40 years. The etiology of SKs is not well known; however, exposure to sunlight was suggested to play a role in the development of them. To our knowledge, no well-designed study has been undertaken in order to investigate the clinical characteristics of SKs in a brown-skinned Korean population. The aim of this study was to assess the prevalence and clinical features of SKs in the Korean males and to investigate the possible relationship of SKs with sun exposure and possible risk factors of developing SKs. METHODS: A total of consecutive 303 male volunteers, aged 40-70 years, were recruited from general community and public health centres. Each volunteer was interviewed regarding demographic data, sunlight sensitivity, lifetime cumulative sun exposure and smoking history. Skin examination was performed except for scalp, buttocks and genitals. All SKs were recorded about the anatomical distribution, the size of each lesion measured with a caliber, color and morphology. RESULTS: The mean overall prevalence of SKs in the Korean males, aged 40-70 years was 88.1%. A considerable increase in the prevalence of SKs was shown from 78.9% at 40 years to 93.9% at 50 years and 98.7% in those over 60 years. The mean number of lesions per person was 5.5 at 40 years, 9.2 at 50 years and 13.4 at 60 years. Seborrheic keratoses were considerably more frequent on exposed areas (0.47 +/- 0.06/percentage of body surface area, BSA) than partly exposed areas (0.04 +/- 0.01/percentage of BSA). The majority of lesions were concentrated on the face (0.98 +/- 0.09/percentage of BSA) and on the dorsum of each hand (0.51 +/- 0.08/percentage of BSA). The size of each lesion on exposed areas also became significantly larger by decade significantly (P < 0.01). The estimated area covered by SKs per percentage of BSA on exposed areas was 5.7-fold larger than that on partly exposed areas at 40 years, 11.2-fold larger at 50 years and 18.3-fold larger at 60 years. Aging by decade showed a 2.08-fold increased risk for SKs (n > or = 6) (95% CI, 1.07-4.08) at 50 years and a 3.47-fold risk (95% CI, 1.67-7.20) at 60 years on exposed areas compared with the 40-year age group, for developing many SKs (n > or = 6). Lifetime cumulative sunlight exposure of more than 6 h per day was associated with a 2.28-fold higher risk of SKs than a sun exposure of less than 3 h per day. A tendency for an odds ratio value reduction was found on increasing Fitzpatrick skin types I-III to VI, V; however, this was without statistical significance. CONCLUSIONS: Seborrheic keratoses are common in the Korean males, aged 40-70 years, and may be a major pigmentary problem. Both aging and cumulative sunlight exposure were found to be independent contributory factors.

Fluoroprolines as Tools for Protein Design and Engineering.

The preference of the peptidyl-fluoroproline amide bond for the cis or trans conformation in the model compounds N-acetyl-4-fluoroproline methyl esters fully correlates with the thermostability of the related mutants of the model protein barstar. Thus, the (4S)-L-FPro mutants show a higher and the(4R)-L-FPro mutants a lower thermal stability than barstar.