Modulation of the Hydrogen Bonding Structure of Water by Renal Osmolytes.

Osmolytes are an integral part of living organism, e.g., the kidney uses sorbitol, trimethylglycine, taurine and myo-inositol to counter the deleterious effects of urea and salt. Therefore, knowing that the osmolytes' act either directly to the protein or mediated through water is of great importance. Our experimental and computational results show that protecting osmolytes, e.g., trimethylglycine and sorbitol, significantly modulate the water H-bonding network structure, although the magnitude and spatial extent of osmolyte-induced perturbation greatly vary. In contrast, urea behaves neutrally toward local water H-bonding network. Protecting osmolytes studied here show strong concentration-dependent behaviors (vibrational frequencies and lifetimes of two different infrared (IR) probes), while denaturant does not. The H-bond donor and/or acceptor (OH/NH) in a given osmolyte molecule play a critical role in defining their action. Our findings highlight the significance of the alteration of H-bonding network of water under biologically relevant environment, often encountered in real biological systems.

Simultaneous enhancement of upconversion and downshifting luminescence via plasmonic structure.

We describe a metal nanodisk-insulator-metal (MIM) structure that enhances lanthanide-based upconversion (UC) and downshifting (DS) simultaneously. The structure was fabricated using a nanotransfer printing method that facilitates large-area applications of nanostructures for optoelectronic devices. The proposed MIM structure is a promising way to harness the entire solar spectrum by converting both ultraviolet and near-infrared to visible light concurrently through resonant-mode excitation. The overall photoluminescence enhancements of the UC and DS were 174- and 29-fold, respectively.

Vibrational dynamics of thiocyanate and selenocyanate bound to horse heart myoglobin.

The structure and vibrational dynamics of SCN- and SeCN-bound myoglobin have been investigated using polarization-controlled IR pump-probe measurements and quantum chemistry calculations. The complexes are found to be in low and high spin states, with the dominant contribution from the latter. In addition, the Mb:SCN high spin complex exhibits a doublet feature in the thiocyanate stretch IR absorption spectra, indicating two distinct molecular conformations around the heme pocket. The binding mode of the high spin complexes was assigned to occur through the nitrogen atom, contrary to the binding through the sulfur atom that was observed in myoglobin derived from Aplysia Limacina. The vibrational energy relaxation process has been found to occur substantially faster than those of free SCN(-) and SeCN(-) ions and neutral SCN- and SeCN-derivatized molecules reported previously. This supports the N-bound configurations of MbNCS and MbNCSe, because S- and Se-bound configurations are expected to have significantly long lifetimes due to the insulation effect by heavy bridge atom like S and Se in such IR probes. Nonetheless, even though their lifetimes are much shorter than those of corresponding free ions in water, the vibrational lifetimes determined for MbNCS and MbNCSe are still fairly long compared to those of azide and cyanide myoglobin systems studied before. Thus, thiocyanate and selenocyanate can be good local probes of local electrostatic environment in the heme pocket. The globin dependence on binding mode and vibrational dynamics is also discussed.

Role of Urodynamic Study in Nocturnal Enuresis: Urodynamic Findings and Treatment Outcome Correlation in Children with Pharmacotherapy-resistant Monosymptomatic Nocturnal Enuresis or Severe Non-monosymptomatic Nocturnal Enuresis.

OBJECTIVES: This study aimed to determine whether or not a urodynamic study (UDS) is beneficial for management of pediatric nocturnal enuresis (NE), especially in pharmacoresistant monosymptomatic nocturnal enuresis (PRMNE) or severe non-monosymptomatic nocturnal enuresis (NMNE) patients. METHODS: Children with PRMNE or severe NMNE who underwent a UDS for the process of NE treatment were retrospectively reviewed. The UDS findings of patients and treatment outcomes of subsequent tailored therapies according to the UDS findings were analyzed. RESULTS: A total of 80 children (50 boys and 30 girls, mean age 8.4 ± 2.2 years), 19 of which were diagnosed with PRMNE and 61 of which were diagnosed with NMNE, were included in the final analysis. Of the 19 PRMNE children, 12 (63.2%) demonstrated abnormal UDS findings. Ten demonstrated detrusor overactivity (DO) with or without decreased cystometric bladder capacity (CBC); the treatment outcomes markedly improved in all of the children after anticholinergics were added to the initial desmopressin therapy. Biofeedback was found to be helpful for two children with detrusor-sphincter dyssynergia. All of the total 61 children with NMNE demonstrated abnormal urodynamic findings of DO with or without decreased CBC, and 42 (68.9%) achieved more than partial response (> 50% decrease in the number of wet nights) when given a combination therapy of anticholinergics and desmopressin. CONCLUSIONS: The urodynamic findings were helpful for guiding children with PRMNE in the proper choice of further treatment strategies. A routine UDS should not be recommended prior to a first-line combination treatment in children with NMNE.

Computational infrared and two-dimensional infrared photon echo spectroscopy of both wild-type and double mutant myoglobin-CO proteins.

The CO stretching mode of both wild-type and double mutant ( T67R / S92D ) MbCO (carbonmonoxymyoglobin) proteins is an ideal infrared (IR) probe for studying the local electrostatic environment inside the myoglobin heme pocket. Recently, to elucidate the conformational switching dynamics between two distinguishable states, extensive IR absorption, IR pump-probe, and two-dimensional (2D) IR spectroscopic studies for various mutant MbCO's have been performed by the Fayer group. They showed that the 2D IR spectroscopy of the double mutant, which has a peroxidase enzyme activity, reveals a rapid chemical exchange between two distinct states, whereas that of the wild-type does not. Despite the fact that a few simulation studies on these systems were already performed and reported, such complicated experimental results have not been fully reproduced nor described in terms of conformational state-to-state transition processes. Here, we first develop a distributed vibrational solvatochromic charge model for describing the CO stretch frequency shift reflecting local electric potential changes. Then, by carrying out molecular dynamic simulations of the two MbCO's and examining their CO frequency trajectories, it becomes possible to identify a proper reaction coordinate consisting of His64 imidazole ring rotation and its distance to the CO ligand. From the 2D surfaces of the resulting potential of mean forces, the spectroscopically distinguished A1 and A3 states of the wild-type as well as two more substates of the double mutant are identified and their vibrational frequencies and distributions are separately examined. Our simulated IR absorption and 2D IR spectra of the two MbCO's are directly compared with the previous experimental results reported by the Fayer group. The chemical exchange rate constants extracted from the two-state kinetic analyses of the simulated 2D IR spectra are in excellent agreement with the experimental values. On the basis of the quantitative agreement between the simulated spectra and experimental ones, we further examine the conformational differences in the heme pockets of the two proteins and show that the double mutation, T67R / S92D , suppresses the A1 population, restricts the imidazole ring rotation, and increases hydrogen-bond strength between the imidazole Nε-H and the oxygen atom of the CO ligand. It is believed that such delicate change of distal His64 imidazole ring dynamics induced by the double mutation may be responsible for its enhanced peroxidase catalytic activity as compared to the wild-type myoglobin.

A case of laparoscopic radical prostatectomy for a prostatic stromal tumor of uncertain malignant potential.

Prostatic stromal tumor of uncertain malignant potential (STUMP) is a rare neoplasm with distinctive clinical and pathological characteristics. Here we report a case of laparoscopic radical prostatectomy performed in a patient with prostatic STUMP.

The efficacy of enuresis alarm treatment in pharmacotherapy-resistant nocturnal enuresis.

OBJECTIVES: To assess the efficacy of enuresis alarm (EA) treatment in pharmacotherapy-resistant nocturnal enuresis (PRNE). MATERIAL AND METHODS: A retrospective study was performed in children who received EA treatment as a form of combination treatment for PRNE from June 1999 to December 2007. The children included 54 monosymptomatic nocturnal enuresis (MNE) children who had partial response or nonresponse to desmopressin (group 1), 25 nonmonosymptomatic nocturnal enuresis (NMNE) children who had partial response or nonresponse to extended release oxybutynin plus desmopressin (group 2), and 21 MNE or NMNE children who relapsed after responding fully to first-line pharmacotherapy (group 3). EA treatment outcomes were determined as outlined by the International Children's Continence Society Standardisation Committee. RESULTS: Overall, 50% and 53.7%, 40%, and 52.4% of children in groups 1, 2, and 3, respectively, responded fully to EA treatment (no significant differences). In groups 1 and 2, 54.4% (31/57) of the partial responders and 36.4% (8/22) of the nonresponders showed full response (FR) after EA treatment was initiated. Of the children with small bladder capacities, 56.7% showed FR. Of the full responders in each group, 60.7%, 88.9%, and 54.5% of groups 1, 2, and 3, respectively, did not have relapse 6 months after cessation of treatment. CONCLUSIONS: Overall, half of the total population achieved FR, and continued success was observed in more than half of full responders irrespective of the groups. Thus, adding EA treatment to pharmacotherapy is an effective second-line therapeutic strategy for children with PRNE.

Outcomes of transurethral removal of intravesical or intraurethral mesh following midurethral sling surgery.

PURPOSE: To present outcomes of transurethral removal (TUR) of intravesical or intraurethral mesh after midurethral slings. MATERIALS AND METHODS: This was a retrospective chart review of 23 consecutive women: 20 with intravesical mesh and 3 with intraurethral mesh. RESULTS: To remove the mesh, transurethral resection with an electrode loop (TUR-E) was used in 16 women and transurethral resection with a holmium laser (TUR-H) was used in 7. The median follow-up was 2.1 months. Twenty-six percent of the women (6/23) had a mesh remnant: 6.2% (1/16) of the women treated with TUR-E and 71.4% (5/7) of the women treated with TUR-H. Of the 5 women treated with TUR-H, 3 underwent concomitant transvaginal removal. On the follow-up cystoscopic exam, a mesh remnant was observed in 3 women (1 treated with TUR-E and 2 treated with TUR-H). Vesico-vaginal fistulas were found in 2 women during and after TUR-E, respectively. Stress urinary incontinence recurred in 1 woman. CONCLUSIONS: TUR-E has a high success rate but carries a risk of bladder perforation. Complete resection using TUR-H depends on the location of the mesh and the range of motion of the instrument.

Efficacy of desmopressin and enuresis alarm as first and second line treatment for primary monosymptomatic nocturnal enuresis: prospective randomized crossover study.

PURPOSE: We compared the efficacy of desmopressin and enuresis alarm as first and second line treatment options for monosymptomatic nocturnal enuresis. MATERIALS AND METHODS: A total of 104 children with monosymptomatic nocturnal enuresis were randomly assigned to either desmopressin (54) or enuresis alarm (50) as first line treatment. Following 12 weeks of first line treatment children with a full response were evaluated for relapse 12 weeks after withdrawal of treatment. Children with partial or no response were switched to the alternative treatment and then evaluated after 12 weeks of crossover treatment. Relapse was defined as more than 1 episode of bedwetting monthly. RESULTS: Following first line treatment 77.8% of the desmopressin group and 82% of the enuresis alarm group achieved a successful result, including full response in 37% and 50% of the groups, respectively (p=0.433). Of the children with a full response 50% in the desmopressin group and 12% in the enuresis alarm group experienced a relapse when treatment stopped (p=0.005). Following second line crossover treatment 71.4% of the enuresis alarm-desmopressin group and 67.8% of the desmopressin-enuresis alarm group achieved a successful result, including full response in 47.6% and 45.2% of the groups, respectively (p=0.961). CONCLUSIONS: There was no difference between desmopressin and enuresis alarm during treatment for achieving dryness, but the chance of relapse after treatment stopped was higher following desmopressin. Switching to the alternative treatment following partial or no response provided an additional benefit.

Relationship between insulin resistance, obesity and serum prostate-specific antigen levels in healthy men.

The purpose of this study was to determine the relationship between insulin resistance, obesity and serum prostate-specific antigen (PSA) levels in healthy men with serum PSA level below 4 ng mL(-1). The men included in the study cohort were 11 827 healthy male employees of the Korea Hydro and Nuclear Power Co., LTD who had undergone medical checkups including fasting glucose, fasting insulin and serum PSA between January 2003 and December 2008. Insulin resistance was calculated by homeostasis model assessment (HOMA [fasting glucose x fasting insulin]/22.5) and quantitative insulin sensitivity check index (QUICKI; 1/[log (fasting insulin) + log (fasting glucose)]). Age-adjusted body mass index (BMI) was significantly increased according to increasing quartile of insulin resistance as determined by HOMA and QUICKI, respectively, in analysis of variance (ANOVA) test and Duncan's multiple comparison test (P < 0.001), but age-adjusted serum PSA concentration was significantly decreased according to increasing quartile of insulin resistance as determined by HOMA and QUICKI (P < 0.001). Age, BMI, insulin resistance by HOMA or QUICKI were significantly independent variables to serum PSA level in a multivariate linear regression analysis (P < 0.001). Insulin resistance was a significant independent variable to serum PSA level along with BMI. Insulin resistance and BMI were negatively correlated with serum PSA level in healthy men. Insulin resistance was positively correlated with BMI.

The utility of fluorescence in situ hybridization for detection of bladder urothelial carcinoma in routine clinical practice.

To evaluate the ability of fluorescence in situ hybridization (FISH) in detecting bladder urothelial carcinoma (BUC), FISH and cytology were compared for the evaluation of 308 consecutive urine samples from patients suspected of having BUC. All patients underwent cystoscopy for identification of bladder lesions. The FISH results were compared with the cytology assessment. In all, 122 patients had confirmed BUC. Among them, 68 (55.7%) were FISH-positive, while only 33 (27%) were positive on cytology. According to disease stage (superficial vs. invasive) and grade (low vs. high), the sensitivities of FISH were also significantly higher than those of cytology in all categories. Moreover, in 36 patients who had no visible tumor with flat, erythematous mucosa (suspicious lesion), FISH was more sensitive than cytology for the detection of BUC (83.3% vs. 33.3%, P=0.002). The FISH was negative in 168 (90.3%) of 186 patients with no histological evidence of BUC or negative cystoscopy findings. The sensitivity of FISH for detecting BUC was superior to that of cytology, regardless of tumor stage and grade. FISH is a significant additional and complementary method for detection of BUC in patients who have suspicious lesions on cystoscopy.

Association between metabolic syndrome and chronic kidney disease in the Korean population.

AIM: We performed a retrospective study to examine the association between the metabolic syndrome (MS)and risk for the development of chronic kidney disease (CKD). METHODS: This cohort study included 60 921 healthy adults recruited from two health promotion centres.Anthropometric measures, blood pressure, fasting glucose, lipid profile and serum creatinine were evaluated. The glomerular filtration rate was estimated (eGFR) using the abbreviated equation developed by the Modification of Diet in Renal Disease (MDRD) formula. CKD was defined as an eGFR of <60 mL/min per 1.73 m2 or the presence of proteinuria. RESULTS: The prevalence of MS and CKD was 19.0% and 7.2% respectively. Those with MS had a higher prevalence of CKD (11.0% vs 6.3%, P < 0.001) than those without MS. As the number of MS components increased, the prevalence of CKD increased and the eGFR decreased. The multiple linear analyses showed that each of the components of the MS was negatively correlated with the eGFR. Unadjusted and multivariate adjusted associations were identified between MS and CKD. Individuals with MS had a multivariate adjusted odds ratio of 1.680 (95% confidence interval, 0.566-1.801) for CKD compared with those without MS. CONCLUSION: Our findings, which were obtained from a large Korean cohort, suggest that MS was associated with CKD.

Clinical inconsistency of lower urinary tract symptoms between questionnaire and bladder diary in children with nocturnal enuresis.

PURPOSE: Classification of pediatric enuresis into monosymptomatic nocturnal enuresis and nonmonosymptomatic nocturnal enuresis is crucial for management because these cases differ in many clinical respects. However, correct classification is frequently confused based on questionnaire and/or bladder diary. We tested the consistency of information obtained on lower urinary tract symptoms between our questionnaire and bladder diary. MATERIALS AND METHODS: A total of 108 physically and neurologically normal patients (mean age 7.2 years) with enuresis were included in the study. All patients filled out the questionnaire and 3-day bladder diary completely. Our questionnaire included items on urinary frequency, daytime incontinence and voiding postponement. A total of 93 patients underwent uroflowmetry and residual urine measurements. We analyzed information on lower urinary tract symptoms from the questionnaire and the bladder diary, as well as the uroflowmetry results. RESULTS: The percentage of children with nonmonosymptomatic nocturnal enuresis was 89.8% and 68.5% based on the questionnaire and bladder diary, respectively. In comparisons between the questionnaire and bladder diary we did not observe any significant consistency regarding urinary frequency (p = 0.912), daytime incontinence (p = 0.356) or voiding postponement (p = 0.505). Maximum voided volume, average voided volume and percent maximum voided volume/expected bladder capacity of children with monosymptomatic nocturnal enuresis were significantly higher than in those with nonmonosymptomatic nocturnal enuresis based on the bladder diary (p = 0.006, 0.001 and 0.041, respectively). By contrast, no significant difference was found between children with monosymptomatic and nonmonosymptomatic nocturnal enuresis based on the questionnaire (p = 0.559, 0.597 and 0.947, respectively). CONCLUSIONS: Significant discrepancies in lower urinary tract symptoms were observed between the questionnaire and bladder diary. Therefore, a detailed history and discussion with the patient and family should be performed to correlate with the questionnaire and bladder diary for the proper treatment of children with enuresis. An updated questionnaire containing a detailed scoring system may be needed.

Efficacy of lidocaine spray as topical anesthesia for outpatient rigid cystoscopy in women: a prospective, randomized, double-blind trial.

OBJECTIVES: To determine the efficacy and feasibility of urethral lidocaine spray for rigid cystoscopy in female outpatients, compared with lidocaine gel for patient tolerance of pain. METHODS: A total of 144 consecutive women scheduled to undergo rigid cystoscopy were randomized to receive either 10 mL of lidocaine gel (group 1, n = 48), five metered doses of 10% lidocaine spray (group 2, n = 48), or 10 mL of plain lubricating gel (group 3, n = 48). Patients recorded their level of pain perception during gel instillation or spray and immediately after the procedure using the visual analogue scale (VAS) and a 5-point verbal descriptor scale. RESULTS: The perception of pain was significantly decreased when lidocaine spray was used (mean VAS scores 1.9 +/- 1.3 for group 2 versus 3.9 +/- 2.2 for group 3; P <0.001). There was no difference in pain perception when lidocaine spray or gel was used (P = 0.113). Four patients in group 1 and 1 in group 2 but 10 in group 3 requested post-cystoscopic analgesics. There was a slight increase in pain perception on the VAS during the intraurethral application with lidocaine spray (2.2 +/- 1.5) compared with lidocaine gel (0.7 +/- 1.1) or plain gel (1.0 +/- 1.4). CONCLUSIONS: Lidocaine spray and lidocaine gel produce similar anesthetic effects in women undergoing rigid cystoscopy. However, concerns about the mild discomfort associated with delivery of the spray need to be resolved through future technical improvement before it gains widespread use.

Imaging features of helical computed tomography suggesting advanced urothelial carcinoma arising from the pelvocalyceal system.

BACKGROUND: Urothelial carcinoma is the most common malignant tumor arising from the pelvocalyceal system. Helical computed tomography (CT) is probably the best preoperative-stage modality for the determination of treatment plan and prognosis. PURPOSE: To obtain helical CT imaging features suggesting advanced pelvocalyceal urothelial carcinoma. MATERIAL AND METHODS: Preoperative CT images in 44 patients with pelvocalyceal urothelial carcinoma were retrospectively reviewed and correlated with the pathological examination to determine imaging features suggesting stage III or IV of the disease. RESULTS: Pathological stages revealed stage I in 16, stage II in three, stage III in 17, and stage IV in eight patients. Seven patients had metastatic lymph nodes. CT imaging showed that renal parenchymal invasion, sinus fat invasion, and lymph node metastasis were highly suggestive of advanced urothelial cell carcinoma (P<0.05). Helical CT sensitivity, specificity, and accuracy for advanced pelvocalyceal urothelial carcinoma were 76% (19/25), 84% (16/19), and 80% (35/44), respectively. CONCLUSION: Preoperative helical CT may suggest imaging features of advanced urothelial carcinoma, influencing treatment plan and patient prognosis, even though its accuracy is not so high.