Soo-Hwan Park

Gallbladder carcinoma and chronic cholecystitis:differentiation with two-phase spiral CT

The objective of the present study was to determine whether an analysis of two-phase spiral computed tomographic (CT) features provides a sound basis for the differential diagnosis between gallbladder carcinoma and chronic cholecystitis. Eighty-two patients, 35 with gallbladder carcinoma and 47 with chronic cholecystitis, underwent two-phase spiral CT. We reviewed the two-phase spiral CT features of thickness and enhancement pattern of the gallbladder wall seen during the arterial and venous phases. Mean wall thicknesses were 12.6 mm in the gallbladder carcinoma group and 6.9 mm in the chronic cholecystitis group. The common enhancement patterns seen in gallbladder carcinoma were (a) a highly enhanced thick inner wall layer during the arterial phase that showed isoattenuation with the adjacent hepatic parenchyma during the venous phase (16 of 35, 45.7%) and (b) a highly enhanced thick inner wall layer during both phases (eight of 35, 22.9%). The most common enhancement pattern of chronic cholecystitis was isoattenuation of the thin inner wall layer during both phases (42 of 47, 89.4%). In conclusion, awareness of the wall thickening and enhancement patterns in gallbladder carcinoma and chronic cholecystitis on two-phase spiral CT appears to be valuable in differentiating these two different disease entities.

Urinary Metabolite Profiling Combined with Computational Analysis Predicts Interstitial Cystitis-Associated Candidate Biomarkers

Interstitial cystitis/painful bladder syndrome (IC) is a chronic syndrome of unknown etiology that presents with bladder pain, urinary frequency, and urgency. The lack of specific biomarkers and a poor understanding of underlying molecular mechanisms present challenges for disease diagnosis and therapy. The goals of this study were to identify noninvasive biomarker candidates for IC from urine specimens and to potentially gain new insight into disease mechanisms using a nuclear magnetic resonance (NMR)-based global metabolomics analysis of urine from female IC patients and controls. Principal component analysis (PCA) suggested that the urinary metabolome of IC and controls was clearly different, with 140 NMR peaks significantly altered in IC patients (FDR < 0.05) compared to that in controls. On the basis of strong correlation scores, fifteen metabolite peaks were nominated as the strongest signature of IC. Among those signals that were higher in the IC group, three peaks were annotated as tyramine, the pain-related neuromodulator. Two peaks were annotated as 2-oxoglutarate. Levels of tyramine and 2-oxoglutarate were significantly elevated in urine specimens of IC subjects. An independent analysis using mass spectrometry also showed significantly increased levels of tyramine and 2-oxoglutarate in IC patients compared to controls. Functional studies showed that 2-oxoglutarate, but not tyramine, retarded growth of normal bladder epithelial cells. These preliminary findings suggest that analysis of urine metabolites has promise in biomarker development in the context of IC.

Chronic bacterial seminal vesiculitis as a potential disease entity in men with chronic prostatitis.

To investigate bacterial infection in the seminal vesicles by bacteriological examination and radionuclide imaging in men with chronic prostatitis.

Penile erection induces angiogenic, survival, and antifibrotic signals: molecular events associated with penile erection induced by cavernous nerve stimulation in mice

To determine the molecular events related to penile erection in the corpus cavernosum tissue of mice after electrical stimulation of the cavernous nerve.

Flow Starting Point and Voiding Mechanisms Measured by Simultaneous Registrations of Intravesical, Intra-abdominal, and Intraurethral Pressures in Awake Rats.

Purpose The aim of this study was to apply a new surgical procedure that allows for the successful monitoring of intraurethral pressure (IUP) changes in the cystometry of awake Sprague-Dawley rats. Methods Twenty-six female Sprague-Dawley rats were grouped according to the catheterization method (bladder only; bladder and urethra; or bladder, urethra, and abdomen). Using an arbitrarily determined initial point of the first phase among four rat micturition phases on the simultaneous curves as a reference point, we compared the time differences to the points on an intravesical pressure (IVP) and those on IUP or a detrusor pressure (DP) curve from intra-abdominal pressure (IAP). Results In awake rat, the start of urethral flow on IUP curve corresponded to the initial point of the second phase, which is same to the results on the anesthetized rat. However, certain results, such as micturition pressure (MP) and intraluminal pressure high-frequency oscillations (IPHFOs), differed between awake and anesthetized rats. Most MP values were checked after the end of urethral flow on the IUP curve, which is due to the peculiar methodology such as transvesical catheterization. Urethral flow was not completely interrupted during the IPHFOs, which suggests the presence of urethral wall tension against the flow during voiding. After removal of the superimposed effects of IAP from IVP, the DP curve clearly showed a peculiar shape, highlighting the possibility of using IAP in place of IUP to detect the flow starting point on the IVP curve. Conclusions Awake rat cystometry results have been interpreted based on those in anesthetized rats. However, our awake cystometry data were substantially different in terms of voiding time compared to those of anesthetized rats. This discovery warrants careful interpretation of the voiding parameters in awake rat cystometry.

Effect of SMAD7 gene overexpression on TGF-β1-induced profibrotic responses in fibroblasts derived from Peyronie's plaque.

Transforming growth factor-β1 (TGF-β1) has been identified as one of the most important fibrogenic cytokines associated with Peyronie′s disease (PD). The mothers against decapentaplegic homolog 7 (SMAD7) is an inhibitory Smad protein that blocks TGF-β signaling pathway. The aim of this study was to examine the anti-fibrotic effect of the SMAD7 gene in primary fibroblasts derived from human PD plaques. PD fibroblasts were pretreated with the SMAD7 gene and then stimulated with TGF-β1. Treated fibroblasts were used for Western blotting, fluorescent immunocytochemistry, hydroxyproline determination, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assays. Overexpression of the SMAD7 gene inhibited TGF-β1-induced phosphorylation and nuclear translocation of SMAD2 and SMAD3, transdifferentiation of fibroblasts into myofibroblasts, and quashed TGF-β1-induced production of extracellular matrix protein and hydroxyproline. Overexpression of the SMAD7 gene decreased the expression of cyclin D1 (a positive cell cycle regulator) and induced the expression of poly (ADP-ribose) polymerase 1, which is known to terminate Smad-mediated transcription, in PD fibroblasts. These findings suggest that the blocking of the TGF-β pathway by use of SMAD7 may be a promising therapeutic strategy for the treatment of PD.

Optimizing in vivo gene transfer into mouse corpus cavernosum by use of surface electroporation

Purpose Electroporation is known to enhance the efficiency of gene transfer through a transient increase in cell membrane permeability. The aim of this study was to determine the optimal conditions for in vivo electroporation-mediated gene delivery into mouse corpus cavernosum. Materials and Methods Diabetes was induced in C57BL/6 mice by intraperitoneal injections of streptozotocin. After intracavernous injection of pCMV-Luc (100 µg/40 µL), different electroporation settings (5-50 V, 8-16 pulses with a duration of 40-100 ms) were applied to the penis to establish the optimal conditions for electroporation. Gene expression was evaluated by luciferase assay. We also assessed the undesired consequences of electroporation by visual inspection and hematoxylin-eosin staining of penile tissue. Results Electroporation profoundly induced gene expression in the corpus cavernosum tissue of normal mice in a voltage-dependent manner. We observed electrical burn scars in the penis of normal mice who received electroporation with eight 40-ms pulses at a voltage of 50 V and sixteen 40-ms pulses, eight 100-ms pulses, and sixteen 100-ms pulses at a voltage of 30 V. No detectable burn scars were noted in normal mice stimulated with eight 40-ms pulses at a voltage of 30 V. Electroporation also significantly induced gene expression in diabetic mice stimulated with 40-ms pulse at a voltage of 30 V without injury to the penis. Conclusions We have established the optimal electroporation conditions for maximizing gene transfer into the corpus cavernosum of mice while avoiding damage to the erectile tissue. The electroporation-mediated gene delivery technique will be a valuable tool for gene therapy in the field of erectile dysfunction.

A case report of testicular sparganosis misdiagnosed as testicular tumor.

Sparganosis is a parasitic infestation of human by plerocercoid larvae. Sparganum is usually reported to be found in the subcutaneous tissues as well as other organs, including scrotum. However, testicular sparganosis is extremely rare, because of strong capsule of tunica albuginea. An urban-living 54-yr-old Korean man presented with left scrotal pain for 6 yr. Both testes look normal physically. Ultrasonography revealed poorly defined, heterogeneous mass with increased echogenicity in the left testis. This case was misdiagnosed as testicular tumor and underwent orchiectomy, but was diagnosed as testicular sparganosis by histopathology. Sparganosis should be included for differential diagnosis of testis tumor in countries where sparganosis is prevalent. Graphical Abstract

MP45-11 DICKKOPF2 PROMOTES ANGIOGENESIS AND NEURAL REGENERATION THROUGH AN ANGIOPOIETIN-1-TIE2 PATHWAY AND RESCUES ERECTILE FUNCTION IN THE DIABETIC MOUSE

penile morphology in normotensive and hypertensive rats after 5-areductase inhibitors treatment. METHODS: Sixty male rats were assigned into 6 groups as following: WKY e group composed by untreated Wistar Kyoto rats (normotensive strain); WKYþD Wistar Kyoto rats treated with dutasteride (0.5 mg/Kg/day); WKYþF Wistar Kyoto rats treated with finasteride (5 mg/Kg/day); H group composed by the strain of spontaneously hypertensive rats (SHR); HþD SHR treated with dutasteride; HþF SHR treated with finasteride. All treatments were given by gavage during 40 days after what the animals were killed and their penis were collected and processed for histomorphometrical analysis. Sections stained with hematoxylin and eosin were used to study the cross-sectional penile area, while Masson’s trichrome was used for study the surface density of smooth muscle fibers, connective tissue, and sinusoidal spaces of the corpus cavernosum. The surface density of elastic system fibers was studied in Weigert’s resorcin fucsin stained section. The results were compared by one-way-ANOVA with Bonferroni’s post test, considering p>0.05 as significant. RESULTS: The cross-sectional penile area of normotensive animals that received dutasteride or finasteride was reduced by 39.9% and 40% in comparison to untreated normotensive animals. The connective tissue of H group was 13.7% higher than WKY, and HþD animals had an increase of 12.9% of connective tissue in comparison to untreated hypertensive animals. The sinusoidal space was reduced by 33.7% in H in comparison to WKY. In respect to the smooth muscle surface density, WKYþD showed a reduction of 26.1% in comparison to WKY, while both HþD and HþF showed reductions of 29.4 and 32.5% in comparison to untreated H. Despite no difference in the elastic system fibers surface density was observed between H and WKY, groups WKYþD, WKYþF, HþD, and HþF had an increase of 35,7%, 41,1% 82,6%, and 31,5% in comparison to WKY. Also, HþD showed a 45,8% increase in comparison to H. CONCLUSIONS: Hypertension promoted important modifications on penile structure. Both 5-a-reductase inhibitors (dutasteride and finasteride) promoted modifications in penile morphology of normotensive and hypertensive rats, although these modifications were more prominent in hypertensive animals. Dutasteride was the drug that most affected the corpus cavernosum in this rodent model.

MP45-13 INTRACAVERNOUS DELIVERY OF DICKKOPF3 GENE OR PEPETIDE RESCUES ERECTILE FUNCTION THROUGH ENHANCED CAVERNOUS ANGIOGENESIS IN THE DIABETIC MOUSE

INTRODUCTION AND OBJECTIVES: Patients with diabetic erectile dysfunction (ED) often have severe endothelial dysfunction, which results in poor response to oral phosphodiesterase-5 inhibitors. Dickkopf-3 (DKK3), originally reported to interact Wnt signaling pathway during embryonic development, is known to involve in the endothelial cell proliferation. However, the role of DKK3 in ED is as yet not reported. The aim of this study was to investigate whether and how DKK3 gene or peptide restores erectile function in diabetic mice. METHODS: Eight-week-old C57BL/6 mice were used, and diabetes was induced by intraperitoneal injection of streptozotocin. At 8 weeks after the diabetes induction, the efficacy of DKK3 peptide or gene were determined by three independent experiments: Experiment 1 (DKK2 peptide; Control, DM þ PBS, DM þ DKK3 peptide [5 mg/20 mL]); Experiment 2 (DKK2 plasmid DNA with electroporation; Control, DM þ empty vector (100 mg/20 mL), DM þ DKK3 plasmid (10 mg, 40 mg, or 100 mg/20 mL, respectively); and Experiment 3 (DKK3 adenovirus; Control, DM þ PBS, DM þ Ad-GPF (1 x 10 vp/20 mL), DM þ Ad-DKK3 (1 x 10, 1 x 10, 1 x 10 vp/20 mL, respectively). One (peptide) or two weeks (gene) after treatment, we measured erectile function by electrical stimulation of the cavernous nerve. The penis was then harvested for histologic examination. We also determined angiogenic activity of DKK3 in primary cultured mouse cavernous endothelial cells (MCECs). RESULTS: The protein expression of DKK3 was significantly lower in cavernous tissue of diabetic mice than in controls. Intracavernous injection of DKK3 peptide or gene partially restored erectile function in diabetic mice, which reached up to 70-80% of the control values. DKK3 significantly restored cavernous endothelial cell content and endothelial cell-cell junction proteins (ZO-1 and claudin-5) in diabetic mice. Treatment of MCECs with DKK3 peptide significantly increased the expression of basic fibroblast growth factor and angiopoietin-1, which accelerated tube formation and endothelial migration, and restored integrity of the endothelial cellcell junction. CONCLUSIONS: DKK3 restored erectile function in diabetic mouse through the restoration of cavernous endothelial cells and the integrity of endothelial cell-cell junction. Therapeutic cavernous endothelial regeneration by use of DKK3 may provide a good opportunity for treating ED from vascular causes.