Shin Young Lee

Clinical significance of the leptin and leptin receptor expressions in prostate tissues

AIMnTo evaluate the expression of leptin and leptin receptor in benign prostatic hyperplasia (BPH) and prostate cancer (PCa), and to investigate whether they are associated with the development and progression of PCa.nnnMETHODSnImmunohistochemical staining was performed to examine the expression of leptin and leptin receptor in BPH and PCa. PCa was divided into three groups: localized PCa, locally advanced PCa and metastatic PCa. The positive staining was identified and the percentage of the positive staining was graded. We also assessed the relationship between both the Gleason score and body mass index (BMI) and PCa.nnnRESULTSnThe percentage of the leptin expression in PCa was significantly higher than that in BPH (P < 0.01). For the PCa group, the expressed levels of leptin showed a considerable correlation with localized PCa and metastatic PCa (P < 0.05). Leptin receptor, however, did not reveal a definite difference between BPH and PCa. The expression of leptin indicated a significant difference between well-differentiated PCa (Gleason score =or< 6) and poorly differentiated PCa (Gleason score 8?0) (P < 0.05). The relation between the leptin expression level in PCa and the BMI was not remarkable (P = 0.447).nnnCONCLUSIONnOur results suggest that leptin might have a promoting effect on the carcinogenesis and progression of PCa.

Extramammary Paget's disease of scrotum treated with radiotherapy.

Extramammary Pagets disease (EMPD) of the scrotum is extremely rare. Most cases are found on the vulva or anus. It is generally accepted that EMPD is associated with an underlying carcinoma in situ. The lesion is located deep in between the dermal to epidermal layer. EMPD must be differentiated from benign papulosquamous disease, squamous cell carcinoma and melanoma. It can be managed by local excision and reconstruction with a skin graft or skin flap. Radiation and topical chemotherapy have also been used as alternative treatment strategies and are effective for local control.

The effects of interleukin-6 on the contraction and relaxation responses of the cavernous smooth muscle from rats

The purpose of this study is to elucidate the effect of IL-6 on the vasomotor reactivity of the corpus cavernosum of the rats. The strips were either left untreated or treated with 1 ng/ml of IL-6 for 60 min. By increasing concentrations of phenylephrine, acetylcholine, or sodium nitroprusside, we assessed concentration-contraction or relaxation responses. The IL-6-treated strips were incubated for 30 min with or without L-NAME (N(W)-nitro-L-arginine methyl ester), L-arginine, indomethacin, BQ-123 (an endothelin receptor A inhibitor), or SQ 29,548 (a thromboxane A(2) [TXA(2)] receptor blocker), and the effects on phenylephrine-induced contraction or acetylcholine-induced relaxation of phenylephrine-induced contraction were measured. The contractile responses to phenylephrine were significantly enhanced in the IL-6-treated strips, compared with the IL-6-nontreated strips, and the relaxation responses to acetylcholine were significantly inhibited in the IL-6-treated group compared with the IL-6-nontreated group. But after endothelial denudation, there was no difference between the IL-6-treated strips and the IL-6-nontreated strips on the contraction-relaxation responses to phenylephrine or acetylcholine. The relaxation responses to sodium nitroprusside were not inhibited in both groups. L-NAME completely inhibited the relaxation response to acetylcholine in the IL-6-treated strips, as well as the IL-6-nontreated strips. Indomethacin and SQ 29,548 significantly inhibited the increased contractile responses to phenylephrine in the IL-6-treated strips. But BQ 123 rarely affected the same responses. L-arginine reversed the inhibited relaxation responses to acetylcholine in the IL-6-treated strips. Therefore, IL-6 inhibits endothelium-dependent, NO-mediated relaxation and also enhances alpha(1)-adrenergic receptor-mediated contraction via an endothelium-dependent TXA(2)-mediated mechanism in the corpus cavernosum of the rat.

Bilateral Recurrent Thigh Abscesses for Five Years after a Transobturator Tape Implantation for Stress Urinary Incontinence

The synthetic, tension-free midurethral sling procedure using transobturator tape (TOT) was introduced in 2001 and has become the most widely used procedure for the treatment of female urinary incontinence worldwide. However, infectious complications associated with erosions have occasionally been reported because of a foreign body reaction to the polypropylene mesh. We observed a case of a bilateral recurrent thigh abscess manifesting 5 years after a TOT sling procedure. The patient had recurrent thigh abscesses with repeated incisions and drainages in the past 1 year. Five months earlier, she had undergone a procedure to remove the eroded suburethral mesh, but incompletely. The right thigh abscess recurred, and ultimately the residual mesh was completely excised with abscess drainage. Complete mesh removal is very important to prevent abscess recurrence, and it is necessary for any urologist treating women who have undergone the TOT procedure to be aware of the possibility of abscesses occurring for a long time after the operation.

A Novel Pathway Underlying the Inhibitory Effects of Melatonin on Isolated Rat Urinary Bladder Contraction

The aim of the present study was to elucidate the direct effects of melatonin on bladder activity and to determine the mechanisms responsible for the detrusor activity of melatonin in the isolated rat bladder. We evaluated the effects of melatonin on the contractions induced by phenylephrine (PE), acetylcholine (ACh), bethanechol (BCh), KCl, and electrical field stimulation (EFS) in 20 detrusor smooth muscle samples from Sprague-Dawley rats. To determine the mechanisms underlying the inhibitory responses to melatonin, melatonin-pretreated muscle strips were exposed to a calcium channel antagonist (verapamil), three potassium channel blockers [tetraethyl ammonium (TEA), 4-aminopyridine (4-AP), and glibenclamide], a direct voltage-dependent calcium channel opener (Bay K 8644), and a specific calcium/calmodulin-dependent kinase II (CaMKII) inhibitor (KN-93). Melatonin pretreatment (10-8~10-6 M) decreased the contractile responses induced by PE (10-9~10-4 M) and Ach (10-9~10-4 M) in a dose-dependent manner. Melatonin (10-7 M) also blocked contraction induced by high KCl ([KCl]ECF; 35 mM, 70 mM, 105 mM, and 140 mM) and EFS. Melatonin (10-7 M) potentiated the relaxation response of the strips by verapamil, but other potassium channel blockers did not change melatonin activity. Melatonin pretreatment significantly decreased contractile responses induced by Bay K 8644 (10-11~10-7 M). KN-93 enhanced melatonin-induced relaxation. The present results suggest that melatonin can inhibit bladder smooth muscle contraction through a voltage-dependent, calcium-antagonistic mechanism and through the inhibition of the calmodulin/CaMKII system.

HNF1B Polymorphism Associated With Development of Prostate Cancer in Korean Patients

OBJECTIVEnTo identify whether the genetic variations in HNF1B are associated with the development of prostate cancer in Korean patients. Genome-wide association studies have found the HNF1B gene at 17q12 to be a major causal gene for the risk of prostate cancer.nnnMETHODSnWe evaluated the association of 47 single nucleotide polymorphisms (SNPs) in the HNF1B gene with prostate cancer risk and clinical characteristics (Gleason score and tumor stage) in Korean men (240 case subjects and 223 control subjects) using unconditional logistic regression analysis.nnnRESULTSnOf the 47 SNPs, 14 were associated with prostate cancer risk (P = .002-.02); 9 SNPs were associated with a lower risk of prostate cancer (odds ratio 0.67-0.71, P = .005-.05), and 5 SNPs were associated with a greater risk of disease (odds ratio 1.49-1.51, P = .002-.02). In an analysis involving only patients with prostate cancer, 1 SNP (rs11868513) in the HNF1B gene was more frequent in patients with tumors with a greater stage than in those with a lower tumor stage. Two SNPs (rs4430796 and rs2074429) and 1 haplotype (Block3_ht1) were more frequent in patients with Gleason score of ≥7 than in those with Gleason score <6.nnnCONCLUSIONnAs in studies from other populations, our findings indicate that HNF1B is also associated with prostate cancer risk in the Korean population.

Effect of low concentrations of hydrogen peroxide on the contractile responses of rat detrusor smooth muscle strips.

This study was designed to determine how the contractility of rat detrusor smooth muscle strips changes in the presence of low concentrations of hydrogen peroxide (H(2)O(2)). The strips were dissected from the base of Sprague-Dawley rat bladders and their contractile responses to a cumulative increase in H(2)O(2) concentration (3 x 10(-6)-3 x 10(-2)g%) were measured. How the duration of exposure to the fixed concentration of 3 x 10(-4)g% H(2)O(2) affected contractility was also examined. Moreover, the effect of 3 x 10(-4)g% H(2)O(2) pretreatment on the response to cumulative increases in the concentrations of phenylephrine or acetylcholine (10(-8)-10(-4)M) was assessed. To elucidate the mechanism by which H(2)O(2) induced contraction, we examined the effect of pretreatment with 10nM Y-27632, 10 microM indomethacin, 10 microM SQ29548, 10 microM verapamil, 10 microM vitamin E, or 1 microM Bay-K 8644 on the contractile responses generated by cumulatively increasing the concentration of H(2)O(2). H(2)O(2)-induced contractile responses in Ca(2+)-free physiological solution were also examined. Low concentrations of H(2)O(2) increased the contractile responses of the strips in a dose-dependent manner but increasing treatment duration decreased these responses. H(2)O(2)-pretreatment significantly augmented the contraction induced by phenylephrine (P<0.05) but had no effect on the response to acetylcholine. Pretreatment with Y-27632, indomethacin, vitamin E, verapamil, and Bay-K 8644 significantly inhibited the H(2)O(2)-induced contraction (P<0.05). SQ 29548-pretreatment had no effect. H(2)O(2) could not increase the contractile responses in Ca(2+)-free physiological solution. Thus, low concentrations of H(2)O(2) may directly affect detrusor smooth muscles and thereby induce detrusor overactivity.

ORIGINAL RESEARCH—BASIC SCIENCE: The Effects of Dehydroepiandrosterone (DHEA)/DHEA-Sulfate (DHEAS) on the Contraction Responses of the Clitoral Cavernous Smooth Muscle from Female Rabbits

INTRODUCTIONnDehydroepiandrosterone (DHEA) is a multifunctional steroid that is increasingly available as a supplement aimed at improving libido and well-being in postmenopausal women in the recent times. Together with its sulfate version, DHEA-sulfate (DHEAS), it is the most abundant steroid in humans. The clitoris is an important component of the female sexual response, with its increased vascular response during sexual arousal that results in erection.nnnAIMSnTo elucidate the direct effects of DHEA/DHEAS on the vasomotor reactivity of the rabbit clitoral cavernosum.nnnMETHODSnTwenty New Zealand white female rabbits weighing approximately 2.5-3 kg were used in the study.nnnMAIN OUTCOME MEASURESnThe contractile response of clitoral cavernous smooth muscle strips in response to phenylephrine (PE; 10(-9)-10(-4) M) were observed in rabbits. Additionally, DHEA/DHEAS effects on phenylephrine-induced contraction and/or acetylcholine-induced relaxation of phenylephrine-induced contraction were measured.nnnRESULTSnDHEA/DHEAS did not elicit any remarkable response in the resting state. However, both DHEA and DHEAS evoked dose-dependent relaxations of PE-induced contraction. The contractile responses to high potassium were significantly decreased in the DHEA/DHEAS-pretreated strips, compared with the DHEA/DHEAS-nontreated strips. Additionally, contractions by Bay K 8644 (10(-7)-10(-6) M) treatment were also significantly inhibited by DHEA/DHEAS. DHEA-induced relaxation responses were stronger than DHEAS-induced relaxation responses. Various K channel blockers, tetraethylammonium (TEA; 1 mM, 10 mM), 4-aminopyridine (10 microM) and glibenclamide (10 microM) did not affect the DHEA/DHEAS-induced relaxation on muscle strips contracted by PE. Relaxation responses by acetylcholine or sodium nitroprusside (SNP) were not changed after DHEA/DHEAS pretreatment.nnnCONCLUSIONSnDHEA/DHEAS was found to induce a relaxation response in rabbit clitoral cavernosal smooth muscle, and this is thought to be mediated by direct inhibition of a voltage-dependent calcium channel.

The Relaxing Effect of α-Defensin 1 on the Adrenergic Responses of Rat Bladder

Defensins, cysteine-rich cationic polypeptides released from neutrophils, are known to have powerful antimicrobial properties. In this study, we sacrificed 30 rats to investigate the effects of α-defensin 1 on detrusor muscle contractions in isolated rat bladder. From the experiments we found relaxing effects of α-defensin 1 on the contractions induced by phenylephrine (PE) but not by bethanechol (BCh) in the detrusor smooth muscles. To determine the mechanisms of the effects of α-defensin 1, the changes of effects on PE-induced contraction by α-defensin 1 pretreatment were observed after pretreatment of Rho kinase inhibitor (Y-27632), protein kinase C (PKC) inhibitor (Calphostin C), potent activator of PKC (PDBu; phorbol 12,13-dibutyrate), and NF-κB inhibitors (PDTC; pyrrolidinedithiocarbamate and sulfasalazine). The contractile responses of PE (10(-9)~10(-4) M) were significantly decreased in some concentrations of α-defensin 1 (5×10(-9) and 5×10(-8) M). When strips were pretreated with NF-κB inhibitors (PDTC and sulfasalazine; 10(-7)~10(-6) M), the relaxing responses by α-defensin 1 pretreatment were disappeared. The present study demonstrated that α-defensin 1 has relaxing effects on the contractions of rat detrusor muscles, through NF-κB pathway. Further studies in vivo are required to clarify whether α-defensin 1 might be clinically related with bladder dysfunction by inflammation process.

Relaxing Effect of Acetylcholine on Phenylephrine-Induced Contraction of Isolated Rabbit Prostate Strips Is Mediated by Neuronal Nitric Oxide Synthase

Purpose The location of acetylcholinesterase-containing nerve fibers suggests a role for acetylcholine in both contractility and secretion in the prostate gland. The colocalization of nitrergic nerves with cholinergic nerves, and the cotransmission of nitric oxide with acetylcholine in cholinergic nerves, has been demonstrated in the prostate glands of various species. Thus, we investigated the effects of acetylcholine on phenylephrine-induced contraction and the correlation between cholinergic transmission and nitric oxide synthase by using isolated prostate strips of rabbits. Materials and Methods Isolated prostate strips were contracted with phenylephrine and then treated with cumulative concentrations of acetylcholine. Changes in acetylcholine-induced relaxation after preincubation with NG-nitroarginine methyl ester, 7-nitroindazole, and aminoguanidine were measured. The effects of selective muscarinic receptor antagonists were also evaluated. Results In the longitudinal phenylephrine-contracted strip, the cumulative application of acetylcholine (10-9 to 10-4 M) elicited a concentration-dependent relaxation effect. Acetylcholine-induced relaxation was inhibited not only by nitric oxide synthase inhibitors (10 µM L-NAME or 10 µM 7-nitroindazole) but also by 10 µM atropine and some selective muscarinic receptor antagonists (10-6 M 11-([2-[(diethylamino)methyl]-1-piperdinyl]acetyl)-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepine-6-one and 10-6 M 4-diphenylacetoxy-N-methyl-piperidine). In contrast, relaxation was significantly increased by pretreatment of the strips with 10 mM L-arginine. Conclusions Acetylcholine relaxed phenylephrine-induced contractions of isolated rabbit prostate strips. This relaxation may be mediated via both cholinergic and constitutive nitric oxide synthase with both the M2 and M3 receptors possibly playing key roles.