Khae Hawn Kim

Alcohol induces apoptosis in TM3 mouse Leydig cells via bax-dependent caspase-3 activation.

To investigate whether ethanol induces apoptosis in Leydig cells, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, terminal deoxynuclotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay, 4,6-diamidino-2-phenylindole (DAPI) staining, DNA fragmentation assay, caspase-3 enzyme assay, reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis were performed on TM3 mouse Leydig cells. Through morphological and biochemical analyses, it was demonstrated that TM3 cells treated with ethanol at concentrations of 50 and 100 mM exhibit classical apoptotic features. In addition, it was shown that ethanol induces increases in levels of bax and caspase-3 and a decrease in bcl-2 expression. Based on the results, alcohol appears to activate specific intracellular death-related pathways leading to bax-dependant caspase-3 activation and the induction of apoptosis in Leydig cells.

Second to fourth digit ratio: a predictor of prostate-specific antigen level and the presence of prostate cancer

Study Type – Diagnostic (exploratory cohort) Level of Evidence 2b

The phosphodiesterase type-5 inhibitor, tadalafil, improves depressive symptoms, ameliorates memory impairment, as well as suppresses apoptosis and enhances cell proliferation in the hippocampus of maternal-separated rat pups

Early adverse experiences resulting from maternal separation may lead to neuronal cell death and eventually cause memory impairment. Maternal separation has been used to create a valid animal model of early life stress and a depression-like syndrome. The phosphodiesterase (PDE)-5 inhibitor, tadalafil (Cialis), is a widely prescribed agent for the treatment of erectile dysfunction. In this study, we investigated the effects of tadalafil on apoptosis and cell proliferation in the hippocampal dentate gyrus of rat pups following maternal separation. Specifically, the immobility time in the forced swim test was increased in the maternal-separated rat pups, and tadalafil treatment decreased the immobility time. The rat pups in the maternal separation group had deceased memory function compared to the rat pups in the maternal care group, and tadalafil treatment increased memory function of the rat pups in the maternal separation group. Apoptotic cell death in the hippocampal dentate gyrus was significantly increased in the maternal-separated rat pups, and tadalafil treatment suppressed maternal separation-induced apoptosis. In contrast, cell proliferation in the dentate gyrus was significantly decreased in the maternal-separated rat pups, and taldalafil treatment increased cell proliferation. The present results suggest that tadalafil improves depressive symptoms and alleviates memory impairment by suppressing apoptotic neuronal cell death and enhancing cell proliferation in maternal-separated rat pups.

Effects of Tamsulosin on Urinary Bladder Function and Neuronal Activity in the Voiding Centers of Rats with Cyclophosphamide-induced Overactive Bladder

Purpose The overactive bladder (OAB) syndrome is characterized by urgency usually with frequency and nocturia. Tamsulosin, α1-adrenergic receptor antagonist, is widely used to reduce symptoms of urinary obstruction and prostatic hyperplasia. Tamsulosin can across the blood-brain barrier. We investigated the effects of tamsulosin on the symptoms of OAB in relation to neuronal activity using rats. Methods Adult female Sprague-Dawley rats, weighing 250±10 g (9 weeks old), were used in this study. The animals were divided into five groups (n=8 in each group): control group, OAB-induced group, OAB-induced and 0.01 mg/kg tamsulosin-treated group, OAB-induced and 0.1 mg/kg tamsulosin-treated group, and OAB-induced and 1 mg/kg tamsulosin-treated group. OAB was induced by intraperitoneal injection of cyclophosphamide (75 mg/kg) every third day for 10 days. The rats in the tamsulosin-treated groups orally received tamsulosin once a day for 14 consecutive days at the respective dose of the groups, starting 1 day after the induction of OAB. Cystometry for bladder pressure determination, immunohistochemistry for c-Fos, nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry for nitric oxide synthase (NOS) in the neuronal voiding centers and western blot for inducible NOS in the bladder were conducted. Results Cyclophosphamide injection enhanced contraction pressure and time, representing the induction of OAB. Contraction pressure and time were significantly suppressed by tamsulosin treatment. c-Fos and NOS expressions in the neuronal voiding centers were enhanced by induction of OAB. OAB-induced c-Fos and NOS expressions were suppressed by tamsulosin treatment. Conclusions Tamsulosin exerts inhibitory effect on neuronal activation in the neuronal voiding centers of OAB. The present results suggest the possibility that tamsulosin is effective therapeutic modality for ameliorating the symptoms of OAB.

Second to fourth digit ratio: a predictor of adult penile length.

The second to fourth digit ratio (2D:4D) has been proposed as a putative biomarker for prenatal testosterone and covaries with the sensitivity of the androgen receptor (AR). Both prenatal testosterone and the AR play a central role in penile growth. In this study, we investigated the relationship between digit ratio and penile length. Korean men who were hospitalized for urological surgery at a single tertiary academic centre were examined in this study, and 144 men aged 20 years or older who gave informed consent were prospectively enrolled. Right-hand second- and fourth-digit lengths were measured by a single investigator prior to measurement of penile length. Under anaesthesia, flaccid and stretched penile lengths were measured by another investigator who did not measure nor have any the information regarding the digit lengths. Univariate and multivariate analysis using linear regression models showed that only height was a significant predictive factor for flaccid penile length (univariate analysis: r=0.185, P=0.026; multivariate analysis: r=0.172, P=0.038) and that only digit ratio was a significant predictive factor for stretched penile length (univariate analysis:r=-0.216, P=0.009; multivariate analysis: r=-0.201, P=0.024; stretched penile length=-9.201×digit ratio + 20.577). Based on this evidence, we suggest that the digit ratio can predict adult penile size and that the effects of prenatal testosterone may in part explain the differences in adult penile length.

Nicotine administration decreases neuropeptide Y expression and increases leptin receptor expression in the hypothalamus of food-deprived rats

The effects of nicotine on the expressions of neuropeptide Y (NPY) and leptin receptor in the rat hypothalamus were investigated via immunohistochemistry. The results show that NPY expression is not affected in the arcuate nucleus (ARN) and is increased only slightly in the paraventricular nucleus (PVN) by nicotine administration under normal (i.e. fed) conditions and that leptin receptor expression is decreased slightly in the ARN and not affected in the PVN following nicotine treatment under the same conditions. Food deprivation enhanced NPY and suppressed leptin receptor expression in the ARN and PVN of the hypothalamus. Nicotine administration resulted in decreased NPY and increased leptin receptor levels.

Treadmill Exercise Ameliorates Short-Term Memory Disturbance in Scopolamine-Induced Amnesia Rats

Purpose Scopolamine is a nonselective muscarinic cholinergic receptor antagonist, which induces impairment of learning ability and memory function. Exercise is known to ameliorate brain disturbance induced by brain injuries. In the present study, we investigated the effect of treadmill exercise on short-term memory in relation to acetylcholinesterase (AChE) expression in the hippocampus, using a scopolamine-induced amnesia model in mice. Methods To induce amnesia, 1 mg/kg scopolamine hydrobromide was administered intraperitoneally once per day for 14 days. A step-down avoidance test for short-term memory was conducted. AChE histochemistry, immunohistochemistry for collagen IV, and doublecortin were performed. Results Short-term memory deteriorated in the mice with scopolamine-induced amnesia, concomitant with enhanced AChE expression and suppression of angiogenesis in the hippocampus. Critically, treadmill exercise ameliorated short-term memory impairment, suppressed AChE expression, and enhanced angiogenesis in the mice with scopolamine-induced amnesia. Conclusions Overexpression of AChE is implicated in both brain and renal disease. The findings of our study indicate that treadmill exercise may be of therapeutic value in neurodegenerative and renal diseases by suppressing the effects of AChE expression.

Circadian Rhythms in Urinary Functions: Possible Roles of Circadian Clocks?

Circadian clocks are the endogenous oscillators that harmonize a variety of physiological processes within the body. Although many urinary functions exhibit clear daily or circadian variation in diurnal humans and nocturnal rodents, the precise mechanisms of these variations are as yet unclear. In this review, we briefly introduce circadian clocks and their organization in mammals. We then summarize known daily or circadian variations in urinary function. Importantly, recent findings by others as well as results obtained by us suggest an active role of circadian clock genes in various urinary functions. Finally, we discuss possible research avenues for the circadian control of urinary function.

Second to fourth digit ratio: its relationship with core cancer volume and Gleason score in prostate biopsy

OBJECTIVE To investigate the relationships between 2nd to 4th digit ratio (digit ratio) and prostate cancer detection rate and biopsy findings, including Gleason score. MATERIALS AND METHODS In 770 consecutive men aged 40 years or older that presented with lower urinary tract symptoms (LUTS), right hand 2nd and 4th digit lengths were measured prior to PSA determinations, DRE and transrectal ultrasonography (TRUS). Among these, 166 men with a prostate specific antigen (PSA) level ≥ 3 ng/mL or abnormal digit rectal examination (DRE) prospectively underwent prostate biopsies. The relationship between digit ratio and prostate cancer detection rate and biopsy findings was investigated. RESULTS The study subjects were allocated to two groups by digit ratio (group A: digit ratio < 0.95; n = 420; group B: digit ratio ≥ 0.95; n = 350). Despite similar biopsy rates (22.4% vs. 20.6%, p = 0.544), group A had higher cancer detection rate (46.8% (44/94) vs. 23.6% (17/72), p = 0.002; OR = 2.847, 95% CI = 1.445-5.610). When we analyzed 408 positive biopsy cores (group A: digit ratio < 0.95, n = 282; group B: digit ratio ≥ 0.95, n = 126), group A had higher percentage of core cancer volume (46.7% vs. 37.1%, p = 0.005) and more biopsy cores with high Gleason score (sum of Gleason score ≥ 9: 18/282 (6.4%) vs. 1/126 (0.8%), p = 0.010; primary Gleason score = 5: 12/282 (4.3%) vs. 0/126 (0.0%), p = 0.021). CONCLUSIONS A lower digit ratio is related to an increased detection rate of prostate cancer, a high percentage of core cancer volume and a high Gleason score.

Effects of acupuncture on abdominal leak point pressure and c-Fos expression in the brain of rats with stress urinary incontinence

Stress urinary incontinence leads to the involuntary loss of urine during abdominal strain caused by sneezing, laughing, and coughing. Acupuncture has been widely used for the treatment and prevention of a variety of diseases in traditional medicine. Acupuncture has also been used to relieve the symptoms of functional disorders of the lower urinary tract. In the present study, we investigated the effect of acupuncture at the Sanyinjiao (SP6) acupoint on stress urinary incontinence in rats. The present results showed that abdominal leak point pressure was decreased in rats with stress urinary incontinence, while acupuncture at the SP6 acupoint significantly enhanced the abdominal leak point pressure. The expression of c-Fos in the pontine micturition center (PMC), ventrolateral periaqueductal gray (vlPAG), and medial preoptic nucleus (MPA) regions was increased by the induction of stress urinary incontinence, and acupuncture at the SP6 acupoint significantly decreased c-Fos expression in these areas. In the present study, we showed that acupuncture has therapeutic effect on the symptoms of stress urinary incontinence, and this effect of acupuncture is associated with modulation of c-Fos expression in the brain.