Purpose-We investigated the effects of intrathecal application of GABA A and GABA B receptor agonists on detrusor overactivity in spinal cord injured rats.Materials and Methods-Adult female Sprague-Dawley rats were used. At 4 weeks after Th9-10 spinal cord transection, awake cystometry and recordings of external urethral sphincter electromyogram were performed to examine the effect of intrathecal application of GABA A and GABA B agonists (muscimol and baclofen, respectively) or GABA A and GABA B antagonists (bicuculline and saclofen, respectively) at the level of L6-S1 spinal cord. Expression of glutamate decarboxylase 67 mRNA in the L6-S1 spinal cord and dorsal root ganglia was also assessed.Results-Both muscimol and baclofen produced a dose-dependent inhibition of the number (51-73% decrease) and amplitude (35-93% decrease) of nonvoiding bladder contractions, and a decrease in micturition pressure. The effects of muscimol and baclofen were antagonized by bicuculline and saclofen, respectively. Bursting activity of external urethral sphincter electromyogram was inhibited corresponding to the inhibition of bladder activity by muscimol and baclofen. Glutamate decarboxylase 67 mRNA levels in the spinal cord and dorsal root ganglia was decreased (55% and 84%, respectively) after spinal cord transection.Conclusions-These results indicate that GABA A and GABA B receptor activation in the spinal cord inhibits detrusor overactiivty. The reduction in glutamate decarboxylase 67 mRNA suggests hypofunction of GABAergic inhibitory mechanisms in the spinal cord. Therefore, stimulation of spinal GABAergic mechanisms could be effective for the treatment of detrusor overactivity after spinal cord injury.

Miyazato M, Sasatomi K, Hiragata S, Sugaya K, Chancellor MB, de Groat WC, Yoshimura N. Suppression of detrusor-sphincter dysynergia by GABA-receptor activation in the lumbosacral spinal cord in spinal cord-injured rats. We investigated the effects of intrathecal application of GABAA-or GABAB-receptor agonists on detrusor-sphincter dyssynergia (DSD) in spinal cord transection (SCT) rats. Adult female Sprague-Dawley rats were used. At 4 wk after Th 9-10 SCT, simultaneous recordings of intravesical pressure and urethral pressure were performed under an awake condition to examine the effect of intrathecal application of GABAA and GABAB agonists (muscimol and baclofen, respectively) or GABAA and GABAB antagonists (bicuculline and saclofen, respectively) at the level of L 6-S1 spinal cord. In spinal-intact rats, the effects of bicuculline and saclofen on bladder and urethral activity were also examined. During urethral pressure measurements, DSD characterized by urethral pressure increases during isovolumetric bladder contractions were observed in 95% of SCT rats. However, after intrathecal application of muscimol or baclofen, urethral pressure showed urethral relaxation during isovolumetric bladder contractions. The effective dose to induce inhibition of urethral activity was lower compared with the dose that inhibited bladder contractions. The effect of muscimol and baclofen was antagonized by intrathecal bicuculline and saclofen, respectively. In spinal-intact rats, intrathecal application of bicuculline induced DSD-like changes. These results indicate that GABAAand GABAB-receptor activation in the spinal cord exerts the inhibitory effects on DSD after SCT. Decreased activation of GABAA receptors due to hypofunction of GABAergic mechanisms in the spinal cord might be responsible, at least in part, for the development of DSD after SCT. bladder; urethra; spinal cord; ␥-aminobutyric acid; detrusor-sphincter dyssynergia MICTURITION DEPENDS ON THE coordination between the bladder and external urethral sphincter (8). However, in the chronic phase of spinal cord injury, the bladder exhibits detrusor overactivity, and bladder-sphincter coordination is impaired, leading to detrusor-sphincter dyssynergia (DSD), which is simultaneous contractions of the external urethral sphincter and bladder during the micturition reflex (4). These lower urinary tract dysfunctions then produce various problems, such as urinary incontinence, recurrent urinary tract infection, and vesicoureteral reflux, with or without upper urinary tract deterioration.It has been reported that glutamate, glycine, and opioids can modulate the activity of the external urethral sphincter in the DSD condition (13,15,21). Glutamate is known to be a major excitatory neurotransmitter (18), and both ionotropic N-methyl-D-aspartate and ␣-amino-3-hydroxy-5-methyl-4-isoxasole propionic acid glutamate receptor antagonists inhibit urethral activity in spinal cord injury rats (15). Glycine is a major inhibitory neurotransmitter in the central nervous system, and intrathecal...

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Abbreviations & AcronymsBcl-2 = B-cell lymphoma 2 CD10 = cluster of differentiation 10 CD99 = cluster of differentiation 99 CN = cystic nephroma MESTK = mixed epithelial and stromal tumor of the kidney PSA = prostate-specific antigen SMA = smooth muscle actin Abstract: Mixed epithelial and stromal tumor of the kidney is a rare benign tumor that consists of both epithelial and stromal cells. To date, eight malignant cases have previously been reported in female patients only. We report the first case of malignant mixed epithelial and stromal tumor of the kidney in a male patient. A 67-year-old Japanese man receiving hormonal therapy for prostatic cancer was found to have a right renal cystic tumor and underwent right nephrectomy. Histologically, the tumor was composed of benign epithelial and stromal cells in addition to malignant undifferentiated stromal cells. Immunohistochemically, the malignant stromal component was positive for cluster of differentiation 99 and B-cell lymphoma 2, but no chimeric transcripts for synovial sarcoma were identified. Finally, a diagnosis of malignant mixed epithelial and stromal tumor of the kidney was recorded. Urologists and pathologists should recognize that malignant mixed epithelial and stromal tumors of the kidney might occur in male patients receiving hormonal therapy for prostatic cancer.