Young-Chol Park

EXISTENCE OF A β3-ADRENOCEPTOR AND ITS FUNCTIONAL ROLE IN THE HUMAN URETER

Purpose: We tried to determine the β-adrenoceptor (AR) subtypes distributed in the human ureter and to clarify their functional role in ureteral relaxation.Materials and Methods: 1) Effects of β-AR agonists on either spontaneous or KCl-induced contractions of the human ureter and the antagonism by β-AR antagonists on isoprenaline (a non-selective β-AR agonist)-induced effects were evaluated in vitro. 2) Displacement by β-AR antagonists of [3H]-dihydroalprenolol binding to a membrane preparation derived from human ureteral smooth muscle was evaluated. 3) A reverse transcription polymerase chain reaction assay was performed to determine the expression of the mRNA for β1-, β2- and β3-ARs in human ureteral smooth muscle.Results: 1) Isoprenaline and procaterol (a β2-AR agonist) concentration-dependently suppressed both spontaneous and KCl-induced contractions of the human ureter. The β3-AR agonists, CGP-12177A and CL-316243, also suppressed these ureteral contractions, but dobutamine (a β1-AR agonist) had litt...

β-Adrenoceptor subtypes in the ureteral smooth muscle of rats, rabbits and dogs

Abstract We investigated the β-adrenoceptor subtypes mediating ureteral relaxation in rats, rabbits and dogs. The relaxing effects of β-adrenoceptor agonists were evaluated on KCl-induced ureteral contractions. The rank order of potency of the catecholamines tested was isoprenaline>noradrenaline>adrenaline in rat ureter; isoprenaline>adrenaline>noradrenaline in rabbit ureter; only isoprenaline was effective in canine tissues. The β1-adrenoceptor agonist, dobutamine, produced relaxation of rat ureter. The β2-adrenoceptor agonist, procaterol, produced more significant relaxation of rabbit ureter than did dobutamine. CL-316243 [(R,R)-5-[2-[[2-(3-chlorophenyl)-2-hydroxyethylamino]propyl]-1,3-benzodioxole-2,2-dicarboxylate] and CGP-12177A [(±)[4-[3[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,3-dihydro-2H-benzimidazol-2-one hydrochloride], β3-adrenoceptor agonists, were more effective in relaxing canine ureter than were dobutamine and procaterol. Isoprenaline-induced relaxation was antagonized by a β1-adrenoceptor antagonist, CGP-20712A [2-hydroxy-5(2-((2-hydroxy-3-(4-((1-methyl-4-trifluoromethyl)1H-imidazole-2-yl)phenoxy)propyl)amino)ethoxy)-benzamide monomethane sulphonate], in rats and by a β2-adrenoceptor antagonist, ICI-118,551 [(±)-1-[(2,3-dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride], in rabbits. The non-selective β-adrenoceptor antagonist, bupranolol, antagonized isoprenaline-induced relaxation in all species tested. In conclusion, β-adrenoceptor agonists may relax ureter by stimulating mainly β1-adrenoceptors in rats, β2-adrenoceptors in rabbits and mainly β3-adrenoceptors in dogs.

Clinical Efficacy of Oxybutynin on Sensory Urgency as Compared with That on Motor Urgency

Objective: Anticholinergic drug is widely accepted as an effective medication for frequency, urgency and urge incontinence related to detrusor overactivity (motor urgency). In order to elucidate whether anticholinergic drug is also effective for these symptoms related to bladder hypersensitivity (sensory urgency), clinical efficacy of oxybutynin on sensory urgency was compared with that on motor urgency. Method: Twenty-four patients with sensory urgency, and 53 patients with motor urgency were treated with oxybutynin (6 mg/day) for 4 weeks and subjective and objective efficacies were evaluated. Subjective parameters were quantified with urge score (grade 0–3) and daily numbers of voiding and incontinence. Objective efficacies were evaluated with pre-/ postcomparison of cystometric parameters. Results: Excellent or good overall efficacy was obtained in 62.5% (15/24) of the sensory urgency group and 60.4% (32/53) of the motor urgency group. There was no statistical difference between these two groups. Objective cystometric parameters, bladder volume at first sensation and maximum cystometric capacity, statistically improved after the treatment in both groups. Conclucion: The results suggest that oxybutynin works as well on sensory urgency as it does on motor urgency.

Partial outlet obstruction of the rat bladder induces a stimulatory response on proliferation of the bladder smooth muscle cells.

Outlet obstruction of the ratbladder induces hypertrophy/hyperplasiacharacterized by increases in bladder mass,smooth muscle content, and collagen deposition.In order to understand the mechanism of theoutlet obstruction-induced hypertrophy andhyperplasia, we first determined the temporalpattern of changes in bladder mass afterinducing the outlet obstruction. Histologicalanalysis revealed that the smooth muscle cellswith hypertrophy and hyperplasia, fibroblastsand connective tissue were increased in atime-dependent manner, corresponding to thetemporal pattern observed in the changes inbladder mass, although the phase of changes inthese tissue components was somewhat different.In order to further determine whether anyproliferation-stimulatory factors were releasedfrom the bladder with obstruction incorrespondence with increased bladder mass,soluble fractions were prepared from thebladders with outlet obstruction for 3–30weeks, and their effects on proliferation ofsmooth muscle cells were examined. The solublefractions prepared from the bladders at 3 to 14weeks after obstruction slightly butsignificantly facilitated the proliferation ofcultured smooth muscle cells, while the solublefractions released after 20 weeks rathersuppressed the proliferation. These resultssuggest that the initial increase in bladdermass might be in part due to the facilitatedproliferation of smooth muscle cells of thebladder body induced by growth factors releasedinto the soluble fractions, and thathypertrophy might then play a role in theincreased bladder mass at later phases.

Sympathetic Skin Response: A New Test to Diagnose Ejaculatory Dysfunction

Sympathetic skin responses were elicited from the palm and sole (plantar) with electrical stimulation on the dorsal nerve of the penis in 24 individuals. The palmar and plantar sympathetic skin responses were obtained in 12 subjects with normal ejaculatory function. On the other hand, the plantar sympathetic skin response was absent in 11 of 12 patients who lacked ejaculation. Since the plantar sympathetic skin response is correlated closely to the mechanism of ejaculation, this test is expected to be helpful to diagnose sexual dysfunction and to monitor the effects of treatment.

EFFECTS OF ISOPROTERENOL AND BUTYLSCOPOLAMINE ON THE FRICTION BETWEEN AN ARTIFICIAL STONE AND THE INTRAURETERAL WALL IN ANESTHETIZED RABBITS

PURPOSE We evaluated the effects of the nonselective beta-adrenoceptor agonist isoproterenol and the nonselective muscarinic antagonist butylscopolamine on ureteral wall tension, namely friction between an artificial stone and the intraureteral wall, in anesthetized rabbits. MATERIALS AND METHODS The relaxing effect of the drugs on the KCl induced tonic contraction was examined in isolated rabbit ureters. The effect of the drugs on the applied force needed for the artificial stone to pass at a constant speed through the ureter, called sliding force, was evaluated in anesthetized rabbits. RESULTS In a concentration dependent manner isoproterenol but not butylscopolamine reduced the KCl induced contraction in isolated ureter (mean pD2 7.35 +/- 0.06). Intravenous administration of 1 and 10 microg./kg. isoproterenol significantly decreased the friction between the artificial stone and intraureteral wall in anesthetized rabbits with sliding force at 15 minutes after drug administration decreased by 54.5% and 63.6%, respectively. In contrast, 100 and 1,000 microg./kg. butylscopolamine intravenously had no evident effect on ureteral wall tension. CONCLUSIONS Our results strongly suggest that ureteral smooth muscle relaxation by beta-adrenergic stimulation reduces ureteral wall tension, thereby, diminishing mechanical effects impeding the movement of a ureteral stone down the ureter.

Endoscopic correction of vesicoureteral reflux in patients with neurogenic bladder dysfunction

Transurethral injection of Teflon paste (TUI) was carried out in 24 ureters of 16 patients with vesicoureteral reflux (VUR) secondary to neurogenic bladder dysfunction at an age ranging from 4 to 77 years, and the results were compared with those of conventional open surgery. During the mean follow-up period of 20.1 months, reflux disappeared in 19 ureters (79%), so that the success rate of endoscopic operation was considered to be satisfactory as compared with that of conventional open surgery, in which reflux disappeared in 16 (80%) of 20 ureters in 16 patients with neurogenic bladder dysfunction at our department. No exacerbation of hydronephrosis was observed postoperatively, and no complication was noted. This procedure, which is minimally invasive and technically simple, may be regarded as the first choice for VUR secondary to neurogenic bladder dysfunction.

Functional electrical stimulation in the management of incontinence: Studies of urodynamics

Intermittent functional electrical stimulation (FES) was employed for the control of incontinence. One FES session lasted for 30 minutes. It was repeated at intervals of 3 days to 1 week via an anal plug electrode.The success rate was 64% in 41 patients with pollakiuria, urgency and/or urge incontinence, and 43% in 7 patients with stress incontinence. Detrusor activity measured by cystometry did not correlate significantly with the effect on subjective symptoms and the urethral pressure did not increase. The remarkable clinical effect was observed in patients with overactive detrusor function.It seems that FES indirectly inhibits detrusor contraction by suppressing the intrasacral pathway for detrusor activity.

Burst activities of cremasteric motor units

Electromyographic activities of the ipsilateral creamaster muscle evoked by electrical stimulation of either the thigh or the penis were analyzed for latencies and burst durations. Response latencies were 30 ms on thigh stimulation and 30–35 ms on penile stimulation. With the increase in stimulus intensity the latencies decreased to 30 ms in both cases. The changes were stepwise, indicating the switching between different reflex arcs. The burst duration on thigh stimulation was about 50 ms, and that for penile stimulation was 45 ms. Impulses producing the burst consisted of larger and smaller spikes, and this indicates the grouping of motor units for wing tonic and phasic units. The results suggest the existence of parallel neuronal circuitries for the spinal cremateric reflex, and it is expected to provide a clue for evaluating the clinical significance of the cremasteric reflex.

Why is transurethral microwave thermotherapy (TUMT) positively effective

Between 1992 and 1994, 157 patients with benign prostatic hyperplasia were treated with transurethral microwave thermotherapy (TUMT). In evaluating the efficacy of TUMT with the International Prostate Symptom Score (I-PSS) in 121 patients, 18 (15%) showed excellent and 42 (35%) showed good response. In evaluation of QOL, the result was 43 patients (33%) excellent and 42 patients (35%) good response. In objective evaluation of uroflow in 93 patients, 12 (13%) showed excellent and 13 (14%) showed good response. The prostatic volume did not show a significant decrease after treatment. In terms of overall improvement, according to the criteria proposed at the 2nd International Consultation on BPH, the treatment was considered effective in 53 of 108 patients (48%). Histological examination of the prostate enucleated from a patient 7 months after TUMT revealed degenerative changes of nerve fibres on S-100 protein immunohistochemical staining, which were more extensive than those in smooth muscle cells on HE staining. Inin vitro tests the isometric contraction force of the rabbit prostatic tissue was measured after exposure to different temperatures, ranging from 37 to 50 °C. No significant change was observed up to 45°C vs. 37°C. After exposure to 48°C, the nerve mediated contractions became completely depressed, although phenylephrine or KCl induced contractions were only partially suppressed. After exposure to 50°C, no contraction was induced by any type of stimuli. In conclusion, it is suggested that good symptomatic improvement after TUMT results from both neural and muscular damage to the prostate. As TUMT is not aiming at a relief of anatomical obstruction, 50°C is thought to be a sufficient thermal condition to cause an irreversible damage to prostatic tissue, which will provide a relief from functional obstruction and urethral instability.