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Changes of ejaculation due to suppression of noradrenaline biosynthesis by diethyldithiocarbamate in dogs: a supplemental report with reference to changes of posterior urethral pressure.

In the preceding paper (Kimura et al.-1979) it was reported that diethyldithiocarbamate suppresses ejaculation, although penile erection is maintained, and that the suppression is not mediated by the central nervous system but by the decrease of catecholamine contents in the organs relating to sperm transport. In this paper, changes of ejaculation following administration of diethyldithiocarbamate was studied with the posterior urethrogram; measurement of the posterior urethral pressure during hypogastric nerve stimulation. From the results obtained in this study the above results were confirmed. It was also confirmed that both seminal emission and ejaculation are under the influence of an alpha-adrenergic receptor mechanism. Also, a dopamine receptor mechanism was suspected to be present in the male accessory sexual glands.

Animals↗

Effect of NS-21, an anticholinergic drug with calcium antagonistic activity, on lower urinary tract function in a rat model of urinary frequency.

BACKGROUND: NS-21 is under development for the treatment of urinary frequency and urinary incontinence. The purpose of this study was to investigate the effects of NS-21 and its active metabolite, RCC-36, on lower urinary tract function in an experimental rat model of urinary frequency. METHODS: Cystometrograms were recorded in anesthetized rats with bilaterally transected hypogastric nerves. All drugs were administered intraduodenally. RESULTS: In sham-operated rats, NS-21 (> or = 50 mg/kg) significantly increased the bladder capacity without significantly decreasing micturition pressure, while RCC-36 (100 mg/kg) significantly increased bladder capacity, and at a dose of > or = 30 mg/kg, also caused a decrease in micturition pressure. This increase in bladder capacity appeared at lower doses of both NS-21 and RCC-36 in the hypogastric nerve-transected rats. Propiverine (100 mg/kg) increased bladder capacity and at > or = 30 mg/kg, decreased micturition pressure in both sham-operated and nerve-transected rats. Oxybutynin (100 mg/kg) and atropine (30 mg/kg) decreased the micturition pressure in both sham-operated and nerve-transected rats without increasing the bladder capacity, while a similar anticholinergic calcium antagonist, terodiline (100 mg/kg) had no effect on bladder capacity in either sham-operated or nerve-transected rats. Flavoxate (500 mg/kg) significantly increased bladder capacity without significantly decreasing micturition pressure in both sham-operated and nerve-transected rats, while 50 mg/kg of verapamil significantly increased bladder capacity without significantly decreasing the micturition pressure in nerve-transected rats. CONCLUSIONS: NS-21 and RCC-36 increased bladder capacity at lower doses in hypogastric nerve-transected rats than in sham-operated rats. Furthermore, NS-21 increased the bladder capacity without suppressing micturition pressure, suggesting that NS-21 may be a more effective therapeutic drug than propiverine, oxybutynin or flavoxate for the treatment of urinary frequency and urinary incontinence.

Animals↗

The long-term voiding function and sexual function after pelvic nerve-sparing radical surgery for rectal cancer.

BACKGROUND: The aim of the present study is to symptomatically analyze the extent to which pelvic nerve-sparing radical surgery for rectal cancer impacts on long-term voiding and male sexual function. METHODS: A self-administered questionnaire was mailed to 68 patients who underwent pelvic nerve-sparing radical surgery for invasive rectal cancer with 52 responses (28 men and 24 women; 27 complete and 25 incomplete preservation; response rate 76.5%). Each patient was asked to record if there had been any changes in lower urinary tract symptoms after surgery. Sexual function was also investigated in men. RESULTS: Of the 52 patients, 48 (92%) maintained voluntary voiding without catheterization in the long term. Clean intermittent self-catheterization was performed in only four patients with incomplete preservation because of persistent voiding dysfunction. Subjectively, approximately 60% of the patients remained unchanged in lower urinary tract symptoms after surgery. The satisfaction rate regarding the current voiding status was significantly higher in women than in men (83% versus 61%, P = 0.0294), but was not significantly different between those with complete (76%) and incomplete preservation (64%). Despite the acceptable urinary status, 88% of men had some deterioration in the erectile function, regardless of the types of surgical procedures. Overall, 64% of men were unsatisfied with the current sexual function. CONCLUSIONS: Pelvic nerve-sparing radical surgery for rectal cancer preserved the long-term voiding function in the majority of patients. In completely preserved patients and in women, symptomatic outcomes were more satisfactory. Postoperative erectile dysfunction was found to be a serious problem, even in complete nerve-sparing procedure.

Aged↗

Penile erectile responses to electric stimulation are enhanced by a new phosphodiesterase type-5 inhibitor.

AIM: This study was conducted to investigate the effect of DA-8159, a new phosphodiesterase type-5 (PDE5) inhibitor, on electrostimulation-induced penile erection in rats. METHODS: Intracavernous pressure (ICP) and arterial blood pressure (BP) were simultaneously recorded through electric pelvic-ganglion stimulation (2-10 Hz) after the oral administration of DA-8159 (3 or 10 mg/kg) in normal and streptozotocin-induced diabetic rats. Statistical analysis was performed on the maximal intracavernous pressure (ICP), detumescence time, maximal intracavernous pressure/blood pressure (ICP/BP) ratio, and the area under the curve (AUC) of the ICP/BP ratio. RESULTS: In normal and diabetic rats, electrical stimulation of the pelvic ganglion induced a frequency- and dose-dependent increase in the intracavernous pressure. The ICP/BP ratio and the corresponding AUC values were also significantly and dose-dependently increased after DA-8159 administration. In addition, the detumescence time significantly increased after DA-8159 administration compared to that of the controls. CONCLUSIONS: These results show that the DA-8159 significantly increased the intracavernous pressure response and prolonged the decay period induced by electrical stimulation of the pelvic ganglion, and suggest that DA-8159 might be a potential therapeutic agent for the treatment of erectile dysfunction.

Animals↗

Central representation of bladder and colon revealed by dual transsynaptic tracing in the rat: substrates for pelvic visceral coordination.

The neurocircuitry underlying regulation of bladder and distal colon function by Barrington's nucleus (the pontine micturition centre) was investigated in rats by identifying neurons which were transsynaptically labelled from these viscera, with pseudorabies virus (PRV) or genetically modified forms of PRV [PRV-beta-galactosidase (PRV-beta-Gal) and PRV-green fluorescent protein (PRV-GFP)]. PRV injection into the bladder or the colon of separate rats suggested an overlap in the distribution of bladder- and colon-related neurons in Barrington's nucleus, as well as a topographical arrangement whereby dorsal neurons were bladder-related and ventral neurons were colon-related. In rats injected with PRV-beta-Gal into one viscera and PRV-GFP into another, neurons in the major pelvic ganglion and lumbosacral spinal cord were primarily single-labelled at relatively early survival times. With longer survival times many double-labelled neurons (>70%) appeared in Barrington's nucleus, suggesting that individual Barrington's nucleus neurons are synaptically linked to preganglionic parasympathetic neurons which independently innervate the colon or the bladder. In addition to these dual-labelled neurons, Barrington's nucleus neurons which were single-labelled from either viscera were observed and these exhibited a viscerotopic organization consistent with the single-labelling studies. Together, these findings suggest the existence of three neuronal populations in Barrington's nucleus, one which is synaptically linked to both the bladder and the colon and the other two populations which are specifically linked to either viscera. These anatomical substrates may underlie the central coordination of bladder and colon function and play a role in disorders characterized by a coexistence of bladder and colonic symptoms.

Animals↗

Convergent responses of Barrington's nucleus neurons to pelvic visceral stimuli in the rat: a juxtacellular labelling study.

Barrington's nucleus impacts on bladder and distal colon function and relays pelvic visceral information to the forebrain. This study investigated processing of information from the bladder and the distal colon by Barrington's nucleus in the rat. The responses of individual Barrington's nucleus neurons to bladder and/or colon distention were characterized using extracellular recording and the recorded neurons were identified using juxtacellular labelling. Most neurons within Barrington's nucleus (79%) were activated by bladder distention, consistent with its role as a pontine micturition centre. Although no neurons were selectively responsive to colon distention, the majority of bladder-responsive neurons (73%) were also activated by colon distention. In a second study, Barrington's nucleus neurons were characterized with respect to their response to colon distention and their immunoreactivity for the stress-related neuropeptide corticotropin-releasing factor (CRF). Of 30 labelled neurons in the central part of Barrington's nucleus, 53% were activated by colon distention and 63% of these were CRF-ir. This is the first report demonstrating that Barrington's nucleus neurons are responsive to colon distention. The results provide evidence for convergence of information from the bladder and the colon onto individual Barrington's nucleus neurons. Taken with evidence that many Barrington's nucleus neurons are synaptically linked to the bladder and colon, the present study suggests a role for these neurons in coordinating peripheral parasympathetic and central responses to both viscera and implicate CRF as a neurotransmitter in this function. Dysfunctions in this circuit may underlie the coexistence of colon and bladder symptoms observed in functional bowel disorders.

Action Potentials↗

Anatomical considerations of the pediatric ilioinguinal/iliohypogastric nerve block.

BACKGROUND: The ilioinguinal/iliohypogastric nerve block is safe, effective and easy to perform in order to provide analgesia for a variety of inguinal surgical procedures in pediatric patients. A relatively high failure rate of 10-25% has been reported, even in experienced hands. The aim of this study was to determine the exact anatomical position of the ilioinguinal and iliohypogastric nerves in relation to an easily identifiable constant bony landmark, the anterior superior iliac spine (ASIS) in neonates and infants. The current ilioinguinal/iliohypogastric nerve block techniques were also evaluated from an anatomical perspective. METHOD: Dissections were performed on a sample of 25 infant and neonatal cadavers (mean weight = 2.2 kg; mean height = 45.6 cm). The distance from the ASIS to both the ilioinguinal and iliohypogastric nerves, on a line connecting the ASIS to the umbilicus was carefully measured using a digital caliper. Three techniques, commonly used in clinical practice, were simulated on the anatomical specimens. RESULT: The left and right ilioinguinal nerves were closer to the ASIS than previously described, i.e. 1.9 +/- 0.9 mm (mean +/- sd) and 2.0 +/- 0.7 mm, respectively. The mean distance from the left and right iliohypogastric nerves to the ASIS are 3.3 +/- 0.8 mm and 3.9 +/- 1.0 mm, respectively. CONCLUSIONS: We suggest that the high failure rate of the ilioinguinal/iliohypogastric nerve block in this age group could be due to lack of specific spatial knowledge of the anatomy of these nerves in infants and neonates. This cadaver-based study suggests an insertion point closer to the ASIS, approximately 2.5 mm (range: 1.0-4.9) from the ASIS on a line drawn between the ipsilateral ASIS and the umbilicus.

Cadaver↗

Relative contributions of smooth and striated muscles to the canine urethral pressure profile.

Canine urethral pressure profiles were analysed using pharmacological and nerve sectioning techniques. The presence of significant sympathetic and somatic neural components was detected and their locations along the proximal urethra were identified. The neural components peaked at different points in the urethra but overlapped. The non-neural component appeared to form an even base along the whole proximal urethra. It was concluded that in the proximal part of the profile the non-neural and the sympathetic components are significant. The sympathetic component becomes larger in the peak pressure zone. More distally and overlapping with the sympathetic component is the contribution of the striated external sphincter.

Animals↗

Diabetes mellitus increases nitric oxide synthase in penises but not in major pelvic ganglia of rats.

OBJECTIVE: To determine the effect of diabetes mellitus (DM) on erectile function and evaluate the levels of nitric oxide synthetase (NOS) activity in streptozotocin-induced diabetic rats. MATERIALS AND METHODS: Rats were studied at 9 weeks and 14 weeks after the induction of DM by streptozotocin and compared with untreated control rats. Erectile potency was assessed physiologically by testing and recording mating behaviour. NOS activity was assayed in penile tissues and major pelvic ganglia (MPG) by conversion of [3H] L-arginine to [3H] citrulline. Histological, ultrastructural and immunohistochemical studies of penile tissues were performed in similar groups of rats. RESULTS: Diabetes mellitus adversely and significantly degraded all parameters of mating behaviour, thus indicating defective erectile potency. However, NOS activities in penile tissues from both groups of diabetic rats were significantly higher than those in controls (P < 0.01). In MPG, NOS activities were not significantly different between diabetic and control rats (P > 0.05). Histological, ultrastructural and immunohistochemical studies of penile tissues revealed no significant differences between control and diabetic rats, indicating an intact effector organ (smooth muscles) in rats with up to 14 weeks of DM. CONCLUSION: The impotence frequently observed in diabetic subjects would suggest that despite the increase in NOS activity in the penis, the pharmacological action of nitric oxide is impaired.

Amino Acid Oxidoreductases↗

Reconstruction of the sympathetic pathway projecting to the prostate, by nerve grafting in the dog.

OBJECTIVES: To examine the possibility of nerve grafting to repair the sympathetic pathway projecting to the prostate, as contraction of the prostate is known to be controlled by the sympathetic pathway via the hypogastric nerve (HGN), and injuries to the pathway cause significant disturbances in prostatic secretion. MATERIALS AND METHODS: In six dogs both of the HGNs were partly removed and immediately repaired with an autologous nerve graft. The left HGN was repaired with a colonic (autonomic) nerve graft and the right with a genitofemoral (somatic) nerve graft. Twenty months after surgery the reconstruction of the sympathetic pathway was assessed by measuring contraction of the prostate after stimulating the lumbar splanchnic nerves (LSNs). RESULTS: Nine of the 17 right LSNs stimulated elicited prostatic contractions. After transecting the left HGN five of these nine responses were restored. Seven of the 11 left LSNs stimulated elicited prostatic contractions; after transection of the left HGN four of these seven responses were preserved. CONCLUSION: The sympathetic pathways via the HGN to the canine prostate can be reconstructed by nerve grafting, regardless of the use of autonomic or somatic nerve grafts, and the cross-innervation mechanism from the LSN to the prostate can also be repaired.

Animals↗

Anatomical studies of the neurovascular bundle and cavernosal nerves.

OBJECTIVE: To accurately define the anatomy of the neurovascular bundle (NVB) in men. MATERIALS AND METHODS: The NVB was microdissected in detail bilaterally in 12 fixed human male adult cadavers. The anatomy of the NVB and its relationship to surrounding pelvic structures was ascertained in each specimen. RESULTS: Previous reports of the anatomy of the NVB have not mentioned its levator ani and anterior rectal component. The anatomy of the cavernosal nerves is such that accurate graft anastomosis to proximal and distal cavernosal nerve segments is extremely difficult. CONCLUSION: The current anatomical description of the cavernosal nerve and NVB is inaccurate.

Aged↗

Anatomical radical retropubic prostatectomy: 'curtain dissection' of the neurovascular bundle.

OBJECTIVE: To investigate the topographical relationship of the cavernosal nerves (CNs) to seminal vesicles, prostate, rhabdosphincter and urethra during the development of the prostate, and to use the resulting morphological data to modify the surgical technique of nerve-sparing radical prostatectomy. MATERIALS AND METHODS: The study included 29 male fetuses (gestational age 9-37 weeks) and eight adult specimens assessed anatomically and histologically. Using the plastination technique and anatomical dissection, the course of the CNs was investigated in all specimens. Based on these morphological results, the technique of dissecting the CNs during nerve-sparing radical retropubic prostatectomy was modified. RESULTS: During early fetal development the fibres of the CNs enclose the prostatic and membranous urethra dorsally and laterally. During the growth of the prostate, the CNs running along the prostate become displaced further anteriorly and spread, thus forming a concave shape (like a 'curtain') of the neurovascular bundles (NVB). Therefore, dissection of the NVB has to start anteriorly to preserve all the nerve fibres that are spread along the surface of the lateral lobes of the prostate. CONCLUSIONS: From these anatomical findings we propose a modified 'curtain dissection' to improve preservation of the CNs running in the NVB, in which the incision of the periprostatic fascia and dissection of the NVB is far more anterior than previously described.

Aged↗

Bladder motility and efferent nerve activity during isotonic and isovolumic recording in the cat.

1. Bladder motility and pelvic nerve efferent activity were recorded in anaesthetized cats under isotonic or isovolumic conditions. In isotonic conditions the bladder was connected to a reservoir and fluid entering or leaving the bladder was monitored for 8 min using different heads of pressure (isotonic recording). Under isovolumic conditions fixed volumes were injected into the bladder and pressure changes recorded (micturition contractions). 2. In isotonic conditions, at low pressures the bladder filled to a roughly constant level, and then developed small amplitude oscillatory contractions. At higher pressures, after the initial filling, the bladder contracted, expelling part of its volume. Depending on the pressure this contraction was either sustained or led to a gradual expansion of the bladder. In both cases transient periods of expansion were superimposed. In contrast after an initial slow build up, the efferent nerve activity increased reaching a sustained level of activity during which transient decreases in rate were seen. 3. The firing frequency of the efferent nerve activity during the sustained phase increased as the intravesical pressure was raised until a plateau was reached at high pressures. The plateau pressure (Pplateau) in a bladder was positively correlated with the peak pressure reached by the bladder during micturition contractions under isovolumic conditions, suggesting that micturition contractions were produced by the maximum output of the reflex pathway. 4. Section of the hypogastric nerves had relatively little effect, but additional section of the pelvic nerves abolished the contractile phase of the bladder response to filling, and resulted in continuous filling of the bladder. 5. The transient bladder expansions (duration, 3-33 s) seen when the innervation was intact were closely related to the transient decreases in efferent nerve activity, suggesting involvement of a central inhibitory mechanism. The threshold pressure for triggering transient expansions was similar to the pressure shown to activate myelinated afferent fibres. 6. Under isovolumic conditions the frequency of micturition contractions increased with increasing vesical volume, and the relaxed interval between contractions shortened. This response could also be evoked by stimulation of the central cut end of the pelvic nerves, suggesting that the central inhibitory mechanism could also be active during isovolumic conditions.

Animals↗

A simplified method of laparoscopic presacral neurectomy for the treatment of central pelvic pain due to endometriosis.

OBJECTIVE: To describe optimal procedures and preliminary results for videolaparoscopic presacral neurectomy as part of the surgical treatment of endometriosis associated with intractable dysmenorrhoea. DESIGN: Observational study with follow up for at least one year. SETTING: Subspecialty practice: Endometriosis Clinic and Centre for Special Pelvic Surgery. SUBJECTS: Eighty five women (18-45 years) with endometriosis and intractable pain, referred because medical and surgical management had failed. Subjects without a central (midline) component to their discomfort were excluded. INTERVENTIONS: Excision and vaporization of endometriotic pathology was followed by presacral neurectomy. OUTCOME MEASURES: During surgery, severity of endometriosis was assessed using revised American Fertility Society scoring. Overall pelvic pain and dysmenorrhoea relief were determined by office visit, telephone interview and questionnaire at a minimum of one year postoperatively. RESULTS: There were no operative complications and all women left hospital within 24 h of surgery. Overall pain relief was reported by 49 (94%) of 52 patients followed. The other three subjects noted no pain abatement. Dysmenorrhoea was reduced in 48 (92%) whereas four (8%) women claimed no relief. CONCLUSIONS: Laparoscopic presacral neurectomy is an option for treating dysmenorrhoea and pelvic pain in selected women, but is indicated only if medical management has failed. Videolaparoscopic presacral neurectomy using the CO2 laser is safe in trained hands. Pain relief achieved is within the range reported for laparotomy.

Adolescent↗

Arylazido aminopropionyl atp (ANAPP3) antagonism of cat urinary bladder contractions.

ANAPP3 produces a transient contraction of the urinary bladder of the cat similar to that produced by ATP and hypogastric nerve stimulation. 2 ANAPP3 partially antagonizes the inhibition of pelvic nerve-evoked bladder contractions induced by adenosine, possibly by blocking P1 receptors. 3 ANAPP3 antagonizes contractions of the cat urinary bladder induced by ATP, beta, gamma-methylene ATP, pelvic nerve stimulation and hypogastric nerve stimulation. 4 ANAPP3 produces no antagonism of either noradrenaline-induced inhibition of pelvic nerve-evoked bladder contractions or acetylcholine-induced bladder contractions, thereby substantiating the specificity of the effect of ANAPP3 against purines.

Adenosine Triphosphate↗

Evidence against purinergic nerve fibres in the hypogastric nerves of the cat.

Hypogastric nerve stimulation (HGS) produced a transient contraction of the cat urinary bladder and inhibition of pelvic nerve evoked bladder contractions. Pretreatment by guanethidine (GUA) antagonized HGS inhibition of pelvic nerve evoked bladder contractions, but had no effect on the HGS-induced transient contractions. GUA pretreatment had no effect on ATP or APPCP-induced contractions of the urinary bladder. Pretreatment by 6-hydroxydopamine (6-OHDA) antagonized both the transient contraction and the inhibition of pelvic nerve evoked bladder contractions induced by HGS. 6-OHDA pretreatment had no effect on ATP or APPCP-induced contractions of the urinary bladder.

Adenosine Triphosphate↗

Pharmacological studies to examine the source of ATP released by pelvic nerve stimulation in the feline lower urinary tract.

1. Pretreatment with 6-OHDA or bilateral sectioning of the hypogastric nerves decreased the noradrenaline content of lower urinary tract tissue. 2. Pelvic nerve stimulation-induced contractions were not significantly changed by either 6-OHDA pretreatment or bilateral sectioning of the hypogastric nerves. 3. Hypogastric nerve stimulation-induced contractions were significantly attenuated by the pretreatments. 4. Neither ATP- nor acetylcholine-induced contractions were significantly altered by either 6-OHDA or bilateral sectioning of the hypogastric nerves. 5. The data indicate that ATP, released by pelvic nerve stimulation, which induces a bladder contraction, is released from parasympathetic, cholinergic nerve fibres in the pelvic nerve trunks and not sympathetic, nor adrenergic nerve fibres also present in the pelvic nerve trunks.

Adenosine Triphosphate↗