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Vas deferens anomalies in paediatric age.

Vas deferens anomalies have been observed with high incidence in cystic fibrosis patients, whereas the overall incidence in the general population is estimated less than 0.05%. Vas deferens anomalies are sometimes associated with renal abnormalities and they are due to a damage occurring within the first weeks of gestational age. In other cases they can be the expression of a mild form of cystic fibrosis. The authors report on 7 patients with 10 anomalies of vas deferens: 2 patients with cystic fibrosis; 3 patients with urinary tract anomalies; 2 patients with no evidence of cystic fibrosis and without urinary tract anomalies. It is suggested that every patient presenting with vas deferens anomalies and no evidence of cystic fibrosis should be further evaluated with renal ultrasound; moreover all patients without evidence of both cystic fibrosis and renal anomalies should have genetic investigations.

Algorithms↗

PREGANGLIONIC AND POSTGANGLIONIC STIMULATION OF THE GUINEA-PIG ISOLATED VAS DEFERENS PREPARATION.

The isolated vas deferens of the guinea-pig contracted when stimulated transmurally with parallel wire electrodes. These contractions persisted in concentrations of hexamethonium, pentolinium, nicotine and mecamylamine which at the same time abolished the responses to hypogastric nerve stimulation. Procaine and lignocaine in local anaesthetic concentrations abolished the responses to transmural stimulation but potentiated the contractions produced by added noradrenaline. Guanethidine and bretylium in concentrations specific for adrenergic neurone blockade abolished the contractions due to transmural stimulation without impairing the responses of the muscle to added noradrenaline or acetylcholine. In contrast, high concentrations of the adrenergic-blocking agents phentolamine and dihydroergotamine were needed to block the contractions due to transmural stimulation; these concentrations also blocked the response to added noradrenaline but simultaneously reduced the responses to added acetylcholine or potassium chloride. Preparations from guinea-pigs previously treated with reserpine at first responded normally to transmural stimulation; thereafter the contractions diminished progressively but were never abolished. Hyoscine and atropine produced a small decrease in the response to transmural stimulation when present in concentrations up to 1x10(-5) and a larger decrease only in concentrations of 1x10(-4) or greater. Hemicholinium produced a small decrease of the contractions due to transmural stimulation in concentrations up to 1x10(-4); concentrations of 5x10(-4) present for 1 hr produced only a slightly greater reduction in response. These experiments show that when the guinea-pig vas deferens is removed without the hypogastric nerve and stimulated transmurally by the method described, contractions are produced mainly by excitation of postganglionic adrenergic nerves.

Acetylcholine↗

A new example of a morphine-sensitive neuro-effector junction: adrenergic transmission in the mouse vas deferens.

The isolated mouse vas deferens possesses an adrenergic excitatory motor innervation which can be inhibited by low concentrations of morphine (ID50=0.5 muM). This effect of morphine is mediated by specific receptors which are blocked by naloxone. Activation of the morphine receptors inhibits noradrenaline release. It is concluded that adrenergic neurotransmission in the mouse vas deferens differs in some important way from that at the more common, morphine-insensitive, adrenergic junctions.

Animals↗

Testosterone metabolism by proximal and distal regions of the vas deferens from immature and mature rats.

The vas deferens, an androgen-dependent organ, may have physical importance in sperm maturation, yet very little is known about its steroid capabilities. To explore the steroid metabolic activities and their possible changes during sexual maturation, a comparative study of [14C]testosterone metabolism by the proximal (VDP) and distal (VDD) segments of the vas deferens from immature and mature rats was carried out in vitro. Approximately 50 mg of the VDP and VDD portions of the vas deferens, devoid of spermatozoa, were incubated in duplicates for 3 h at 37 degrees C with [14C]testosterone (53.5 microCi/mmol) and the essential cofactors. After the addition of appropriate 3H-labeled recovery tracers to the incubates, the steroids were extracted, separated by paper and thin-layer chromatography and crystallized to constant 3H/14C ratio in 3 consecutive crystals. The results showed that all tissues metabolized [14C]testosterone into 4 major steroids: dihydrotestosterone (DHT), 5 alpha-androstane-3 alpha-17 beta diol (5 alpha-3 alpha-diol), delta 4-androstenedione and androsterone. The metabolites accounted for approximately 16% and approximately 6% of the conversion products in the immature and mature vas deferens respectively. There was no significant difference in [14C]testosterone metabolism when VDP and VDD were compared within either age group of animals. However, the immature vas deferens was significantly more active compared to mature vas deferens in the synthesis of these metabolites, indicating that the activities of 5 alpha-reductase, 3 alpha-hydroxysteroid dehydrogenase and 17 beta-hydroxysteroid dehydrogenase diminish during sexual maturation. The possible physiological significance of these changes during maturation of the vas deferens is discussed.

Aging↗

Prevention of supersensitivity-like phenomena in rat vas deferens by colchicine.

Rat vas deferens has been shown to become supersensitive to alpha-adrenergic agonists on brief treatment with epinephrine (Epi-treatment). Epi-treatment increased the contractile response and the number of alpha-adrenoceptors in the tissue. The application of colchicine (2.5 mM) during Epi-treatment prevented the supersensitivity-like phenomena and increase in number of alpha-adrenoceptors. Vinblastine (10 microM) also counteracted the effect of Epi-treatment but cytochalasin B (100 microM) and strychnine (2.5 mM) did not. It is suggested that the supersensitivity-like phenomena induced in rat vas deferens by Epi-treatment were due to a change in microtubular components of the membrane.

Animals↗

Long-term use of sertraline leads to alterations in contractility of rat isolated vas deferens.

Previous experiments with rat isolated vas deferens have shown that sertraline pretreatment inhibits contractile responses to noradrenaline, KCl, serotonin and electrical field stimulation. In the present study, the aim was to investigate the effects of long-term use of sertraline on contractile responses of rat isolated vas deferens. Fifteen Sprague-Dawley rats were given long-term (21 days) sertraline treatment, while another 15 were used as control. Both vas deferens were excised. Epididymal and prostatic segments of each underwent electrical field and chemical stimulation (noradrenaline, serotonin, acetylcholine, adenosine-triphosphate). Epididymal and prostatic segments had different contraction characteristics. Long-term sertraline treatment inhibited contractile responses of vas deferens segments to electrical field stimulation. The responses to noradrenaline were amplified with a left shift on both segments. Responses to serotonin had only a left shift on epididymal segments, while no contractile responses were observed on prostatic segments of the groups. Long-term treatment with sertraline had peripheral effects on rat vas deferens contractility, and some of the effects may be through mechanisms other than the inhibition of serotonin re-uptake.

Acetylcholine↗

Enhancement by elevated external potassium of the maximal responses to acetylcholine and norepinephrine in the rat vas deferens.

In the rat vas deferens, the maximal response to acetylcholine increased almost linearly as a function of external potassium concentration, [K+]0. The magnitudes of the maximal responses in 10, 15 and 20 mM [K+]0 were 128, 155 and 184% of the maximal response in 6 mM [K+]0, respectively. The response to carbachol also increased in 20 mM [K+]0 to almost the same extent. The enhancement of the norepinephrine response was observed only in 20 mM [K+]0; its magnitude was only 125%. The increase in [K+]0 from 6 to 20 mM did not affect the sensitivity (expressed as the geometric mean ED50) either to norepinephrine or to acetylcholine. Denervation of the postganglionic nerves to the vas deferens did not affect the enhancement of the maximal responses in 20 mM [K+]0, indicating that the release of neuronal transmitters may not be involved.

Acetylcholine↗

[Routing reseach of vas deferens on anatomy and clinical application].

OBJECTIVE: Studying on the routes of vas deferens to provide anatomy basis for surgical operation, especially, reconstruction of long segment loss of vas deferens. METHODS: The routes of vas deferens were observed and anatomic distances along epididymal, infrainguinal, inguinal, retroperitoneal and ampullar segments of vas deferens, the distances from external ring to extremity of vas deferens were measured respectively in 18 formalin fixed adult cadavers. RESULTS: The vas deferens have a large curve from external ring to extremity in its route, draw it out from the external ring. Eliminating this curve will allow to shorten this segment of vas deferens for vasovasostomy by 6.1 - 12.9 (9.31 +/- 1.30) cm. The length of each segment of vas deferens, respectively, is epididymal: 3.2 - 5.6 (4.53 +/- 0.79) cm, infrainguinal: 4.5 - 9.5 (7.31 +/- 1.78) cm, inguinal: 4.4 - 7.5 (5.52 +/- 0.74) cm, retroperitoneal: 12.5 - 19.5 (16.75 +/- 1.87) cm and ampullar: 2.9 - 3.8 (3.63 +/- 0.23) cm. There was no significant differences in segment length and the distances from external ring to extremity of vas deferens between the right and left. CONCLUSION: Reconstruction of long segment loss of vas deferens can be performed by mobilization retroperitoneal vas deferens and draw it out from external ring. There were no significant differences in lengths of vas deferens and the distances from external ring to vassal extremity between the left and right in adults. The surgical operations of vas deferens are closely related each segment of vasa.

Adult↗

Nitric oxide synthase is co-localized with vasoactive intestinal polypeptide in postganglionic parasympathetic nerves innervating the rat vas deferens.

Cross-sections of the vas deferens taken from control adult male rats showed positive histochemical reactivity to acetylcholinesterase and immunoreactivity for antibodies to protein gene product 9.5, tyrosine hydroxylase, neuropeptide Y, vasoactive intestinal polypeptide, nitric oxide synthase and calcitonin gene-related peptide. Immunoreactivity to substance P was very sparse. Histochemical reactivity to acetylcholinesterase and immunoreactivity to vasoactive intestinal polypeptide and nitric oxide synthase was concentrated in the subepithelial lamina propria and inner smooth muscle layers. Complete surgical denervation resulting from transection of the nerve arising from the pelvic ganglion which supplies the vas deferens totally abolished the immunoreactivity to all of the antibodies tested as well as the histochemical reactivity to acetylcholinesterase. In sections of the prostatic end of the vas deferens taken from rats neonatally pretreated with capsaicin, immunoreactivity to calcitonin gene-related peptide and substance P was reduced by 75 and 83%, respectively. Immunoreactivity to neuropeptide Y, vasoactive intestinal polypeptide and nitric oxide synthase was similar in tissue sections taken from capsaicin-treated rats and those taken from control tissues. Pretreatment of rats with guanethidine or 6-hydroxydopamine decreased immunoreactivity to tyrosine hydroxylase and neuropeptide Y by 60-70%, but immunoreactivity to substance P, vasoactive intestinal polypeptide and nitric oxide synthase was unchanged, while immunoreactivity to calcitonin gene-related peptide and acetylcholinesterase staining was increased by guanethidine but not by 6-hydroxydopamine treatment. Triple labelling experiments showed nitric oxide synthase, vasoactive intestinal polypeptide and acetylcholinesterase all to be co-localized in some nerve fibres. These results indicate that the nitric oxide synthase contained in the nerve fibres innervating the rat vas deferens is unaffected by pretreatment of rats with capsaicin, 6-hydroxydopamine or guanethidine but is abolished by surgical denervation, of postganglionic parasympathetic, sympathetic and sensory nerves. Therefore it appears that nitric oxide synthase is co-localized with vasoactive intestinal polypeptide in the postganglionic parasympathetic nerves which innervate the rat vas deferens.

Animals↗

Injury to the pre-pubertal vas deferens. I. Histological analysis of pre-pubertal human vas.

There is very little information in the literature on the development of the human vas deferens. Therefore, the age at which the pre- or para-pubertal vas deferens becomes large enough for a vasovasostomy to be technically feasible is unknown. To determine the age or degree of sexual maturity at which a microscopic vasovasostomy is technically feasible, we collected surgical or autopsy vasa from 34 young males over a three year period, and correlated vasal size to age and Tanner stage (degree of sexual maturity ranging from 1-childhood to 5-adult). The specimens were embedded and sectioned transversely in glycol methacrylate. Using image analysis, the total transverse area and diameter, and luminal area and diameter was determined for each specimen. Surprisingly, there was no change in vasal size from birth up through 11 years. From age 15 years and on, the vas was adult in size. The vas develops to adult size between Tanner stages 2 and 3. The average external and luminal diameters of pre-midpuberty specimens (Tanner stages 1 and 2) were 1.0 and 0.19 (mm.) and the diameters of post-midpuberty specimens were 2.1 and 0.43 (mm.), respectively. These results suggest that, in the event of a recognized iatrogenic injury to the vas deferens after midpuberty, a repair by a traditional microsurgical vasovasostomy is possible. If the vas is injured before midpuberty it may be technically difficult to repair by traditional microsurgical methods.

Adolescent↗

Heterogeneity for mutations in the CFTR gene and clinical correlations in patients with congenital absence of the vas deferens.

Congenital absence of the vas deferens (CAVD) is a heterogeneous disorder, largely due to mutations in the cystic fibrosis (CFTR) gene. Patients with unilateral absence of the vas deferens (CUAVD) and patients with CAVD in association with renal agenesis appear to have a different aetiology to those with isolated CAVD. We have studied 134 Spanish CAVD patients [110 congenital bilateral absence of the vas deferens (CBAVD) and 24 CUAVD], 16 of whom (six CBAVD, 10 CUAVD) had additional renal anomalies. Forty-two different CFTR mutations were identified, seven of them being novel. Some 45% of the CFTR mutations were specific to CAVD, and were not found in patients with cystic fibrosis or in the general Spanish population. CFTR mutations were detected in 85% of CBAVD patients and in 38% of those with CUAVD. Among those patients with renal anomalies, 31% carried one CFTR mutation. Anomalies in seminal vesicles and ejaculatory ducts were common in patients with CAVD. The prevalence of cryptorchidism and inguinal hernia appeared to be increased in CAVD patients, as well as nasal pathology and frequent respiratory infections. This study confirms the molecular heterogeneity of CFTR mutations in CAVD, and emphasizes the importance of an extensive CFTR analysis in these patients. In contrast with previous studies, this report suggests that CFTR might have a role in urogenital anomalies.

Abnormalities, Multiple↗

Metabolism of sex steroids in the human and canine vas deferens.

The contribution of the vas deferens to the metabolism of steroids was investigated in the human and in the dog by perfusion experiments and in vitro incubation. Perfusion of testosterone or androstenedione through the canine vas deferens resulted in the formation of dihydrotestosterone; no significant formation of estrogens could be detected. When dihydrotestosterone was perfused, 3alpha- and 3beta-androstanediols were isolated. In vitro incubation experiments with human was deferencs have shown an active metabolism of androgens by this time and, therefore, confer a new role to the vas deferens in the male.

Androgens↗

The effects of photoperiod on the responses of the hamster vas deferens to nerve stimulation.

Hamster vas deferens responds to nerve stimulation with a biphasic contraction which is completely blocked by guanethidine and tetrodotoxin. The second component of the contraction is inhibited by phentolamine, whereas the initial component is slightly potentiated by phentolamine. When hamsters are subjected to short photoperiods or castration, the vas deferens becomes supersensitive to nerve stimulation and shows spontaneous mechanical activity. The supersensitivity is not due to increased postsynaptic adrenergic supersensitivity, decreased neuronal uptake of catecholamine, decreased presynaptic feedback by prostaglandin or adrenergic agonist. The supersensitivity is still demonstrable in the presence of 4-aminopyridine, suggesting that the release of transmitter is also not different in animals kept in short photoperiods. The activity of the Na+/K+ pump is increased in vasa deferentia from hamsters kept in short photoperiods and the postsynaptic response to the ATP receptor agonist, diadenosine pentaphosphate, is also enhanced. It is suggested that the supersensitivity induced in the hamster vas deferens by short photoperiod is caused by testosterone withdrawal and is due to increased responsiveness to ATP, which could be acting as a cotransmitter in this tissue.

Animals↗

Metabolism and presynaptic inhibitory activity of 2',3' and 5'-adenine nucleotides in rat vas deferens.

In the isolated rat vas deferens stimulated at 0.2 Hz, [14C]labelled 5'-AMP, 5'-ADP and 5'-ATP (10 microM) inhibited twitch responses, were broken down to [14C]adenosine in the medium and incorporated into [14C]adenine ribonucleotides in the tissue. Pretreatment of tissues with 6-(2-hydroxy-5-nitrobenzyl)-thioguanosine (NBTGR), a potent inhibitor of adenosine transport, potentiated the presynaptic inhibitory action of these 5' nucleotides and reduced their incorporation in [14C]adenine nucleotides, but did not alter the appearance of [14C]adenosine in the medium. A series of 2', 3' and 5'-substituted adenine nucleotides (10 microM) inhibited the twitch responses of the vas deferens stimulated at 0.2 Hz. This effect was potentiated by NBTGR. Addition of exogenous adenosine deaminase very significantly reduced the inhibitory actions of adenosine, 5'-AMP, 5'-ADP and 5'-ATP and also reduced those of 2', 5'-ADP, NAD+ and dePCoA. The inhibitory actions of the other 2', 3' and 5' adenine nucleotides studied were not altered by exogenous adenosine deaminase. These results indicated that the presynaptic inhibitory actions of 5'-AMP, 5'-ADP and 5'-ATP in rat vas deferens predominantly result from their prior hydrolysis to adenosine whereas the 2', 3' and 5'-substituted adenine nucleotides appear to act mainly directly to inhibit transmitter release.

Adenine Nucleotides↗

Different sites of action for alpha 2-adrenoceptor antagonists in the modulation of noradrenaline release and contraction response in the vas deferens of the rat.

Rat vas deferens was prepared, loaded with [3H]noradrenaline, and superfused to measure the release of tritium in resting conditions and in response to electrical field stimulation. The alpha 2-adrenoceptor antagonists yohimbine, CH-38083 (7,8-(methylenedioxi)-14 alpha-hydroxyalloberbane HCl), and idazoxan increased the electrically induced release of tritium in a concentration-dependent manner, whereas noradrenaline and the alpha 2-adrenoceptor agonist xylazine exerted opposite effects. The inhibitory effect of noradrenaline on electrically induced tritium release was antagonized by yohimbine, CH-38083, and idazoxan. Of the alpha 2-adrenoceptor antagonists tested, yohimbine and CH-38083 reversed the xylazine-induced inhibition of tritium release, and idazoxan was found to be completely ineffective against xylazine. Idazoxan, yohimbine and CH-38083 antagonized the inhibitory effect of xylazine on electrical stimulation-induced contractions of the vas deferens, as was evidenced by the apparent pA2 values. We conclude from the present experiments that noradrenaline and xylazine inhibit noradrenaline release by acting on distinct prejunctional alpha 2-adrenoceptors and that the receptor subtype that responds to xylazine is insensitive to idazoxan. In addition, inhibition by xylazine of contractility but not of noradrenaline release was antagonized by idazoxan, suggesting that besides noradrenergic neurotransmission, other motor transmitter systems (purinergic) may also be involved in the inhibition by alpha 2-adrenoceptor antagonists of mechanical responses in the rat vas deferens.

Adrenergic alpha-Antagonists↗

Preliminary characterization, androgen-dependence and ontogeny of an abundant protein from mouse vas deferens.

Polyacrylamide gel electrophoresis analysis revealed that the vas deferens of adult mouse contains a major protein. Mouse vas deferens protein is a basic glycoprotein with a molecular weight of 34,800 +/- 300. The protein represents 17 +/- 0.7% and 42 +/- 2.4% of soluble proteins from homogenate and luminal fluid respectively, an estimate based on densitometric scanning of polyacrylamide gels. The protein originated from the vas deferens since it was not detected in blood plasma or in sexual organs and it was still present after ligation of the epididymis. Changes in androgen status of the animal markedly affected the vas deferens protein. After castration a progressive decrease in the protein was observed and its relative percentage dropped to 2 +/- 0.4% after 45 days. The concentration of the protein returned to precastration levels after 2 weeks of testosterone treatment but oestradiol, progesterone and corticosterone were ineffective in this respect. The vas deferens protein was not synthesized in significant amounts until animals were 20 days old and its concentration increased rapidly from 20 to 30 days in concert with the pubertal increase of androgens in the vas deferens.

Animals↗

Effects of isoxuprine and nylidrin on adrenoreceptors in rat vas deferens.

The interaction of isoxuprine and nylidrin with alpha 1- and beta 2-adrenoreceptors in rat vas deferens was examined using radioligand binding assays and physiological studies in vitro. Isoxuprine and nylidrin have a greater affinity for binding to alpha 1 (isoxuprine KD = 59 +/- 15 nM; nylidrin KD = 41 +/- 3 nM) than beta 2-(isoxuprine KD = 3,900 +/- 500 nM; nylidrin KD = 900 +/- 50 nM) adrenoreceptors in rat vas deferens. Vas deferens from rats pretreated for 16-24 h with reserpine (3 mg/kg i.p.) were exposed to 10 microM phenoxybenzamine for 15 min to inactivate alpha-adrenoreceptors. Under these conditions high concentrations of both isoxuprine and nylidrin relaxed vas deferens contracted with 55 mM K+, however the relaxation was not blocked by the beta-adrenoreceptor antagonist propranolol (10 microM). Both isoxuprine and nylidrin were potent competitive antagonists of alpha 1-adrenoreceptor mediated contraction of vas deferens. pA2 values for isoxuprine (6.9 +/- .05) and nylidrin (7.1 +/- .08) agreed well with KD values for binding to alpha 1-adrenoreceptors in vas deferens. The greater potency of isoxuprine and nylidrin in inhibiting alpha 1-adrenoreceptors than binding to beta 2-adrenoreceptors or causing nonspecific relaxation suggest that alpha-adrenoreceptor antagonist actions of these drugs may be important in their ability to inhibit smooth muscle tone.

Animals↗