The mechanisms of human ejaculation – a critical analysis

The current mechanism for human ejaculation is a two-part model consisting of a postulated “pressure chamber” created in the prostatic urethra by initial closure of both distal and proximal sphincters with secretions loaded in by adrenergic-mediated smooth muscle contractions of the vas deferens and capsules of the internal genital organs. The pressure build up is claimed then to “trigger” the intermittent relaxation/contraction of the distal sphincter and activate the contractions of the striated pelvic musculature, especially that of the bulbocavernosus, which forcefully expels the semen along the urethra by powerful, rhythmical spurts. A number of difficulties with this model are examined critically against experimental findings which indicate that the so-called pressure chamber is unlikely to be the valid trigger for ejaculation. The most recent finding of a specialised group of lumbar sacral neurons in the spinal cord of rat that function as the spinal ejaculation generator is more likely to be the “trigger” for ejaculation but confirmation that these cells also exist in the human cord is waiting.     

近段输精管道获得性梗阻性无精子症经阴囊超声特征分析

目的探讨近段输精管道获得性梗阻性无精子症的经阴囊超声表现。方法对92例近段输精管道获得性梗阻性无精子症患者(病例组)行经阴囊超声检查,其中附睾炎性梗阻79例,输精管医源性梗阻13例(2例合并对侧附睾炎性梗阻),观察睾丸、附睾、阴囊段输精管的声像图表现。以65例精液检查正常者为对照组。结果病例组与对照组睾丸体积比较,差异无统计学意义(P>0.05)。92例患者184条附睾声像图均出现异常,其中附睾头、体、尾部的厚度与对照组比较,差异均有统计学意义(P<0.05);声像图表现为附睾整条或局部增厚,增厚部位附睾管扩张,呈细网状改变,附睾管内径为0.03 cm。39条(24.4%)炎性梗阻的附睾内合并出现炎性偏高回声结节。在160条附睾炎性梗阻的阴囊段输精管中,159条(99.4%)平均内径与对照组相同。24条医源性梗阻患者手术近端输精管均为扩张状态。结论近段输精管道获得性梗阻性无精子症由于梗阻的原因和部位不同,附睾与输精管存在不同特征的声像图表现,经阴囊超声可为该类疾病的诊断提供可靠的影像学依据。     

输精管粘堵剂的毒理学研究

本文报道输精管粘堵剂(504P)的代谢与毒理研究结果。动物实验结果表明:504部分地被机体吸收后较快排出体外,无长期蓄积作用。504P、504对动物无明显急毒作用;对所测生理指标、血细胞及生化指标亦无明显影响;组织学观察见堵塞处输精管腔纤维化闭塞,其近端输精管精子淤积;致癌试验表明该剂无致癌作用;Ames试验、染色体畸变分析、微核试验及显性致死试验表明该剂无致突变作用。     

Constraints in the development of contraceptives for men

Considerable efforts have been made to develop a male contraceptive and the studies have provided very useful information in this field. At least five different strategies to develop a male contraceptive have been pursued, namely: inhibition of sperm production, interference with sperm function, interruption of sperm transport, prevention of sperm deposition, and prevention of sperm-egg interaction. Of all these approaches, inhibition of sperm production by using androgens either alone or in combination with progestins have given the most encouraging results. A number of clinical trials substantiate that it is indeed possible to have a reversible, effective and safe hormonal method of contraception. A postmeiotic and epididymal approach to interfere with sperm function or the secretory and metabolic processes of the epididymis is another attractive option of male contraceptive development. A number of chemical compounds have been identified which interfere with sperm function in the epididymis without affecting sperm production, however, the compounds evaluated so far were found to be toxic. Interruption of sperm transport through the vas either by vasectomy or percutaneous intravasal injection of liquids which form cure-in-place plugs is also an attractive option. However, reversibility of the methods is of concern in their wide scale use. The major constraint in developing a long-acting male contraceptive seems to be the need for greater investment for product development. The clinical trials for evaluating the efficacy and safety of the new products and formulations stretch over several years and require enormous financial commitment. Nevertheless, the long-term gain of having a long-acting reversible contraceptive for men is far greater than the financial commitments over few years. Male attitude towards using methods of family planning is much more favourable than originally believed. The pharmaceutical industry as well as the health care providers theretbre have a greater responsibility. For early development of a contraceptive for men, it is essential to increase investment and simplify the drug regulatory procedures. The advent of newer technologies coupled with the convergent efforts of scientists will certainly make it possible to have an effective, safe and reversible male contraceptive in the near future.     

Effect of ageing on the number of neuronal noradrenaline uptake sites in the rat vas deferens

Summary Previous work has shown an age-related reduction in neuronal uptake of noradrenaline in the prostatic, but not in the epididymal portion of the rat vas deferens. In the present paper, the influence of ageing on the number of [³H]desipramine binding sites and on the effect of lithium on neuronal [³H]noradrenaline uptake were studied in the prostatic and epididymal portions of vasa deferentia from 4- and 20-month-old rats. The affinity for [³H]desipramine (K _d values) in the epididymal and prostatic portions did not change with age. However, ageing reduced the maximal number of [³H]desipramine binding sites (B_max values) in the prostatic, but not in the epididymal portion. Lithium potentiated neuronal [³H]noradrenaline uptake only in the prostatic portion and this potentiation was not changed by ageing. The results showed differences in neuronal noradrenaline uptake between the two portions of the vas deferens. Furthermore, the data suggest that the age-related reduction in neuronal uptake in the prostatic portion is due to a reduction in the number of neuronal uptake sites for noradrenaline. Correspondence to R. Pekelmann Markus at the above address     

Analysis of spermatozoa from the proximal vas deferens of fertile men

Fluids from the left and right proximal vas deferens were collected from 105 normal fertile men by cannulating the vas deferens during vasectomy, and sperm parameters analysed. Sperm motility (73.1 k 13.3Y0), normal sperm morphology (75.2 k 11.1"/o), sperm viability (72.7 k 18.8%) and the hypo-osmotic swelling test (73.3 k 19.2%) were in the normal range, compared with that of ejaculated spermatozoa. However, sperm Concentration in the proximal vas deferens (6274.6 k 5103.8 × 10" ml^-' was higher than that in semen. Sperm concentration in the right vas deferens was significantly higher (P<0.05) than that in the left and the percentage of spermatozoa showing abnormal cervical mucus penetration was Significantly higher (47%) for the left than for the right (18%). There were no anti-sperm antibodies on the surface of spermatozoa from the vas deferens as determined by the sperm cervical mucus contact test and immuno bead test. These parameters of spermatozoa from the proximal vas may reflect those of spermatozoa from the human cauda epididymis.     

Eine Modifikation des isolierten N. hypogastricus-Vas deferens-Präparates vom Meerschweinchen für die Prüfung von ganglionären Wirkungen

Zusammenfassung Es wurde eine Methode entwickelt, die eine selektive Applikation von Arzneistoffen am Plexus hypogastricus des isolierten N. hypogastricus-Vas deferens-Präparates des Meerschweinchens ermöglicht. Mit Hilfe einer kleinen Kunststoffkapsel, in der die organnah liegende Plexus-Gegend eingeschlossen wird, kann der Plexus getrennt perfundiert werden. Außerdem können Elektroden für eine prä- und postganglionäre Reizung angebracht werden. Einige typische ganglionstimulierende und ganglionblockierende Substanzen wurden an diesem Präparat untersucht. Die Ergebnisse weisen darauf hin, daß dieses Präparat als eine Routinemethode für die Untersuchung ganglionärer Wirkungen von Arzneimitteln verwendet werden kann.Herrn Prof. Dr. med. L. Lendle zum 70. Geburtstag gewidmet.     

Non-catechol phenylethanolamines: agonistic and antagonistic actions on β-adrenoreceptors in isolated tissues from the guinea-pig

SUMMARY 1. Agonistic and antagonistic activities on β-adrenoreceptors have been assessed for orciprenaline, terbutaline, soterenol and MJ7999–1 using isolated guinea-pig atrial (β₁-receptor) and tracheal (β₂-receptor) preparations.
2. As agonists MJ7999–1 is more selective for β₂-receptors than soterenol because of its increased activity in trachea, whereas terbutaline is more selective for β₂-receptors than orciprenaline because of its decreased activity in atrial preparations.
3. Antagonistic activity was assessed from shifts in concentration-effect curves to (-)-isoprenaline.
4. MJ7999–1 and soterenol possess competitive β-receptor blocking actions in atrial (pA₂≈6.5) and tracheal (pA₂≈6.0) preparations.
5. Orciprenaline and terbutaline are relatively selective competitive β-receptor antagonists, being more potent in atrial (pA₂≈6.3) than in tracheal (pA₂∼4.9) preparations. In atria non-competitive antagonistic actions are apparent with these two drugs.
6. In rat vas deferens preparations only (-)-isoprenaline and soterenol display agonistic actions on α-receptors. None of the compounds possesses α-receptor antagonistic activity.     

Pharmacological evaluation of a new Ca2+ antagonist, 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate hydrochloride (TMB-8): studies in smooth muscles

The pharmacology of 8-(N,N-diethylamino)-octyl-3,4,5-trimethoxybenzoate (TMB-8) has been studied using guinea pig ileum and vas deferens preparations. TMB-8 inhibited responses to drugs that excite specific receptors (acetylcholine and norepinephrine) as well as to agents whose actions are not mediated via specific receptors (KCl and BaCl₂) with ID₅₀'s of 3.8 × 10^?6 to 1 × 10^?4 M. TMB-8 inhibited responses to acetylcholine, norepinephrine, nicotine, dimethylphenylpiperazinium and KCl in an insurmountable manner in the guinea pig ileum, while responses to BaCl₂ were inhibited in a competitive manner. Increasing Ca²⁺ concentrations of the bathing medium from 1.35 to 5.40 mM effectively antagonized the TMB-8 inhibition of responses to KCl in the guinea pig ileum and vas deferens preparations. These results indicate that TMB-8 may produce its inhibitory effects in smooth muscle by interfering with the availability of Ca²⁺ for muscle contraction by blocking the Ca²⁺ release from intracellular bound stores.     

Potentiation of sympathetic neuromuscular transmission mediated by muscarinic receptors in guinea pig isolated vas deferens

In guinea-pig isolated vasa deferentia, purinergic neurogenic contractions and responses to applied adenosine 5-triphosphate (ATP) were potentiated by carbachol; responses to adrenergic transmission and applied noradrenaline were not. Following blockade of P2 receptors and -adrenoceptors, the residual neurogenic response was massively potentiated by carbachol, suggesting the presence of a non-purinergic, non-adrenergic component. In the presence of guanethidine, carbachol had no significant effect, indicating that sympathetic transmission was the only element involved. Use of oxotremorine and selective muscarinic receptor antagonists suggested that the potentiating effect of carbachol and oxotremorine was mediated via M3 muscarinic receptors without involvement of nicotinic receptors.