A reproductive role for the nonapeptides vasotocin and isotocin in male zebrafish (Danio rerio).

Two distinct nonapeptide systems, vasotocin- and oxytocin-related peptides, evolved in vertebrates. Their role in male zebrafish reproduction has not been formally investigated. We hypothesized that the teleost nonapeptides vasotocin and isotocin stimulate male zebrafish reproductive physiology and success by affecting central neuronal and/or peripheral endocrine pathways. Pharmacological inhibition experiments revealed that both vasotocin and isotocin contribute significantly to male reproductive success, which in the case of vasotocin correlated significantly with indices of male courtship behavior. Interestingly, co-administration of vasotocin and isotocin antagonists completely abolished male reproductive success without affecting male courtship behavior and endocrine indices, possibly linked to a synergistic action of nonapeptides on male pheromone release. To further probe the nonapeptides' role in male zebrafish reproduction, we subsequently tested whether male zebrafish nonapeptide systems were acutely activated by the female releaser pheromone PGF2α, a strong chemoattractant and important reproductive cue in males which stimulates courtship behavior. Male zebrafish attracted to PGF2α in a choice assay exhibited acute increases in neuronal activation marker p-ERK immunoreactivity in the ventral glomerulus of the olfactory bulb and the preoptic area, however no co-localization with isotocin was observed. Conversely, PGF2α time-dependently stimulated whole brain isotocin mRNA abundance, suggesting secondary longer-term effects of PGF2α exposure on the central isotocinergic system. While the current lack of vasotocin-specific antibodies for zebrafish does not allow to probe acute activation of vasotocinergic neurons, whole brain vasotocin mRNA was not significantly affected by PGF2α exposure. Together, our results identify a role for nonapeptides in male zebrafish reproductive physiology and success.

Immobilized fluorescent cyclodextrin on a cellulose membrane as a chemosensor for molecule detection.

Dansylglycine-modified cyclodextrin (DnsC4-beta-CD) was prepared as a fluorescent host that is capable of being immobilized on a cellulose membrane (DnsC4-beta-CD membrane). DnsC4-beta-CD immobilized on the cellulose membrane decreased its fluorescence intensity with increasing concentration of guest molecules, indicating that the host changes the location of the dansyl group from inside to outside the cyclodextrin cavity upon guest accommodation, which is similar to DnsC4-beta-CD in solution; thereby, the DnsC4-beta-CD membrane is useful as a novel chemosensor for detecting molecules. This result demonstrates that the cellulose membrane is useful as a practical supporting material for various chromophore-modified cyclodextrins.

Fluorescent cyclodextrin immobilized on a cellulose membrane as a chemosensor system for detecting molecules.

Dansyl glutamate-modified cyclodextrin (DnsGlu-beta-CD) was prepared as a fluorescent host, which is capable of being immobilized on a cellulose membrane (DnsGlu-beta-CD-membrane). The fluorescence intensity of DnsGlu-beta-CD decreased with increasing concentration of guest molecules, indicating that the host changes the location of the dansyl group from inside to outside the cyclodextrin cavity upon guest accommodation. Similar guest-induced decrease in the fluorescence intensity was observed for DnsGlu-beta-CD immobilized to a cellulose membrane. This result demonstrates that the cellulose membrane may be used as a practical supporting material of various chromophore-modified cyclodextrins and that DnsGlu-beta-CD-membrane is useful as a novel disposable chemosensor for molecules.

Treatment of premature ejaculation with paroxetine hydrochloride.

AIMS OF THIS STUDY: To evaluate the efficacy of chronic and 'on demand' administration of paroxetine hydrochloride in the drug treatment of premature ejaculation (PE). MATERIALS AND METHODS: Ninety-four normally potent men, aged 18-61 y (mean 39 y) with premature ejaculation were treated between January 1996 and March 1997, with oral paroxetine hydrochloride, a selective serotonin re-uptake inhibitor (SSRI). All men were either married or in a stable relationship. Sixty-four out of ninety-four men (Group A) were initially treated with paroxetine hydrochloride 20 mg administered once daily. Those men who responded with improved ejaculatory control within four weeks, were then treated with 'on-demand' paroxetine hydrochloride (20 mg) administered 3-4 h prior to planned intercourse. The remaining 33 out of 94 men (Group B) were initially treated with 'on-demand' paroxetine hydrochloride 20 mg administered 3-4 h prior to planned intercourse. RESULTS: The mean pre-treatment ejaculatory latency time (ELT) of both group A and B was 0.4 min (range 0-1 min) in 205 intercourses at a frequency of 0.4 intercourses per week. In group A after four weeks of daily administration of paroxetine, the mean ELT was 4.5 min (range 1-anejac.) in 761 intercourses at a frequency of 2.4 intercourses per week. Fifty-three out of sixty-one men in group A regarded their ejaculatory control as improved and were then treated with 'on-demand' paroxetine, achieving an ELT of 3.9 min (range 0-10) in 608 intercourses at a frequency of 2.6 intercourses per week. Thirty-six men in this group of 53 regarded that they had maintained improved ejaculatory control with a mean ELT of 5.5 min (range 2-20 min) after a further four weeks of treatment (P < 0.001). The remaining 17 men reported a recurrence of poor ejaculatory control with a mean ELT of 0.7 min (range 0-2 min). In group B with initial 'on-demand' paroxetine after a mean of 4.5 weeks of treatment, the mean ELT was 1.5 min (range 0-5 min) in 298 intercourses at a frequency of 2.2 intercourses per week. Adverse effects were only recorded in men taking daily paroxetine and included anejaculation in 5 out of 61, inhibited orgasm in 3 out of 61 and reduced libido on 3 out of 61. Erectile dysfunction was not reported and 'on demand' paroxetine was not associated with any adverse effects. CONCLUSIONS: Paroxetine hydrochloride appears to be a useful agent in the pharmacological treatment of premature ejaculation when administered on a chronic, an 'on-demand' basis following chronic treatment or initial 'on demand' basis.

Treatment of premature ejaculation with paroxetine hydrochloride as needed: 2 single-blind placebo controlled crossover studies.

PURPOSE: We evaluate the efficacy of paroxetine hydrochloride as needed for the treatment of premature ejaculation. MATERIALS AND METHOD: Study 1 comprised 26 potent men with a mean age of 39.5 years with premature ejaculation who were randomized to receive 20 mg. oral paroxetine (group A) or placebo (group B) as needed 3 to 4 hours before planned intercourse in a controlled single-blind crossover trial. Study 2 comprised 42 potent men with a mean age of 40.5 years with premature ejaculation who were randomized to receive 10 mg. paroxetine daily for 3 weeks and then 20 mg. paroxetine as needed (group C) for 4 weeks or placebo daily for 3 weeks and then placebo as needed (group D) for 4 weeks. RESULTS: Mean pretreatment ejaculatory latency time was 0.3 minute for study 1. At 4 weeks mean ejaculatory latency time was 3.2 minutes in the paroxetine as needed and 0.45 in the placebo as needed phase for group A (p < 0.001), and 0.6 in the placebo as needed and 3.5 in the paroxetine as needed phase for group B (p < 0.001). There were no adverse effects with paroxetine or placebo in study 1. Mean pretreatment ejaculatory latency time was 0.5 minute for study 2. At 3 weeks mean ejaculatory latency time was 4.3 minutes in the paroxetine daily and 5.8 in the paroxetine as needed phase, and 0.9 in the placebo daily and 0.6 in the placebo as needed phase for group C (p < 0.001). At 3 weeks mean ejaculatory latency time was 0.8 minutes in the placebo daily and 1.1 in the placebo as needed phase, and 3.3 in the paroxetine daily and 6.1 in the paroxetine as needed phase for group D (p < 0.001). Adverse effects in 7 of 42 men (17%) given paroxetine daily included an ejaculation in 3, anorexia in 1, gastrointestinal upset in 3 and reduced libido in 2. Mean ejaculatory latency time was greater in the paroxetine as needed phase of study 2 than that of study 1 (p < 0.05), suggesting that ejaculatory control achieved with paroxetine as needed is significantly better if patients are initially treated with the drug daily. CONCLUSIONS: Paroxetine appears to be superior to placebo in the pharmacological treatment of premature ejaculation when administered on a chronic or as needed basis.

Predictive value of patient history and correlation of nocturnal penile tumescence, colour duplex Doppler ultrasonography and dynamic cavernosometry and cavernosography in the evaluation of erectile dysfunction.

AIMS: The results of history and physical examination, nocturnal penile tumescence testing (NPT), colour flow duplex Doppler ultrasonography and dynamic infusion cavernosometry and cavernosography (DICC) were retrospectively correlated in 207 patients with erectile dysfunction. METHODS AND MATERIALS: The predictive value of the patient's own subjective assessment of early morning and nocturnal erections, history of cigarette smoking, the presence of vascular risk factors was correlated to the outcome of investigations. The result of Rigiscan NPT was correlated to the peak systolic velocity (PSV) and the resistance index (RI) determined at colour flow duplex Doppler ultrasonography, and the maintenance flow rate (Qm) determined at DICC. RESULTS: Eighty-five out of two hundred and seven patients (41%) had normal NPT comprising 48 out of 85 patients (56%) who described rigid early morning and nocturnal erections, 15 out of 85 patients (18%) who smoked cigarettes and 9 out of 85 patients (11%) with other positive vascular risk factors. 72 out of 85 patients (85%) had a normal PSV (>30 cm/s), 80 out of 85 patients (94%) had a normal RI (>0.85) and 82 out of 85 patients (96%) had a normal Qm), (<10 ml/min). Vascular investigations in this group identified 71 out of 85 patients (84%) with no penile vascular disease, 11 out of 85 patients (13%) with arteriogenic impotence, 2 out of 85 patients (2%) with mixed vasculogenic impotence and 1 out of 85 patients (1%) with cavernosal venous leakage (CVL). One hundred and twenty-two out of two hundred and seven patients (59%) had an abnormal NPT comprising 18 out of 122 patients (15%) who continued to experience rigid early morning erections, 65 out of 122 patients (53%) who smoked cigarettes, 59 out of 112 patients (48%) with other positive vascular risk factors, 36 out of 112 patients (29%) had an abnormal PSV (<30 cm/s), 49 out of 122 patients (40%) had an abnormal RI (<0.85) and 55 out of 122 patients (45%) had an abnormal Qm (>10 ml/min). Vascular investigations in this group identified five patients with no penile vascular disease, 51 out of 122 patients (41%) with arteriogenic impotence, 31 out of 122 patients (25%) with cavernosal venous leakage (CVL) and 35 out of 122 patients (29%) with mixed vasculogenic impotence. CONCLUSIONS: (1) a history of cigarette smoking and positive vascular risk factors are good predictors of organic impotence whereas the patient's subjective assessment of his own early morning erections is unreliable; (2) normal NPT correlates well with normal PSV, RI and Qm but does not exclude organic impotence; (3) abnormal NPT correlates well with abnormal PSV, RI and Qm.