The 5-HT2c receptor gene Cys23Ser polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation

It has been postulated that the persistent short intravaginal ejaculation latency time （IELT） of men with lifelong premature ejaculation （LPE） is related to 5-hydroxytryptamine （HT）2c receptor functioning. The aim of this study was to investigate the relationship of Cys23Ser 5-HT2c receptor gene polymorphism and the duration of IELT in men with LPE. Therefore, a prospective study was conducted in 64 Dutch Caucasian men with LPE. Baseline IELT during coitus was assessed by stopwatch over a 1-month period. All men were genotyped for Cys23Ser 5-HT2c receptor gene polymorphism. Allele frequencies and genotypes of Cys and Ser variants of 5-HT2c receptor gene polymorphism were determined. Association between Cys/Cys and Ser/Ser genotypes and the natural logarithm of the IELT in men with LPE were.investigated. As a result, the geometric mean, median and natural mean IELT were 25.2, 27.0, 33.9s, respectively. Of all men, 20.0%, 10.8%, 23.1% and 41.5% ejaculated within 10, 10-20, 20-30 and 30-60s after vaginal penetration. Of the 64 men, the Cys/Cys and Ser/Ser genotype frequency for the Cys23Ser polymorphism of the 5-HT2c receptor gene was 81% and 19%, respectively. The geometric mean IELT of the wildtypes （Cys/Cys） is significantly lower （22.6s; 95% CI 18.3-27.8s） than in male homozygous mutants （Ser/Ser） （40.4s; 95% CI 20.3-80.4s） （P = 0.03）. It is concluded that Cys23Ser 5-HT2c receptor gene polymorphism is associated with the IELT in men with LPE. Men with Cys/Cys genotype have shorter IELTs than men with Ser/Ser genotypes.

Evaluating Potential Vaccine Antigens in both the <i>Chlamydia trachomatis</i>and <i>Chlamydia muridarum</i>Intravaginal Mouse Challenge Models

Identifying relevant animal challenge models adds to the complexity of human vaccine development. Murine challenge models have been the most utilized animal model for Chlamydia trachomatis vaccine development. The question arises as to whether the C. trachomatis or C. muridarum pre-clinical model is optimal. We compared C. muridarum and C. trachomatis intravaginal challenge models in a combined total of seventy-five studies evaluating potential vaccine candidates. In 100% (42/42) of C. muridarum studies, mice immunized with Chlamydia elementary bodies (EB) demonstrated a significant reduction in urogenital bacterial shedding as measured by qPCR (p C. trachomatis studies. We have evaluated proposed vaccine antigens in both models and observed immunization with Chlamydia major outer membrane protein (MOMP) vaccine formulations to be protective (p C. trachomatis model, and immunization with PmpD p82 translocator domain was not protective in either model. We also observed in both models that depletion of CD4+ T-cells in MOMP-immunized mice resulted in diminished protective immunity but animals were still able to reduce the infection level. In contrast, mice immunized with live EBs by intraperitoneal route did not require CD4+ T-cells to resolve urogenital infection from intravaginal challenge in either model. Overall, we have found the C. muridarum model to be a more robust, reliable, and reproducible model for vaccine antigen discovery.

THE PHYSICAL PROPERTIES OF POLY(2-HYDROXYETHYL METHACRYLATE)COPOLYMER HYDROGELS USED AS INTRAVAGINAL RINGS

Poly(2-hydroxyethyl methacrylate)(PHEMA)and poly(2-hydroxyethyl methacrylate-co-sodium methacrylate) [P(HEMA-co-SMA)]hydrogels with different compositions were prepared to be used as intravaginal rings,and their gelation time,water content,mechanical properties and morphology were investigated.The water content of PHEMA and P(HEMA-co-SMA) hydrogels decreased as the concentration of the monomer and the degree of crosslinking increased,while the water content significantly increased as the content of SMA,the hydrophilic monomer,increased.The increasing of the concentration of the crosslinking agent affected the tensile and flexural properties highly.The presence of a proper small amount of SMA also led the tensile and flexural modulus to move to a higher level.The results showed that P(HEMA-co-SMA) hydrogel with high drug load and good mechanical properties at optimum preparation conditions can be prepared for intravaginal rings to deliver nonhormonal contraceptives.These results may be applied to prepare better intravaginal drug delivery devices.

射精功能障碍

在射精功能障碍(ejaculatory dysfunction)中,早泄(premature ejaculation,PE),射精延迟(delayed ejaculation,DE),不射精(anejaculation,AE)和逆行射精(retrograde ejaculation,RE)是最为常见的射精功能障碍类型,其他还包括高潮障碍(orgasmic disorder)、射精疼痛(painful ejaculation)、射精后综合征(postorgasmic illness syndrome)等少见情况[1],根据临床的常见情况,本文重点介绍PE和DE。

Safety and efficacy of tramadol hydrochloride on treatment of premature ejaculation

Premature ejaculation （PE） is the most common sexual disorder. It affects 20%-30% of adult men; the aetiology of this condition has not yet been elucidated. The aim of this study is to evaluate the efficacy, safety, tolerability, undesirable effects and improved satisfaction with sexual intercourse with tramadol hydrochloride at different dosages for the treatment of PE. A total of 300 patients who presented with lifelong （primary） PE were included in this study. The study was performed for 28 weeks, in which placebo （starch tablet） was given for 4 weeks, and active ingredient （tramadol hydrochloride） was administered at different therapeutic dosages for 24 weeks. Patients were divided into three equal groups, each consisting of 100 patients. The first group （A） was given tramadol hydrochloride capsule 25 mg. The second group （B） was given tramadol hydrochloride capsule 50 mg. The third group （C） was given tramadol hydrochloride capsule 100 mg. All of the 300 participants included completed the study voluntarily. The age of the patients varied from 25 to 50 years. After the treatment period, the recorded data were collected for each group and analysed. The results showed a highly significant increase in the mean intravaginal ejaculatory latency time （IELT） in all groups compared to baseline data （P〈0.0001）. We concluded that using tramadol hydrochloride at different doses on demand for the treatment of PE is effective, safe and tolerable, with minimal undesirable effects, and approval for this indication should be souRht.

Comparative study of on-demand and daily use of sertraline in treatment of premature ejaculation:A randomized clinical trial

Objective:The intravaginal ejaculatory latency time(IELT)may increase less in on-demand compared to daily intake,but may fulfill a suitable treatment for specific patients.We decided to compare the efficacy and safety of on-demand and daily use of sertraline in order to find the most effective and least complicated method in treatment of premature ejaculation(PE).Methods:This study was parallel or concurrent control randomized clinical trial.Two hundred and forty patients with PE diagnosed by urologist in the two groups of 120 from July 2017 to February 2019 enrolled in the study.In the first group,it is prescribed 50 mg sertraline each 12 h daily and the second group received 50 mg 4 h before coitus for 4 and 8 weeks.The IELT before treatment and during all coitus after treatment were recorded by the patient’s wife with a stopwatch.Results:Mean IELT before,4 and 8 weeks after treatment in two groups were:On-demand group 101.62±65.44 s,208.75±128.02 s and 265.87±145.70 s;daily use group 102.50-81.22 s,276.87±181.08 s and 353.75±176.45 s,respectively.The ejaculation time increased significantly in both groups(p<0.05).However,increase in ejaculation time in daily use group was significantly higher than the on-demand group in 4 weeks(p=0.036),especially in 8 weeks(p=0.009).The percent of side effects in daily use group(26.7%)was higher than on-demand group(20%)(p<0.05).Drowsiness,diarrhea and vertigo were significantly higher in the daily use than on-demand(p<0.05).Conclusions:On-demand and daily use of sertraline are effective and usually have no serious complications,but the on-demand method is considerably more tolerable.In patients who did not tolerate to daily use of this drug,on-demand could be used as a salvage therapy.

Severe Pelvic Organ Prolapse with Large Vaginal Mucosal Defect Underwent Laparoscopic Shull’s Uterosacral Ligament Colpo-Suspension and TVM Operation by Two Stage Surgery

A 75-year-old woman complained of anuria and a sense of discomfort with severe pelvic organ prolapse (POP). We planned tension-free vaginal mesh (TVM) surgery after curing mucosal defects and completing treatment for diabetes mellitus. Anuria and pyelonephritis relapsed repeatedly due to the failure of ring pessary therapy. Surgical treatment was required emergently. We performed a total laparoscopic hysterectomy and uterosacral ligament colpo-suspension (Shull’s method). Although the vaginal apex was supported to a good position, cystocele occurred six months after the initial surgery. A TVM procedure for recurrent cystocele was performed after curing the mucosal defects, and after the improvement of glycemic control. Transvaginal native tissue repair has the advantages of low risk of ureter injury, firm colpo-suspension, and no need for mesh usage. On the other hand, it is not good at treating cystocele. Transvaginal native tissue repair should prove to be a useful surgical option for apical support without mesh.

Efficacy and safety of oral solution dosed misoprostol versus misoprostol vaginally in labour induction

Background: Labour induction is one of the most common medical procedures in obstetrics. The aim is to end the pregnancy when continuity is a risk to mother or fetus. Its main side effect is the increase in the cesarean rate, compared to spontaneous onset deliveries. On the other hand, mortality and morbidity in cesareans are higher. The most common pharmacological drugs used for induction are prostaglandins: dinoprostone and misoprostol. The “gold standard” for labour induction is vaginal misoprostol. The oral route is also effective and also has several benefits like faster onset and easear administration. In recent years several publications state that the administration of misoprostol oral solution, given in doses gradually, is associated with a lower cesarean and hyperstimulation rate than the cases where vaginal misoprostol has been used in pregnant women with unripe cervix. Furthermore, being its half life shorter, it may be very useful in case of uterine hyperstimulation and, probably, a high percentage of women prefer this oral administration to the vaginal one. The objective of this study is to compare the efficacy, safety and side effects on mother and fetus on use of oral versus vaginal administration for induction of labour for prolonged gestation (41 weeks) and premature rupture of membranes, both with live fetus. Methods/Design: Design: double blind controlled trial. Study population: Pregnant women whose labour will be induced due to premature rupture of membranes or prolonged gestation. Inclusion Criteria: 1) Bishop Test equal to or less than 7;2) Single pregnancy;3) Pregnancy at term (37 - 42 weeks);4) No history of uterine surgery;5) Cephalic presentation;6) Live fetus;7) No prostaglandins contraindications. Discussion: Nowadays induction rates are very high, ranging from 25% to 30% approximately. In these cases caesarean rates are higher than when the delivery starts spontaneously. That is one of the main reasons why caesareans have increased, mainly in the cases of nuliparous women with immature cervix. If we can prove the hypothetical good results obtained through the use of dosed oral misoprotol, we will be able to reduce the number of induced deliveries by cesarean, and so improve the levels of security for the mother and the foetus, and, as a consequence, provide a higher quality of medical attention to the newborn and the mother.

Mucus-penetrating nonviral gene vaccine processed in the epithelium for inducing advanced vaginal mucosal immune responses

Establishment of vaginal immune defenses at the mucosal interface layer through gene vaccines promise to prevent infectious diseases among females.Mucosal barriers composed of a flowing mucus hydrogel and tightly conjugated epithelial cells(ECs),which represent the main technical difficulties for vaccine development,reside in the harsh,acidic human vaginal environment.Different from frequently employed viral vectors,two types of nonviral nanocarriers were designed to concurrently overcome the barriers and induce immune responses.Differing design concepts include the charge-reversal property(DRLS)to mimic a virus that uses any cells as factories,as well as the addition of a hyaluronic acid coating(HA/RLS)to directly target dendritic cells(DCs).With a suitable size and electrostatic neutrality,these two nanoparticles penetrate a mucus hydrogel with similar diffusivity.The DRLS system expressed a higher level of the carried human papillomavirus type 16 L1 gene compared to HA/RLS in vivo.Therefore it induced more robust mucosal,cellular,and humoral immune responses.Moreover,the DLRS applied to intravaginal immunization induced high IgA levels compared with intramuscularly injected DNA(naked),indicating timely protection against pathogens at the mucus layer.These findings also offer important approaches for the design and fabrication of nonviral gene vaccines in other mucosal systems.

Short‐term effect of the prone masturbation training on premature ejaculation

Background:Whether conventional behavioral therapies for premature ejaculation can significantly improve the intravaginal ejaculatory latency time is still controversial.Prone masturbation is rare and observed in some patients with delayed ejaculation.Therefore,we tried to verify whether the regular prone masturbation training method had a therapeutic effect on premature ejaculation.Methods:From July to December 2018,a total of 21 patients met the enrollment criteria and volunteered to participate.Participants were diagnosed with premature ejaculation with an intravaginal ejaculatory latency time of less than 3min and a Premature Ejaculation Diagnostic Tool score greater than 9.Participants performed 12‐week prone masturbation training.Results:Ten patients completed the entire treatment regimen.The mean age of the 10 participants was 30.4±6.1 years,the mean frequency of sexual intercourse was 1.9±0.83 times a week,and the median duration of premature ejaculation was 1.5 years.After 3 months of prone masturbation training,the median self‐reported intravaginal ejaculatory latency time significantly increased from 60 to 105 s(p=0.011),and the mean Premature Ejaculation Diagnostic Tool scores decreased from15.0±3.7 to 12.7±3.7 points(p=0.119).Conclusions:The regular prone masturbation training method,as a novel behavioral therapy,probably has a therapeutic effect on premature ejaculation.

Effect of Sophora flavescens alkaloid on aerobic vaginitis in gel form for local treatment

OBJECTIVE: To investigate the effect of Sophora flavescens alkaloid(SFA) in gel form on aerobic vaginitis(AV) and the possible mechanism underlying the effects.METHODS: AV rat models were prepared by intravaginal inoculation of Escherichia coli and Staphylococcus aureus. SFA gel and placebo gel were intravaginally administered. In vivo antibacterial effects,vaginal microenvironment, vaginal smears, pathological tissues of vaginas, and retention of gel in the vaginal cavity were investigated.RESULTS: SFA gel had much higher antibacterial effect than placebo gel. SFA gel protected the vaginal mucosa from erosion of bacteria. At the same time,they inhibited the inflammatory responses, exhibiting little leukocytes and parabasal cells. Furthermore, the number of vaginal Lactobacilli remarkably increased following administration of SFA gel.However, the vaginal p H did not recover to thehealthy acidic levels after treatment due to the buffering effect of gel. The gel of a fluorescent agent,Cyanine 7, showed very long retention time in the vaginal cavity, up to more than 24 h, much longer than the solutions.CONCLUSION: The SFA gel is a promising medicine for local treatment of AV with the advantages of anti-bacteria, protection of vaginal mucosa, increase of Lactobacilli, and long retention time in the vaginal cavity.

Pelvic muscle floor rehabilitation as a therapeutic option in lifelong premature ejaculation： long-term outcomes

The aim of the study was to evaluate the long-term outcomes of pelvic floor muscle （PFM） rehabilitation in males with lifelong premature ejaculation （PE）, using intravaginal ejaculatory latency time （IELT） and the self-report Premature Ejaculation Diagnostic Tool （PEDT） as primary outcomes. A total of 154 participants were retrospectively reviewed in this study, with 122 completing the training protocol. At baseline, all participants had an IELT 〈60 s and PEDT score 〉11. Participants completed a 12-week program of PFM rehabilitation, including physio-kinesiotherapy treatment, electrostimulation, and biofeedback, with three sessions per week, with 20 min for each component completed at each session. The effectiveness of intervention was evaluated by comparing the change in the geometric mean of IELT and PEDT values, from baseline, at 3, 6, and 12 months during the intervention, and at 24 and 36 months postintervention, using a paired sample 2-tailed t-test, including the associated 95% confidence intervals. Of the 122 participants who completed PFM rehabilitation, 111 gained control of their ejaculation reflex, with a mean IELT of 161.6 s and PEDT score of 2.3 at the 12-week endpoint of the intervention, representing an increase from baseline of 40.4 s and 17.0 scores, respectively, for IELT and PEDT （P 〈 0.0001）. Of the 95 participants who completed the 36-month follow-up, 64% and 56% maintained satisfactory eiaculation control at 24 and 36 months oostintervention, respectively.