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Molecules (Basel, Switzerland) Dec 2023Zika virus (ZIKV) belongs to the genus of the family, and is a pathogen posing a significant threat to human health. Currently, there is a lack of internationally...
Zika virus (ZIKV) belongs to the genus of the family, and is a pathogen posing a significant threat to human health. Currently, there is a lack of internationally approved antiviral drugs for the treatment of ZIKV infection, and symptomatic management remains the primary clinical approach. Consequently, the exploration of safe and effective anti-ZIKV drugs has emerged as a paramount imperative in ZIKV control efforts. In this study, we performed a screening of a compound library consisting of 1789 FDA-approved drugs to identify potential agents with anti-ZIKV activity. We have identified dapoxetine, an orally administered selective serotonin reuptake inhibitor (SSRI) commonly employed for the clinical management of premature ejaculation (PE), as a potential inhibitor of ZIKV RNA-dependent RNA polymerase (RdRp). Consequently, we conducted surface plasmon resonance (SPR) analysis to validate the specific binding of dapoxetine to ZIKV RdRp, and further evaluated its inhibitory effect on ZIKV RdRp synthesis using the ZIKV Gluc reporter gene assay. Furthermore, we substantiated the efficacy of dapoxetine in suppressing intracellular replication of ZIKV, thereby demonstrating a concentration-dependent antiviral effect (EC values ranging from 4.20 μM to 12.6 μM) and negligible cytotoxicity (CC > 50 μM) across diverse cell lines. Moreover, cell fluorescence staining and Western blotting assays revealed that dapoxetine effectively reduced the expression of ZIKV proteins. Collectively, our findings suggest that dapoxetine exhibits anti-ZIKV effects by inhibiting ZIKV RdRp activity, positioning it as a potential candidate for clinical therapeutic intervention against ZIKV infection.
Topics: Male; Humans; Zika Virus Infection; Zika Virus; Selective Serotonin Reuptake Inhibitors; RNA-Dependent RNA Polymerase; Antiviral Agents; Virus Replication
PubMed: 38138628
DOI: 10.3390/molecules28248142 -
Basic and Clinical Andrology Dec 2023
PubMed: 38110891
DOI: 10.1186/s12610-023-00216-9 -
Basic and Clinical Andrology Dec 2023Premature ejaculation (PE) is considered to be the most common male sexual disorder affecting 20% to 66% of sexually active men. Most of the patients had already tried...
BACKGROUND
Premature ejaculation (PE) is considered to be the most common male sexual disorder affecting 20% to 66% of sexually active men. Most of the patients had already tried on demand dapoxitine with no improvement. We aimed in the current study to assert the efficacy and safety profile of daily intake of 30 mg duloxetine in treating patients with lifelong premature ejaculation (LPE) as well as patients with acquired premature ejaculation (APE).
RESULTS
The current study showed significant improvement in intravaginal ejaculatory latency time (IELT) after intake of duloxetine. All participants had a median Arabic index of premature ejaculation (AIPE) of 26, median IELT of 180 s, median male sexual quality of life (SQOL) of 43 after being treated with duloxetine (p value < 0.001 for all). While median AIPE after placebo was 19, median IELT after placebo was 60 s and median male SQOL after placebo was 21. Paired comparison of AIPE, IELT (Secs), inter quartile range (IQR) and male SQOL in group (A) patients at baseline and after duloxetine intake showed statistically significant improvement among treated patients (p values < 0.001 for all). Paired comparison of AIPE, IELT (Secs), IQR and male SQOL in group (A) patients at baseline and after placebo treatment showed no significant improvement of male SQOL. Furthermore, AIPE and IELT returned to baseline scores after discontinuation of duloxetine (p values 0.729; 0.892, respectively). Paired comparison of AIPE, IELT (Secs), IQR and male SQOL in group (B) patients at baseline and after placebo treatment showed almost same scores of patients in group (A) who received placebo for 2 months after a 2 month washout period (p values 1.000 for all). Paired comparison of AIPE, IELT (Secs), IQR and male SQOL in group (B) patients at baseline and after duloxetine treatment showed statistically significant improvement among all treated patients (p values < 0.001 for all).
CONCLUSION
Duloxetine is an effective drug for treatment of LPE and APE patients. Further, larger studies are needed to compare duloxetine to different known therapeutic modalities for PE to assert it's efficacy and superiority.
PubMed: 38049720
DOI: 10.1186/s12610-023-00210-1 -
Sexual Medicine Oct 2023Premature ejaculation (PE) is one of the most common male sexual dysfunctions with prominent psychological consequences. Type D personality (TDP) is also associated with...
BACKGROUND
Premature ejaculation (PE) is one of the most common male sexual dysfunctions with prominent psychological consequences. Type D personality (TDP) is also associated with multiple psychological disorders, such as depression and anxiety. However, the correlation between PE and TDP remains unknown.
AIM
The study sought to investigate the relationships between depressive symptoms, TDP, and PE.
METHODS
Adult males in Taiwan who were 20 to 40 years of age and who had sexual intercourse in the past 6 months were recruited to complete online questionnaires composed of general demographics, the Premature Ejaculation Diagnostic Tool (PEDT), 5-item International Index of Erectile Function (IIEF-5), Type D Scale-14, and Depression and Somatic Symptom Scale (DSSS). Chi-square test and independent Student's test were used to compare the parameters between the TDP and non-TDP groups. Univariate and multivariate logistic regression analyses were conducted to evaluate factors related to PE.
OUTCOMES
Outcomes were the prevalence of PE and TDP in young Taiwanese men, the associations between depressive symptoms and PE and TDP, and the predictive factors of PE.
RESULTS
In total, 2558 men with a mean age of 31.3 ± 5.3 years were included in the present study. Among them, 315 (12.3%) and 767 (30.1%) participants were classified as having PE and moderate-to-severe erectile dysfunction (ED), respectively. In total, 1249 (48.8%) participants met the criteria for TDP. The PEDT, IIEF-5, and DSSS, including the total scores and depression and somatic subscales, were significantly higher in men with TDP (all < .001). PE prevalence was significantly greater in men with TDP than in those without TDP (16.2% vs 8.6%; < .001). Most parameters, including age, moderate-to-severe ED, the Type D Scale-14 subscales, and the DSSS somatic and depressive subscales, were significantly associated with PE in the univariate analysis. Only the depressive subscale of the DSSS and moderate-to-severe ED (IIEF-5 ≤16) were the independent predictors of PE in the multivariate analysis.
CLINICAL IMPLICATIONS
The results suggest that it is important to consider the psychological effects of PE in young men, and the study has provided a biopsychosocial aspect to manage patients with PE.
STRENGTHS AND LIMITATIONS
This is the first study to evaluate the association between PE, TDP, and depression in a large population of young adult males. However, the cross-sectional design may have limited the investigation of causality, and selection bias may be present.
CONCLUSION
Men with TDP tended to have higher PEDT scores and a prevalence of PE and ED. Moderate-to-severe ED and depressive symptoms are the independent predictive factors of PE.
PubMed: 38028734
DOI: 10.1093/sexmed/qfad055 -
International Journal of Pharmaceutics Jan 2024Sildenafil citrate is an approved drug used for the treatment of erectile dysfunction and premature ejaculation. Despite a widespread application, sildenafil citrate...
Sildenafil citrate is an approved drug used for the treatment of erectile dysfunction and premature ejaculation. Despite a widespread application, sildenafil citrate shows numerous adverse cardiovascular effects in high-risk patients. Local transdermal drug delivery of this drug is therefore being explored as an interesting and noninvasive alternative administration method that avoids adverse effects arised from peak plasma drug concentrations. Although human and animal skin represents the most reliable models to perform penetration studies, they involve a series of ethical issues and restrictions. For these reasons new in vitro approaches based on artificially reconstructed human skin or "human skin equivalents" are being developed as possible alternatives for transdermal testing. There is little information, however, on the efficiency of such new in vitro methods on cutaneous penetration of active ingredients. The objective of the current study was to investigate the sildenafil citrate loaded in three commercial transdermal vehicles using 3D full-thickness skin equivalent and compare the results with the permeability experiments using porcine skin. Our results demonstrated that, while the formulation plays an imperative role in an appropriate dermal uptake of sildenafil citrate, the D coefficient results obtained by using the 3D skin equivalent are comparable to those obtained by using the porcine skin when a simple drug suspension is applied (1.17 × 10 ± 0.92 × 10 cm/s vs 3.5 × 10 ± 3.3 × 10 cm/s), suggesting that in such case, this 3D skin model can be a valid alternative for ex-vivo skin absorption experiments.
Topics: Male; Animals; Swine; Humans; Sildenafil Citrate; Foreskin; Skin; Skin Absorption; Administration, Cutaneous
PubMed: 37992980
DOI: 10.1016/j.ijpharm.2023.123612 -
Translational Andrology and Urology Oct 2023Premature ejaculation (PE) is a common sexual disorder among male adults and negatively impacts a man's sexual life. Currently, the mainstay treatment of PE is still... (Review)
Review
BACKGROUND AND OBJECTIVE
Premature ejaculation (PE) is a common sexual disorder among male adults and negatively impacts a man's sexual life. Currently, the mainstay treatment of PE is still medical therapy which has drawbacks among patients as a consequence of side effects. Despite the new definitions, the evolution of medical therapy, and the consensus for the management of PE, it remains challenging to treat for many clinicians especially when medical treatment fails. However, the International Society for Sexual Medicine (ISSM) and the American Urological Association (AUA) guidelines ignored surgical therapy due to conflicting medical reports and doubts about the safety of surgical management. This article discusses the surgical management of PE based on recent guidelines, reviews, and evolving techniques.
METHODS
We reviewed the literature using PubMed and searched for the following keywords: premature ejaculation, selective dorsal neurectomy, hyaluronic acid, dorsal nerve neuromodulation, cryo-ablation of the dorsal nerve and inner condom technique until May 2023. Seventeen studies were found.
KEY CONTENT AND FINDINGS
Even though the widespread use of many surgical modalities in Asia such as glans penis augmentation (GPA) using hyaluronic acid (HA) selective dorsal neurectomy (SDN), cryo-ablation of the dorsal nerve, neuromodulation of the dorsal nerve (NMDN), and circumcision are still considered as controversial for the guidelines.
CONCLUSIONS
The mainstay treatment of PE is still pharmaceutical. However, the current body of evidence on surgical treatments for PE is limited. Men considering surgical therapy for PE should be counseled well for the risks and benefits as there may be chronic disabilities. Further, well-designed trials are needed to establish safety and efficacy for the surgical treatment.
PubMed: 37969778
DOI: 10.21037/tau-23-240 -
Sexual & Reproductive Healthcare :... Dec 2023A mixed-methods study was conducted to investigate sexual function among infertile patients undergoing medically assisted procreation for the first time. The study...
A mixed-methods study was conducted to investigate sexual function among infertile patients undergoing medically assisted procreation for the first time. The study employed an interview and content analysis approach, involving 45 infertile patients prior to their medically assisted procreation procedures. The findings revealed that infertile patients are a group at risk for sexual distress. Furthermore, patients with sexual dysfunctions exhibited lower levels of sexual activity, potentially diminishing their chances of achieving pregnancy. Participants faced challenges in openly discussing their sexual problems and demonstrated limited knowledge of sexual functioning. Among infertile women with sexual dysfunctions, the most frequently reported issues were sexual interest/arousal disorders, with a majority also experiencing pain during sexual activity and associated genital-pelvic pain disorders. In contrast, delayed ejaculation and erectile disorder seem to be more common in infertile men, while sexual desire and excitement disorders and premature ejaculation disorders appeared to be as common as in the general population. While the relationship between infertility and sexuality is complex, our study suggests that sexual dysfunctions or the absence of sexual activity may explain infertility. Therefore, it is imperative for clinicians to evaluate the sexual functioning of both men and women undergoing medically assisted procreation treatment, to increase their chances of procreation and offer them sexological support if needed. Future studies should expand their scope to include a larger sample size and delve into the potential etiological factors associated with sexual dysfunctions.
Topics: Male; Pregnancy; Humans; Female; Infertility, Female; Sexual Behavior; Sexual Dysfunctions, Psychological; Sexual Dysfunction, Physiological; Sexuality
PubMed: 37951081
DOI: 10.1016/j.srhc.2023.100922 -
Applied Bionics and Biomechanics 2023[This retracts the article DOI: 10.1155/2022/8260640.].
Retracted: Evaluation and Correlation Analysis of Mental and Psychological Factors and Premature Ejaculation in Patients with Benign Prostatic Hyperplasia in Mobile Medical System.
[This retracts the article DOI: 10.1155/2022/8260640.].
PubMed: 37946822
DOI: 10.1155/2023/9849308 -
Biomedicines Oct 2023Hypericum species are widely acknowledged for their biological attributes, with notable attention being paid to , commonly known as St. John's wort (SJW) within the... (Review)
Review
BACKGROUND
Hypericum species are widely acknowledged for their biological attributes, with notable attention being paid to , commonly known as St. John's wort (SJW) within the Hypericum section of the Hypericaceae family. This species is among the most thoroughly investigated herbal medicines, particularly in terms of its application in the management of mild to moderate depression. SJW is used to treat depression, menopausal symptoms, attention-deficit hyperactivity disorder (ADHD), somatic symptom disorder, obsessive-compulsive disorder, and skin conditions, such as wounds and muscle pain. However, the usefulness and effectiveness of SJW for male sexual and reproductive health (SRH) are not well known.
OBJECTIVE
To assess the current evidence in the literature on the effect of SJW on male SRH.
METHODS
This narrative review followed a predetermined protocol and used MEDLINE and PubMed to identify articles published in English on the effects of SJW on male SRH. The search used various keywords, such as "", "St. John's Wort", and terms related to sexual and reproductive health issues. Articles published between the inception of the database and August 2023 were included.
RESULTS
We identified 12 articles published from 1999 to 2019, the majority of which were experimental and conducted on animals. These studies demonstrate variability in terms of design, sample size, type of SJW extract used, the dosage administered, and duration of treatment. Studies have indicated potential sexual dysfunction (SD) due to SJW, which includes reduced libido, delayed ejaculation, delayed orgasm, and erectile dysfunction. Additionally, reproductive toxicity has been suggested, as evidenced by spermicidal effects through the inhibition of sperm motility, abnormal spermatozoa, chromosomal aberrations, and DNA denaturation. Furthermore, some studies have reported potential adverse events during maternal exposure, inhibition of fertilization, and disruption of reproductive parameters.
CONCLUSIONS
Our review suggests that the safety and efficacy of SJW in the treatment of human SRH remain unclear. Further comprehensive, well-designed studies with larger samples, longer exposure periods, and specific dosages are needed to clarify SJW's effects of SJW. Therefore, consultation with healthcare professionals before using herbal remedies or supplements is crucial.
PubMed: 37893173
DOI: 10.3390/biomedicines11102800 -
JMIR Formative Research Oct 2023Web-based sexual health interventions may be more acceptable to people compared with face-to-face support, given the stigma and embarrassment often associated with...
BACKGROUND
Web-based sexual health interventions may be more acceptable to people compared with face-to-face support, given the stigma and embarrassment often associated with sexual problems. The Dutch public sexual health clinics (SHCs) conducted an implementation pilot with 4 web-based self-training programs on sexual dysfunctions (WSTPs) for young people. In addition to a basic sexuality program, the WSTPs focused on the following complaints: pain during intercourse, premature ejaculation, and no sex drive.
OBJECTIVE
This study aims to gain insight into the potential reach of the freely offered WSTPs; use, acceptance, evaluation, and perceived impact of the WSTPs by young people; and evaluation and acceptance of the WSTPs by nurses of the SHCs.
METHODS
A quantitative baseline measurement (BM) and a follow-up measurement (FM) were conducted among the users. In addition, qualitative data were gathered through video interviews with a sample of respondents of the FM and nurses of the SHCs to gain more in-depth insights into their assessment of the WSTPs. Participants were recruited via social media, posters, and referrals by nurses of the SHCs. Quantitative data were analyzed using descriptive statistics. Independent 2-tailed t tests and one-way independent ANOVAs were used to compare the scores between subgroups based on background characteristics. Dependent 2-tailed t tests were used to assess the possible changes between BM and FM. The interviews were analyzed using a thematic analysis.
RESULTS
A total of 1028 young people (aged 16-24 y) completed the BM, 666 started with 1 of the WSTPs, and 104 participants completed the FM. In addition, 8 users and 8 nurses were interviewed. Of the participants who completed the BM, 87.74% (902/1028) experienced moderate (411/1028, 39.98%) to high (491/1028, 47.76%) severity of complaints, of which 20.43% (210/1028) had had them for >1 year and 27.82% (286/1028) even for ≥2 years, and 38.91% (400/1028) were dissatisfied with their sex lives. Only 8.75% (90/1028) had sought professional help in the past 2 years. At FM, users rated satisfaction with their sex life more positively than they did at BM, and they experienced less discomfort from their complaints. The overall rating was positive, with a mean report grade of 7.3 (SD 1.45; on a 10-point scale). Anonymity, clear information and explanation, and practical exercises are indicated as strengths of the WSTPs, leading to more understanding and normalization. Nurses appreciate the high quality of information and accessibility of the WSTPs. They consider them as a valuable addition to the consultation hours.
CONCLUSIONS
WSTPs can reach a large number of young people with sexual problems who are less likely to seek professional help. This can result in an improved understanding of their issues, a decrease in complaints, and reduced barriers to communicating with a partner or professional.
PubMed: 37883172
DOI: 10.2196/49009