Vaginal Mucosa Research Articles

Laparoscopic correction of combined forms of genital prolapse

BACKGROUND: The significance of pelvic organ prolapse is determined by the absence of a downward trend in its frequency and severity and by the steadily high number of recurrences in every third woman who underwent surgery. According to most authors, surgical correction is the primary treatment for genital prolapse. Therefore, the search for an effective and safe surgical treatment of this pathology is important. Currently, various minimally invasive surgical interventions have been performed via laparoscopic access, which reduces the risk of tissue or adjacent organ damage, possible intraoperative bleeding, and potential complications.
 AIM: This study aimed to assess the efficiency and safety of laparoscopic techniques for the correction of genital prolapse.
 MATERIALS AND METHODS: The study included 12 patients with pelvic organ prolapse quantification system grades IIIV who underwent surgical correction using a combined laparoscopic approach. The inclusion criterion was the presence of prolapse, including recurrent forms. At the outpatient stage, the patients medical history was collected, and complaints, and degree of pelvic organ prolapse were assessed. Genital prolapse was diagnosed based on medical history, clinical data, and additional methods of examination.
 RESULTS: With this surgical intervention technique, intraoperative bleeding was avoided, the number of possible postoperative complications was reduced, and disease recurrence was prevented. The criteria for assessing the surgical intervention included improvement of the pelvic floor anatomy, elimination of symptoms, patients satisfaction with treatment results and quality of life, and reduced risk of recurrence of complications. Mesh-associated complications were excluded by avoiding contact of the synthetic implanted material with the vaginal mucosa.
 CONCLUSIONS: Through laparoscopic access, the length of hospital stay was reduced, and compared with abdominal access, a better cosmetic effect was achieved. A comprehensive system considering the assessment of the anatomical outcome, functional status of the pelvic floor, and patients quality of life may become the most objective tool to evaluate the success of surgical treatment of genital prolapse.

Potential Extract of Lerak Fruit (Sapindus Rarak), Pegagan (Centella Asiatica,) Mimba Seed (Azadirachta Indica A.Juss) and Mixing of Third Extract to Motility and Viability of Spermatozoa Guinea Pigs (Cavia Porcellus)

Spermicides are substances that can kill spermatozoa. Spermicide circulating in the community contains Nonoxynol9 which, if used for a long time, can irritate the vaginal mucosa and penis. Indonesia has a variety of plants that have the potential to act as anti-fertility, including Sapindus rarak, Centella asiatica, and Azadirachta indica. Objective: This study aim to evaluate extract Sapindus rarak, Centella asiatica, and Azadirachta indica. and mixing of third etract to motility and viability of spermatozoa Guinea pigs. Methods: The sample of this research was 15 guinea pig spermatozoa, 3-4 months old male guinea pigs taken from the cauda epididymis and vas deferens. Guinea pigs were divided into 5 group treatments with each group treatment incubated for 1, 10, and 30 minutes and repeated each for 5 times. The treatments in this study is control, 200 μl of spermatozoa suspension + 50 μl of Sapindus rarak fruit pulp extract 0.9%; 200 μl of spermatozoa suspension + 50 μl of gotu kola extract 0.9%; 200 μl of spermatozoa suspension + 50 μl of 0.9% neem seed extract; 200 μl of spermatozoa suspension + 50 μl of the third mixture extract 0.9%. This study used a completely randomized design (CRD). The observations in this study were the motility of guinea pig spermatozoa categories a + b and the viability of guinea pig spermatozoa using a microscope. The data obtained were analyzed statistically using One Way ANOVA. The results of this study indicated that the administration of extract Sapindus rarak, Centella asiatica, and Azadirachta indica and a mixture of the three extracts had a significant effect (P < 0.05) on the motility of guinea pig spermatozoa categories a + b and viability of guinea pig spermatozoa. Conclution: This study concludes that the mixture of the three extracts has more potential in reducing the motility of spermatozoa categories a + b and the viability of guinea pig spermatozoa compared to single extracts. The mixture of the three extracts may contribute for reduce quality of sperm.

Development of probiotic loaded multilayer microcapsules incorporated into dissolving microneedles for potential improvement treatment of vulvovaginal candidiasis: A proof of concept study

Vulvovaginal candidiasis (VVC) is a vaginal infection caused by abnormal growth of Candida sp., especially Candida albicans, in the vaginal mucosa. A shift in vaginal microbiota is prominent in VVC. The presence of Lactobacillus plays a vital role in maintaining vaginal health. However, several studies have reported resistance of Candida sp. against azoles drugs, which is recommended as VVC treatment. The use of L. plantarum as a probiotic would be an alternative to treat VVC. In order to exert their therapeutic activity, the probiotics needed to remain viable. Multilayer double emulsion was formulated to obtain L. plantarum loaded microcapsules (MCs), thus improving its viability. Furthermore, a vaginal drug delivery system using dissolving microneedles (DMNs) for VVC treatment was developed for the first time. These DMNs showed sufficient mechanical and insertion properties, dissolved rapidly upon insertion, facilitating probiotic release. All formulations proved non-irritating, non-toxic, and safe to apply on the vaginal mucosa. Essentially, the DMNs could inhibit the growth of Candida albicans up to 3-fold than hydrogel and patch dosage forms in ex vivo infection model. Therefore, this study successfully developed the formulation of L. plantarum-loaded MCs with multilayer double emulsion and its combination in DMNs for vaginal delivery to treat VVC.

Cross-neutralizing protection of vaginal and oral mucosa from HPV challenge by vaccination in a mouse model

The species and tissue specificities of HPV (human papillomavirus) for human infection and disease complicates the process of prophylactic vaccine development in animal models. HPV pseudoviruses (PsV) that carry only a reporter plasmid have been utilized in vivo to demonstrate cell internalization in mouse mucosal epithelium. The current study sought to expand the application of this HPV PsV challenge model with both oral and vaginal inoculation and to demonstrate its utility for testing vaccine-mediated dual-site immune protection against several HPV PsV types. We observed that passive transfer of sera from mice vaccinated with the novel experimental HPV prophylactic vaccine RG1-VLPs (virus-like particles) conferred HPV16-neutralizing as well as cross-neutralizing Abs against HPV39 in naïve recipient mice. Moreover, active vaccination with RG1-VLPs also conferred protection to challenge with either HPV16 or HPV39 PsVs at both vaginal and oral sites of mucosal inoculation. These data support the use of the HPV PsV challenge model as suitable for testing against diverse HPV types at two sites of challenge (vaginal vault and oral cavity) associated with the origin of the most common HPV-associated cancers, cervical cancer and oropharyngeal cancer.

Pharmacokinetic and pharmacodynamic studies of an altrenogest diffusing intravaginal ring for estrus suppression in the mare

Managing mares through unpredictable behaviors associated with fluctuating hormones is frustrating, particularly during performance. A variety of solutions have been explored, but without reliable success. The synthetic progestin altrenogest, marketed for estrus suppression in the mare, is the current industry paradigm. Commonly administered orally or sustained release injectable formulations, both pose risks, leading to poor owner compliance. We investigated the ability of a novel biomedical device to deliver altrenogest through the vaginal mucosa directly compared with conventional oral administration. In total, 12 grade mares were utilized for this study during the physiologic breeding season. Mares were enrolled within a treatment group spanning three estrous cycles in a crossover design. Intravaginal ring altrenogest (IVRA), oral altrenogest (OA) and a control placebo vaginal ring (IVRP). Group IVRA: 14.2cm diameter silicone ring containing 1% powder altrenogest placed into the cranial vaginal vault day 5 of diestrus (0d = ovulation). Group OA: administered commercially available altrenogest (Regu-Mate®, Merck & Co., Inc., Rahway, NJ) orally daily at 0.044 mg/kg. Group IVRP: insertion of a silicone vaginal ring without altrenogest into the vaginal vault. Blood was collected at each trial initiation (T0) and at 2h, 24h, 72h, 10 days and plasma stored at -80°C until pharmacokinetic (PK) evaluation utilizing modern liquid chromatography tandem mass spectrometry(LC/MS/MS). Blood samples were also collected (days 5, 11, 15, 22) to determine native progesterone levels. Transrectal ultrasonographic evaluation was performed every five days following ovulation. Controlled exposure to a stallion occurred every other day. Values are given as mean ± standard error of mean. IVRA peak plasma levels: 1.45 ng/ml following ring insertion; average steady state level: 0.3 ng/ml. OA peak plasma levels: 1.8 ng/ml following administration; average steady state: 0.55 ng/ml. IVRP: no altrenogest detected. Cmax for IVRA and OA groups was reached within 2 hours. IVRA eliminated peaks/troughs identified in group OA, demonstrating a steady state. Transrectal ultrasonography revealed group IVRA maintained a CL an average of 20.8 ± 1.3, group OA for 21.4 ± 0.75 and IVRP for 14.4 ± 1.2 days. There was no difference in native progesterone levels amongst groups. Groups IVRA and OA maintained significantly longer luteal phases than IVRP (p<0.0001 and p<0.002, respectively). Mares in group IVRA displayed significantly lower teasing scores than IVRP (p<0.009). Groups IVRA and OA were not significantly different (p<0.188). Previous studies determined therapeutic levels of altrenogest at or above 0.5 ng/ml but our observations with mare behavior and PK data suggest efficacy at lower limits of quantification (0.1 ng/ml). An equine intravaginal ring represents a novel medical device for effective delivery of therapeutics and future applications.

Anthocyanins in Mulberry Leaves (Morus rubra L.) Ethanol Extract as the Inhibitor for the Growth of Candida albicans

Infections caused by Candida albicans are generally common in the vaginal mucosa or called Vulvovaginal Candidiasis. Herbal medicine is proven to be an alternative to treat vaginal candidiasis. Mulberry leaves have many chemical compounds, one of which is anthocyanins. Anthocyanins have pharmacological benefits and biological activity that can protect against human pathogenic bacteria. This study aims to observe the effect of anthocyanin compounds extracted from mulberry leaves (Morus Rubra L) on the growth of Candida albicans. Identification of compounds on mulberry leaves used the TLC spectrophotodensitometry on silica gel 60 F254. TLC plates were washed with methanol and activated at 110 degrees C for 30 minutes. The plates were eluted in a chamber that had been saturated with the mobile phase of n-butanol:glacial acetic acid:water (4:1:2) and transferred using a CMAG TLC densitometer with a spectrum in the wavelength range of 200-700 nm. Design study is experimental study with a short Post-Test Only Control Group. This study was conducted at the Pharmaceutical Biology Laboratory of PGRI Adi Buana University and the Laboratory of Professor Nidhom Foundation. The results showed that there was a content of anthocyanin compounds in mulberry leaves with antifungal function against Candida albicans.

Impact of vaginal submucosal platelet-rich plasma combined with non-cross-linked hyaluronic acid injections on dyspareunia and sexual satisfaction in a Hodgkin lymphoma cancer survivor: a case report

Vaginal atrophy is a commonly encountered problem among young cancer survivors. Patients suffer from vaginal dryness, irritation, and dyspareunia secondary to oestrogen deficiency. Oestrogenbased hormone replacement therapy is effective, but unfortunately health concerns or contraindications in cancer survivors frequently limit its use. A 35-year-old female patient with dyspareunia that markedly affected her sexual relationship was referred to the gynaecology clinic. Treatment using topical oestrogen cream and sexual counselling were not successful. We treated her using two submucosal injections of PRP-non-cross-linked hyaluronic acid injections into the vestibule and lower third of the anterior vaginal wall mucosa, spaced a month apart. The patient reported marked reduction of dyspareunia and demonstrated an improvement of FSFI total score 1 month after the second injection. Both the patient and her husband showed an improvement of the index of sexual satisfaction score one month after the second injection compared to their pretreatment scores. Examination of the vaginal mucosa showed improvement of thickness and integrity of the mucosa and increased lubrication. PRP-non-cross-linked hyaluronic acid submucosal injections can be effective for cancer therapy-related vaginal atrophy, coitus-related pain, and sexual satisfaction.

Mucosal CCL28 Chemokine Improves Protection against Genital Herpes through Mobilization of Antiviral Effector Memory CCR10+CD44+ CD62L-CD8+ T Cells and Memory CCR10+B220+CD27+ B Cells into the Infected Vaginal Mucosa.

Four major mucosal-associated chemokines, CCL25, CCL28, CXCL14, and CXCL17, play an important role in protecting mucosal surfaces from infectious pathogens. However, their role in protection against genital herpes remains to be fully explored. The CCL28 is a chemoattractant for the CCR10 receptor-expressing immune cells and is produced homeostatically in the human vaginal mucosa (VM). In this study, we investigated the role of the CCL28/CCR10 chemokine axis in mobilizing protective antiviral B and T cell subsets into the VM site of herpes infection. We report a significant increase in the frequencies of HSV-specific memory CCR10+CD44+CD8+ T cells, expressing high levels of CCR10, in herpes-infected asymptomatic (ASYMP) women compared with symptomatic women. Similarly, a significant increase in the CCL28 chemokine (a ligand of CCR10), was detected in the VM of herpes-infected ASYMP C57BL/6 mice, associated with the mobilization of high frequencies of HSV-specific effector memory CCR10+CD44+CD62L-CD8+ TEM cells and memory CCR10+B220+CD27+ B cells in the VM of HSV-infected ASYMP mice. Inversely, compared with wild-type C57BL/6 mice, the CCL28 knockout (CCL28-/-) mice (1) appeared to be more susceptible to intravaginal infection and reinfection with HSV type 2, and (2) exhibited a significant decrease in the frequencies of HSV-specific effector memory CCR10+CD44+CD62L-CD8+ TEM cells and of memory CD27+B220+ B cells in the infected VM. These findings suggest a critical role of the CCL28/CCR10 chemokine axis in the mobilization of antiviral memory B and T cells within the VM to protect against genital herpes infection and disease.

Complete Genome Sequences of 37 Bacteria from the Human Vaginal Tract.

Microorganisms colonizing the human vaginal mucosa are associated with healthy states, as well as conditions such as bacterial vaginosis and infection-associated preterm birth. Here, we report complete genome sequences of 37 bacterial isolates from the human vaginal tract.

(477) Ablation Vaginectomy is a Safe and Effective Technique in Transmasculine Gender Affirmation Surgery

Abstract Introduction Genital gender affirmation surgery ameliorates gender incongruence with the aim to align an individual’s genital appearance more closely to their experienced gender identity. Vaginectomy is commonly requested because it allows closure of the vaginal vault resulting in a masculine appearance to the perineum. Vaginectomy also allows a more appealing sac-like scrotoplasty and may reduce the risk of urethral complications. Transvaginal, laparoscopic (often combined with transvaginal) and robotically assisted approaches have been described. The transvaginal approach involves the excision of vaginal mucosa but blood loss may be significant and there is a risk of injury to adjacent organs like the bladder or rectum. Alternatively, the vaginal mucosa can be obliterated by high power electrocautery without excision. This technique has not been formally described in the literature before. Objective Pilot study to describe the technique for ablation vaginectomy (AV) and to assess the safety and efficacy of AV compared to traditional transvaginal excision vaginectomy (EV). Methods Retrospective review of a comprehensive prospective database and supplemented by medical records of transgender and non-binary persons requesting vaginectomy for gender affirmation surgery. AV was performed using high power electrocautery while EV was by a transvaginal approach. Follow-up was 30 days post-surgery. Data were reported as mean (standard error) unless specified otherwise. Results A hundred and thirty-seven patients were included in the study (62 following AV, 75 following EV). The median age (interquartile range) of both cohorts were similar [AV, 38 years (29-48); EV 37.7 years (31.5-43)]. Patients who underwent AV had a higher BMI but despite this, they had a lower intra-operative blood loss (99.8 ± 12.7mL vs 646.7 ± 63.4mL) and post-operative drain loss (90.9 ± 11.6mL vs 242.8 ± 23.6mL). More patients following EV required a transfusion (n=11) of 2.34 ± 0.5 units of packed red cells. Six patients had an intraoperative complication during EV (none for AV). Two patients had a recognised urethral perforation (one combined with a bladder injury) and 3 others had a bladder injury. All were repaired at the time. Complication rates after 30 days were similar although there was a trend for higher complications following EV (24% vs 11.3%, p=0.06). These were all related to bleeding and haematoma formation with 3.4% (AV cohort) and 8% (EV cohort) Clavien-Dindo grade 3b complications. Conclusions AV may be a feasible and safe approach when requested for gender affirmation surgery. Further prospective data with longer follow-up are required. Disclosure No

(522) Possible Role of the Sex Script in the Orgasm Gap Between Genders: How Sodomy is an Egalitarian Practice

Abstract Introduction The orgasm gap between genders is found in scientific and generalist literature: men, of all sexual orientations, report reaching orgasm during nearly 90% of sexual intercourses, while heterosexual women only achieve orgasm during 65% of intercourse. Objective We want to demonstrate that the sexual script of penis/vagina penetration is anatomically less satisfactory than anal penetration, and carries risks for women: unwanted pregnancy, iatrogenic risks of contraception We want to highlight, that in terms of gender, this script is unequal, while during sodomy, role can be exchanged, with the help of a dildo, the man can discover his passivity, and no longuer submit to the erection's performance. Methods Literature review: -we introduced the words “orgasm gap” on PubMed for the last five years -press articles Results We have found only four survey about the orgasm gender gap on PubMed When the women can't achieve orgasm, they are generally advised clitoral stimulation During the consultation we hear the women say: I do not feel anything during vaginal penetration, indeed the vaginal mucosa is weakly innervated, and vagina does not have sphincters, which decreases the sensation after childbirth. Conversely the anal region and the rectal mucosa are strongly innervated. Conclusions Sodomy requires learning as sport or music. This learning can cause unpleasant sensations, but when the technique is acquired, as for sport or music, the pleasure is deep intense and continuous. We do not stop sport or music because of aches and pains of the beginner. Sodomy is egalitarian, that can be practiced by all genders, bringing intense pleasure, too often reserved for initiates, and therefore we can say that sodomy is sacred, leaving to the laymen the few orgasmic tremors obtained painfully by external stimulation of the penis or the clitoris. Disclosure No

A probiotic nanozyme hydrogel regulates vaginal microenvironment for Candida vaginitis therapy.

Molecular therapeutics are limited for Candida vaginitis because they damage normal cells and tissues of vagina, aggravating the imbalance of vaginal microbiota and increasing the recurrence. To tackle this limitation, through the combination of peroxidase-like rGO@FeS2 nanozymes [reduced graphene oxide (rGO)] with Lactobacillus-produced lactic acid and H2O2, a responsive hyaluronic acid (HA) hydrogel rGO@FeS2/Lactobacillus@HA (FeLab) is developed. FeLab has simultaneous anti-Candida albicans and vaginal microbiota-modulating activities. In particular, the hydroxyl radical produced from rGO@FeS2 nanozymes and Lactobacillus kills C. albicans isolated from clinical specimens without affecting Lactobacillus. In mice with Candida vaginitis, FeLab has obvious anti-C. albicans activity but hardly damages vaginal mucosa cells, which is beneficial to vaginal mucosa repair. Moreover, a higher proportion of Firmicutes (especially Lactobacillus) and a decrease in Proteobacteria reshape a healthy vaginal microbiota to reduce the recurrence. These results provide a combined therapeutic of nanozymes and probiotics with translational promise for Candida vaginitis therapy.

Isolation of Vaginal Epithelial Cells: In Preparation of Autologous Vaginal Tissue Lining for Congenital Absence of Vagina Patients.

Infertility is a condition affecting women who are born with an underdeveloped or absent vagina, a birth defect known as congenital absence of the vagina. It is a rare disorder where the development of the Mullerian duct is obstructed by unidentified causes. The case is seldom reported due to the low prevalence and sparse epidemiology studies worldwide. A potential solution for the disorder is neovaginal creation with in vitro cultured vaginal mucosa. Limited studies have reported its application, but none are reproducible or specific regarding the established processes for acquiring vaginal epithelial cells from vaginal biopsies. These research gaps were adequately answered with an epidemiology study of inpatient details in Hospital Canselor Tuanku Muhriz, Malaysia, established methods and outcomes of vaginal tissue processing and isolation, and characterization of vaginal epithelial cells using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and immunofluorescence assays. The reported evidence and speculation that the disorder arises because of a cellular transition event between epithelial and mesenchymal cells during the development of the Mullerian duct could be key in the creation of neovaginas using established culture procedures to improve surgical results and restore fertility.

Reproductive Performance of Female Rabbits Inseminated with Extenders Supplemented with GnRH Analogue Entrapped in Chitosan-Based Nanoparticles.

Rabbit is a reflexively ovulating species. Accordingly, in the practice of artificial insemination (AI) ovulation must be induced via exogenous GnRH (Gonadotropin-Releasing Hormone) administration, which may be performed intramuscularly, subcutaneously, or intravaginally. Unfortunately, the bioavailability of the GnRH analogue when added to the extender is lower due to the proteolytic activity in the seminal plasma and the poor permeability of the vaginal mucosa. The aim of the study was to refine the practice of AI practice in rabbits by replacing parenteral GnRH analogue administration (subcutaneous, intravenous, or intramuscular injection) with intravaginal application, while reducing its concentration in the diluent. Extenders containing the buserelin acetate in chitosan-dextran sulphate and chitosan-alginate nanoparticles were designed and 356 females were inseminated. Reproductive performance of females inseminated with the two experimental extenders, receiving 4 μg of buserelin acetate intravaginally per doe, was compared with that in the control group, the does of which were inseminated with the extender without the GnRH analogue and induced to ovulate with 1 μg of buserelin acetate administered intramuscularly. The entrapment efficiency of the chitosan-dextran sulphate complex was higher than that of chitosan-alginate. However, females inseminated with both systems showed similar reproductive performance. We conclude that both nanoencapsulation systems are an efficient way of intravaginal ovulation induction, allowing a reduction in the level of the GnRH analogue normally used in seminal doses from 15-25 μg to 4 μg.

Anti-Candidal Activity of Reboxetine and Sertraline Antidepressants: Effects on Pre-Formed Biofilms.

Reboxetine (REB) and sertraline (SER) are antidepressants. The antifungal potential of these drugs against planktonic Candida has been recently reported with limited data about their effects on Candidal biofilms. Biofilms are self-derived extracellular matrixes produced by the microbial population that is attached to biotic surfaces, such as vaginal and oral mucosa, or abiotic surfaces, such as biomedical devices, resulting in persistent fungal infections. The commonly prescribed antifungals, azoles, are usually less effective when biofilms are formed, and most of the prescribed antifungals are only fungistatic. Therefore, the current study investigates the antifungal potentials of REB and SER, alone and in combination with fluconazole (FLC) and itraconazole (ITR) against Candidal biofilms. Using proper controls, Candida species (Candida albicans, C. albicans; Candida krusei, C. krusei; and Candida glabrata, C. glabrata) were used to form biofilms in 96-well microplates. Serial dilutions corresponding to concentrations ranging from 2 to 4096 µg/mL of the target drugs (REB, SER, FLC, ITR) were prepared and added to the plates. Impairment of the biofilm biomass and biofilm metabolic viability was detected using the crystal violet (CV) assay and 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, respectively. In the checkerboard assay, the sessile fractional inhibitory concentration index (SFICI) was calculated to evaluate the effects of drug combinations. SER was more effective in reducing the biomass than REB for C. albicans and C. glabrata, but both were equal for C. krusei. For the reduction in metabolic activity in C. albicans and C. glabrata, SER had a slight advantage over REB. In C. krusei, REB was slightly more potent. Overall, FLC and ITR were almost equal and produced more significant reductions in metabolic activity when compared to SER and REB, except for C. glabrata, where SER was almost equal to FLC. Synergism was detected between REB + FLC and REB + ITR against biofilm cells of C. albicans. Synergism was detected between REB + ITR against biofilm cells of C. krusei. Synergism was detected between REB + FLC and REB + ITR against biofilm cells of C. albicans, C. krusei, and C. glabrata. The results of the present study support the potential of SER and REB as anti-Candidal biofilm agents that are beneficial as a new antifungal to combat Candidal resistance.

The Interplay between Candida albicans, Vaginal Mucosa, Host Immunity and Resident Microbiota in Health and Disease: An Overview and Future Perspectives

Vulvovaginal candidiasis (VVC), which is primarily caused by Candida albicans, is an infection that affects up to 75% of all reproductive-age women worldwide. Recurrent VVC (RVVC) is defined as &gt;3 episodes per year and affects nearly 8% of women globally. At mucosal sites of the vagina, a delicate and complex balance exists between Candida spp., host immunity and local microbial communities. In fact, both immune response and microbiota composition play a central role in counteracting overgrowth of the fungus and maintaining homeostasis in the host. If this balance is perturbed, the conditions may favor C. albicans overgrowth and the yeast-to-hyphal transition, predisposing the host to VVC. To date, the factors that affect the equilibrium between Candida spp. and the host and drive the transition from C. albicans commensalism to pathogenicity are not yet fully understood. Understanding the host- and fungus-related factors that drive VVC pathogenesis is of paramount importance for the development of adequate therapeutic interventions to combat this common genital infection. This review focuses on the latest advances in the pathogenic mechanisms implicated in the onset of VVC and also discusses novel potential strategies, with a special focus on the use of probiotics and vaginal microbiota transplantation in the treatment and/or prevention of recurrent VVC.

Effects of topical dehydroepiandrosterone therapy in women after pelvic organ prolapse surgery.

Pelvic organ prolapse (POP) occurs predominantly in postmenopausal women. Restoration of the proper estrogenization of vaginal mucosa is important in preoperative and postoperative treatment, increasing the effectiveness of this approach. The objective of this study was the development of intravaginal vaginal suppositories containing DHEA and comparison of the clinical effects of vaginal topical therapy with DHEA, estradiol, or antibiotic after POP surgery. Nine types of vaginal suppositories containing 6.5 mg DHEA in different bases were prepared to find optimal formulation for the vaginal conditions. Ninety women referred for POP surgery were randomly assigned to one of three groups receiving topical treatment in the postoperative period (estradiol, DHEA, or antibiotic). On admission to hospital and during follow-up vaginal pH, vaginal maturation index and vaginal symptoms were assessed. Vaginal suppositories with the base made from polyethylene glycol 1,000 without surfactants characterized the highest percentage of the released DHEA. In women treated with topical estradiol or DHEA a significant decrease in the number of parabasal cells, increase in superficial and intermediate cells in the vaginal smears, decrease in vaginal pH, and reduction of vaginal symptoms were observed. The use of topical therapy with DHEA or the use of topical therapy with estradiol in the postoperative period were both shown to improve maturation index, vaginal pH, and vaginal symptoms. The benefits of topical therapy with DHEA after pelvic organ prolapse repair brings similar results as estradiol, without potential systemic exposure to increased concentrations of sex steroids above levels observed in postmenopausal women.

Establishment of a vaginal organoid system to study local resident memory T cell differentiation

Abstract Over a million sexually transmitted diseases (STDs) are acquired every day worldwide, many of which preferentially target the female reproductive tract (FRT). Resident memory T cells (TRM) in the vaginal mucosa have proven protective roles against these STDs. Accordingly, a crucial objective of STD vaccinations is to establish a higher quantity and quality of TRM in the FRT. The vaginal epithelium has been implicated in regulation of local TRM differentiation and function, but the biological nature of this interaction has not been investigated. Here, we established a murine three dimensional (3D) vaginal organoid-CD8 coculture system to examine epithelial-T cell interactions at the molecular level. Differentiation of single epithelial stem cells led to the formation of 3D epithelial organoids. These organoids can be maintained long-term through serial passage and structurally resembled vaginal epithelium with a multilayer specialized epithelium. After culturing activated CD8 T cells with the organoids, we assessed the transcriptional and phenotypic composition of the T cells. We found that cocultured CD8 T cells were integrated into the extracellular matrix and acquired phenotypic and functional traits of in vivo TRM. This TRM-biased differentiation could be suppressed by a small molecule inhibitor of the cytokine TGF-β. Overall, the vaginal organoid coculture model recapitulates the in vivo environment far better than traditional 2D cell culture, while retaining high-throughput abilities. Importantly, it will enable highly reductionist experiments to examine the complex epithelial cell-T cell crosstalk to devise targeted approaches for improving CD8 T cell mediated immunosurveillance in the FRT. Supported by grants from NIH (2P20GM109035 &amp; P20GM121298) and by the Searle Scholars award.

The estriol use in the perioperative period by patients with genital prolapse

Introduction. Postmenopausal women in a state of oestrogen deficiency often experience pelvic prolapse with underlying genitourinary menopausal syndrome, when the progression of atrophic processes in the vaginal mucosa comes to the forefront.Aim. To evaluate the results of the use of topical hormonal therapy in the perioperative period to improve the vaginal epithelial surface appearance in postmenopausal women who need surgical treatment of pelvic prolapse.Materials and methods. A comparative prospective randomized clinical trial included 60 postmenopausal patients aged 60 to 69 years with a postmenopausal period of 10 to 20 years, suffering from POP-Q stage II–IV pelvic prolapse (ICS, 1996). All patients were recommended surgical treatment using vaginal approach. The treatment group (Group 1) included 30 patients who received topical hormonal therapy with an estriol drug (Ovestin cream, 1 mg/g) within 1 month before reconstructive plastic surgery. The comparison group (Group 2) included 30 patients who did not receive hormonal treatment in the perioperative period.Results. No complications were observed in the treatment group after reconstructive plastic surgery in the early and late postoperative periods. In the comparison group, natural urination was not achieved in 9 of 30 (35.0%) women on Day 2 after surgery, in 4 of 30 (13.3%) patients on Day 3. Also in that group, 4 of 30 (13.3%) patients experienced infectious and inflammatory complications in the postoperative period, the mucous membrane healing in 5/30 (16.6%) patients took a long time, over 1 month.Conclusions. The use of topical hormonal therapy with an estriol drug in the perioperative period in patients who require surgical treatment of pelvic prolapse results in the relief of vulvovaginal atrophy symptoms and adequate regeneration of the vaginal mucosa, which helps reduce the likelihood of complications in both early and late postoperative periods.

Intravaginal injection of Lactobacillus johnsonii may modulates oviductal microbiota and mucosal barrier function of laying hens

The avian oviduct connects to the gastrointestinal tract through cloaca, where it is exposed to pathogenic bacteria from intestinal contents. Therefore, improvement of mucosal barrier function in the oviduct is important for safe poultry production. Lactic acid bacteria are known to contribute to strengthening the mucosal barrier function in the intestinal tract, and a similar effect is expected in the oviduct mucosa of chickens. This study aimed to clarify the effects of vaginal administration of lactic acid bacteria on the mucosal barrier function of the oviduct. White Leghorn laying hens (500-days old) were intravaginally administered 1 mL of Lactobacillus johnsonii suspension (1 × 105 and 1 × 108 cfu/mL: low concentration of Lactobacillus (LL) and high concentration of Lactobacillus (HL) groups, respectively) or without bacteria (control: C group) for 7 d (n = 6). The oviductal magnum, uterus, and vagina were collected for histological observations and mucosal barrier function-related gene expression analysis. Amplicon sequence analysis of oviductal mucus bacteria was also performed. Eggs were collected during the experimental period and their weight was measured. Vaginally administering L. johnsonii for 7 d caused 1) an increase in α-diversity of vaginal mucosa microbiota with an increase in the abundance ratio of beneficial bacteria and a decrease in pathogenic bacteria, 2) enhanced claudin (CLA) 1 and 3 gene expression in the magnum and vaginal mucosa, and 3) a decrease in avian β-defensin (AvBD) 10, 11, and 12 gene expression in the magnum, uterus, and vaginal mucosa. These results suggest that transvaginal administration of L. johnsonii contributes to protection against infection in the oviduct by improving the microflora of the oviductal mucosa and strengthening the mechanical barrier function of the tight junctions. In contrast, transvaginal administration of lactic acid bacteria does not enhance the production of AvBD10, 11, and 12 in the oviduct.