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1.
Urology ; 182: 79-83, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37716457

RESUMO

OBJECTIVE: To qualitatively analyze the knowledge, attitudes, and beliefs of women regarding genitourinary syndrome of menopause (GSM) and vaginal estrogen therapy as expressed on Reddit, a public, anonymous internet forum for discussion and information sharing. METHODS: "r/menopause," a Subreddit with >30,000 subscribers, was queried for "vaginal estrogen" to collect postings related to vaginal estrogen in October 2022. Posts were analyzed qualitatively by 2 independent researchers. The principles of grounded theory were applied, and preliminary themes were generated. These themes were used to derive emergent concepts. RESULTS: Sixty-seven unique posts with 1101 responses were analyzed. Qualitative analysis revealed 5 preliminary themes: (1) questions regarding medication usage, (2) medication side effects, (3) medication alternatives, (4) frustration with the medical system, and (5) seeking validation for symptoms and experiences. Three emergent concepts were derived: (1) women experience bothersome side effects from menopause, and they desire compassionate and effective medical treatment; (2) women are engaged and active participants in their health and health care decisions; and (3) women perceive that their concerns are not taken seriously and seek validation for their medical conditions. CONCLUSION: Peri- and post-menopausal women have many questions and concerns about the condition of GSM and vaginal estrogen as treatment. They also have a broad range of frustrations including access to health care and questions about the usage of vaginal estrogen. By better understanding patient perspectives, physicians can better meet women's needs and improve care for GSM.


Assuntos
Menopausa , Vagina , Feminino , Humanos , Emoções , Estrogênios/uso terapêutico , Resultado do Tratamento , Vagina/efeitos dos fármacos , Pesquisa Qualitativa , Conhecimentos, Atitudes e Prática em Saúde
2.
JAMA ; 330(7): 615-625, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37581673

RESUMO

Importance: Surgical repairs of apical/uterovaginal prolapse are commonly performed using native tissue pelvic ligaments as the point of attachment for the vaginal cuff after a hysterectomy. Clinicians may recommend vaginal estrogen in an effort to reduce prolapse recurrence, but the effects of intravaginal estrogen on surgical prolapse management are uncertain. Objective: To compare the efficacy of perioperative vaginal estrogen vs placebo cream on prolapse recurrence following native tissue surgical prolapse repair. Design, Setting, and Participants: This randomized superiority clinical trial was conducted at 3 tertiary US clinical sites (Texas, Alabama, Rhode Island). Postmenopausal women (N = 206) with bothersome anterior and apical vaginal prolapse interested in surgical repair were enrolled in urogynecology clinics between December 2016 and February 2020. Interventions: The intervention was 1 g of conjugated estrogen cream (0.625 mg/g) or placebo, inserted vaginally nightly for 2 weeks and then twice weekly to complete at least 5 weeks of application preoperatively; this continued twice weekly for 12 months postoperatively. Participants underwent a vaginal hysterectomy (if uterus present) and standardized apical fixation (either uterosacral or sacrospinous ligament fixation). Main Outcomes and Measures: The primary outcome was time to failure of prolapse repair by 12 months after surgery defined by at least 1 of the following 3 outcomes: anatomical/objective prolapse of the anterior or posterior walls beyond the hymen or the apex descending more than one-third of the vaginal length, subjective vaginal bulge symptoms, or repeated prolapse treatment. Secondary outcomes included measures of urinary and sexual function, symptoms and signs of urogenital atrophy, and adverse events. Results: Of 206 postmenopausal women, 199 were randomized and 186 underwent surgery. The mean (SD) age of participants was 65 (6.7) years. The primary outcome was not significantly different for women receiving vaginal estrogen vs placebo through 12 months: 12-month failure incidence of 19% (n = 20) for vaginal estrogen vs 9% (n = 10) for placebo (adjusted hazard ratio, 1.97 [95% CI, 0.92-4.22]), with the anatomic recurrence component being most common, rather than vaginal bulge symptoms or prolapse repeated treatment. Masked surgeon assessment of vaginal tissue quality and estrogenization was significantly better in the vaginal estrogen group at the time of the operation. In the subset of participants with at least moderately bothersome vaginal atrophy symptoms at baseline (n = 109), the vaginal atrophy score for most bothersome symptom was significantly better at 12 months with vaginal estrogen. Conclusions and Relevance: Adjunctive perioperative vaginal estrogen application did not improve surgical success rates after native tissue transvaginal prolapse repair. Trial Registration: ClinicalTrials.gov Identifier: NCT02431897.


Assuntos
Estrogênios Conjugados (USP) , Prolapso de Órgão Pélvico , Prolapso Uterino , Vagina , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Administração Intravaginal , Estrogênios Conjugados (USP)/administração & dosagem , Procedimentos Cirúrgicos em Ginecologia , Histerectomia , Histerectomia Vaginal , Prolapso de Órgão Pélvico/tratamento farmacológico , Prolapso de Órgão Pélvico/etiologia , Prolapso de Órgão Pélvico/prevenção & controle , Prolapso de Órgão Pélvico/cirurgia , Prevenção Secundária , Resultado do Tratamento , Prolapso Uterino/tratamento farmacológico , Prolapso Uterino/prevenção & controle , Prolapso Uterino/cirurgia , Vagina/efeitos dos fármacos , Vagina/cirurgia , Cremes, Espumas e Géis Vaginais/administração & dosagem
3.
Hum Exp Toxicol ; 41: 9603271221080235, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35102757

RESUMO

Silver nanoparticles (AgNPs) are widely applied in the field of personal protection for their powerful toxic effects on cells, and recently, a new type of vaginal gel with AgNPs is used to protect the female reproductive tract from microbes and viruses. However, a high risk of AgNPs to the fetus and the underlying mechanism of AgNPs to interfere in embryo development still remain unclear. Thus, this study investigated the impact of two drugs of vaginal gel with AgNPs on reproductive capability of the female mouse by animal experiment. Then, kinetics of AgNPs affecting embryo development was investigated by in vitro embryos culturing, and cell membrane potential (CMP) of zygotes was analyzed by DiBAC4(3) staining. Results indicated that one of the drugs of vaginal gel certainly injured embryo development in spite of no apparent histological change found in ovaries and uteruses of drug-treated mice. In vitro embryo culturing discovered that the toxic effect of AgNPs on embryo development presented particle sizes and dose dependent, and AgNP treatment could rapidly trigger depolarization of the cell membrane of zygotes. Moreover, AgNPs changed the gene expression pattern of Oct-4 and Cdx2 in blastocysts. All these findings suggest that AgNPs can interfere with normal cellular status including cell membrane potential, which has not been noticed in previous studies on the impact of AgNPs on mammalian embryos. Thus, findings of this study alarm us the risk of applying vaginal gel with AgNPs in individual caring and protection of the female reproductive system.


Assuntos
Desenvolvimento Embrionário/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Reprodução/efeitos dos fármacos , Prata/toxicidade , Vagina/efeitos dos fármacos , Cremes, Espumas e Géis Vaginais/toxicidade , Animais , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos
4.
BMC Microbiol ; 22(1): 23, 2022 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-35026981

RESUMO

BACKGROUND: Streptococcus agalactiae or Group B Streptococcus (GBS) is an encapsulated gram-positive bacterial pathobiont that commonly colonizes the lower gastrointestinal tract and reproductive tract of human hosts. This bacterium can infect the gravid reproductive tract and cause invasive infections of pregnant patients and neonates. Upon colonizing the reproductive tract, the bacterial cell is presented with numerous nutritional challenges imposed by the host. One strategy employed by the host innate immune system is intoxication of bacterial invaders with certain transition metals such as zinc. METHODOLOGY: Previous work has demonstrated that GBS must employ elegant strategies to circumnavigate zinc stress in order to survive in the vertebrate host. We assessed 30 strains of GBS from diverse isolation sources, capsular serotypes, and sequence types for susceptibility or resistance to zinc intoxication. RESULTS: Invasive strains, such as those isolated from early onset disease manifestations of GBS infection were significantly less susceptible to zinc toxicity than colonizing strains isolated from rectovaginal swabs of pregnant patients. Additionally, capsular type III (cpsIII) strains and the ST-17 and ST-19 strains exhibited the greatest resilience to zinc stress, whereas ST-1 and ST-12 strains as well as those possessing capsular type Ib (cpsIb) were more sensitive to zinc intoxication. Thus, this study demonstrates that the transition metal zinc possesses antimicrobial properties against a wide range of GBS strains, with isolation source, capsular serotype, and sequence type contributing to susceptibility or resistance to zinc stress.


Assuntos
Antibacterianos/farmacologia , Cloretos/farmacocinética , Sorogrupo , Streptococcus agalactiae/efeitos dos fármacos , Streptococcus agalactiae/genética , Compostos de Zinco/farmacocinética , Antibacterianos/metabolismo , Cápsulas Bacterianas/classificação , Cápsulas Bacterianas/efeitos dos fármacos , Cloretos/metabolismo , Feminino , Humanos , Recém-Nascido , Testes de Sensibilidade Microbiana , Gravidez , Sorotipagem , Infecções Estreptocócicas/sangue , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/classificação , Streptococcus agalactiae/crescimento & desenvolvimento , Vagina/efeitos dos fármacos , Vagina/microbiologia , Compostos de Zinco/metabolismo
5.
Gynecol Endocrinol ; 38(1): 78-82, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34463164

RESUMO

OBJECTIVE: To assess vaginal health, endometrial thickness, and changes in bone markers in postmenopausal women with vulvovaginal atrophy (VVA) treated with 60 mg/day of ospemifene under routine clinical practice. METHODS: The AYSEX study is a Spanish observational and prospective study performed in one center in which 5 gynecologists recruited postmenopausal women with VVA in routine clinical practice treated continuously with ospemifene 60 mg/day for 12 months as an appropriate therapeutic option. This article refers to the 3- and 6-months analysis. Vaginal health was assessed by pH and using Vaginal Health Index (VHI) at baseline and 3 months later. Endometrial thickness, measured by vaginal ultrasonography, and bone resorption marker (CTx) were assessed at baseline and 6 months later. RESULTS: A total of 100 postmenopausal women cytologically and clinically diagnosed with VVA were included in the study. After 3 months of treatment with ospemifene, pH improved from 6.1 to 4.5 (p < .0001), and VHI improved from 10 to 19 points (p < .0001). The percentage of patients with VVA according to VHI decreased from 100% to 5.2% (p < .0001). After 6 months, mean CTx levels decreased from 0.42 pg/ml at baseline to 0.37 pg/ml 6 months later (p = .0018), and mean endometrial thickness changed from 2.24 to 2.15 mm (p = .6066). CONCLUSIONS: Up to date, this is the only prospective and observational study with ospemifene in routine clinical practice conditions and confirms the results previously reported from randomized controlled clinical trials, improving VVA, not increasing endometrial thickness, and decreasing CTx levels by exerting an anti-resorptive function.


Assuntos
Osso e Ossos/fisiologia , Endométrio/anatomia & histologia , Pós-Menopausa/fisiologia , Tamoxifeno/análogos & derivados , Vagina/fisiologia , Biomarcadores/sangue , Reabsorção Óssea , Osso e Ossos/efeitos dos fármacos , Endométrio/efeitos dos fármacos , Feminino , Humanos , Pós-Menopausa/efeitos dos fármacos , Estudos Prospectivos , Tamoxifeno/administração & dosagem , Ultrassonografia , Vagina/efeitos dos fármacos
6.
Cell Mol Biol (Noisy-le-grand) ; 67(1): 80-88, 2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-34817364

RESUMO

Bacterial vaginosis is a vaginal infection that affects 60% of women of reproductive age worldwide. It is mainly caused by the bacterium Gardnerella vaginalis and is a factor that increases the probability of getting sexually transmitted diseases. We aimed to develop a new pharmaceutical form for the treatment of vaginal infections. We employed the solving-casting method to fabricate a polymeric film with Xanthan gum, a natural polymer produced by the bacterium Xanthomonas campestris, and metronidazole, one of the most commonly used drugs for vaginal infections. In order to characterize the film, we measured pH, dose uniformity, dissolution profile, and the percentage of swelling. Moreover, we performed a thermogravimetric analysis and scanning electron microscopy. The results demonstrated a pH suitable for vaginal application and uniform distribution of the drug in the film. Also, the formulation exhibited a high percentage of swelling and a slow release of the drug in a simulated vaginal fluid medium. All these attributes indicated that the manufactured film has ideal characteristics to be used and administered vaginally. It could be an excellent alternative to treat bacterial vaginosis and also improve user adherence.


Assuntos
Gardnerella vaginalis/efeitos dos fármacos , Metronidazol/uso terapêutico , Polissacarídeos Bacterianos/química , Vagina/efeitos dos fármacos , Vaginose Bacteriana/tratamento farmacológico , Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Antibacterianos/uso terapêutico , Liberação Controlada de Fármacos , Feminino , Gardnerella vaginalis/fisiologia , Humanos , Concentração de Íons de Hidrogênio , Membranas Artificiais , Metronidazol/administração & dosagem , Metronidazol/farmacocinética , Microscopia Eletrônica de Varredura , Polímeros/química , Polissacarídeos Bacterianos/ultraestrutura , Temperatura , Termogravimetria/métodos , Resultado do Tratamento , Vagina/microbiologia , Vaginose Bacteriana/microbiologia
7.
Sci Rep ; 11(1): 23069, 2021 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-34845288

RESUMO

We compared the effect of commercial vaginal douching products on Lactobacillus crispatus, L. jensenii, L. gasseri, L. iners, E. coli, and immortalized vaginal epithelial cells (VK2). All studied douching products (vinegar, iodine and baking soda based) induced epithelial cell death, and all inhibited growth of E. coli. Co-culture of vaginal epithelial cells with any of the lactobacilli immediately following exposure to douching products resulted in a trend to less human cell death. However, co-culture of epithelial cells with L. iners was associated with higher production of IL6 and IL8, and lower IL1RA regardless of presence or type of douching solution. Co-culture with L. crispatus or L. jensenii decreased IL6 production in the absence of douches, but increased IL6 production after exposure to vinegar. Douching products may be associated with epithelial disruption and inflammation, and may reduce the anti-inflammatory effects of beneficial lactobacilli.


Assuntos
Epitélio/efeitos dos fármacos , Epitélio/microbiologia , Escherichia coli/efeitos dos fármacos , Lactobacillus/efeitos dos fármacos , Ducha Vaginal/efeitos adversos , Ácido Acético , Sobrevivência Celular , Técnicas de Cocultura , Citocinas/metabolismo , Feminino , Humanos , Concentração de Íons de Hidrogênio , Sistema Imunitário , Interleucina-6/biossíntese , Interleucina-8/biossíntese , Iodo , Lactobacillus crispatus , Lactobacillus gasseri , Testes de Sensibilidade Microbiana , Risco , Bicarbonato de Sódio , Infecções Urinárias/etiologia , Infecções Urinárias/prevenção & controle , Vagina/efeitos dos fármacos
8.
Int J Biol Macromol ; 193(Pt B): 2140-2152, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34780894

RESUMO

Large surface area, rich vascularisation, well defined mucous membrane, balanced pH and relatively low enzymatic activity makes vagina a suitable site for drugs associated with women's health issues like Urinary tract infection (UTI) and vaginal infections. Therapeutic performance of intravaginal dosage forms largely depends on the properties of polymers and drugs. Chitosan (CS) because of its unique physical, chemical, pharmaceutical and biopharmaceutical properties have received a great deal of attention as an essential component in vaginal drug delivery systems. Further the presence of free amino and hydroxyl groups on the chitosan skeleton allows easy derivatization under mild conditions to meet specific application requirements. Moreover, CS-based nanopharmaceuticals like nanoparticles, nanofiber, nanogel, nanofilm, liposomes and micelles are widely studied to improve therapeutic performance of vaginal formulations. However, susceptibility of CS to the acidic pH of vagina, poor loading of hydrophobic drugs, rapid mucosal turn over are the key issues need to be addressed for successful outcomes. In this review, we have discussed the application of CS and CS derivatives in vaginal drug delivery and also highlight the recent progress in chitosan based nanocarrier platforms in terms of their limitations and potentials.


Assuntos
Quitosana/química , Nanopartículas/química , Vagina/efeitos dos fármacos , Animais , Sistemas de Liberação de Medicamentos/métodos , Feminino , Humanos , Lipossomos/química , Micelas , Nanofibras/química , Polímeros/química
9.
Int J Mol Sci ; 22(19)2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34639109

RESUMO

The uterine first-pass effect occurs when drugs are delivered vaginally. However, the effect of vaginally administered recombinant human follicle-stimulating hormone (rhFSH) on ovarian folliculogenesis and endometrial receptivity is not well established. We aimed to compare the efficacy of rhFSH administered vaginally and abdominally in clinical in vitro fertilization (IVF) treatment, pharmacokinetic study, and animal study. In IVF treatment, the number of oocytes retrieved, endometrial thickness and uterine artery blood perfusion were not different between women who received the rhFSH either vaginally or abdominally. For serum pharmacokinetic parameters, significantly lower Tmax, clearance, and higher AUC and T1/2_elimination of rhFSH were observed in women who received rhFSH vaginally, but urine parameters were not different. Immature female rats that received daily abdominal or vaginal injections (1 IU twice daily for 4 days) or intermittent vaginal injections (4 IU every other day for two doses) of rhFSH had more total follicles than the control group. In addition, the serum progesterone and progesterone receptors in the local endometrium were significantly higher in the groups treated with intermittent abdominal or vaginal injection of rhFSH, compared with those who recieved daily injection. In summary, vaginal administration of rhFSH may provide an alternative treatment regimen in women receiving IVF.


Assuntos
Endométrio/fisiologia , Fertilização In Vitro/métodos , Hormônio Foliculoestimulante Humano/administração & dosagem , Infertilidade Feminina/terapia , Folículo Ovariano/citologia , Proteínas Recombinantes/administração & dosagem , Útero/fisiologia , Adulto , Animais , Estudos Cross-Over , Endométrio/efeitos dos fármacos , Feminino , Humanos , Pessoa de Meia-Idade , Folículo Ovariano/fisiologia , Ratos , Ratos Sprague-Dawley , Injeções de Esperma Intracitoplásmicas , Útero/efeitos dos fármacos , Vagina/efeitos dos fármacos , Vagina/fisiologia
10.
Curr Issues Mol Biol ; 43(3): 1669-1684, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34698102

RESUMO

Postmenopausal syndrome refers to symptoms caused by the gradual decrease in female hormones after mid-40 years. As a target organ of estrogen, decrease in estrogen causes various changes in brain function such as a decrease in choline acetyltransferase and brain-derived neurotrophic factor; thus, postmenopausal women experience cognitive decline and more depressive symptoms than age-matched men. Radix Polygalae has been used for memory boosting and as a mood stabilizer and its components have shown neuroprotective, antidepressant, and stress relief properties. In a mouse model of estrogen depletion induced by 4-vinylcyclohexene diepoxide, Radix Polygalae was orally administered for 3 weeks. In these animals, cognitive and depression-related behaviors and molecular changes related to these behaviors were measured in the prefrontal cortex and hippocampus. Radix Polygalae improved working memory and contextual memory and despair-related behaviors in 4-vinylcyclohexene diepoxide-treated mice without increasing serum estradiol levels in this model. In relation to these behaviors, choline acetyltransferase and brain-derived neurotrophic factor in the prefrontal cortex and hippocampus and bcl-2-associated athanogene expression increased in the hippocampus. These results implicate the possible benefit of Radix Polygalae in use as a supplement of estrogen to prevent conditions such as postmenopausal depression and cognitive decline.


Assuntos
Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Depressão/etiologia , Depressão/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Estradiol/metabolismo , Menopausa/efeitos dos fármacos , Menopausa/metabolismo , Animais , Comportamento Animal , Disfunção Cognitiva/tratamento farmacológico , Depressão/tratamento farmacológico , Modelos Animais de Doenças , Ciclo Estral/efeitos dos fármacos , Ciclo Estral/metabolismo , Feminino , Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Camundongos , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Vagina/efeitos dos fármacos , Vagina/metabolismo , Vagina/patologia
11.
Front Immunol ; 12: 730986, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594336

RESUMO

The standard treatment for bacterial vaginosis (BV) with oral metronidazole is often ineffective, and recurrence rates are high among African women. BV-associated anaerobes are closely associated with genital inflammation and HIV risk, which underscores the importance of understanding the interplay between vaginal microbiota and genital inflammation in response to treatment. In this cohort study, we therefore investigated the effects of metronidazole treatment on the vaginal microbiota and genital cytokines among symptomatic South African women with BV [defined as Nugent score (NS) ≥4] using 16S rRNA gene sequencing and multiplex bead arrays. Among 56 BV-positive women, we observed short-term BV clearance (NS <4) in a proportion of women six weeks after metronidazole treatment, with more than half of these experiencing recurrence by 12 weeks post-treatment. BV treatment temporarily reduced the relative abundance of BV-associated anaerobes (particularly Gardnerella vaginalis and Atopobium vaginae) and increased lactobacilli species (mainly L. iners), resulting in significantly altered mucosal immune milieu over time. In a linear mixed model, the median concentrations of pro-inflammatory cytokines and chemokines were significantly reduced in women who cleared BV compared to pre-treatment. BV persistence and recurrence were strongly associated with mucosal cytokine profiles that may increase the risk of HIV acquisition. Concentrations of these cytokines were differentially regulated by changes in the relative abundance of BVAB1 and G. vaginalis. We conclude that metronidazole for the treatment of BV induced short-term shifts in the vaginal microbiota and mucosal cytokines, while treatment failures promoted persistent elevation of pro-inflammatory cytokine concentrations in the genital tract. These data suggest the need to improve clinical management of BV to minimize BV related reproductive risk factors.


Assuntos
Antibacterianos/administração & dosagem , Bactérias/efeitos dos fármacos , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Metronidazol/administração & dosagem , Mucosa/efeitos dos fármacos , Vagina/efeitos dos fármacos , Vaginose Bacteriana/tratamento farmacológico , Administração Oral , Adulto , Antibacterianos/efeitos adversos , Bactérias/imunologia , Bactérias/patogenicidade , Disbiose , Feminino , Interações Hospedeiro-Patógeno , Humanos , Estudos Longitudinais , Metronidazol/efeitos adversos , Mucosa/imunologia , Mucosa/metabolismo , Mucosa/microbiologia , Estudos Prospectivos , Reinfecção , África do Sul , Fatores de Tempo , Resultado do Tratamento , Vagina/imunologia , Vagina/metabolismo , Vagina/microbiologia , Vaginose Bacteriana/diagnóstico , Vaginose Bacteriana/imunologia , Vaginose Bacteriana/microbiologia , Adulto Jovem
12.
Drug Deliv ; 28(1): 2278-2288, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34668816

RESUMO

Chitosan glutamate (gCS) spray-dried microparticles appear promising carriers to overcome challenges associated with vaginal microbicide delivery. This study aimed at elucidating the penetration and mucoadhesive behavior of developed gCS multiunit carriers with zidovudine (ZVD) as a model antiretroviral agent in contact with excised human vaginal epithelium followed with an examination of in vitro antiherpes activity in immortal human keratinocytes HaCaT and human vaginal epithelial cells VK2-E6/E7. Both ZVD dispersion and placebo microparticles served as controls. Microparticles displayed feasible (comparable to commercial vaginal product) mucoadhesive and mucoretention characteristics to isolated human vaginal tissue. Ex vivo penetration studies revealed that gCS increased the accumulation of active agent in the vaginal epithelium but surprisingly did not facilitate its penetration across human tissue. Finally, the obtained antiviral results demonstrated the potential of gCS as an antiherpes adjunctive, whose mode of action was related to blocking viral attachment.


Assuntos
Antivirais/farmacologia , Herpes Labial/tratamento farmacológico , Nanopartículas/química , Vagina/efeitos dos fármacos , Zidovudina/farmacologia , Antivirais/administração & dosagem , Antivirais/farmacocinética , Quitosana/química , Portadores de Fármacos/química , Feminino , Ácido Glutâmico/química , Humanos , Queratinócitos , Tecnologia Farmacêutica , Zidovudina/administração & dosagem , Zidovudina/farmacocinética
13.
Food Chem Toxicol ; 156: 112515, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34400204

RESUMO

Chlorpyrifos (CPF), the most used insecticide in Argentina, can act as an endocrine disruptor at low doses. We previously demonstrated that chronic exposure to CPF induces hormonal imbalance in vivo. The aim of this work was to study the effects of low concentrations of CPF (0.01 and 1 mg/kg/day) on the reproductive system of virgin adult rats. In the ovary, we studied the effects of CPF on steroidogenesis by determining steroid hormone content by RIA and CYP11 and CYP19 enzyme expression by qRT-PCR. The estrous cycle was evaluated by microscopic observation of vaginal smear, as well as by changes in uterine histology. In endometrium, we determined the fractal dimension and expression of PCNA, ERα and PR by IHC. Our results showed that chronic exposure to CPF affects ovarian steroid synthesis, causing alterations in the normal cyclicity of animals. In addition, CPF induced proliferative changes in the uterus, suggesting that it could affect reproduction or act as a risk factor in the development of uterine proliferative pathologies.


Assuntos
Clorpirifos/administração & dosagem , Clorpirifos/toxicidade , Ciclo Estral/efeitos dos fármacos , Ovário/efeitos dos fármacos , Útero/efeitos dos fármacos , Animais , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Inseticidas/administração & dosagem , Inseticidas/toxicidade , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Vagina/efeitos dos fármacos
14.
Front Immunol ; 12: 702172, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34447373

RESUMO

Containment of the AIDS pandemic requires reducing HIV transmission. HIV infection is initiated by the fusion of the membrane between the virus and the cell membrane of the host. 2P23 is an effective HIV membrane fusion inhibitor that may be a good entry inhibitor microbicide candidate. This study evaluated the potential of using gel-formulated 2P23 as a topical microbicide to prevent sexual transmission of HIV in the rectum and vagina. Our data revealed that 2P23 formulated in gel is effective against HIV. There was no change in antiviral activity at 25°C for 4 months or 60°C for 1 week. In addition, we demonstrated that the 2P23 gel was stable and fully functional at pH 4.0-8.0 and under different concentrations of H2O2. Finally, the 2P23 gel exhibited no cytotoxicity or antimicrobial activity and did not induce inflammatory changes in the rectal or vaginal mucosal epithelium in New Zealand rabbits after 20 mg/day daily rectovaginal application for 14 consecutive days. Despite repeated tissue sampling and 2P23 gel treatment, the inflammatory cytokines and microbiota of the rectum and vagina remained stable. These results add to general knowledge on the in vivo evaluation of anti-HIV microbicide application concerning inflammatory cytokines and microbiota changes in the rectum and vagina. These findings suggest that the 2P23 gel is an excellent candidate for further development as a safe and effective pre-exposure prophylactic microbicide for the prevention of HIV transmission.


Assuntos
Fármacos Anti-HIV/farmacologia , Infecções por HIV/prevenção & controle , Microbiota/efeitos dos fármacos , Reto/efeitos dos fármacos , Vagina/efeitos dos fármacos , Animais , Feminino , Géis , HIV-1 , Masculino , Coelhos , Reto/microbiologia , Reto/virologia , Vagina/microbiologia , Vagina/virologia
15.
Tissue Cell ; 73: 101585, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34375824

RESUMO

The involvement of endometrial IGF-1R/IGF-1/Bcl-2 pathways and the potential regulatory effects of exogenously administrated melatonin on this expression is investigated in the experimental PCOS model in the present study. Thirty-two 6-8 week old Sprague Dawley rats were divided into four groups: the Sham Control Group (1% CMC/day by oral gavage [o.g.]); the Melatonin Group (2 mg/kg/day melatonin by subcutaneous administration [s.c.]); the Experimental PCOS Group (1 mg/kg/day Letrozole by o.g.); and the Experimental PCOS + Melatonin Group (1 mg/kg/day Letrozole by o.g. and 2 mg/kg/day melatonin by s.c. administration). Vaginal smear samples were taken from the 14th day to the end of the experiment for colpocytological measurements. At the end of the 21 day experimental period, uterine tissues were taken; Hematoxylin-Eosin histochemical, IGF-1R/IGF-1/Bcl-2, PCNA immuno-histochemical stainings and western blot analyses were performed for related antibodies. All of the data was supported statistically. The epithelium of endometrium lost its single-layer structure in some parts, separation was observed between the epithelium and the basal membrane junction, intracellular edema was found in the uterine glands by the polycystic ovary-induction. Also this induction increased the expression of IGF-1R/IGF-1, Bcl-2, and PCNA proteins. Morphological degenerations returned to its normal appearance generally by the melatonin administrations and melatonin also regulated the increased expression of endometrial IGF-1R/IGF-1/Bcl-2 and PCNA pathways. It is concluded that additional studies are needed, using melatonin as a supporting agent may be appropriate in cases of PCOS.


Assuntos
Endométrio/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Melatonina/farmacologia , Síndrome do Ovário Policístico/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Receptor IGF Tipo 1/metabolismo , Transdução de Sinais , Animais , Peso Corporal/efeitos dos fármacos , Endométrio/efeitos dos fármacos , Endométrio/patologia , Feminino , Ovário/efeitos dos fármacos , Ovário/patologia , Síndrome do Ovário Policístico/patologia , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos Sprague-Dawley , Análise de Regressão , Coloração e Rotulagem , Vagina/efeitos dos fármacos
16.
Biosci Rep ; 41(9)2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34397086

RESUMO

The reproductive tract microbiota plays a crucial role in maintenance of normal pregnancy and influences reproductive outcomes. Microbe-host interactions in pregnancy remain poorly understood and their role in shaping immune modulation is still being uncovered. In this review, we describe the composition of vaginal microbial communities in the reproductive tract and their association with reproductive outcomes. We also consider strategies for manipulating microbiota composition by using live biotherapeutics, selective eradication of pathogenic bacteria with antibiotics and vaginal microbiota transplantation. Finally, future developments in this field and the need for mechanistic studies to explore the functional significance of reproductive tract microbial communities are highlighted.


Assuntos
Bactérias/patogenicidade , Microbiota , Complicações Infecciosas na Gravidez/microbiologia , Reprodução , Vagina/microbiologia , Vaginose Bacteriana/microbiologia , Animais , Antibacterianos/uso terapêutico , Bactérias/efeitos dos fármacos , Bactérias/imunologia , Terapia Biológica , Disbiose , Feminino , Interações Hospedeiro-Patógeno , Humanos , Gravidez , Complicações Infecciosas na Gravidez/imunologia , Complicações Infecciosas na Gravidez/terapia , Resultado da Gravidez , Vagina/efeitos dos fármacos , Vagina/imunologia , Vaginose Bacteriana/imunologia , Vaginose Bacteriana/terapia
17.
Reprod Biomed Online ; 43(3): 503-514, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34315695

RESUMO

RESEARCH QUESTION: Does oral probiotic supplementation influence the relative abundance of different vaginal microbiota in women experiencing infertility? DESIGN: A prospective, monocentric randomized controlled trial. To study the influence of probiotics on infertility, 80 patients with primary or secondary infertility were included. Patients were assigned to either a probiotic treatment or a control group. Participants in the treatment group (n = 40) took one sachet (2 g) a day of a defined probiotic supplement limiting Lactobacillus strains. Patients in the control group did not receive any additional probiotic supplements. Vaginal samples were taken on day 20 of the menstrual cycle and 4 weeks later, on day 20, of the consecutive cycle. Subsequently, 16s rRNA gene analysis of the vaginal samples was conducted. RESULTS: After the intervention phase, no effects on alpha diversity resulting from treatment could be observed. The between sample diversity of different women (beta diversity) at baseline had no effects of age, treatment group or body mass index. Primary or secondary sterility, however, had a significant effect on community. Three clusters (Lactobacillus crispatus, Lactobacillus iners and Lactobacillus gasseri) were identified as the leading representatives. Furthermore, patients treated with probiotics showed limited growth of Ureaplasma parvum compared with the control group (P = 0.021). CONCLUSIONS: This study points to a possible protective effect of probiotic supplements on the vaginal microbiota. It is tempting to speculate that this effect assists in containing the growth of non-beneficial bacteria and helps to prevent or cure a dysbiotic vaginal flora.


Assuntos
Infertilidade Feminina/dietoterapia , Probióticos/farmacologia , Infecções por Ureaplasma/dietoterapia , Vagina/efeitos dos fármacos , Vaginose Bacteriana/dietoterapia , Adolescente , Adulto , Áustria , Suplementos Nutricionais , Disbiose/complicações , Disbiose/dietoterapia , Feminino , Humanos , Infertilidade Feminina/microbiologia , Lactobacillus/fisiologia , Probióticos/administração & dosagem , Ureaplasma/efeitos dos fármacos , Infecções por Ureaplasma/complicações , Vagina/microbiologia , Vaginose Bacteriana/complicações , Adulto Jovem
18.
J Microbiol Biotechnol ; 31(9): 1281-1287, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34319260

RESUMO

Clinical and preclinical studies have reported that Lactobacillus gasseri BNR17, a probiotic bacterial strain isolated from human breast milk, reduces body weight and white adipose tissue volume. In order to further explore the actions of L. gasseri BNR17, we investigated the anti-menopausal effects of L. gasseri BNR17 in an ovariectomized (OVX) rat model. The serum alanine aminotransferase levels of the rats in the OVX-BNR17 group were lower than those of the rats in the OVX-vehicle only (OVX-Veh) group. Upon administration of L. gasseri BNR17 after ovariectomy, calcitonin and Serotonin 2A levels increased significantly, whereas serum osteocalcin levels showed a decreasing tendency. Compared to the rats in the OVX-Veh group, those in the OVX-BNR17 group showed lower urine deoxypyridinoline levels, lower pain sensitivity, and improved vaginal cornification. Furthermore, L. gasseri BNR17 administration increased bone mineral density in the rats with OVX-induced femoral bone loss. These results suggest that L. gasseri BNR17 administration could alleviate menopausal symptoms, indicating that this bacterium could be a good functional probiotic for managing the health of older women.


Assuntos
Lactobacillus gasseri , Ovariectomia/efeitos adversos , Pós-Menopausa/efeitos dos fármacos , Probióticos/farmacologia , Animais , Biomarcadores/sangue , Biomarcadores/urina , Densidade Óssea/efeitos dos fármacos , Feminino , Pós-Menopausa/sangue , Pós-Menopausa/urina , Probióticos/administração & dosagem , Ratos , Vagina/efeitos dos fármacos , Vagina/patologia
19.
Molecules ; 26(11)2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34199433

RESUMO

Gelam honey (GH) is a prized natural product synthesized from the nectar of flowers from Gelam trees (Melaleuca sp.). Gelam is an evergreen tree species that grows in tropical regions such as Malaysia. GH is a multifloral honey with proven antioxidant and anti-inflammatory properties. However, the beneficial effect of GH on female reproductive tissue has yet to be substantiated. Herein, we investigated the effects of GH administration on the uterine and vaginal epithelial thickness of sexually mature Sprague-Dawley rats. Epithelia thickness could be an indicator of an atrophy manifesting as a symptom of a cardio syndrome. Rats were given oral doses of GH in four groups for 14 days; the lowest dose was 0.2 g GH/kg body weight (bw) rat/day and the highest dose was 8 g GH/kg bw rat/day. The physicochemical characteristics of GH were assessed through hydroxymethylfurfural and moisture content determination and sugar identification. GH attenuated the atrophy of the uterine and vaginal epithelia and increased the thickness of the endometrial stroma and endometrial surface endothelial layer. However, the dissonance observed in the effect of GH administration on the vaginal epithelium requires further investigation. Nevertheless, GH may have a strong potential in attenuating uterine and vaginal atrophies.


Assuntos
Produtos Biológicos/administração & dosagem , Mel/análise , Melaleuca/química , Útero/efeitos dos fármacos , Vagina/efeitos dos fármacos , Animais , Atrofia , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Feminino , Néctar de Plantas/química , Ratos , Ratos Sprague-Dawley , Útero/patologia , Vagina/patologia
20.
J Immunol ; 206(12): 2937-2948, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34088770

RESUMO

Tissue-resident memory CD8 T cells (CD8 TRM) are critical for maintaining barrier immunity. CD8 TRM have been mainly studied in the skin, lung and gut, with recent studies suggesting that the signals that control tissue residence and phenotype are highly tissue dependent. We examined the T cell compartment in healthy human cervicovaginal tissue (CVT) and found that most CD8 T cells were granzyme B+ and TCF-1- To address if this phenotype is driven by CVT tissue residence, we used a mouse model to control for environmental factors. Using localized and systemic infection models, we found that CD8 TRM in the mouse CVT gradually acquired a granzyme B+, TCF-1- phenotype as seen in human CVT. In contrast to CD8 TRM in the gut, these CD8 TRM were not stably maintained regardless of the initial infection route, which led to reductions in local immunity. Our data show that residence in the CVT is sufficient to progressively shape the size and function of its CD8 TRM compartment.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Colo do Útero/imunologia , Herpes Simples/imunologia , Vagina/imunologia , Adulto , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Colo do Útero/efeitos dos fármacos , Colo do Útero/virologia , Feminino , Herpes Simples/tratamento farmacológico , Herpes Simples/virologia , Herpesvirus Humano 2/efeitos dos fármacos , Herpesvirus Humano 2/imunologia , Humanos , Injeções Subcutâneas , Acetato de Medroxiprogesterona/administração & dosagem , Acetato de Medroxiprogesterona/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Vagina/efeitos dos fármacos , Vagina/virologia , Adulto Jovem
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