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Minlu Hu, Tian Zhou, Charlene S Dezzutti, Lisa C Rohan
Pharmaceutical excipients are widely used in vaginal drug products. The epithelial integrity of the cervicovaginal tissue is important for HIV-1 prevention. However, the effects of excipients on cervicovaginal epithelium remain unknown. This study aims at assessing the effects of vaginal product excipients on the integrity of human cervicovaginal epithelium and on a lead HIV prevention antiretroviral drug, tenofovir (TFV). In the current study, nine excipients commonly used in vaginal formulations were incubated for 6 h with excised human ectocervical tissue...
October 2016: AIDS Research and Human Retroviruses
Fridolin Mujuni, Mariam M Mirambo, Peter Rambau, Korn Klaus, Muller Andreas, Dismas Matovelo, Mtebe Majigo, Christa Kasang, Stephen E Mshana
BACKGROUND: High risk (HR) human papilloma Virus (HPV) genotypes have been associated with cervical cancer. In Tanzania there is a limited data on the epidemiology of HPV and genotypes distribution among HIV infected women. Here we document varieties of HPV genotypes associated with cervical squamous intraepithelial lesions (SIL) among HIV- infected women at Bugando Medical Centre, Mwanza-Tanzania. METHODS: A cross sectional hospital based study involving HIV infected women was conducted between August and October, 2014...
2016: Infectious Agents and Cancer
Claudia D Andl, Grégoire F Le Bras, Holli Loomans, Annette S Kim, Linli Zhou, Yuhang Zhang, Thomas Andl
A dogma in squamous epithelial biology is that proliferation occurs in the basal cell layer. Notable exceptions are squamous epithelia of the human oral cavity, esophagus, ectocervix, and vagina. In these human epithelia, proliferation is rare in the basal cell layer, and the vast majority of cells positive for Ki67 and other proliferation markers are found in para- and suprabasal cell layers. This unique human feature of a generally quiescent basal cell layer overlaid by highly proliferative cells offers the rare opportunity to study the molecular features of undifferentiated, quiescent, putative stem cells in their natural context...
November 2016: Histochemistry and Cell Biology
Zheng Shen, Marta Rodriguez-Garcia, Mickey V Patel, Fiona D Barr, Charles R Wira
PROBLEM: The programmed death 1 (PD-1)/PD-L1 pathway regulates peripheral tolerance, immune responses, and is up-regulated in chronic viral infections, including HIV infection. However, expression of PD-1/PD-L1 on immune cells from the human female reproductive tract (FRT) and possible regulation by menopause and sex hormones are poorly understood. METHOD OF STUDY: PD-1/PD-L1 expression was analyzed on CD4(+) and CD8(+) T cells, CD163(+) macrophages, and CD11c(+) dendritic cells (DC) from endometrium (EM), endocervix (CX) and ectocervix (ECX)...
August 2016: American Journal of Reproductive Immunology: AJRI
Geneva A DeGregorio, Leslie S Bradford, Simon Manga, Pius M Tih, Richard Wamai, Rebecca Ogembo, Zacharie Sando, Yuxin Liu, Constance Schwaiger, Sowmya R Rao, Karen Kalmakis, Lisa Kennedy Sheldon, Kathleen Nulah, Edith Welty, Thomas Welty, Javier Gordon Ogembo
BACKGROUND: In 2007, the Cameroon Baptist Convention Health Services (CBCHS) implemented a screen-and-treat cervical cancer prevention program using visual inspection with acetic acid enhanced by digital cervicography (VIA-DC). METHODS: We retrospectively analyzed 46,048 medical records of women who received care through the CBCHS Women's Health Program from 2007 through 2014 to determine the prevalence and predictors of positive VIA-DC, rates of same day treatment, and cohort prevalence of invasive cervical cancer (ICC)...
2016: PloS One
Ming Zeng, Anthony J Smith, Liang Shang, Stephen W Wietgrefe, James E Voss, John V Carlis, Qingsheng Li, Michael Piatak, Jeffrey D Lifson, R Paul Johnson, Ashley T Haase
Live attenuated vaccines such as SIV with a deleted nef gene have provided the most robust protection against subsequent vaginal challenge with wild-type (WT) SIV in the SIV-rhesus macaque model of HIV-1 transmission to women. Hence, identifying correlates of this protection could enable design of an effective HIV-1 vaccine. One such prechallenge correlate of protection from vaginal challenge has recently been identified as a system with three components: 1) IgG Abs reacting with the viral envelope glycoprotein trimeric gp41; 2) produced by plasma cells in the submucosa and ectopic tertiary lymphoid follicles in the ectocervix and vagina; and 3) concentrated on the path of virus entry by the neonatal FcR in the overlying epithelium...
March 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Xueya Qian, Yanmin Jiang, Lei Liu, Shao-Qing Shi, Robert E Garfield, Huishu Liu
OBJECTIVE: The objective of this study is to estimate changes in the surface area of the ectocervix (CA) in women during pregnancy and compare this to postpartum and non-pregnant states. METHODS: CA was evaluated in 210 normal nulliparous women divided into groups from early to late gestation, 40 postpartum women, and 25 non-pregnant women. CA in cm(2) was estimated from analysis of images taken with an endoscope of the cervical face and an mm scale. An mm scale was also used to determine fornix length and fornix area computed...
November 2016: Journal of Maternal-fetal & Neonatal Medicine
Andrea Ries Thurman, Neelima Chandra, Nazita Yousefieh, Irina Zalenskaya, Thomas Kimble, Susana Asin, Christiane Rollenhagen, Sharon M Anderson, Betsy Herold, Pedro M M Mesquita, Nicola Richardson-Harman, Tina Cunningham, Jill L Schwartz, Gustavo F Doncel
The purpose of this study was to evaluate differences in vaginal immune cell populations, vaginal tissue gene expression, antimicrobial activity of the cervicovaginal (CV) lavage (CVL), vaginal flora, and p24 antigen production from CV tissues after ex vivo human immunodeficiency virus (HIV) infection between follicular (FOL) and luteal (LUT) phases of the menstrual cycle. CV tissue biopsies, CV secretions, and blood samples were obtained as part of two longitudinal clinical trials of healthy women (CONRAD D11-119 and A12-124 studies)...
June 2016: AIDS Research and Human Retroviruses
Marla J Keller, Pedro M Mesquita, Mark A Marzinke, Ryan Teller, Lilia Espinoza, Jessica M Atrio, Yungtai Lo, Bruce Frank, Sujatha Srinivasan, David N Fredricks, Lorna Rabe, Peter L Anderson, Craig W Hendrix, Patrick F Kiser, Betsy C Herold
BACKGROUND: Tenofovir disoproxil fumarate (TDF), a prodrug of tenofovir (TFV), may be ideal for topical HIV preexposure prophylaxis because it has higher tissue and cell permeability than TFV; is not adversely impacted by seminal proteins; and its active metabolite, TFV-diphosphate (TFV-DP), has a long intracellular half-life. We engineered a TDF eluting polyurethane reservoir intravaginal ring (IVR) to provide near constant mucosal antiretroviral concentrations. METHODS: A first-in-human randomized placebo-controlled trial was conducted to assess the safety and pharmacokinetics of the TDF IVR in healthy, sexually abstinent women (15 TDF and 15 placebo)...
March 13, 2016: AIDS
Alexia Toller, Ana Carolina Scopin, Vanessa Apfel, Karla Calaça Kabbach Prigenzi, Fernanda Kesselring Tso, Gustavo Rubino de Azevedo Focchi, Neila Speck, Julisa Ribalta
Schistosoma hematobium infection is an endemic parasitic disease in Africa, which is frequently associated with urinary schistosomiasis. The parasite infection causes epithelial changes and disruption, facilitating the infection by the human papilloma virus and human immunodeficiency virus (HIV). The authors report the case of a 44-year-old African HIV-positive woman who presented an abnormal routine Pap smear. Colposcopy examination revealed dense acetowhite micropapillary epithelium covering the ectocervix, iodine-negative, an erosion area in endocervical canal, and atypical vessels...
April 2015: Autopsy & case reports
Mariia Patyka, Daniel Malamud, Drew Weissman, William R Abrams, Zoya Kurago
Studies have shown that the transmission of HIV is most likely to occur via rectal or vaginal routes, and rarely through oral exposure. However, the mechanisms of virus entry at mucosal surfaces remain incompletely understood. Prophylactic strategies against HIV infection may be attainable once gaps in current knowledge are filled. To address these gaps, we evaluated essentially normal epithelial surfaces and mapped the periluminal distribution of CD4+ HIV target cells, including T cells and antigen-presenting cells, and an HIV-binding molecule gp340 that can be expressed by epithelial cells in secreted and cell-associated forms...
2015: PloS One
Karolin Hijazi, Anna M Cuppone, Kieron Smith, Maria A Stincarelli, Julia Ekeruche-Makinde, Giulia De Falco, Georgina L Hold, Robin Shattock, Charles G Kelly, Gianni Pozzi, Francesco Iannelli
Anti-retroviral (ARV) -based microbicides are one of the strategies pursued to prevent HIV-1 transmission. Delivery of ARV drugs to subepithelial CD4+ T cells at concentrations for protection is likely determined by drug transporters expressed in the cervicovaginal epithelium. To define the role of drug transporters in mucosal disposition of topically applied ARV-based microbicides, these must be tested in epithelial cell line-based biopharmaceutical assays factoring the effect of relevant drug transporters...
2015: PloS One
Edward J Fuchs, Jill L Schwartz, David R Friend, Jenell S Coleman, Craig W Hendrix
Vaginal microbicide gels containing tenofovir have proven effective in HIV prevention, offering the advantage of reduced systemic toxicity. We studied the vaginal distribution and effect on mucosal permeability of a gel vehicle. Six premenopausal women were enrolled. In Phase 1, a spreading gel containing (99m)technetium-DTPA ((99m)Tc) radiolabel and gadolinium contrast for magnetic resonance imaging (MRI) was dosed intravaginally. MRI was obtained at 0.5, 4, and 24 h, and single photon emission computed tomography with conventional computed tomography (SPECT/CT) at 1...
November 2015: AIDS Research and Human Retroviruses
Wendy V Norman, Danielle Stothart
BACKGROUND: Intrauterine devices are increasingly the preferred method of contraception chosen by Canadian women. IUD strings are commonly not visible at follow-up, but rarely are visible yet not located within the endocervical canal. We report a case of IUD strings perforating the ectocervix. CASE: An asymptomatic, 26-year-old woman presented for removal of her levonorgestrel-releasing intrauterine system, over a year following insertion of the device. Upon examination the IUD strings were found to be emerging from within the cervical tissue, 10 mm above the external os...
April 2015: Journal of Obstetrics and Gynaecology Canada: JOGC, Journal D'obstétrique et Gynécologie du Canada: JOGC
Sybil G Dessie, Michele Park, Peter L Rosenblatt
INTRODUCTION AND HYPOTHESIS: The objective is to describe our surgical approach for management of uterine prolapse using 5-mm skin incisions and transcervical morcellation. METHODS: This video presents a novel approach for laparoscopic supracervical hysterectomy, bilateral salpingectomy, and sacrocervicopexy using only 5-mm skin incisions and transcervical morcellation. The procedure begins with a laparoscopic supracervical hysterectomy with bilateral salpingectomy...
January 2016: International Urogynecology Journal
Silvia Franceschi
HPV vaccination has the potential to prevent the vast majority of cervical cancer cases but cervical cancer screening remains the only prevention strategy in adult unvaccinated women. The range of primary screening tests has expanded to include, in addition to cytology, visual inspection with acetic acid (VIA) and HPV-testing. HPV-testing has the best sensitivity and negative predictive value, and a low-cost HPV test may make large-scale high-quality cervical cancer screening possible in low- and medium-income countries (LMICs)...
2015: Ecancermedicalscience
George I Gorodeski
Purinergic effects in vivo are local, specific, transient, and affect target cells in a paracrine or autocrine manner. Purinergic signalling is involved in the regulation of numerous functions in the male and female reproductive tract organs. Analysis of functional expression of purinoceptors suggests that P2Y2 receptors are involved in the regulation of luminal fluid secretion in vivo; P2X1 and P2X2 in the regulation of smooth muscle cell contraction of blood vessels and tubular organs; P2X2 in the regulation of sperm cell maturation; P2X3 in activation of sensory nerve fibers involved in reflex activities and pain; P2X4 in the regulation of tight junctional resistance and epithelial transport in female reproductive tract epithelia, and in the regulation of luminal acidification in the epididymis, vas deferens and probably the vagina and ectocervix; P2Y1 and P2Y2 in the regulation of cell proliferation; P2X5 and P2X7A in the regulation of epithelial cell terminal differentiation and apoptosis; and A1 receptors in the regulation of sperm cell capacitation...
September 2015: Autonomic Neuroscience: Basic & Clinical
D G Ferris, D M Harper, B Callahan, T Robinson, M S Litaker, M Messing, L Mensah
OBJECTIVES: Our goal was to determine the effectiveness of topical 20% benzocaine gel in providing anesthesia prior to cervical biopsy and endocervical curettage (ECC) and to identify specific patient characteristics that would predict which patients would be more likely to benefit from the application of benzocaine gel before cervical procedures. MATERIALS AND METHODS: Women requiring cervical biopsy and ECC completed a questionnaire that obtained demographical and pertinent gynecological information, perceived pain thresholds, and anxiety levels prior to the cervical biopsy procedures...
October 1997: Journal of Lower Genital Tract Disease
S P Sarma, L V Enrique Lofton
OBJECTIVE: The purpose of this article is to present a case of pelvic inflammatory disease (PID) after cryotherapy and to discuss the need for routine testing of gonococcal and chlamydial infections at the time of cryotherapy and prophylactic antibiotics. METHODS AND MATERIALS: A 21-year-old nulliparous woman was treated with cryotherapy for low-grade squamous intraepithelial lesion. RESULT: Two days after the procedure, she developed PID...
October 1998: Journal of Lower Genital Tract Disease
Maurish Bukhari, Han Deng, Noelle Jones, Zachary Towne, Craig D Woodworth, Damien S K Samways
Extracellular ATP is known to permeabilize certain cell types to polyatomic cations like YO-PRO1. Here, we report that extracellularly applied ATP stimulated rapid uptake and accumulation of an otherwise weakly membrane permeable fluorescent DNA-binding cytotoxin, Hoechst 33258, into cervical cancer cells. While ATP stimulated Hoechst 33258 uptake in 20-70% of cells from seven cervical cancer cell lines, it stimulated uptake in less than 8% of cervical epithelial cells obtained from the normal transformation zone and ectocervix tissue of 11 patients...
June 4, 2015: FEBS Letters
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