Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0851184 (thinning)
 11,252 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A clinician's view of the menopause describes the condition and its treatment in some patients. The symptoms of the menopause include hot flushes, dryness of the vagina, osteoporosis, and a thinning of the epidermis. There are many nonspecific symptoms frequently blamed on the menopause but are unrelated to hormonal imbalance. However, estrogen therapy can create a general feeling of well-being which can relieve other discomforts. Many women dread the end to their menstrual function. Some do find that they are released from the worry over pregnancy and can be more relaxed. Menopause usually occurs over an extended period of time. The last menstruation after an interval of 12 months is considered to be the menopause. The general practitioner should be availabel to discuss menopause although menopausal clinics are being established as well. Hormone therapy can help the woman with extreme symptoms.
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PMID:A clinician's view. 95 91

Several small studies conducted by the Centers for Disease Control and Prevention (CDC) have shown that although progesterone appears to increase the likelihood of simian immunodeficiency virus (SIV) transmission in exposed monkeys, women using hormone contraceptives do not appear to have the same increased risk for HIV. The results, published in the May issue of Science, show little, if any, increase in the rate of HIV infection in women on Depo-Provera, an injectable contraception containing progestin, compared to those who were not taking it. Another study, conducted in Thailand, found similar results. However, this contrasts sharply with the results of a monkey study that found that rhesus monkeys given progesterone experienced significant thinning of the vaginal wall. Researchers are examining the effects of progesterone on the lining of the vagina. Researchers are finding some thinning, but not to a significant degree. The CDC continues to stress that only abstinence or the use of latex condoms can prevent the spread of AIDS.
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PMID:Progesterone-HIV link questioned by new studies. 1136 49

Aging and menopause related decline in circulating levels of estrogen has been shown to adversely affect female sexual arousal function. Our aim was to study the effects of circulating levels of estrogen on the hemodynamic mechanism of vaginal and clitoral engorgement and on the structure of the vaginal and clitoral cavernosal tissue in the rabbit. New Zealand White female rabbits (3.5-4 kg) were randomly divided into three groups with five rabbits in each group: control; bilateral oophorectomy; bilateral oophorectomy undergoing subcutaneous injection of estrogen (40 microg/kg/day). After 6 weeks, the serum levels of 17 beta-estradiol were measured and systemic blood pressure was monitored. Vaginal and clitoral cavernosal blood flows were measured with laser Doppler flowmeter before and after pelvic nerve stimulation. Cross sections of the clitoris and vagina were processed for histologic examination and histomorphometric image analysis. Serum level of 17 beta-estradiol (pg/ml; mean+/-s.d.) revealed a significant decrease in the oophorectomy group (25.4+/-5.1) compared with the control (38.5+/-7.6) and estrogen replacement (115.9+/-57.3) groups (P<0.05). Nerve stimulation-induced peak vaginal and clitoral intracavernosal blood flows in the oophorectomy group (28.9+/-16.3 and 6.1+/-1.4, respectively) were significantly less than those recorded in the control (48.9+/-6.5 and 11.0+/-2.4, respectively) or estrogen replacement (48.7+/-12.2 and 10.1+/-2.8, respectively) group (P<0.05). In histology, marked thinning of the vaginal epithelial layers, decreased vaginal submucosal microvasculature, and diffuse clitoral cavernosal fibrosis were evident in the oophorectomy group but not in the estrogen supplement and control groups. In histomorphometry, the percentage of clitoral cavernosal smooth muscle in the oophorectomy group (49.6+/-6.2) was significantly decreased compared with the control (56.8+/-2.6) and estrogen replacement (58+/-3.0) groups (P<0.05). Our studies show that decline in circulating levels of estrogen impairs the hemodynamic mechanism of vaginal and clitoral engorgement and leads to histopathologic changes in the vagina and clitoral cavernosal tissue. These observations suggest that decreased circulating levels of estrogen, a physiologic change in the menopausal state, may play a role in the development of female sexual arousal dysfunction.
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PMID:Decreased circulating levels of estrogen alter vaginal and clitoral blood flow and structure in the rabbit. 1142 51

ELASTOHYDRODYNAMIC LUBRICATION OVER SOFT SUBSTRATES IS OF IMPORTANCE IN A NUMBER OF BIOMEDICAL PROBLEMS: From lubrication of the eye surface by the tear film, to lubrication of joints by synovial fluid, to lubrication between the pleural surfaces that protect the lungs and other organs. Such flows are also important for the drug delivery functions of vehicles for anti-HIV topical microbicides. These are intended to inhibit transmission into vulnerable mucosa, e.g., in the vagina. First generation prototype microbicides have gel vehicles, which spread after insertion and coat luminal surfaces. Effectiveness derives from potency of the active ingredients and completeness and durability of coating. Delivery vehicle rheology, luminal biomechanical properties, and the force due to gravity influence the coating mechanics. We develop a framework for understanding the relative importance of boundary squeezing and body forces on the extent and speed of the coating that results. A single dimensionless number, independent of viscosity, characterizes the relative influences of squeezing and gravitational acceleration on the shape of spreading in the Newtonian case. A second scale, involving viscosity, determines the spreading rate. In the case of a shear-thinning fluid, the Carreau number also plays a role. Numerical solutions were developed for a range of the dimensionless parameter and compared well with asymptotic theory in the limited case where such results can be obtained. Results were interpreted with respect to trade-offs between wall elasticity, longitudinal forces, bolus viscosity, and bolus volume. These provide initial insights of practical value for formulators of gel delivery vehicles for anti-HIV microbicidal formulations.
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PMID:A model of transluminal flow of an anti-HIV microbicide vehicle: Combined elastic squeezing and gravitational sliding. 1954 22

Methotrexate (MTX) an antifolate drug and leucovorin its antidote, are used in the treatment of both neoplastic and non-neoplastic diseases in young women. We hypothesize that MTX treatment might comprise a deleterious effect on fast proliferating reproductive cells, an unavoidable and unwanted side effect. MTX given dose dependently to rats for 20 days prevented vaginal cyclicity and caused a reduction in serum progesterone and estradiol. External morphology of reproductive tract displayed thinning of organs and reduction in their weights. To reveal mechanism of MTX action, we examined the histology of ovary, oviduct, uterus, cervix and vagina. Results suggested that in a dose-dependent fashion MTX restrained preantral and antral follicular growth in ovary. Epithelium and stroma of oviduct, uterus, cervix and vagina were disrupted and lost their normal structures. Such alterations in ovarian function raised serum follicle stimulating hormone, luteinizing hormonal profiles. Expression of steroidogenic acute regulatory protein and P450 cholesterol side chain cleavage gene, which are both essential for steroidogenesis, markedly decreased in ovary upon MTX treatment. Total RNA, DNA and protein concentrations, glucose 6 phosphate dehydrogenase, lactate dehydrogenase and alkaline phosphatase enzyme activities in ovary were distinctly altered. Leucovorin supplementation and withdrawal of the treatment, improved MTX caused effects partially. These results for the first time indicate that the malfunction of female reproductive organs by MTX treatment in young women is not only correlated to the disrupted circulating levels of hormones and histoarchitecture of tissues but also discrepancies in steroidogenic genes and hormone regulated enzyme activities in ovary.
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PMID:Effect of methotrexate and leucovorin on female reproductive tract of albino rats. 2121 37

A recent study in South Africa has confirmed, for the first time, that a vaginal gel formulation of the antiretroviral drug Tenofovir, when topically applied, significantly inhibits sexual HIV transmission to women [Karim et al., Science 329, 1168 (2010)]. However, the gel for this drug and anti-HIV microbicide gels in general have not been designed using an understanding of how gel spreading and retention in the vagina govern successful drug delivery. Elastohydrodynamic lubrication theory can be applied to model spreading of microbicide gels [Szeri et al., Phys. Fluids 20, 083101 (2008)]. This should incorporate the full rheological behavior of a gel, including how rheological properties change due to contact with, and dilution by, ambient vaginal fluids. Here, we extend our initial analysis, incorporating the effects of gel dilution due to contact with vaginal fluid produced at the gel-tissue interface. Our original model is supplemented with a convective-diffusive transport equation to characterize water transport into the gel and, thus, local gel dilution. The problem is solved using a multi-step scheme in a moving domain. The association between local dilution of gel and rheological properties is obtained experimentally, delineating the way constitutive parameters of a shear-thinning gel are modified by dilution. Results show that dilution accelerates the coating flow by creating a slippery region near the vaginal wall akin to a dilution boundary layer, especially if the boundary flux exceeds a certain value. On the other hand, if the diffusion coefficient of boundary fluid is increased, the slippery region diminishes in extent and the overall rate of gel spreading decreases.
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PMID:The effects of inhomogeneous boundary dilution on the coating flow of an anti-HIV microbicide vehicle. 2199 95

Drug delivery of topical microbicidal molecules against HIV offers promise as a modality to prevent sexual transmission of the virus. Success of any microbicide product depends, in an interactive way, upon its drug (the microbicide active pharmaceutical ingredient, API) and its delivery system (e.g. a gel, film or intravaginal ring). There is a widespread agreement that more effective drug delivery vehicles, as well as better APIs, must be developed to improve the efficacy of microbicide products. Non-Newtonian gels are primary microbicide vehicles, but those to date have been created with limited understanding of how their properties govern their spreading and retention in the vagina, which, in turn, govern successful drug delivery. Here, we apply fundamental fluid mechanical and physicochemical transport theory to help better understand how successful microbicide API delivery depends upon properties of a gel and the vaginal environment. We address several critical components of this complex process, including: elastohydrodynamic flow of the bolus of a non-Newtonian fluid; and mass transfer due to inhomogeneous dilution of the gel by vaginal fluid contacting it along a moving boundary (the locally deforming vaginal epithelial surface). Local dilution of gel alters local rheological properties. We evaluated this experimentally, delin-eating the way that constitutive parameters of a shear-thinning gel are modified by dilution. We supplement the Reynolds lubrication equation with a mass conservation equation to model diluting fluid movement across the moving vaginal epithelial surface and into the gel bolus. This is a physicochemically complex phenomenon that is not well understood. We implement a boundary flux model based upon the elevated hydrodynamic pressures in the cells. Results show that this model produces fluxes that lie within the range of mean values that have been reported. Further experimental characterization of the vaginal wall is required for a more precise set of parameters and a more sophisticated theoretical treatment of epithelium.
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PMID:Transient spreading and swelling behavior of a gel deploying an anti-HIV topical microbicide. 2342 96

Pelvic organ prolapse (POP) is the most common gynaecological disorder requiring surgical treatment in postmenopausal women. Surgical treatment of POP might include anterior or posterior vaginal repair, vaginal hysterectomy, vault fixation procedures like sacrocolpopexy and sacrospinous fixation. Complications of POP surgery include excessive bleeding, visceral injuries, postoperative wound infection, urinary tract infection (UTI), sexual dysfunction secondary to vaginal scarring and recurrence. Postmenopausal vaginal atrophy may increase the risk of visceral injuries due to thinning of vaginal wall and also increases the risk of surgical site wound infections due to alteration of vaginal flora and urinary tract infections (UTI). Use of vaginal low dose oestrogens to treat atrophy of the vagina may improve the subjective cure rates and minimise surgical site wound infections by altering the vaginal flora to premenopausal levels. To date there has not been any data on the outcomes of POP surgery when low dose vaginal oestrogens are used perioperatively. Hence we want to study the effectiveness of vaginal low dose oestrogen on the outcome of POP surgery in postmenopausal women.
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PMID:Role of perioperative low dose vaginal oestrogens in improving the outcomes of pelvic organ prolapse surgery. 2409 82

Postmenopausal atrophic vagina (PAV) is the thinning of the walls of the vagina and decreased lugae of the vagina. PAV is caused by decreased estrogen levels in postmenopausal women. However, the harmful effects of hormone replacement therapy (HRT) have resulted in considerable caution in its use. Various estrogen agonist treatment options are available. Vitamin D is influences the regulation of differentiation and proliferation of various cells, especially tissues lining stratified squamous epithelium, such as the vaginal epithelium. In this study, we hypothesized that vitamin D could provide an alternative and a safe treatment option for PAV by promoting the proliferation and differentiation of the vaginal epithelium. Thirty six patients were enrolled in this case-control study. Vitamin D associated proteins in a vitamin D and sex hormone treated vaginal epithelial cell line as well as normal and PAV tissues were measured. To confirm of cell-to-cell junction protein expression, cell line and tissue studies included RT-PCR, immunohistochemistry staining, and immunoblot analyses. The expression of cell-to-cell junction proteins was higher in women with symptoms of atrophic vagina tissue compared to women without the symptoms. Vitamin D stimulated the proliferation of the vaginal epithelium by activating p-RhoA and Erzin through the vitamin D receptor (VDR). The results suggest that vitamin D positively regulates cell-to-cell junction by increasing the VDR/p-RhoA/p-Ezrin pathway. This is the first study to verify the relationship of the expression of RhoA and Ezrin proteins in vaginal tissue of PAV.
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PMID:Vitamin D Proliferates Vaginal Epithelium through RhoA Expression in Postmenopausal Atrophic Vagina tissue. 2884 71

This open, prospective, multicenter, observational study was performed to investigate the efficacy and safety of a non-hormonal cream in women undergoing breast cancer treatment and experiencing vulvovaginal dryness symptoms. Overall, 128 patients from 22 study centers participated. The cream was applied to the vagina and vulva for 28 days. For the efficacy analysis, changes in subjective symptoms (feeling of dryness, itching, burning, pain independent of sexual intercourse, dyspareunia, urinary incontinence) were evaluated. Additionally, the following objective diagnostic findings were assessed by a physician: thinning of vaginal epithelium, redness, petechiae, and discharge. Safety and tolerability were assessed by evaluating type and frequency of adverse events, including adverse medical device-related effects. The frequency and intensity of all subjective symptoms significantly improved from baseline at 28 days (p<0.0001). Additionally, 21.4% of patients were completely free of symptoms (p<0.0001) and urinary incontinence was improved or eliminated in 30.8% of women. The overall sum score for all four objective findings was significantly improved from baseline at 28 days (p<0.0001). The frequency of petechial bleedings was significantly reduced (p<0.0001). Further, significant decreases in the severity of vaginal epithelium thinning, redness and petechiae were observed (p<0.0001). More than 88% of patients and investigators assessed the efficacy and tolerability as being good or very good. No serious adverse events were documented. This study demonstrates that the investigated cream is an effective and safe non-hormonal, topical option in the treatment of vulvovaginal dryness symptoms in patients undergoing breast cancer treatment for. However, the study duration and follow-up time of 4 weeks as well as the non-randomized trial design are limitations of the study.
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PMID:Topical treatment of vaginal dryness with a non-hormonal cream in women undergoing breast cancer treatment - An open prospective multicenter study. 3067 65


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