A Multiwell Microfluidic Device for Analyzing and Screening Nonhormonal Contraceptive Agents.

Birth control and family planning play pivotal roles in the economic growth and reduction of maternal, infant, and child mortality. Current contraceptives, such as hormonal agents and intrauterine devices, target only a small subset of reproductive processes and can have serious side effects on the health of women. To develop novel contraceptive agents, a scalable microfluidic device is established for analyzing and screening the effects of potential contraceptive agents on the maturation of the cumulus-oocyte complex. The microfluidic device performs on-chip incubation for studying oocyte maturation and cumulus expansion and isolates the microwells by oil-water interfaces to avoid crosstalk between the wells. A filter membrane is incorporated in the device to simplify incubation, medium exchange, washing, and fluorescence staining of oocytes. Cumulus expansion can be monitored directly in the device and oocyte maturation can be examined after enzymatic removal of cumulus cells and on-chip fluorescence staining. The performance of the device is evaluated by studying the influence of three drugs known to block oocyte maturation and/or cumulus expansion.

Electrospun Transdermal Patch for Contraceptive Hormone Delivery.

BACKGROUND: A transdermal patch for delivery of Levonorgestrel (LNG) can be used for long-acting contraception. OBJECTIVE: In this study, we designed and characterized a patch made of nonwoven electrospun microfibers comprised of Polycaprolactone (PCL) encapsulating LNG for slow release in a mineral oil matrix. METHODS AND RESULTS: Scanning electron microscopy showed uniform, randomly oriented PCL fibers with large interconnected voids filled with mineral oil. Thermogravimetric analysis indicated that LNG loaded into PCL fibers had thermal stability up to ~200°C. Differential Scanning Calorimetry suggested that LNG was dispersed in the electrospun fibers without interaction between the LNG and PCL, and without formation of drug crystals. Fourier Transform Infrared spectroscopy and X-ray diffraction results further supported the conclusion that there was no chemical drug-polymer interaction in LNGloaded fibers. Effective in vitro flux (i) from patches into mineral oil was 1.9 µgcm-2h-1, (ii) from mineral oil across porcine skin was 4.6 µgcm-2h-1 and (iii) from patches across porcine skin was 1.7 µgcm- 2h-1, indicating that transdermal delivery rate was controlled by a combination of the patch and the skin. CONCLUSION: The LNG-loaded patches demonstrated steady delivery of LNG across skin for up to 5 days in vitro. With additional development, LNG-loaded electrospun PCL patches could be used for long-acting contraception.

The association between estradiol levels, hormonal contraceptive use, and responsiveness to one-session-treatment for spider phobia in women.

Preclinical studies have demonstrated that conditioned fear extinction is impaired in females with low endogenous levels of the sex hormone estradiol, due to menstrual fluctuations or hormonal contraceptive use. As fear extinction is a laboratory model of exposure therapy for anxiety and trauma disorders, here we assessed the hypothesis that treatment outcomes may be diminished when exposure therapy occurs during periods of low estradiol. 90 women with spider phobia (60 cycling and 30 using hormonal contraceptives) underwent a one-session exposure treatment for spider phobia, following which, serum estradiol levels were assessed. A median split in estradiol level was used to divide cycling participants into two groups; lower and higher estradiol. Behavioral avoidance and self-reported fear of spiders were measured pre-treatment, post-treatment, and at a 12 week follow-up assessment. Women using hormonal contraceptives exhibited a significantly slower rate of improvement across treatment, greater behavioral avoidance at post-treatment and follow-up, and fewer self-initiated post-treatment exposure tasks, relative to both groups of cycling women, who did not differ. No group differences in self-reported fear were evident. Correlational analyses revealed that across the whole sample, lower estradiol levels were associated with slower rates of improvement across treatment, and greater self-reported fear and behavioral avoidance at post-treatment, but not follow-up. These results provide the first evidence of an association between endogenous estradiol, hormonal contraceptive use, and exposure therapy outcomes in spider phobic women. Hormonal profile may partly account for variability in responsiveness to psychological treatments for anxiety and trauma disorders in women.

Determination of 20, 25-diazacholesterol in avian matrices by high performance liquid chromatography/tandem mass spectrometry.

Wildlife contraceptives are an emerging tool for minimizing human-wildlife conflicts. One promising avian contraceptive compound, 20,25-diazacholesterol (DAC), reduces fertility by inhibiting cholesterol synthesis. A reliable analytical method for DAC was required in support of its registration for use as a reproductive control agent in pest bird species. A liquid chromatographic method employing tandem mass spectrometry (LC-MS/MS) was developed for the analysis of tissue extracts following solid phase extraction clean-up. Tissues analyzed were whole body samples from crows, monk parakeets, and quails and liver samples from crows and quails. Excellent sensitivity and selectivity was afforded by tandem mass spectrometry. The method accuracy of DAC from various tissue samples fortified at parts-per-million (ppm) and parts-per-billion (ppb) concentrations was high (>90%) with excellent precision (<10% relative standard deviation). Lower limits of detection were excellent in all tissues types, ranging from 1 to 11ppb in whole body matrices and 9.9-34ppb in liver matrices.

Quantification of collagen fibers in canine uteri treated with medroxyprogesterone acetate

Collagen plays essential roles in remodeling uterine tissue during decidualization, implantation, pregnancy and involution. To understand whether the progestational agent medroxyprogesterone acetate (MPA) can modify the organization and deposit of collagen in the uteri of normal bitches (Canis Tlupus familiaris), we assessed uterine tissues by histochemistry. Uteri were grouped as: nulliparous (n=11), multiparous (n=11) and treated with MPA (n=11; nulliparous with two treatments; 5mg/kg; i.m.). The amount, location and birefringence of interstitial collagen types I and III in the fold and base of the endometrial stroma and the myometrial muscular layers were studied on sections stained with Picrosirius Red by polarized light microscopy and evaluated by ANOVA. No differences were observed in the endometrium. In the myometrium, differences were observed in collagen type I between MPA-treated and nulliparous uteri vs. multiparous (p<0.05), and differences in collagen type III between nulliparous and multiparous uteri vs. MPA-treated (p=0.0001). In conclusion, two doses of MPA had no significant effect on the investigated collagens in the extracellular matrix.(AU)

Métodos anticonceptivos: entonces y ahora / Contraceptive methods: then and now

Comparar los métodos anticonceptivos utilizados en la década de 1990 con los utilizados en la década de 2000. Unidad de Ginecología Reproducción y Salud Integral, Valencia, Edo. Carabobo. La muestra la integraron 1 000 pacientes, 500 en 1997-1998 (grupo A) y 500 en 2007-2008 (grupo B). Revisamos las historias médicas de las pacientes que practicaban anticoncepción. Predominaron los anticonceptivos orales en ambos grupos con 29,6 por ciento (grupo A) y 31,4 por ciento (grupo B). Los de mayor uso fueron levonorgestrel+etinilestradiol (25,9 por ciento) y drospirenona+etinilestradiol (24,7 por ciento) respectivamente. En el grupo A los anticonceptivos inyectables fueron mayormente acetato de medroxiprogesterona (66,7 por ciento), y en el grupo B sólo noretindrona+valerianato de estradiol (100 por ciento). El uso de implantes no superó el 1 por ciento en ambos grupos. En el grupo B 8,4 por ciento usaban métodos naturales en contraposición a 23,4 por ciento utilizados en el A. El grupo A usó preservativos en 17,8 por ciento comparado con el grupo B 24,4 por ciento. La esterilización en la cesárea es el método irreversible más frecuente (grupo A 56,9 por ciento y grupo B 67,5 por ciento). No hubo esterilización por laparoscopia en el grupo A, pero sí en el grupo B (10,3 por ciento). En solo una década, se aprecian diferencias significativas en los métodos anticonceptivos que utilizan nuestras mujeres. Los métodos anticonceptivos más utilizados siguen siendo los de administración oral aunque su composición y dosis han sufrido variaciones. El empleo de preservativos ha aumentado. El uso de los métodos naturales ha disminuido. Aparecieron nuevos métodos como los de emergencia, parches y anillos vaginales. La laparoscopia se ha popularizado como método de esterilización

To compare contraceptive methods utilized during 1990 decade with those utilized during decade 2000. Unidad de Ginecologia Reproduccion y Salud Integral, Valencia, Edo. Carabobo. One thousand Unidad de Ginecología Reproducción y Salud Integral patients charts were reviewed, 500 belonged to decade of 1990 (group A) and 500 to decade of 2000 (group B). All patients were utilizing some contraceptive method. Oral contraceptives predominated in both groups (29.6 percent in group A and 31.4 percent in group B). The most utilized contraceptives were levonorgestrel+ethynilestradiol (25.9 percent) and drospirenone+ethynilestradiol (24.7 percent) respectively. In group A injectable contraceptive mainly utilized were medroxyprogesterone acetate (66.7 percent) and only norethindrone+estradiol valerianate (100 percent) in group B. Use of implants didn’t surpass 1 percent in both groups. Group A utilized natural methods in 23.4 percent contrarily to group B that only utilized them in 8.4 percent. Condoms were utilized in 17.8 percent in group A compared with 24.4 percent in group B. Surgical sterilization during cesarean section continues to be the most frequent irreversible method (56 percent in group A and 67.5 percent in group B). There were no laparoscopic sterilizations in group A in opposition to group B in which there were 10.3 percent. In only one decade significative differences in contraceptive methods utilized in our women are observed. The most frequent contraceptive utilized continues to be the oral contraceptives even if its composition and dose have suffered variations. Use of condoms has increased, use of natural methods has decreased, new methods have appeared like emergency contraceptives, patches and vaginal rings. Laparoscopic sterilization has become a popular method of sterilization

Environmental exposure assessment of ethinyl estradiol (EE) from a combined hormonal vaginal contraceptive ring after disposal; leaching from landfills.

In this study an environmental exposure assessment and experiments were carried out to identify the leaching potential of ethinyl estradiol (EE) present in a vaginal contraceptive (NuvaRing) when disposed of in landfills. Landfill material and a sandy soil were used to investigate the mobility of EE. Log K(oc) values determined in the range of 3 to 4 indicate that EE does not have a high mobility in landfills and soils. Column experiments were used to estimate that it takes approximately 40 years before EE leaches from a column of 1 m of landfill material or sandy soil. This column experiment, which was performed with an EE concentration based on worst-case assumptions, demonstrates that the emission of EE from landfills is negligible. Sandy soils below landfills also act as a strong sorbent of EE, thereby further reducing the potential for groundwater contamination.

Determination of DiazaCon in quail feed and quail serum by ion pair reversed-phase chromatography.

Liquid chromatographic (LC) methods were developed for quantitating the potential avian contraceptive DiazaCon in quail feed and serum. DiazaCon was extracted from ground quail feed with basic n-butyl chloride. The n-butyl chloride extract was evaporated to dryness. The DiazaCon residues were dissolved in an aqueous methanolic ion pairing solution and quantitated by LC at 206 nm. Avian sera was combined with an equal volume of a pH 4 aqueous solution of ion pairing reagent and filtered to remove interfering proteins. DiazaCon was quantitated by LC. Mean recoveries for 500 and 2000 ppm fortified feed were 89.1 and 91.0%, respectively. The mean recovery for sera fortified at 5 levels ranging from 35 to 2000 ppm was 84.9%. Method limits of detection were approximately 14 and 13 ppm for feed and sera, respectively.

Métodos Anticonceptivos / Anticonceptive methods

Los métodos anticonceptivos son los recursos y procedimientos que se utilizan con el fin de evitar la unión del óvulo o gameto femenino con el espermatozoide o gameto masculino, y que permiten la cópula entre la pareja sin el riesgo de embarazo. Los métodos anticonceptivos se clasifican en temporales y permanentes. De los primeros se destaca lo siguiente, los hormonales, elaborados con base en hormonas sintéticas derivadas de los estrógenos y la progesterona que administradas regularmente, son capaces de evitar el embarazo, existen dos vias de administracion la forma oral y la forma inyectable; los dispositivos intrauterino que son objetos de forma, tamaño y material diferentes, adecuados para ser colocados en la cavidad uterina con el fin de evitar el embarazo; los métodos de barrera que son agentes mécanicos o substancias químicas que sirven para impedir que los espermatozoides alcancen la cavidad uterina y fecunden el óvulo, entre ellos se encuentran el preservativo, los espermaticidas y los óvulos vaginales; los métodos naturales son aquellos que no requieren de ningún agente extraño o substancia química que impida la concepción, entre ellos se encuentran: el ritmo o abstinencia sexual programada y el coito interrumpido. Los métodos permanentes son la oclusión tubaria bilateral y la vasectomía. En todos los casos antes referidos se anotan las indicaciones, las contraindicaciones, las ventajas, desventajas y efectividad

Identification of senecionine and senecionine N-oxide as antifertility constituents in Senecio vulgaris.

The MeOH extract of Senecio vulgaris L., administered po to rats on Days 1-10 postcoitum, significantly decreased the number of normal fetuses per pregnant rat found at autopsy on Day 16. Additional experiments showed a similar activity for its hepatotoxic constituents senecionine and senecionine N-oxide, suggesting that the latter two compounds were probably responsible for the effect seen with the extract. No antifertility effects were seen in MeOH extract-treated hamsters.