Sustained-release progesterone vaginal suppositories 1--development of sustained-release granule--.

Science.gov (United States)

Nakayama, Ayako; Sunada, Hisakazu; Okamoto, Hirokazu; Furuhashi, Kaoru; Ohno, Yukiko; Ito, Mikio

2009-02-01

Progesterone (P) is an important hormone for the establishment of pregnancy, and its administration is useful for luteal insufficiency. Considering the problems of commercially available oral and injection drugs, hospital-formulated vaginal suppositories are clinically used. However, since the half-life of P suppositories is short, it is difficult to maintain its constant blood concentration. To sustain drug efficacy and prevent side-effects, we are attempting to develop sustained-release suppositories by examining the degree of sustained-release of active ingredients. In this study, we examined the combinations of granulation methods and release systems for the preparation of sustained-release granules of P, and produced 13 types of sustained-release granules. We also examined the diameter, content, and dissolution of each type of granules, and confirmed that the sustained-release of all types of granules was satisfactory. Among the sustained-release granules, we selected granules with a content and a degree of sustained-release suitable for sustained-release suppositories.

Circulating progesterone concentrations in nonlactating Holstein cows during reuse of intravaginal progesterone implants sanitized by autoclave or chemical disinfection.

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Melo, L F; Monteiro, P L J; Oliveira, L H; Guardieiro, M M; Drum, J N; Wiltbank, M C; Sartori, R

2018-04-01

The aim of this study was to compare plasma progesterone (P4) concentrations in nonlactating, multiparous Holstein cows (n = 24) treated with 2 types of intravaginal implants containing either 1.0 or 1.9 g of P4 either at the first use or during reuse of the implants after sanitizing the implant by autoclave or chemical disinfection. In a completely randomized design with a 2 × 3 factorial arrangement and 2 replicates, every cow underwent 2 of 6 treatments. Two sources of P4 [controlled internal drug release (1.9 g of P4) from Zoetis (São Paulo, Brazil), and Sincrogest (1.0 g of P4) from Ourofino (Cravinhos, Brazil)] and 3 types of processing, new (N), reused after autoclave (RA), and reused after chemical disinfection (RC), were used. After inducing luteolysis to avoid endogenous circulating P4, the cows were randomized in 1 of 6 treatments (1.9 g of N, 1.9 g of RA, 1.9 g of RC, 1.0 g of N, 1.0 g of RA, and 1.0 g RC). Cows were treated with the implants for 8 d and during this period blood samples were collected at 0, 2, 12, 24, 48, 72, 96, 120, 144, 168, and 192 h. Statistical analyses were performed using Proc-Mixed and the mean ± standard error of the mean P4 concentrations were calculated using the Proc-Means procedures of SAS 9.4 (SAS Institute Inc., Cary, NC). No interaction between treatments was observed. Comparing types of implant, average P4 concentrations during treatments were greater for 1.9 g than 1.0 g (1.46 vs. 1.14 ± 0.04 ng/mL). When types of processing were compared, average P4 concentrations did not differ between autoclaved and new inserts (1.46 vs. 1.37 ± 0.05 ng/mL; respectively), but both were greater than chemically disinfected implants (1.09 ± 0.04 ng/mL). Within 1.9-g P4 inserts, P4 concentrations from autoclaved implants were greater than new, which were greater than chemically disinfected (1.67 ± 0.06 vs. 1.49 ± 0.07 vs. 1.21 ± 0.05 ng/mL; respectively). For 1.0-g P4 implants, P4 concentrations from autoclaved did not differ

Extending the duration of treatment with progesterone and equine chorionic gonadotropin improves fertility in suckled beef cows with low body condition score subjected to timed artificial insemination.

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Bilbao, M G; Massara, N; Ramos, S; Zapata, L O; Farcey, M F; Pesoa, J; Turic, E; Vázquez, M I; Bartolome, J A

2016-07-15

The objective of this study was to evaluate the effect of an extended progesterone treatment on follicular development and fertility in postpartum, suckled beef cows subjected to timed artificial insemination (TAI). In experiment 1, cows (n = 24) with body condition score (BCS) ≥4.5 received either a 2-g progesterone intravaginal device on Day -23 or a 0.558-g progesterone intravaginal device on Day -9. Then, all cows received 2 mg of estradiol benzoate on Day -9; removal of the device, 1-mg estradiol cypionate, and PGF2α on Day -2; and TAI on Day 0. Metabolic status was assessed between Days -9 and -2. Ovarian structures and plasma progesterone were determined weekly from Day -23 to -9, daily from Day -9 to 0, and weekly until Day 28. In experiment 2, cows (n = 302) with BCS ≥4.5 received identical treatment to cows in experiment 1, but on Day -2, cows received 400 IU of two different commercial preparations of equine chorionic gonadotropin (eCG). Ovarian structures were determined on Days -23 and -9 on a subset of cows (n = 40). Pregnancy was determined 39 days after TAI. In experiment 3, multiparous cows (n = 244) with BCS cows in experiment 1 initiated on Day -18, and on Day -2, cows received 400 IU of eCG or no treatment. Ovarian structures were determined in a subset of cows (n = 31) on Days -3, -2, -1, 0, 1, and on Day 10. Pregnancy was determined 39 days after TAI. The results indicated that in experiment 1, plasma progesterone was higher in treated than nontreated (control cows) during the first 14 days (P = 0.0001). The extended progesterone treatment increased the size of the largest follicle between Days -23 and Day -5 (Group by Day, P = 0.04) and tended to increase the size of the dominant follicle from Day -5 to Day -1 (Group by Day, P = 0.06). There was no effect of metabolic status or interaction between metabolic status and day on follicular growth. In experiment 2, extended progesterone treatment tended to increase the

Rationale and Safety Assessment of a Novel Intravaginal Drug-Delivery System with Sustained DL-Lactic Acid Release, Intended for Long-Term Protection of the Vaginal Microbiome.

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Verstraelen, Hans; Vervaet, Chris; Remon, Jean-Paul

2016-01-01

Bacterial vaginosis is a prevalent state of dysbiosis of the vaginal microbiota with wide-ranging impact on human reproductive health. Based on recent insights in community ecology of the vaginal microbiome, we hypothesize that sustained vaginal DL-lactic acid enrichment will enhance the recruitment of lactobacilli, while counteracting bacterial vaginosis-associated bacteria. We therefore aimed to develop an intravaginal device that would be easy to insert and remove, while providing sustained DL-lactic acid release into the vaginal lumen. The final prototype selected is a vaginal ring matrix system consisting of a mixture of ethylene vinyl acetate and methacrylic acid-methyl methacrylate copolymer loaded with 150 mg DL-lactic acid with an L/D-lactic acid ratio of 1:1. Preclinical safety assessment was performed by use of the Slug Mucosal Irritation test, a non-vertebrate assay to evaluate vaginal mucosal irritation, which revealed no irritation. Clinical safety was evaluated in a phase I trial with six healthy nulliparous premenopausal volunteering women, with the investigational drug left in place for 7 days. Colposcopic monitoring according to the WHO/CONRAD guidelines for the evaluation of vaginal products, revealed no visible cervicovaginal mucosal changes. No adverse events related to the investigational product occurred. Total release from the intravaginal ring over 7 days was estimated through high performance liquid chromatography at 37.1 (standard deviation 0.9) mg DL-lactic acid. Semisolid lactic acid formulations have been studied to a limited extent in the past and typically consist of a large volume of excipients and very high doses of lactic acid, which is of major concern to mucosal safety. We have documented the feasability of enriching the vaginal environment with pure DL-lactic acid with a prototype intravaginal ring. Though the efficacy of this platform remains to be established possibly requiring further development, this approach may offer a

Engineering a degradable polyurethane intravaginal ring for sustained delivery of dapivirine.

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Kaur, Manpreet; Gupta, Kavita M; Poursaid, Azadeh E; Karra, Prasoona; Mahalingam, Alamelu; Aliyar, Hyder A; Kiser, Patrick F

2011-06-01

We describe the engineering of a degradable intravaginal ring (IVR) for the delivery of the potent HIV-1 reverse transcriptase inhibitor dapivirine. The degradable polymer used in fabricating the device incorporated poly(caprolactone) ester blocks in a poly(tetramethylene ether) glycol ABA type polyurethane backbone. The polymer was designed to maintain its structure for 1 month during usage and then degrade in the environment post-disposal. In vitro release of dapivirine showed zero-order kinetics for up to 1 month and significant levels of drug release into engineered vaginal tissue. The mechanical properties of the degradable IVR were comparable to those of a widely used contraceptive intravaginal ring upon exposure to simulated vaginal conditions. Incubation under simulated vaginal conditions for a month caused minimal degradation with minimal effect on the mechanical properties of the ring and polymer. The cytotoxicity evaluation of the drug-loaded IVRs against Vk2/E6E7 human vaginal epithelial cells, Lactobacillus jensenii, and engineered vaginal tissue constructs showed the degradable polyurethane to be non-toxic. In vitro evaluation of inflammatory potential monitored through the levels of inflammatory cytokines IL-8, IL-1α, IL-6, IL-1β, and MIP-3α when engineered EpiVaginal™ tissue was incubated with the polyurethanes suggested that the degradable polyurethane was comparable to commercial medical grade polyurethane. These results are encouraging for further development of this degradable IVR for topical vaginal delivery of microbicides.

Investigating the feasibility of temperature-controlled accelerated drug release testing for an intravaginal ring.

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Externbrink, Anna; Clark, Meredith R; Friend, David R; Klein, Sandra

2013-11-01

The objective of the present study was to investigate if temperature can be utilized to accelerate drug release from Nuvaring®, a reservoir type intravaginal ring based on polyethylene vinyl acetate copolymer that releases a constant dose of contraceptive steroids over a duration of 3 weeks. The reciprocating holder apparatus (USP 7) was utilized to determine real-time and accelerated etonogestrel release from ring segments. It was demonstrated that drug release increased with increasing temperature which can be attributed to enhanced drug diffusion. An Arrhenius relationship of the zero-order release constants was established, indicating that temperature is a valid parameter to accelerate drug release from this dosage form and that the release mechanism is maintained under these accelerated test conditions. Accelerated release tests are particularly useful for routine quality control to assist during batch release of extended release formulations that typically release the active over several weeks, months or even years, since they can increase the product shelf life. The accelerated method should therefore be able to discriminate between formulations with different release characteristics that can result from normal manufacturing variance. In the case of Nuvaring®, it is well known that the process parameters during the extrusion process strongly influence the polymeric structure. These changes in the polymeric structure can affect the permeability which, in turn, is reflected in the release properties. Results from this study indicate that changes in the polymeric structure can lead to a different temperature dependence of the release rate, and as a consequence, the accelerated method can become less sensitive to detect changes in the release properties. When the accelerated method is utilized during batch release, it is therefore important to take this possible restriction into account and to evaluate the accelerated method with samples from non

Clean copy association of production diseases with motor activity-sensing devices and milk progesterone concentrations in dairy cows.

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Williams, J; Ntallaris, T; Routly, J E; Jones, D N; Cameron, J; Holman-Coates, A; Smith, R F; Humblot, P; Dobson, H

2018-05-31

We have previously established that the efficiency of identifying oestrus with activity-sensing devices can be compromised by common production diseases; the present study was undertaken to determine how these diseases may affect device readings. A total of 67 Holstein-Friesian cows, >20 days postpartum, were equipped with activity-sensing neck collars and pedometers, and simultaneous milk progesterone profiles were also monitored twice a week. The influences of common production stressors on maximum activity and progesterone values were analysed. Approximately 30% potential oestrus events (low progesterone value between two high values) remained unrecognised by both activity methods, and progesterone values in these animals were higher on the potential day of oestrus when both activity methods did not detect an event (0.043 ± 0.004 versus 0.029 ± 0.004 ng/mL; P = 0.03). Data from a subset of 45 cows (two events each) were subjected to mixed models and multiple regression modelling to investigate associations with production diseases. Cow motor activity was lower in lame cows. Maximum progesterone concentrations prior to oestrus increased as time postpartum and body condition score (BCS) increased. There were also fewer days of low progesterone prior to oestrus associated with increases in BCS and maximum progesterone concentrations prior to oestrus. In conclusion, lameness was associated with lower activity values, but this suppression was insufficient to account for lowered oestrus detection efficiency of either device. However, associations were identified between production diseases and progesterone profiles. Copyright © 2018. Published by Elsevier Inc.

Progesterone release from magnetic alginate/chitosan microcapsules

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Leite, Melina Vasconcelos; Castro, Mayara de Freitas e; Sanchez Rodriguez, Ruben J., E-mail: sanchez@uenf.br [Universidade Estadual do Norte Fluminense (UENF), Campos dos Goytacazes, RJ (Brazil); Rojas-Ayala, Chachi; Baggio-Saitovitch, Elisa Maria [Centro Brasileiro de Pesquisa Fisicas (CBPF), Rio de Janeir, RJ (Brazil)

2015-07-01

Magnetite nanoparticles (Fe{sub 3}O{sub 4}) were prepared using the hydrothermal method (160°C) in a closed system and characterized with the aid of the techniques of X-ray Diffraction patterns (DRX), Mössbauer spectroscopy and Vibrating Sample Magnetometer (VSM). The Fe{sub 3}O{sub 4} phase showed high crystallinity and medium crystallite size of 19nm with superparamagnetic properties, reversible behavior and saturation magnetization of 43 emu g{sup -1}. The nanoparticles coated with alginate / chitosan were characterized morphologically by Scanning and Transmission Electron Microscope. The microcapsules have a regular spherical shape with the main contribution of the size distribution in the range of 34-53μm. The progesterone released was 14% higher when external magnetic field was applied. (author)

Progesterone release from magnetic alginate/chitosan microcapsules

International Nuclear Information System (INIS)

Leite, Melina Vasconcelos; Castro, Mayara de Freitas e; Sanchez Rodriguez, Ruben J.; Rojas-Ayala, Chachi; Baggio-Saitovitch, Elisa Maria

2015-01-01

Magnetite nanoparticles (Fe_3O_4) were prepared using the hydrothermal method (160°C) in a closed system and characterized with the aid of the techniques of X-ray Diffraction patterns (DRX), Mössbauer spectroscopy and Vibrating Sample Magnetometer (VSM). The Fe_3O_4 phase showed high crystallinity and medium crystallite size of 19nm with superparamagnetic properties, reversible behavior and saturation magnetization of 43 emu g"-"1. The nanoparticles coated with alginate / chitosan were characterized morphologically by Scanning and Transmission Electron Microscope. The microcapsules have a regular spherical shape with the main contribution of the size distribution in the range of 34-53μm. The progesterone released was 14% higher when external magnetic field was applied. (author)

Certain hormonal profiles of postpartum anestrus jersey crossbred cows treated with controlled internal drug release and ovsynch protocol

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Dayanidhi Jena

2016-10-01

Full Text Available Aim: The study was conducted to determine the serum levels of certain hormones in post-partum anestrus cows following treatment with controlled internal drug release (CIDR and Ovsynch protocol. Materials and Methods: A total of 30 postpartum anestrus cows were divided into three equal groups after thorough gynecoclinical examination. The Group 1 animals received an intravaginal progesterone device on day 0 and 2 ml of prostaglandin F2α (PGF2α on day of CIDR removal (7th day, Group 2 cows were treated with ovsynch protocol (gonadotropinreleasing hormone [GnRH]-PGF2α-GnRH on day 0, 7 and 9, respectively, and Group 3 cows were supplemented with mineral mixture and treated as control. The serum estrogen, progesterone, triiodothyronine, and thyroxine concentration were estimated using enzyme-linked immunosorbent assay kit and absorbance was read at 450 nm with Perkin Elmer Wallac 1420 Microplate Reader. Results: There was a significant increase in progesterone level in Group 1 after withdrawal of CIDR as compared to other two groups. However, the estrogen assay revealed a greater concentration in Group 2 against Group 1 on day 7 of sampling. However, there was no significant difference for serum triiodothyronine (T3 and thyroxine (T4 irrespective of treatment protocols and days of sampling. Conclusion: Treatment with CIDR based progesterone therapy and drug combinations may affect the reproductive hormonal balance like estrogen and progesterone, which is inevitable for successful return to cyclicity and subsequent fertilization and conception. However, as far as serum T3 and T4 concentration concerned it may not give an astounding result.

Characterization of endocrine events during the periestrous period in sheep after estrous synchronization with controlled internal drug release (CIDR) device.

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Van Cleeff, J; Karsch, F J; Padmanabhan, V

1998-01-01

The Controlled Internal Drug Releasing (CIDR) device is an intravaginal pessary containing progesterone (P4) designed for synchronizing estrus in ruminants. To date, there has been little information available on the timing, duration, and quality of the follicular phase after CIDR removal and how those characteristics compare with natural periovulatory endocrine events. The present communication relates the results of methods we used to characterize the endocrine events that followed CIDR synchronization. Breeding-season ewes were given an injection (10 mg) of Lutalyse (PGF2 alpha), and then studied during three consecutive estrous cycles, beginning in the luteal phase after the estrus induced by PGF2 alpha. Cycle 1 estrus was synchronized with 1 CIDR (Type G) inserted for 8 d beginning 10 d after PGF2 alpha. Cycles 2 and 3 were synchronized with two CIDRs for 8 d beginning 10 d after previous CIDR removal. Cycle 1 estrous behavior and serum gonadotropins showed a follicular phase (the interval from CIDR withdrawal to gonadotropin surge [surge] peak) of 38.2 +/- 1.5 hr. Two CIDRs lengthened the interval to 46.2 +/- 1.5 hr (P synchronization concentrated surges within a 24-hr period in 92% of the ewes in Cycles 1 and 2. Cycles 3 ewes were euthanized at estimated luteal, early follicular, late follicular, LH surge, and secondary FSH rise timepoints. Endocrine data and ovaries showed that 88% of the ewes synchronized with two CIDRs were in the predicted stage of the estrous cycle. These data demonstrate that the CIDR device applied during the luteal phase effectively synchronizes estrus and results in a CIDR removal-to-surge interval of similar length to a natural follicular phase.

Effects of different five-day progesterone-based fixed-time AI protocols on follicular/luteal dynamics and fertility in dairy cows

Science.gov (United States)

GARCIA-ISPIERTO, Irina; LÓPEZ-GATIUS, Fernando

2014-01-01

This study compares in two experiments the responses of lactating dairy cows to four different progesterone-based protocols for fixed-time artificial insemination (FTAI) in terms of their effects on follicular/luteal dynamics and fertility. The protocols consisted of a progesterone intravaginal device fitted for five days, along with the administration of different combinations of gonadotropin releasing hormone, equine chorionic gonadotropin and a single or double dose (24 h apart) of prostaglandin F2α. In Experiment I, the data were derived from 232 lactating cows. Binary logistic regression identified no effects of treatment on ovulation failure or multiple ovulation 10 days post artificial insemination (AI). Based on the odds ratio, the likelihood of ovulation failure was lower (by a factor of 0.1) in cows showing at least one corpus luteum (CL) upon treatment than in cows lacking a CL; repeat breeders (> 3 AI) and cows with multiple CLs at treatment showed lower (by a factor of 0.44) and higher (by a factor of 9.0) risks of multiple ovulation, respectively, than the remaining animals. In Experiment II, the data were derived from 5173 AIs. The independent variable treatment failed to affect the conception rate 28–34 days post AI, twin pregnancy or early fetal loss 58–64 days post AI. The results of this study demonstrate the efficacy of 5-day progesterone-based protocols for FTAI. All four protocols examined were able to induce ovulation in both cyclic and non-cyclic animals so that FTAI returned a similar pregnancy rate to spontaneous estrus. Our results suggest that the ovarian response and fertility resulting from each treatment are due more to the effect of ovarian structures at treatment than to the different combinations of hormones investigated. PMID:25196275

Motivations for Intravaginal Product Use among a Cohort of Women in Los Angeles.

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Joelle M Brown

Full Text Available Intravaginal practices-including behaviors such as intravaginal cleansing and insertion of products-have been linked to a number of adverse reproductive health outcomes, including increased risk for bacterial vaginosis, sexually transmitted infections, and HIV. Currently, little is known about the motivations for intravaginal practices among women in the United States. The objective of this study was to identify and describe motivations for intravaginal washing and intravaginal insertion of products among women of differing ages and racial/ethnic groups.Between 2008 and 2010, we enrolled a convenience sample of sexually active women aged 18-65 years living in Los Angeles recruited through community education and outreach activities in HIV/AIDS service organizations, women's health clinics, community-based organizations, and HIV testing sites. At the enrollment visit, women completed a self-administered, computer-assisted questionnaire covering demographics, sexual behaviors, intravaginal practices, and motivations for intravaginal practices over the past month and past year.We enrolled 141 women; 34% of participants were Caucasian, 40% African American, and 26% Latina. Peri-sexual intravaginal washing was common in all groups, whether to clean up after sex (70% or to prepare for sex (54%. African American women were more likely to report learning to wash intravaginally from their mothers compared to Latina or Caucasian women (70% vs. 49%, P = 0.04. Sixty-one percent of African American women reported using a douching device over the past year compared to 41% of Latina and 40% of Caucasian women (p = 0.02. Younger women were more likely to report that their male partners wanted them to wash intravaginally than older women (77% vs. 24%, P<0.01, and more likely to report the removal of odors as a motive than older women (65% vs. 40%, P = 0.04. The most commonly used intravaginal products included sexual lubricants, petroleum jelly, body lotions

Control, communication and monitoring of intravaginal drug delivery in dairy cows.

Science.gov (United States)

Cross, Peter S; Künnemeyer, Rainer; Bunt, Craig R; Carnegie, Dale A; Rathbone, Michael J

2004-09-10

We present the design of an electronically controlled drug delivery system. The intravaginally located device is a low-invasive platform that can measure and react inside the cow vagina while providing external control and monitoring ability. The electronics manufactured from off the shelf components occupies 16 mL of a Theratron syringe. A microcontroller reads and logs sensor data and controls a gascell. The generated gas pressure propels the syringe piston and releases the formulation. A two way radio link allows communication between other devices or a base station. Proof of principle experiments confirm variable-rate, arbitrary profile drug delivery qualified by internal sensors. A total volume of 30 mL was dispensed over a 7-day-period with a volume error of +/- 1 mL or +/- 7% for larger volumes. Delivery was controlled or overridden via the wireless link, and proximity to other devices was detected and recorded. The results suggest that temperature and activity sensing or social grouping determined via proximity can be used to detect oestrus and trigger appropriate responses.

Validation of kinetic modeling of progesterone release from polymeric membranes

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Analia Irma Romero

2018-01-01

Full Text Available Mathematical modeling in drug release systems is fundamental in development and optimization of these systems, since it allows to predict drug release rates and to elucidate the physical transport mechanisms involved. In this paper we validate a novel mathematical model that describes progesterone (Prg controlled release from poly-3-hydroxybutyric acid (PHB membranes. A statistical analysis was conducted to compare the fitting of our model with six different models and the Akaike information criterion (AIC was used to find the equation with best-fit. A simple relation between mass and drug released rate was found, which allows predicting the effect of Prg loads on the release behavior. Our proposed model was the one with minimum AIC value, and therefore it was the one that statistically fitted better the experimental data obtained for all the Prg loads tested. Furthermore, the initial release rate was calculated and therefore, the interface mass transfer coefficient estimated and the equilibrium distribution constant of Prg between the PHB and the release medium was also determined. The results lead us to conclude that our proposed model is the one which best fits the experimental data and can be successfully used to describe Prg drug release in PHB membranes.

Progesterone supplementation postinsemination improves fertility of cooled dairy cows during the summer.

Science.gov (United States)

Friedman, E; Roth, Z; Voet, H; Lavon, Y; Wolfenson, D

2012-06-01

Reduced fertility of dairy cows during periods of elevated temperature, humidity, or both might be associated with low plasma progesterone concentration. Alleviation of thermal stress by efficient cooling is a prerequisite for improving fertility by hormonal treatment. We examined whether insertion of a controlled intravaginal drug-releasing (CIDR) insert containing progesterone following artificial insemination (AI) would improve summer conception rate. Control (n = 195) and treated (CIDR; n=165) cows, yielding on average 42.3 kg milk/d, were inseminated following estrus detection during the summer (July to October) in 2 commercial dairy herds in Israel. Mean maximal air temperature and relative humidity during the study were 30.2°C and 86%, respectively. All experimental cows were efficiently cooled throughout the study, as confirmed by measuring the body temperature of random cows. Treated cows received a CIDR insert on d 5 ± 1 post-AI for 13 d and pregnancy was confirmed by palpation 45 d post-AI. Plasma progesterone concentration in treated cows was elevated by approximately 1.5 ng/mL. Multiple logistic regressions were used to analyze conception rate. Treatment did not alter the overall conception rate; however, probability of conception increased in CIDR-treated cows with low body condition score (BCS) compared with their control counterparts (53 vs. 27%, respectively). A pronounced increase in probability of conception was recorded in CIDR-treated cows exhibiting both low BCS and postpartum reproductive disorders, compared with their control counterparts (58 vs. 14%, respectively). Exogenous progesterone supplementation on d 5 post-AI for 13 d improves summer fertility of subpopulations of cows exhibiting low BCS and postpartum reproductive disorders. Reproductive management based on specific hormonal treatment of designated subgroups of cows known to derive beneficial effects from it might improve treatment efficiency and reduce expenses. Copyright �

Novel multipurpose pod-intravaginal ring for the prevention of HIV, HSV, and unintended pregnancy: Pharmacokinetic evaluation in a macaque model.

Science.gov (United States)

Smith, James M; Moss, John A; Srinivasan, Priya; Butkyavichene, Irina; Gunawardana, Manjula; Fanter, Rob; Miller, Christine S; Sanchez, Debbie; Yang, Flora; Ellis, Shanon; Zhang, Jining; Marzinke, Mark A; Hendrix, Craig W; Kapoor, Amita; Baum, Marc M

2017-01-01

Globally, women bear an uneven burden for sexual HIV acquisition. Results from two clinical trials evaluating intravaginal rings (IVRs) delivering the antiretroviral agent dapivirine have shown that protection from HIV infection can be achieved with this modality, but high adherence is essential. Multipurpose prevention technologies (MPTs) can potentially increase product adherence by offering protection against multiple vaginally transmitted infections and unintended pregnancy. Here we describe a coitally independent, long-acting pod-IVR MPT that could potentially prevent HIV and HSV infection as well as unintended pregnancy. The pharmacokinetics of MPT pod-IVRs delivering tenofovir alafenamide hemifumarate (TAF2) to prevent HIV, acyclovir (ACV) to prevent HSV, and etonogestrel (ENG) in combination with ethinyl estradiol (EE), FDA-approved hormonal contraceptives, were evaluated in pigtailed macaques (N = 6) over 35 days. Pod IVRs were exchanged at 14 days with the only modification being lower ENG release rates in the second IVR. Plasma progesterone was monitored weekly to determine the effect of ENG/EE on menstrual cycle. The mean in vivo release rates (mg d-1) for the two formulations over 30 days ranged as follows: TAF2 0.35-0.40; ACV 0.56-0.70; EE 0.03-0.08; ENG (high releasing) 0.63; and ENG (low releasing) 0.05. Mean peak progesterone levels were 4.4 ± 1.8 ng mL-1 prior to IVR insertion and 0.075 ± 0.064 ng mL-1 for 5 weeks after insertion, suggesting that systemic EE/ENG levels were sufficient to suppress menstruation. The TAF2 and ACV release rates and resulting vaginal tissue drug concentrations (medians: TFV, 2.4 ng mg-1; ACV, 0.2 ng mg-1) may be sufficient to protect against HIV and HSV infection, respectively. This proof of principle study demonstrates that MPT-pod IVRs could serve as a potent biomedical prevention tool to protect women's sexual and reproductive health and may increase adherence to HIV PrEP even among younger high-risk populations.

Novel multipurpose pod-intravaginal ring for the prevention of HIV, HSV, and unintended pregnancy: Pharmacokinetic evaluation in a macaque model.

Directory of Open Access Journals (Sweden)

James M Smith

Full Text Available Globally, women bear an uneven burden for sexual HIV acquisition. Results from two clinical trials evaluating intravaginal rings (IVRs delivering the antiretroviral agent dapivirine have shown that protection from HIV infection can be achieved with this modality, but high adherence is essential. Multipurpose prevention technologies (MPTs can potentially increase product adherence by offering protection against multiple vaginally transmitted infections and unintended pregnancy. Here we describe a coitally independent, long-acting pod-IVR MPT that could potentially prevent HIV and HSV infection as well as unintended pregnancy. The pharmacokinetics of MPT pod-IVRs delivering tenofovir alafenamide hemifumarate (TAF2 to prevent HIV, acyclovir (ACV to prevent HSV, and etonogestrel (ENG in combination with ethinyl estradiol (EE, FDA-approved hormonal contraceptives, were evaluated in pigtailed macaques (N = 6 over 35 days. Pod IVRs were exchanged at 14 days with the only modification being lower ENG release rates in the second IVR. Plasma progesterone was monitored weekly to determine the effect of ENG/EE on menstrual cycle. The mean in vivo release rates (mg d-1 for the two formulations over 30 days ranged as follows: TAF2 0.35-0.40; ACV 0.56-0.70; EE 0.03-0.08; ENG (high releasing 0.63; and ENG (low releasing 0.05. Mean peak progesterone levels were 4.4 ± 1.8 ng mL-1 prior to IVR insertion and 0.075 ± 0.064 ng mL-1 for 5 weeks after insertion, suggesting that systemic EE/ENG levels were sufficient to suppress menstruation. The TAF2 and ACV release rates and resulting vaginal tissue drug concentrations (medians: TFV, 2.4 ng mg-1; ACV, 0.2 ng mg-1 may be sufficient to protect against HIV and HSV infection, respectively. This proof of principle study demonstrates that MPT-pod IVRs could serve as a potent biomedical prevention tool to protect women's sexual and reproductive health and may increase adherence to HIV PrEP even among younger high

Comparison of estrus synchronization by controlled internal drug release device (CIDR) and adhesive transdermal progestin patch in postpartum beef cows.

Science.gov (United States)

Kajaysri, Jatuporn; Chumchoung, Chaiwat; Wutthiwitthayaphong, Supphathat; Suthikrai, Wanvipa; Sangkamanee, Praphai

2017-09-15

Estrous synchronization with progesterone based protocols has been essentially used in cattle industry. Although intravaginal devices have been commonly used, this technique may induce vaginitis. This study aimed at examining the efficiency of novel transdermal progestin patch on follicle development and comparing the progestin patch versus CIDR device on estrous synchronization, complication at treated site and pregnancy in beef cattle. In experiment 1, seven beef cows were treated with an adhesive transdermal progestin patch on the ventral surface of the proximal part of the tail for 7 days. The cows were daily examined the follicular development using ultrasonography starting on Day 0 till 3 days after hormone removal. Experiment 2, forty beef cows were divided into two equal groups (20 cows per group). The cows randomly allocated to received either vaginal insertion of CIDR (n = 20) or treated with an adhesive transdermal progestin patch (n = 20). The levels of plasma progesterone during the experiment and the numbers of standing estrous cows were recorded. Timed artificial inseminated (TAI) was performed at 60 h after CIDR or patch termination. Pregnancy rates were determined at 60 days after TAI. Experiment 1 revealed that the novel transdermal progestin patch could efficiently control follicular growth. All the seven treated cows had dominant follicle upon dermal patch removal indicating the effectiveness of the progestin patch. In experiment 2, the percentages of cows exhibited standing estrus were similar between transdermal patch (72.22%) and CIDR (70.00%). The levels of plasma progesterone during CIDR treatment were significantly higher (4.06 ± 1.65 ng/mL on Day 1 and 3.62 ± 1.60 ng/mL on Day 7) compared with transdermal patch (2.60 ± 1.43 ng/mL on Day 1 and 1.81 ± 1.57 ng/mL on Day 7). Three cows treated with CIDR (15%) developed vaginitis while none of cows had physically dermal reaction at adhesive site. Cows synchronized with

Follicular dynamics, circulating progesterone, and fertility in Holstein cows synchronized with reused intravaginal progesterone implants that were sanitized by autoclave or chemical disinfection.

Science.gov (United States)

Melo, L F; Monteiro, P L J; Nascimento, A B; Drum, J N; Spies, C; Prata, A B; Wiltbank, M C; Sartori, R

2018-04-01

This experiment aimed to compare circulating progesterone (P4), follicular dynamics, and fertility during reuse of intravaginal P4 implants that were sanitized by autoclave or chemical disinfection in lactating Holstein cows submitted to fixed-time artificial insemination (FTAI). For this, 123 primiparous and 226 multiparous cows from 2 farms, averaging (mean ± standard deviation) 163.9 ± 141.9 d in milk, 35.7 ± 11.3 kg of milk/d, and a body condition score of 2.9 ± 0.5, were enrolled in the study. Cows were randomly assigned to 1 of 2 treatments using a completely randomized design and each cow received a reused implant (1.9 g of P4; previously used for 8 d) that was either autoclaved (AUT; n = 177) or chemically disinfected (CHEM; n = 172) on d -10. Also on d -10, cows received 2 mg of estradiol benzoate and 100 μg of GnRH. On d -3, cows received 25 mg of dinoprost (PGF 2α ). A second PGF 2α was given on d -2, along with 1 mg of estradiol cypionate and P4 implant removal. Cows received FTAI on d 0. A subset of cows (n = 143) was evaluated by ultrasound on d -10, -8, -6, -3, -2, 0, and 5 to identify ovarian structures, and blood was sampled on d -10, -3, and -2 for P4 concentrations by RIA. Pregnancy diagnoses were performed at d 32 and 60. Statistical analyses was performed using PROC-MIXED for continuous variables and PROC-GLIMMIX of SAS 9.4 (SAS Institute Inc., Cary, NC) for binomial variables. The treatments did not differ in circulating P4 on d -10 or -3, but P4 was greater on d -2 in CHEM cows. Ovulation to the treatments on d -10 was associated with lower circulating P4 on d -10 (2.0 vs. 3.1 ng/mL) and resulted in greater P4 on d -3 (4.0 vs. 2.4 ng/mL) and more cows with a corpus luteum on d -3 (100 vs. 40%) than nonovulating cows. Cows that ovulated to d -10 treatments were more likely to have a synchronized new follicular wave (97.9 vs. 63.2%) and had an earlier wave emergence (1.9 vs. 2.6 d), resulting in less cows ovulating a persistent follicle

Development of polyether urethane intravaginal rings for the sustained delivery of hydroxychloroquine

Science.gov (United States)

Chen, Yufei; Traore, Yannick Leandre; Li, Amanda; Fowke, Keith R; Ho, Emmanuel A

2014-01-01

Hydroxychloroquine (HCQ) has been shown to demonstrate anti-inflammatory properties and direct anti-HIV activity. In this study, we describe for the first time the fabrication and in vitro evaluation of two types of intravaginal ring (IVR) devices (a surfaced-modified matrix IVR and a reservoir segmental IVR) for achieving sustained delivery (>14 days) of HCQ as a strategy for preventing male-to-female transmission of HIV. Both IVRs were fabricated by hot-melt injection molding. Surface-modified matrix IVRs with polyvinylpyrrolidone or poly(vinyl alcohol) coatings exhibited significantly reduced burst release on the first day (6.45% and 15.72% reduction, respectively). Reservoir IVR segments designed to release lower amounts of HCQ displayed near-zero-order release kinetics with an average release rate of 28.38 μg/mL per day for IVRs loaded with aqueous HCQ and 32.23 μg/mL per day for IVRs loaded with HCQ mixed with a rate-controlling excipient. Stability studies demonstrated that HCQ was stable in coated or noncoated IVRs for 30 days. The IVR segments had no significant effect on cell viability, pro-inflammatory cytokine production, or colony formation of vaginal and ectocervical epithelial cells. Both IVR systems may be suitable for the prevention of HIV transmission and other sexually transmitted infections. PMID:25336923

Use of controlled internal drug releasing (CIDR) devices to control reproduction in goats: A review.

Science.gov (United States)

Knights, Marlon; Singh-Knights, Doolarie

2016-09-01

High reproductive rates are necessary in order to increase the productivity of goat operations. Progesterone and its analogues are widely used in other species to control the reproductive system to facilitate synchronized births, induce fertile estrus or to facilitate the use of assisted reproductive techniques with the goal of increasing productivity of livestock. Progesterone impregnated controlled internal drug releasing (CIDR) devices are approved for delivery of the natural hormone progesterone to synchronize and induce fertile estrus in sheep. A few studies have reported a high estrous response and pregnancy rates when CIDRs are used to induce estrus in goats. However, significant variation exists in the duration of treatment (5-16 days) and in the use of exogenous gonadotropins as part of the treatment protocol. As gonadotropins are not currently approved for commercial use in small ruminants in the USA, studies are needed to determine the necessity for exogenous gonadotropins and whether they can be replaced by enhancing endogenous secretion through photoperiodic manipulation of the doe and \\ or increase stimulation through the 'buck-effect'. Future studies must not only evaluate efficacy, but should consider the economic feasibility of using CIDRs in commercial production systems. © 2016 Japanese Society of Animal Science.

Effect of a copper intrauterine contraceptive device of estrogen and progesterone uptake by the Rabbit uterus and cervix

International Nuclear Information System (INIS)

Ghosh, Maya; Roy, S.K.

1976-01-01

The uptake of labelled estrogen 17β-6,7- 3 H and progesterone 1,2- 3 H by the uterus and cervix of rabbit fitted with inert (nylon) and active (copper wire) IUCD was studied by the in vitro method. The estrogen uptake was significantly high in IUCD fitted horn as compared to its contralateral control with both types of devices. The contralateral control-horn of copper treated animals showed significantly high estrogen uptake than that of intact control horn. This may be due to the bilateral effect of active (copper) IUCD. Similar offsets were not observed with nylon device. Estrogen uptake in the cervix was higher due to either of the devices used compared to that of intact control. The progesterone uptake was not modified in the IUCD horn by copper wire but there was an increase when a nylon suture was used. It appears that the mechanism of action of 'active' IUCDs may be different from that of 'inert' devices. (author)

Static and dynamic MRI of a urinary control intra-vaginal device

International Nuclear Information System (INIS)

Maubon, A.J.; Boncoeur-Martel, M.P.; Juhan, V.; Rouanet, J.P.; Courtieu, C.R.; Thurmond, A.S.; Aubas, P.; Mares, P.

2000-01-01

The aim of this study was to describe by MRI, in dynamic conditions at rest and straining, the anatomical modifications induced by a commercially available intravaginal device (IVD) aimed at relieving female stress urinary incontinence. Ten female patients complaining of stress urinary incontinence (SUI) had pelvic MRI with static and dynamic sequences, without and with a self-inserted IVD. We studied positions and angulations of the IVD in the pelvis. Paired t-test allowed comparisons of: position of the bladder neck; urethral angulation with the pubis axis; position of the urethra; and posterior urethro-vesical angle (PUVA) without and with IVD. At rest, in ten of ten cases IVD laid cranial to the pubo-rectal muscle; with an average angulation of 95 ± 10 with the pubis axis, laterally tilted in three of ten cases. In maximum straining with IVD bladder neck descent was lower by an average of 5.2 ± 3.1 mm (p = 0.001), pubo-urethral angle opening was smaller by an average of 22 ± 20 (p = 0.015), and bladder neck to pubis distance was shorter by an average of 5.7 ± 4 mm. Posterior urethro-vesical angle was not significantly modified. Dynamic MRI allowed a non-invasive assessment of the mode of action of an IVD. The main modifications were a support of the bladder base and bladder neck, with a superior displacement of the urethra toward the pubis. (orig.)

Static and dynamic MRI of a urinary control intra-vaginal device

Energy Technology Data Exchange (ETDEWEB)

Maubon, A.J. [Department of Medical Imaging, C. M. C. Beausoleil, Montpellier (France); Department of Radiology, CHU Dupuytren, Limoges (France); Boncoeur-Martel, M.P. [Department of Radiology, CHU Dupuytren, Limoges (France); Juhan, V.; Rouanet, J.P. [Department of Medical Imaging, C. M. C. Beausoleil, Montpellier (France); Courtieu, C.R. [Department of Gynecology, C. M. C. Beausoleil, Montpellier (France); Department of Obstetrics and Gynecology, C. H. U., F-30029 Nimes (France); Thurmond, A.S. [Women' s Imaging, Meridian Park Hospital, Portland, OR (United States); Aubas, P. [Department of Medical Information, Hopital Arnaud de Villeneuve, F-34295 Montpellier (France); Mares, P. [Department of Obstetrics and Gynecology, C. H. U., F-30029 Nimes (France)

2000-06-01

The aim of this study was to describe by MRI, in dynamic conditions at rest and straining, the anatomical modifications induced by a commercially available intravaginal device (IVD) aimed at relieving female stress urinary incontinence. Ten female patients complaining of stress urinary incontinence (SUI) had pelvic MRI with static and dynamic sequences, without and with a self-inserted IVD. We studied positions and angulations of the IVD in the pelvis. Paired t-test allowed comparisons of: position of the bladder neck; urethral angulation with the pubis axis; position of the urethra; and posterior urethro-vesical angle (PUVA) without and with IVD. At rest, in ten of ten cases IVD laid cranial to the pubo-rectal muscle; with an average angulation of 95 {+-} 10 with the pubis axis, laterally tilted in three of ten cases. In maximum straining with IVD bladder neck descent was lower by an average of 5.2 {+-} 3.1 mm (p = 0.001), pubo-urethral angle opening was smaller by an average of 22 {+-} 20 (p = 0.015), and bladder neck to pubis distance was shorter by an average of 5.7 {+-} 4 mm. Posterior urethro-vesical angle was not significantly modified. Dynamic MRI allowed a non-invasive assessment of the mode of action of an IVD. The main modifications were a support of the bladder base and bladder neck, with a superior displacement of the urethra toward the pubis. (orig.)

[Rehabilitation for intravaginal ejaculatory dysfunction with using a masturbation aid].

Science.gov (United States)

Kobori, Yoshitomo; Aoki, Hiroaki; Nishio, Koujiro; Sato, Ryo; Ashizawa, Yoshio; Yagi, Hiroshi; So, Shigehiro; Arai, Gaku; Okada, Hiroshi

2012-05-01

Recently the incidence of intravaginal ejaculatory dysfunction is increasing among infertile couples in Japan. Some unusual ways of masturbation and psychogenic issues were reported to cause this disorder. Patients, who had done masturbation in an unusual way for long time since their adolescence, were difficult to gain normal intravaginal ejaculation by the behavior therapy which was used for erectile dysfunction. We, therefore, used a masturbation aid (TENGA) for rehabilitation of ejaculation to overcome this condition. From January, 2010 through March, 2011, a total of 16 patients with intravaginal ejaculatory dysfunction underwent rehabilitation of ejaculation using TENGA. Patients' satisfaction and achievement of intravaginal ejaculation were evaluated by the questionnaire. Twelve patients (75%) could ejaculate in the masturbation aid (TENGA). Five patients (31%) succeeded to ejaculate in the partner's vagina after rehabilitation. A masturbation aid (TENGA) was a useful tool to correct the way of masturbation and achieve normal intravaginal ejaculation. This masturbation aid can be one of the effective options for the treatment of intravaginal ejaculatory dysfunction.

Radioimmunoassay of progesterone in unextracted serum

International Nuclear Information System (INIS)

Haynes, S.P.; Corcoran, J.M.; Eastman, C.J.; Doy, F.A.

1980-01-01

A rapid, precise radioimmunoassay for progesterone in 25 μL of unextracted serum is described. Progesterone is released from its binding protein by adding an optimal amount of cortisol, which binds to the same protein (cortisol binding globulin) as progesterone. The amount of cortisol required does not cross react with the specific progesterone antibody used. This approach considerably shortens assay time and removes a tedious and imprecise stage in the conventional assay of serum progesterone. Results correlated well (r = 0.97) with a method involving organic solvent extraction of progesterone from serum. During the two years we have used this mehod in a busy diagnostic endocrine laboratory, the between-assay precision (CV) for low-, medium-, and high-concentration quality control sera was 12, 7, and 9%, respectively. Data from participation in an independent external quality-control program verified the adequacies of the method

Release strategies for making transferable semiconductor structures, devices and device components

Science.gov (United States)

Rogers, John A; Nuzzo, Ralph G; Meitl, Matthew; Ko, Heung Cho; Yoon, Jongseung; Menard, Etienne; Baca, Alfred J

2014-11-25

Provided are methods for making a device or device component by providing a multilayer structure having a plurality of functional layers and a plurality of release layers and releasing the functional layers from the multilayer structure by separating one or more of the release layers to generate a plurality of transferable structures. The transferable structures are printed onto a device substrate or device component supported by a device substrate. The methods and systems provide means for making high-quality and low-cost photovoltaic devices, transferable semiconductor structures, (opto-)electronic devices and device components.

Neuroendocrine circuitry and endometriosis: progesterone derivative dampens corticotropin-releasing hormone-induced inflammation by peritoneal cells in vitro.

Science.gov (United States)

Tariverdian, Nadja; Rücke, Mirjam; Szekeres-Bartho, Julia; Blois, Sandra M; Karpf, Eva F; Sedlmayr, Peter; Klapp, Burghard F; Kentenich, Heribert; Siedentopf, Friederike; Arck, Petra C

2010-03-01

Clinical symptoms of endometriosis, such as pain and infertility, can be described as persistent stressors. Such continuous exposure to stress may severely affect the equilibrium and bidirectional communication of the endocrine and immune system, hereby further aggravating the progression of endometriosis. In the present study, we aimed to tease apart mediators that are involved in the stress response as well as in the progression of endometriosis. Women undergoing diagnostic laparoscopy due to infertility were recruited (n = 69). Within this cohort, early stage of endometriosis were diagnosed in n = 30 and advanced stage of endometriosis in n = 8. Levels of progesterone in serum were determined. Frequency of progesterone receptor (PR) expression on CD56(+) and CD8(+) peritoneal lymphocytes was analysed by flow cytometry. The production of tumour necrosis factor (TNF) and interleukin (IL)-10 by peritoneal leukocytes upon stimulation with the potent stress mediator corticotropin-releasing hormone (CRH) and the progesterone derivative dydrogesterone, or both, were evaluated. Furthermore, the production of progesterone-induced blocking factor (PIBF) by peritoneal leukocytes and the expression of PR in endometriotic tissue were investigated. Levels of progesterone in serum were decreased in women with endometriosis and inversely correlated to pain scores. Furthermore, an increased frequency of CD56(+)PR(+) and CD8(+)PR(+) peritoneal lymphocytes was present in advanced endometriosis. The TNF/IL-10 ratio, reflecting cytokine secretion by peritoneal cells, was higher in cells derived from endometriosis patients and could be further heightened by CRH stimulation, whereas stimulation with dydrogesterone abrogated the CRH-mediated inflammation. Finally, the expression of PIBF by peritoneal leukocytes was increased in endometriosis. Low levels of progesterone in the follicular phase could be responsible for the progression of endometriosis and related pain. Peripheral CRH

Progesterone for the prevention of preterm birth: indications, when to initiate, efficacy and safety

Directory of Open Access Journals (Sweden)

Helen Y How

2008-12-01

Full Text Available Helen Y How, Baha M SibaiDivision of Maternal Fetal Medicine, Department of Obstetrics and Gynecology, University of Cincinnati, Cincinnati, OH USAAbstract: Preterm birth is the leading cause of neonatal mortality and morbidity and long-term disability of non-anomalous infants. Previous studies have identified a prior early spontaneous preterm birth as the risk factor with the highest predictive value for recurrence. Two recent double blind randomized placebo controlled trials reported lower preterm birth rate with the use of either intramuscular 17 alpha-hydroxyprogesterone caproate (IM 17OHP-C or intravaginal micronized progesterone suppositories in women at risk for preterm delivery. However, it is still unclear which high-risk women would truly benefit from this treatment in a general clinical setting and whether socio-cultural, racial and genetic differences play a role in patient’s response to supplemental progesterone. In addition the patient’s acceptance of such recommendation is also in question. More research is still required on identification of at risk group, the optimal gestational age at initiation, mode of administration, dose of progesterone and long-term safety.Keywords: preterm birth prevention, 17-alpha-hydroxyprogesterone caproate

Intravaginal ring delivery of the reverse transcriptase inhibitor TMC 120 as an HIV microbicide.

Science.gov (United States)

Woolfson, A David; Malcolm, R Karl; Morrow, Ryan J; Toner, Clare F; McCullagh, Stephen D

2006-11-15

TMC 120 (Dapivirine) is a potent non-nucleoside reverse transcriptase inhibitor that is presently being developed as a vaginal HIV microbicide. To date, most vaginal microbicides under clinical investigation have been formulated as single-dose semi-solid gels, designed for application to the vagina before each act of intercourse. However, a clear rationale exists for providing long-term, controlled release of vaginal microbicides in order to afford continuous protection against heterosexually transmitted HIV infection and to improve user compliance. In this study we report on the incorporation of various pharmaceutical excipients into TMC 120 silicone, reservoir-type intravaginal rings (IVRs) in order to modify the controlled release characteristics of the microbicide. The results demonstrate that TMC 120 is released in zero-order fashion from the rings over a 28-day period and that release parameters could be modified by the inclusion of release-modifying excipients in the IVR. The hydrophobic liquid excipient isopropyl myristate had little effect on steady-state daily release rates, but did increase the magnitude and duration of burst release in proportion to excipient loading in the IVR. By comparison, the hydrophobic liquid poly(dimethylsiloxane) had little effect on TMC 120 release parameters. A hydrophilic excipient, lactose, had the surprising effect of decreasing TMC 120 burst release while increasing the apparent steady-state daily release in a concentration-dependent manner. Based on previous cell culture data and vaginal physiology, TMC120 is released from the various ring formulations in amounts potentially capable of maintaining a protective vaginal concentration. It is further predicted that the observed release rates may be maintained for at least a period of 1 year from a single ring device. TMC 120 release profiles and the mechanical properties of rings could be modified by the physicochemical nature of hydrophobic and hydrophilic excipients

Circulating progesterone dynamics after intravaginal instillation of prostaglandin-F2α to lactating dairy cows.

Science.gov (United States)

Wijma, R; Stangaferro, M L; Giordano, J O

2016-06-01

Our objectives were to evaluate circulating progesterone (P4) concentration dynamics and test the feasibility of inducing luteal regression after intravaginal (IVG) instillation of the PGF2α analogue dinoprost (PGF) in lactating dairy cows. In two experiments, cows were synchronized using the Ovsynch protocol to induce the formation of a corpus luteum (CL). Cows with at least one functional (P4 ≥1 ng/mL) CL ≥15 mm 7.5 days after Ovsynch remained in the studies. In experiment 1, cows (n = 31) were stratified by parity group and received 5 mL of saline IVG (SAL-IVG, n = 6), 25 mg of PGF intramuscular (IM) (PGF25-IM, n = 7), 25 mg of PGF IVG (PGF25-IVG, n = 6), 50 mg of PGF IVG (PGF50-IVG, n = 6), and 125 mg of PGF IVG (PGF125-IVG, n = 6). Experiment 2 was conducted to test the hypothesis that IVG instillation of two 25 mg doses of PGF 12 hours apart would be more effective than a 25- or 50-mg dose in a single application. Cows (n = 32) were stratified by parity and received SAL-IVG (n = 7), PGF25-IM (n = 7), PGF25-IVG (n = 6), and PGF50-IVG (n = 6) as in experiment 1, whereas another group received two IVG instillations of 25 mg of PGF 12 hours apart (PGF25-2X-IVG, n = 6). Blood was collected at -1 hour, every 6 hours from 0 hour to 24 hours, and every 12 hours up to 96 hours after treatment (trt). In experiment 1, there was an effect of trt (P cows in the SAL-IVG group from 12 to 96 hours after trt. Although an initial decline in P4 concentrations was induced in all PGF-treated cows, some cows in the IVG-treated groups presented a rebound in plasma P4, indicating CL recovery. More cows in the PGF25-IVG and PGF125-IVG groups than in the PGF50-IVG and PGF25-IM groups presented CL recovery, suggesting that greater doses of PGF may not necessarily improve CL regression. In experiment 2, there was an effect of trt (P Cows in the PGF25-2X-IVG group had a P4 profile that was similar to that of cows in the PGF25-IM group and

Efficiency of fixed-time artificial insemination using a progesterone device combined with GnRH or estradiol benzoate in Nellore heifers

Directory of Open Access Journals (Sweden)

Vinícius Antônio Pelissari Poncio

2015-10-01

Full Text Available he use of estrogens in artificial insemination protocols for cattle is the least expensive and most efficient method currently available. However, the trend to prohibit the use of estrogens for this purpose has made it necessary to find alternatives that replace estrogens without compromising the reproductive performance of the animals. The objective of this study was to evaluate conception rates in Bos indicus beef heifers treated with a progesterone device (P4 combined with GnRH or an estradiol ester. On day 0, pubertal Nellore heifers (n = 100 received an intravaginal device containing 1 g P4 and were randomly divided into two groups. The GnRH group (n = 49 received an intramuscular injection of 100 µg GnRH, while the E2 group (n = 51 received 2 mg estradiol benzoate (EB. The P4 device was removed after 5 (GnRH group or 8 days (E2 group, followed by an injection of 125 µg of the PGF2α, analog cloprostenol. On that occasion, the E2 group received an additional injection of 300 IU eCG. Twenty-four hours later, the GnRH group received a second injection of 125 µg cloprostenol, while the E2 group received 1 mg EB. The heifers were inseminated 72 (GnRH group or 54 hours (E2 group after removal of the P4 device. At the time of insemination, the GnRH group received additionally an injection of 100 µg GnRH. Estrus was monitored during the period of cloprostenol injection until the time of artificial insemination and pregnancy was diagnosed 40 days after insemination by transrectal ultrasonography. The data were analyzed by Fisher’s exact test. The pregnancy rate was 38.8% and 31.4% in the GnRH and E2 groups, respectively (P>0.05. The ovarian condition of the heifers (estrus or anestrus tended to influence (P=0.07 pregnancy rates in the GnRH group, but not in the E2 group. At the time of artificial insemination, 33.3% of heifers in the GnRH group showed signs of estrus versus 88.2% in the E2 group (P<0.05. However, the time of estrus

Pressure releasing device for reactor container

International Nuclear Information System (INIS)

Takeda, Mika.

1994-01-01

In the present invention, dose rate to public caused by radioactive rare gases can be decreased. That is, a reactor container contains a reactor pressure vessel incorporating a reactor core. There are disposed a pressure releasing system for releasing the pressure in the reactor pressure vessel to the outside, and a burning device for burning gases released from the pressure releasing system. An exhaustion pipe is disposed to the pressure releasing system. A burning device is disposed to the exhaustion pipe. It is effective to dispose a ventilation port at a portion of the exhaustion pipe upstream of the burning device. In addition, the burning device may preferably be disposed in a multi-stage in the axial direction of the exhaustion pipe. With such procedures, hydrogen in gases discharged along with the release of the pressure in the container is burned. Buoyancy is caused to the exhaustion gases by heat energy upon burning. Since the exhaustion gases can reach a higher level by the buoyancy, the dose rate due to the rare gases can be reduced. (I.S.)

[Fertility after treatment with Eazi-breedTM CIDR G for 6 or 12 days outside the breeding season in Lacaune dairy sheep].

Science.gov (United States)

Fleisch, A; Piechotta, M; Bollwein, H; Janett, F

2013-07-01

This study compares the fertility after short- and long-term synchronization using a progesterone intravaginal device in Lacaune dairy sheep outside the breeding season. For the experiment 108 Lacaune sheep were treated with Eazi-breed™ CIDR® G intravaginal devices (Pfizer Animal Health, Zürich) for 12 days (Group L, n = 60) or 6 days (Group K, n = 48) in combination with eCG (Group L) or with eCG and 125 μg Cloprostenol (Group K) at device removal. Thereafter the ewes were kept together with rams for 60 days, ewes in estrus were recorded and the fertility was assessed after lambing. Blood progesterone concentration was measured at device application, withdrawal and 14 days later. Results show that neither treatment nor parity had an influence on estrus rate (Group L 91.7 %, Group K 93.8 %, nulli- and pluriparous animals 96.9 % and 90.8 %, respectively). Group L showed a tendency towards a better first cycle lambing rate and a significantly (P sheep of Group K (71.7 % vs. 60.4 % and 83.3 % vs. 72.9 %). Pluriparous ewes had higher (P synchronized ewe than nulliparous sheep for the first cycle (75.0 % vs. 46.9 % and 1.4 ± 1.0 vs. 0.9 ± 1.1) as well as for the overall service period (92.1 % vs. 46.9 % and 1.7 ± 0.8 vs. 0.9 ± 1.1). Fourteen days after insert withdrawal progesterone concentrations were higher (P progesterone treatment and nulliparous ewes were less suitable for estrus induction outside the breeding season.

Effects of a progesterone-based oestrous synchronization protocol in 51- to 57-day postpartum high-producing dairy cows.

Science.gov (United States)

Garcia-Ispierto, I; López-Gatius, F; Bech-Sàbat, G; Yániz, J L; Angulo, E; Maris, C; Floc'h, S; Martino, A

2010-10-01

The aim of this study was to investigate the effect of applying a progesterone-based oestrous synchronization protocol at 51-57 days postpartum in high-producing dairy cows. The data analysed were derived from 1345 lactating cows. Cows between 51 and 57 days postpartum were assigned to the groups: control, PRID (receiving a progesterone-releasing intravaginal device for 9 days, and prostaglandin F(2α) 24 h before PRID removal) or GnRH-PRID (the same as the PRID group plus GnRH at PRID insertion). Oestrus was detected by using pedometers and confirmed by examination of the genital tract at AI. Oestrous and conception rates before days 71-77 postpartum, pregnancy loss in early pregnant cows or the cumulative conception rate registered on day 120 postpartum were considered as the dependent variables in four consecutive logistic regression analyses. Based on the odds ratios, the oestrous rate increased by a factor of 1.73 in cows showing oestrus before treatment for each unit increase in the number of previous oestruses; decreased by a factor of 0.44 in the control group with respect to the treatment groups; and by a factor of 0.61 in cows without luteal structures at treatment with respect to cows with corpora lutea. The conception rates of cows inseminated before days 71-77 postpartum remained similar across the groups, whereas the likelihood of pregnancy loss for cows becoming pregnant during this period was 0.11 times lower in the PRID group than in the control. Based on the odds ratio, the likelihood of a higher cumulative conception rate on day 120 postpartum: increased in cows showing oestrus before treatment by a factor of 1.41 for each unit increase in the number of previous oestruses, was reduced 0.56-fold in control cows compared with treated cows, and was also reduced by a factor of 0.98 for each kilogram of milk production increase recorded at treatment. In conclusion, although oestrous synchronization programmes performed in this study did not improve

Pharmacokinetics and Preliminary Safety of Pod-Intravaginal Rings Delivering the Monoclonal Antibody VRC01-N for HIV Prophylaxis in a Macaque Model.

Science.gov (United States)

Zhao, Chunxia; Gunawardana, Manjula; Villinger, Francois; Baum, Marc M; Remedios-Chan, Mariana; Moench, Thomas R; Zeitlin, Larry; Whaley, Kevin J; Bohorov, Ognian; Smith, Thomas J; Anderson, Deborah J; Moss, John A

2017-07-01

The broadly neutralizing antibody (bNAb) VRC01, capable of neutralizing 91% of known human immunodeficiency virus type 1 (HIV-1) isolates in vitro , is a promising candidate microbicide for preventing sexual HIV infection when administered topically to the vagina; however, accessibility to antibody-based prophylactic treatment by target populations in sub-Saharan Africa and other underdeveloped regions may be limited by the high cost of conventionally produced antibodies and the limited capacity to manufacture such antibodies. Intravaginal rings of the pod design (pod-IVRs) delivering Nicotiana -manufactured VRC01 (VRC01-N) over a range of release rates have been developed. The pharmacokinetics and preliminary safety of VRC01-N pod-IVRs were evaluated in a rhesus macaque model. The devices sustained VRC01-N release for up to 21 days at controlled rates, with mean steady-state VRC01-N levels in vaginal fluids in the range of 10 2 to 10 3 μg g -1 being correlated with in vitro release rates. No adverse safety indications were observed. These findings indicate that pod-IVRs are promising devices for the delivery of the candidate topical microbicide VRC01-N against HIV-1 infection and merit further preclinical evaluation. Copyright © 2017 American Society for Microbiology.

Radioimmunological progesteron determination in peripheral bovine blood

International Nuclear Information System (INIS)

Ender, M.

1974-01-01

A radioimmunological method of determination of the progesterone level in peripheral bovine blood is described which enables a monitoring of the corpus luteum function under varying conditions. There is no dependence of the corpus luteum function on the pituitary gland after endogenous prolactin inhibition with a synthetic prolactin inhibitor in the oestrus cycle and in the end-phase of gravidity. In hysterectomized animals, however, the inhibition of endogenous LH leads to luteolysis. The release of endogenous LH, induced by the administration of an LH release hormone, causes a short increase in progesterone production in the middle phase of the cycle only. The administration of exogenous glucocorticoids during the oestrus cycle did not influence the corpus luteum function. The method described is used in a field test to determine the right time for artificial insemination. There is a significant difference between the progesterone values of impregnated and non-pregnant animals at 16-18 days after insemination. (BSC/AK) [de

Comparison of the effects of pretreatment with Veramix sponge (medroxyprogesterone acetate) or CIDR (natural progesterone) in combination with an injection of estradiol-17β on ovarian activity, endocrine profiles, and embryo yields in cyclic ewes superovulated in the multiple-dose Folltropin-V (porcine FSH) regimen.

Science.gov (United States)

Bartlewski, Pawel M; Seaton, Patricia; Szpila, Patrycja; Oliveira, Maria E F; Murawski, Maciej; Schwarz, Tomasz; Kridli, Rami T; Zieba, Dorota A

2015-10-15

Follicular wave status at the beginning of exogenous FSH administration is an important contributor to variability in superovulatory responses in ruminants. Studies in ewes have shown a decrease in the number of ovulations when superovulation is initiated in the presence of ostensibly ovulatory-sized ovarian follicles. Hormonal ablation of large antral follicles with the progestin-estradiol (E2-17β) treatment significantly reduces this variability in superovulated anestrous ewes, but the effects of the treatment in cycling ewes have not yet been assessed. Sixteen Rideau Arcott × Polled Dorset ewes (November-December) received either medroxyprogesterone acetate (MAP)-releasing intravaginal sponges (60 mg) or controlled internal drug release (CIDR) devices (containing 300 mg of natural progesterone) for 14 days (Days 0-14), with a single intramuscular injection of 350 μg of E2-17β on Day 6. The superovulatory treatment consisted of six injections of porcine FSH (Folltropin-V) given twice daily, followed by a bolus GnRH injection (50 μg intramuscular) on Day 15. There were no differences (P ewes. In both subsets of animals, the next follicular wave emerged ∼2.5 days after an E2-17β injection (P > 0.05). A decline in maximum follicle size after an E2-17β injection was more abrupt in CIDR- compared with MAP-treated animals, and the ewes pretreated with exogenous progesterone had significantly more 3-mm follicles at the start of the superovulatory treatment. The metabolic clearance rate of exogenous E2-17β appeared to be greater in MAP-treated ewes, but circulating concentrations of porcine FSH failed to increase significantly after each Folltropin-V injection in CIDR-treated animals. The CIDR-treated ewes exceeded (P ewes receiving E2-17β before ovarian superstimulation, there were no differences in superovulatory responses. Copyright © 2015 Elsevier Inc. All rights reserved.

The use of equine chorionic gonadotropin in the treatment of anestrous dairy cows in gonadotropin-releasing hormone/progesterone protocols of 6 or 7 days.

Science.gov (United States)

Bryan, M A; Bó, G; Mapletoft, R J; Emslie, F R

2013-01-01

In seasonally calving, pasture-based dairy farm systems, the interval from calving to first estrus is a critical factor affecting reproductive efficiency. This study evaluated the effects of equine chorionic gonadotropin (eCG) on the reproductive response of lactating, seasonally calving dairy cows diagnosed with anovulatory anestrus by rectal palpation. Cows on 15 commercial dairy farms were selected for initial inclusion based on nonobserved estrus by 7 d before the planned start of mating. All cows were palpated rectally and evaluated for body condition score and ovary score, and were included for treatment according to the trial protocol if diagnosed with anovulatory anestrus. All cows received a standard anestrous treatment protocol consisting of insertion of a progesterone device, injection of 100 µg of GnRH at the time of device insertion, and injection of PGF(2α) at device removal (GPG/P4). Cows were randomly assigned to 1 of 2 groups (6 d or 7 d) for duration of progesterone device insertion. Within each of these groups, cows were further randomly assigned to receive either 400 IU of eCG at device removal or to remain untreated as controls, resulting in a 2×2 arrangement of treatment groups: (1) 6-d device and no eCG (n=484); (2) 6-d device and eCG (n=462); (3) 7-d device and no eCG (n=546); and (4) 7-d device and eCG (n=499). Cows were detected for estrus from the time of progesterone device removal and were inseminated; those not detected in estrus within 60 h after progesterone device removal received 100 µg of GnRH and were inseminated at 72 h. The primary outcomes considered were proportion of cows conceiving within 7 d of the beginning of breeding (7-d conception rate; 7-d CR), proportion pregnant within 28 d (28-d in calf rate; 28-d ICR), and days to conception (DTC). We found no significant differences between the 6- and 7-d insertion periods and found no 6- or 7-d insertion period × eCG treatment interactions. Inclusion of eCG into either

Successful induction of oestrus, ovulation and pregnancy in adult ewes and ewe lambs out of the breeding season using a GnRH+progesterone oestrus synchronisation protocol.

Science.gov (United States)

Martinez, M F; McLeod, B; Tattersfield, G; Smaill, B; Quirke, L D; Juengel, J L

2015-04-01

A series of experiments was designed to assess the effect of a treatment protocol (U-synch) for inducing oestrus and ovulation out of the breeding season in adult ewes and ewe lambs. The protocol consisted of a 7-day treatment with an intravaginal progesterone-releasing device (IPRD), administration of GnRH at IPRD insertion on Day 0, and equine chorionic gonadotropin (eCG) and prostaglandin F2α at IPRD removal on Day 7. In Experiment 1, 50 or 100 μg GnRH were sufficient to induce ovulation at the beginning of the protocol in 3/9 and 4/9 ewes, respectively; while the resulting proportion of sheep ovulating after the treatment protocol was 88.9% and 77.8% in ewes initially treated with 50 or 100 μg GnRH, respectively. In Experiment 2, the proportion of Romney-cross ewe lambs ovulating was greater (P<0.0001) in the U-synch group (95.4%) than in the untreated Control group (3.2%). In Experiment 3, pregnancy rates of Dorset-cross sheep in the U-synch (60.7%) and Standard (12-day IPRD and eCG treatment; 56.5%) groups were greater (P=0.01) than in the untreated Control group (43.4%). The incidence of twin pregnancies was greater (P=0.005) in the U-synch group than in the Control group. A 7-day IPRD treatment including GnRH treatment at device insertion and eCG treatment at device removal induced oestrus and ovulation during the non-breeding season in a high proportion of mature ewes and ewe lambs. High pregnancy rates to natural mating, with a low rate of triplet pregnancies, were also observed. Copyright © 2015 Elsevier B.V. All rights reserved.

Sensor and instrumentation for progesterone detection

KAUST Repository

Zia, Asif I.

2012-05-01

The reported research work uses a real time and noninvasive method to detect progesterone hormone concentration in purified water using Electrochemical Impedance Spectroscopy (E.I.S.) technique. Planar capacitive sensor, consisting of inter-digitated microelectrodes, is designed and fabricated on silicon substrate using thin-film Microelectromechanical system (MEMS) based semiconductor device fabrication technology. The sensor in conjunction with EIS is used to evaluate conductivity, permeability and dielectric properties of reproductive hormone progesterone and its concentration quantification in purified water. Impedance spectrums are obtained with various concentrations of the hormone in purified water by using an electric circuit in order to extract sample conductance. Relationship of sample conductance with progesterone concentration level is studied in this research work. The ability of E.I.S. to detect progesterone concentration is aimed to be used in dairy farming industry in order to obtain better reproductive performance of the dairy cattle. © 2012 IEEE.

Sensor and instrumentation for progesterone detection

KAUST Repository

Zia, Asif I.; Mohd. Syaifudin, A. R.; Mukhopadhyay, Subhas Chandra; Yu, Paklam; Al-Bahadly, Ibrahim H.; Kosel, Jü rgen; Gooneratne, Chinthaka Pasan

2012-01-01

The reported research work uses a real time and noninvasive method to detect progesterone hormone concentration in purified water using Electrochemical Impedance Spectroscopy (E.I.S.) technique. Planar capacitive sensor, consisting of inter-digitated microelectrodes, is designed and fabricated on silicon substrate using thin-film Microelectromechanical system (MEMS) based semiconductor device fabrication technology. The sensor in conjunction with EIS is used to evaluate conductivity, permeability and dielectric properties of reproductive hormone progesterone and its concentration quantification in purified water. Impedance spectrums are obtained with various concentrations of the hormone in purified water by using an electric circuit in order to extract sample conductance. Relationship of sample conductance with progesterone concentration level is studied in this research work. The ability of E.I.S. to detect progesterone concentration is aimed to be used in dairy farming industry in order to obtain better reproductive performance of the dairy cattle. © 2012 IEEE.

Controlled breeding and reproductive management in water buffaloes (Bubalus bubalis) using Eazi Breed controlled internal drug release.

Science.gov (United States)

Hiremath, Shivayogi; Ramesha, Kerekoppa P

2015-06-04

Buffalo reproduction is considerably affected by late maturity, poor oestrus symptoms and long postpartum periods. This study was undertaken to evaluate the efficiency of Eazi Breed controlled internal drug release (CIDR), an intravaginal progesterone-releasing device, in relation to oestrus and fertility. Five hundred true anoestrus buffalo cows, in the age group 4-6 years in 10 villages of Dharwad district in Karnataka state in India, were randomly selected and treated with CIDR for 9 days. Two mL of Cidirol (1 mg oestradiol benzoate) was administered intramuscularly to all animals on day 10. Forty-two buffaloes (8.4%) that failed to show oestrus signs (1.6%) or showed weak signs of oestrus (6.8%) after the first treatment were treated again 72 h after the Cidriol injection with a new device, and inseminated after the expression of oestrus. After the second treatment all the animals showed oestrus signs. The percentage of buffaloes showing intense oestrus was 67.40%, intermediate oestrus was shown by 25.80%, whilst 6.80% buffaloes showed weak oestrus even after the second treatment. The buffaloes showing oestrus signs were inseminated twice with an interval of 12 h, starting 12 h after the start of the oestrus signs. In 86 buffaloes showing prolonged oestrus signs a third insemination was done. The conception rates were 85.16%, 60.47% and 44.11% respectively in buffaloes showing intense, intermediate and weak oestrus. Transrectal palpation of the genital tract was performed 45-60 days post-insemination to diagnose pregnancy status, and in doubtful cases pregnancy was reconfirmed at 90 days after insemination. Out of 500 buffaloes treated in this way 380 animals became pregnant and the pregnancy rate was 76%. This study revealed the usefulness of Eazi Breed CIDR along with Cidirol treatment in buffaloes to improve their reproductive performance.

Controlled breeding and reproductive management in water buffaloes (Bubalus bubalis using Eazi Breed controlled internal drug release

Directory of Open Access Journals (Sweden)

Shivayogi Hiremath

2015-06-01

Full Text Available Buffalo reproduction is considerably affected by late maturity, poor oestrus symptoms and long postpartum periods. This study was undertaken to evaluate the efficiency of Eazi Breed controlled internal drug release (CIDR, an intravaginal progesterone-releasing device, in relation to oestrus and fertility. Five hundred true anoestrus buffalo cows, in the age group 4–6 years in 10 villages of Dharwad district in Karnataka state in India, were randomly selected and treated with CIDR for 9 days. Two mL of Cidirol (1 mg oestradiol benzoate was administered intramuscularly to all animals on day 10. Forty-two buffaloes (8.4% that failed to show oestrus signs (1.6% or showed weak signs of oestrus (6.8% after the first treatment were treated again 72 h after the Cidriol injection with a new device, and inseminated after the expression of oestrus. After the second treatment all the animals showed oestrus signs. The percentage of buffaloes showing intense oestrus was 67.40%, intermediate oestrus was shown by 25.80%, whilst 6.80% buffaloes showed weak oestrus even after the second treatment. The buffaloes showing oestrus signs were inseminated twice with an interval of 12 h, starting 12 h after the start of the oestrus signs. In 86 buffaloes showing prolonged oestrus signs a third insemination was done. The conception rates were 85.16%, 60.47% and 44.11% respectively in buffaloes showing intense, intermediate and weak oestrus. Transrectal palpation of the genital tract was performed 45–60 days post-insemination to diagnose pregnancy status, and in doubtful cases pregnancy was reconfirmed at 90 days after insemination. Out of 500 buffaloes treated in this way 380 animals became pregnant and the pregnancy rate was 76%. This study revealed the usefulness of Eazi Breed CIDR along with Cidirol treatment in buffaloes to improve their reproductive performance.

Immune Aspects and Myometrial Actions of Progesterone and CRH in Labor

OpenAIRE

Vrachnis, Nikolaos; Malamas, Fotodotis M.; Sifakis, Stavros; Tsikouras, Panayiotis; Iliodromiti, Zoe

2011-01-01

Progesterone and corticotropin-releasing hormone (CRH) have a critical role in pregnancy and labor, as changes related to these hormones are crucial for the transition from myometrial quiescence to contractility. The mechanisms related to their effect differ between humans and other species, thus, despite extensive research, many questions remain to be answered regarding their mediation in human labor. Immune responses to progesterone and CRH are important for labor. Progesterone acts as an i...

Effect of progesterone supplementation in the first week post conception on embryo survival in beef heifers.

Science.gov (United States)

Beltman, M E; Lonergan, P; Diskin, M G; Roche, J F; Crowe, M A

2009-04-15

Progesterone is essential for establishment and maintenance of pregnancy in mammals. The objective of this study was to examine the effect of elevating progesterone during the different physiological stages of early embryo development on embryo survival. Estrus was synchronized in cross-bred beef heifers (n=197, approximately 2-years old) and they were inseminated 12-18h after estrus onset (=Day 0). Inseminated heifers were randomly assigned to 1 of 3 treatments: (1) Control, n=69; (2) progesterone supplementation using a Controlled Internal Drug Release Device (CIDR) from Day 3 to 6.5, n=64; or (3) progesterone supplementation using a CIDR from Day 4.5 to 8, n=64. Body condition (BCS) and locomotion scores (scale of 1-5) were recorded for all animals. Animals with a locomotion score >/=4 (very lame) were excluded. Embryo survival rate was determined at slaughter on Day 25. Conceptus length and weight were recorded and the corpus luteum (CL) of all pregnant animals was dissected and weighed. Supplementation with exogenous progesterone increased (Prate compared with controls. Mean CL weight, conceptus length and conceptus weight were not different between treatments. There was a positive relationship (Prate in treated heifers and a similar trend existed between the increase from Days 4.5 to 8 (Prate in treated heifers. A direct correlation was seen between locomotion score and embryo survival rate, with higher (Prates in heifers with a lower locomotion score. In conclusion, supplementation with progesterone at different stages of early embryo development increased peripheral progesterone concentration and resulted in a positive association between changes in progesterone concentration during the early luteal phase and embryo survival rate. Supplementation with progesterone had no effect on either CL weight or conceptus size in pregnant animals. Lameness had a significant negative effect on early embryo survival.

Plasma progesterone levels in progesterone treated cows

International Nuclear Information System (INIS)

Grosskopf, J.F.W.; Van Niekerk, C.H.; Morgenthal, J.C.

1979-01-01

A technique for the radioimmunoassay of progesterone in plasma is described. In one trial the oestrous cycles of four cycling cows and in another trial of one non-cycling cow and two cycling heifers were synchronized by the administration of progesterone. Each female received either 50 mg or 0,1 mg/kg of progesterone intramuscularly on alternate days in two courses of four and six injections respectively. Blood samples of the animals were collected either daily or two-daily before, over the entire period of treatment and for eight days after the last progesterone injection. The results of the progesterone assays are represented graphically for each individual cow or heifer. The plasma progesterone levels during treatment were maintained reasonably well at levels corresponding to those normally encountered during the luteal phase of the cycle. The progesterone levels, however, did not drop as rapidly as desired after the last injection but might have been influenced by a residual corpus luteum from a previous ovulation

Progesterone PLGA/mPEG-PLGA Hybrid Nanoparticle Sustained-Release System by Intramuscular Injection.

Science.gov (United States)

Xie, Bin; Liu, Yang; Guo, Yuting; Zhang, Enbo; Pu, Chenguang; He, Haibing; Yin, Tian; Tang, Xing

2018-02-14

To prepare sustained-release PLGA/mPEG-PLGA hybrid nanoparticles of progesterone (PRG), and evaluate the descending required administration dosage in vivo. PRG hybrid nanoparticles (PRG H-NPs) based on PLGA/mPEG-PLGA were compared with PRG nanoparticles (PRG-NPs) of pure PLGA as the matrix and PRG-oil solutions. Nanoparticles (NPs) were formed by the method of nanoemulsion, and the pharmacokinetics of the sustained-release PRG H-NPs in male Sprague dawley (SD) rats were investigated. The rats were randomly divided into four groups, each group received: single dose of PRG H-NPs (14.58 mg/kg, i.m.) and PRG-NPs (14.58 mg/kg, i.m.), repeated dosing for 7 days of PRG-oil (2.08 mg/kg, i.m.) solution (Oil-L) and a higher dosage of PRG-oil (6.24 mg/kg, i.m.) solution (Oil-H), respectively. In the pharmacokinetic test, the PRG H-NPs exhibited a comparatively good sustained-release effect against the PRG-NPs without mPEG-PLGA and PRG-oil solution. The pharmacokinetic parameters of the PRG H-NPs, PRG-NPs, Oil-L and Oil-H were AUC 0-t (ng·h·mL -1 ) 8762.1, 1546.1, 1914.5, and 12,138.9, t 1/2 (h)52.7, 44.1, 8.4 and 44.6 respectively. Owing to the modification of PEG, PRG H-NPs can act as safe delivery platforms for sustained-release of drugs with a lower dosage required.

Progesterone resistance in endometriosis: origins, consequences and interventions.

Science.gov (United States)

Patel, Bansari G; Rudnicki, Martin; Yu, Jie; Shu, Yimin; Taylor, Robert N

2017-06-01

Endometriosis is a common cause of pelvic pain and affects up to 10% of women of reproductive age. Aberrant progesterone signaling in the endometrium plays a significant role in impaired decidualization and establishment of ectopic endometrial implants. Eutopic endometrial cells from women with endometriosis fail to downregulate genes needed for decidualization, such as those involved in cell cycle regulation, leading to unbridled proliferation. Several causes of progesterone resistance in the endometrium have been postulated, including congenital "preconditioning", whereby the in utero environment renders infants susceptible to neonatal uterine bleeding and endometriosis. Progesterone action is crucial to decreasing inflammation in the endometrium, and deviant progesterone signaling results in a proinflammatory phenotype. Conversely, chronic inflammation can induce a progesterone-resistant state. Repetitive retrograde endometrial shedding begets chronic peritoneal inflammation, which further exacerbates progesterone resistance. Genetic causes of progesterone resistance include progesterone receptor gene polymorphisms, altered microRNA expression, and epigenetic modifications to progesterone receptors and their targets. Environmental toxins such as dioxin play a possible role in the genesis of endometriosis by permitting an inflammatory milieu. A consequence of impaired progesterone action is that hormonal therapy is rendered ineffective for a subset of women with endometriosis. Synthetic progestins, such as dienogest, may overcome this phenomenon by increasing progesterone receptor expression and decreasing proinflammatory cytokines. Other modalities include high dose depot formulations of progestins, medicated intrauterine devices and the likely advent of oral GnRH antagonists. Unearthing root causes of progesterone inaction in endometriosis will aid in the development of novel therapeutics geared toward prevention and treatment. © 2017 Nordic Federation of

Development of poly(lactic acid) nanostructured membranes for the controlled delivery of progesterone to livestock animals

International Nuclear Information System (INIS)

Oliveira, Juliano Elvis; Medeiros, Eliton Souto; Cardozo, Lucio; Voll, Fernando; Madureira, Ed Hoffmann; Mattoso, Luiz Henrique Capparelli; Assis, Odilio Benedito Garrido

2013-01-01

Solution blow spinning (SBS) is a novel technology feasible to produce nanostructured polymeric membranes loaded with active agents. In the present study, nanofibrous mats of poly(lactic acid) (PLA) loaded with progesterone (P4) were produced by SBS at different P4 concentrations. The spun membranes were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). The in vitro releasing of P4 was evaluated using high-performance liquid chromatography (HPLC). Interactions between progesterone and PLA were confirmed by rheological measurements of the PLA/P4 solutions and in the spun mats by microscopy (SEM), thermal (DSC) and spectral (FTIR) analyses. SEM micrographs provided evidences of a smooth and homogeneous structure for nanostructured membranes without progesterone crystals on fiber surface. FTIR spectroscopy indicated miscibility and interaction between the ester of PLA and the ketone groups of the P4 in the nanofibers. X-ray analysis indicated that the size of PLA crystallites increased with progesterone content. Finally, by in vitro release experiments it was possible to observe that the progesterone releasing follows nearly first-order kinetics, probably due to the diffusion of hormone into PLA nanofibers. - Highlights: ► Nanofibers of PLA loading with progesterone were prepared via solution blow spinning. ► Their morphology, FTIR, and XRD and DSC characterization were analyzed. ► Fibers of PLA/progesterone with diameters from 280 to 440 nm were obtained. ► The effect of progesterone content in fiber properties was studied.

A review of slow-release fluoride devices.

Science.gov (United States)

Toumba, K J; Al-Ibrahim, N S; Curzon, M E J

2009-09-01

Fluoride has been used to combat dental caries using a number of different clinical approaches. An exciting relatively new development is fluoride slow-releasing devices that consistently elevate intra-oral fluoride levels of plaque and saliva for prolonged periods of up to two years. The literature on the use of slow-releasing fluoride devices in dentistry were reviewed. A Medline search on key words was carried out. All papers in English were individually reviewed. Slow-releasing fluoride devices have been shown to be effective in elevating salivary fluoride levels in both animals and human studies and to enhance the remineralisation of dental enamel. They have been demonstrated to be safe to use and without the risk of fluoride toxicity. A double blind randomised clinical trial demonstrated 76% fewer new carious surface increment in high caries-risk children after two years. These devices have a number of potential uses in dentistry and in particular have great potential for caries prevention of non-compliant high caries-risk groups.

Monitoring reproductive performance of cross-bred dairy cattle on smallholder farms in Malaysia

International Nuclear Information System (INIS)

Wahab, S.; Jainudeen, M.R.; Azizuddin, K.

1990-01-01

The paper reports on the reproductive performance of smallholder dairy cross-bred cattle in Malaysia, as monitored by milk progesterone radioimmunoassay and rectal palpation. Infertility was identified as the major problem faced by the smallholder farmers. The results show that there is a strong and significant association between suckling and delayed post-partum ovarian activity. The longer calving intervals in smallholder dairy herds compared with those in institutional herds are due to inactive ovaries rather than failure to detect oestrus. The use of a progesterone releasing intravaginal device (PRID) for treatment of anoestrus resulted in 93% of cows cycling, with a conception rate of 46% to insemination at the induced oestrus. Cows that suckled their calves had significantly longer calving intervals. The mean body score for cattle on smallholder herds was 3.8 -+ 1.1, and fertile cows had significantly higher scores than infertile cows. There was strong evidence to suggest that increased body scores corresponded to shorter intervals between calving and resumption of sexual activity, calving and conception, and successive calvings. (author). 12 refs, 4 tabs

Development of poly(lactic acid) nanostructured membranes for the controlled delivery of progesterone to livestock animals

Energy Technology Data Exchange (ETDEWEB)

Oliveira, Juliano Elvis [Laboratorio Nacional de Nanotecnologia para o Agronegocio (LNNA), Embrapa Instrumentacao (CNPDIA), Rua XV de Novembro, 1452, Centro, 13.560, 970 Sao Carlos, SP (Brazil); Medeiros, Eliton Souto [Universidade Federal da Paraiba (UFPB), Departamento de Engenharia de Materiais (DEMAT), Cidade Universitaria, 58.051-900, Joao Pessoa, PB (Brazil); Cardozo, Lucio; Voll, Fernando [Departamento de Engenharia Quimica, Universidade Estadual de Maringa (UEM), 87.020, 900 Maringa, PR (Brazil); Madureira, Ed Hoffmann [Departamento de Reproducao Animal, Faculdade de Medicina Veterinaria e Zootecnia (FMVZ), Universidade de Sao Paulo (USP), Pirassununga-SP (Brazil); Mattoso, Luiz Henrique Capparelli, E-mail: mattoso@cnpdia.embrapa.br [Laboratorio Nacional de Nanotecnologia para o Agronegocio (LNNA), Embrapa Instrumentacao (CNPDIA), Rua XV de Novembro, 1452, Centro, 13.560, 970 Sao Carlos, SP (Brazil); Assis, Odilio Benedito Garrido [Laboratorio Nacional de Nanotecnologia para o Agronegocio (LNNA), Embrapa Instrumentacao (CNPDIA), Rua XV de Novembro, 1452, Centro, 13.560, 970 Sao Carlos, SP (Brazil)

2013-03-01

Solution blow spinning (SBS) is a novel technology feasible to produce nanostructured polymeric membranes loaded with active agents. In the present study, nanofibrous mats of poly(lactic acid) (PLA) loaded with progesterone (P4) were produced by SBS at different P4 concentrations. The spun membranes were characterized by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). The in vitro releasing of P4 was evaluated using high-performance liquid chromatography (HPLC). Interactions between progesterone and PLA were confirmed by rheological measurements of the PLA/P4 solutions and in the spun mats by microscopy (SEM), thermal (DSC) and spectral (FTIR) analyses. SEM micrographs provided evidences of a smooth and homogeneous structure for nanostructured membranes without progesterone crystals on fiber surface. FTIR spectroscopy indicated miscibility and interaction between the ester of PLA and the ketone groups of the P4 in the nanofibers. X-ray analysis indicated that the size of PLA crystallites increased with progesterone content. Finally, by in vitro release experiments it was possible to observe that the progesterone releasing follows nearly first-order kinetics, probably due to the diffusion of hormone into PLA nanofibers. - Highlights: Black-Right-Pointing-Pointer Nanofibers of PLA loading with progesterone were prepared via solution blow spinning. Black-Right-Pointing-Pointer Their morphology, FTIR, and XRD and DSC characterization were analyzed. Black-Right-Pointing-Pointer Fibers of PLA/progesterone with diameters from 280 to 440 nm were obtained. Black-Right-Pointing-Pointer The effect of progesterone content in fiber properties was studied.

Effect of resynchronization with GnRH or progesterone (P4) intravaginal device (CIDR) on Day 23 after timed artificial insemination on cumulative pregnancy and embryonic losses in CIDR-GnRH synchronized Nili-Ravi buffaloes.

Science.gov (United States)

Arshad, Usman; Qayyum, Arslan; Hassan, Mubbashar; Husnain, Ali; Sattar, Abdul; Ahmad, Nasim

2017-11-01

The objective of the present study was to determine the effect of resynchronization on Day 23 with either GnRH or P4 (controlled internal drug release device containing progesterone; CIDR) on pregnancy rate, cumulative pregnancy, and embryonic and fetal losses in CIDR-GnRH synchronized Nili-Ravi buffaloes. Buffaloes (n = 181) of mixed parity, lactating, 181 ± 73 days postpartum, a body condition score (BCS) of 3.2 ± 0.5 (scale of 1-5), and 450-600 kg weight were subjected to synchronization and resynchronization. All buffaloes received CIDR on Day -9.5. In addition, GnRH was injected 36 h after CIDR removal, and timed artificial insemination (TAI) was performed 18 h later (Day 0). On Day 23, buffaloes were randomly assigned to receive one of the following treatments: 1) CON (n = 63), 2) P4 (n = 55), and 3) GnRH (n = 63) for resynchronization (2nd AI). Pregnancy rate, and embryonic and fetal losses were monitored by serial ultrasonography on Days 30, 45, 60, and 90 after synchronization (1st TAI), respectively. The pregnancy rate in GnRH-treated buffaloes remained significantly and consistently higher (P  0.05) between the OVS and CIDR groups; whereas the, cumulative pregnancy rate in GnRH + OVS buffaloes (81%) after 1st and 2 nd AI when determined on Day 64 was higher (P losses were significantly lower (P losses were fewer and did not differ (P > 0.05) due to treatments on Day 60 or 90 post 1st AI. In conclusion, 1) the pregnancy rate and cumulative pregnancy rate in GnRH-treated buffaloes were higher than in CON buffaloes on Day 64 after synchronization and resynchronization, and 2) embryonic and fetal losses were lower in GnRH-treated buffaloes than in CON buffaloes when determined from Day 31-90 post 1st TAI. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of intravenous glucose infusion and nutritional balance on serum concentrations of nonesterified fatty acids, glucose, insulin, and progesterone in nonlactating dairy cows.

Science.gov (United States)

Vieira, F V R; Lopes, C N; Cappellozza, B I; Scarpa, A B; Cooke, R F; Vasconcelos, J L M

2010-07-01

The objective of this study was to evaluate serum concentrations of nonesterified fatty acids, glucose, insulin, and progesterone in nonlactating dairy cows according to nutritional balance and glucose infusion. Ten nonlactating, ovariectomized Gir x Holstein cows were stratified by body weight (BW) and body condition score (BCS) on d -28 of the study, and randomly assigned to 1) negative nutrient balance (NB) or 2) positive nutrient balance (PB). From d -28 to d 0, cows were allocated according to nutritional treatment (5 cows/treatment) into 2 low-quality pastures with reduced forage availability. However, PB cows individually received, on average, 3 kg/cow per day (as-fed) of a concentrate during the study. All cows had an intravaginal progesterone releasing device inserted on d -14, which remained in cows until the end of the study. Cow BW and BCS were assessed again on d 0. On d 0, cows within nutritional treatment were randomly assigned to receive, in a crossover design containing 2 periods of 24h each, 1) intravenous glucose infusion (GLU; 0.5 g of glucose/kg of BW, as a 5% glucose solution administered, on average, at 32 mL/min over a 3-h period), or 2) intravenous saline infusion (SAL; 0.9% solution infused on average at 32 mL/min over a 3-h period). Prior to the beginning of each period, all cows were fasted for 12h. Blood samples were collected, relative to the beginning of the infusion, at -12 and -11.5h (beginning of fasting), and at -0.5, 0, 0.5, 1, 2, 3, 4, 5, and 6h. Following the last blood collection of period 1, cows received (PB) or not (NB) concentrate and were returned to their respective pastures. Changes in BCS and BW were greater in NB cows compared with PB cows (-0.60 and -0.25+/-0.090 for BCS, respectively; -22.4 and 1.2+/-6.58 kg for BW, respectively). Cows receiving GLUC had greater glucose concentrations from 0.5 to 3h relative to infusion compared with SAL cows. Insulin concentrations were greater in PB cows assigned to GLUC compared

Decreased endogenous progesterone and ratio of progesterone to ...

African Journals Online (AJOL)

Progesterone and estrogen are two steroid hormones whose exposure may decrease the risk and delay the onset of ischemic stroke. The main objective of this study was to determine the plasma level of progesterone, estrogen and ratio of progesterone/estrogen in ischemic stroke patients. The plasma levels of ...

Intravaginal practices, bacterial vaginosis, and HIV infection in women: individual participant data meta-analysis.

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Nicola Low

2011-02-01

Full Text Available Identifying modifiable factors that increase women's vulnerability to HIV is a critical step in developing effective female-initiated prevention interventions. The primary objective of this study was to pool individual participant data from prospective longitudinal studies to investigate the association between intravaginal practices and acquisition of HIV infection among women in sub-Saharan Africa. Secondary objectives were to investigate associations between intravaginal practices and disrupted vaginal flora; and between disrupted vaginal flora and HIV acquisition.We conducted a meta-analysis of individual participant data from 13 prospective cohort studies involving 14,874 women, of whom 791 acquired HIV infection during 21,218 woman years of follow-up. Data were pooled using random-effects meta-analysis. The level of between-study heterogeneity was low in all analyses (I(2 values 0.0%-16.1%. Intravaginal use of cloth or paper (pooled adjusted hazard ratio [aHR] 1.47, 95% confidence interval [CI] 1.18-1.83, insertion of products to dry or tighten the vagina (aHR 1.31, 95% CI 1.00-1.71, and intravaginal cleaning with soap (aHR 1.24, 95% CI 1.01-1.53 remained associated with HIV acquisition after controlling for age, marital status, and number of sex partners in the past 3 months. Intravaginal cleaning with soap was also associated with the development of intermediate vaginal flora and bacterial vaginosis in women with normal vaginal flora at baseline (pooled adjusted odds ratio [OR] 1.24, 95% CI 1.04-1.47. Use of cloth or paper was not associated with the development of disrupted vaginal flora. Intermediate vaginal flora and bacterial vaginosis were each associated with HIV acquisition in multivariable models when measured at baseline (aHR 1.54 and 1.69, p<0.001 or at the visit before the estimated date of HIV infection (aHR 1.41 and 1.53, p<0.001, respectively.This study provides evidence to suggest that some intravaginal practices increase

An intravaginal ring that releases the NNRTI MIV-150 reduces SHIV transmission in macaques.

Science.gov (United States)

Singer, Rachel; Mawson, Paul; Derby, Nina; Rodriguez, Aixa; Kizima, Larisa; Menon, Radhika; Goldman, Daniel; Kenney, Jessica; Aravantinou, Meropi; Seidor, Samantha; Gettie, Agegnehu; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D; Fernández-Romero, José A; Robbiani, Melissa; Zydowsky, Thomas M

2012-09-05

Microbicides may prevent HIV and sexually transmitted infections (STIs) in women; however, determining the optimal means of delivery of active pharmaceutical ingredients remains a major challenge. We previously demonstrated that a vaginal gel containing the non-nucleoside reverse transcriptase inhibitor MIV-150 partially protected macaques from SHIV-RT (simian/HIV reverse transcriptase) infection, and the addition of zinc acetate rendered the gel significantly protective. We test the activity of MIV-150 without the addition of zinc acetate when delivered from either ethylene vinyl acetate (EVA) or silicone intravaginal rings (IVRs). MIV-150 was successfully delivered, because it was detected in vaginal fluids and tissues by radioimmunoassay in pharmacokinetic studies. Moreover, EVA IVRs significantly protected macaques from SHIV-RT infection. Our results demonstrate that MIV-150-containing IVRs have the potential to prevent HIV infection and highlight the possible use of IVRs for delivering drugs that block HIV and other STIs.

Progesterone lipid nanoparticles: Scaling up and in vivo human study.

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Esposito, Elisabetta; Sguizzato, Maddalena; Drechsler, Markus; Mariani, Paolo; Carducci, Federica; Nastruzzi, Claudio; Cortesi, Rita

2017-10-01

This investigation describes a scaling up study aimed at producing progesterone containing nanoparticles in a pilot scale. Particularly hot homogenization techniques based on ultrasound homogenization or high pressure homogenization have been employed to produce lipid nanoparticles constituted of tristearin or tristearin in association with caprylic-capric triglyceride. It was found that the high pressure homogenization method enabled to obtain nanoparticles without agglomerates and smaller mean diameters with respect to ultrasound homogenization method. X-ray characterization suggested a lamellar structural organization of both type of nanoparticles. Progesterone encapsulation efficiency was almost 100% in the case of high pressure homogenization method. Shelf life study indicated a double fold stability of progesterone when encapsulated in nanoparticles produced by the high pressure homogenization method. Dialysis and Franz cell methods were performed to mimic subcutaneous and skin administration. Nanoparticles constituted of tristearin in mixture with caprylic/capric triglyceride display a slower release of progesterone with respect to nanoparticles constituted of pure tristearin. Franz cell evidenced a higher progesterone skin uptake in the case of pure tristearin nanoparticles. A human in vivo study, based on tape stripping, was conducted to investigate the performance of nanoparticles as progesterone skin delivery systems. Tape stripping results indicated a decrease of progesterone concentration in stratum corneum within six hours, suggesting an interaction between nanoparticle material and skin lipids. Copyright © 2017 Elsevier B.V. All rights reserved.

Direct radioimmunoassay of serum progesterone using heterologous bridge tracer and antibody

International Nuclear Information System (INIS)

Kothari, K.; Pillai, M.R.A.

1998-01-01

The standardisation of a direct radioimmunoassay for progesterone using an 125 I labeled progesterone prepared by iodinating the tyrosine methyl ester (TME) conjugated to a progesterone hemiphthalate derivative and an antibody prepared using a progesterone linked to bovine serum albumin through 11α hemisuccinate derivative is described. The hemiphthalate derivative of progesterone was prepared by reacting 11α-hydroxy progesterone with phthalic anhydride which was then conjugated to TME by using isobutyl chloroformate. The conjugate was iodinated with 125 I using chloramine-T as oxidising agent and purified by thin layer chromatography. Radiochemical purity of the tracer was >95% in all batches. The tracer gave 70-75% binding with excess antibody. Assays were optimised with 8-anilino-1-naphthalene sulphonic acid (ANS) and sodium salicylate as blocking agents to release the progesterone from binding proteins. The assays optimised with sodium salicylate as blocking agent has a sensitivity of 0.25 ng/ml and a working range of 0.25-50 ng/ml, whereas the assay with ANS has a sensitivity of 0.75 ng/ml and a working range of 0.75-100 ng/ml. Serum samples were analysed and compared with the values obtained with a homologous bridge assay. (author)

Levonorgestrel-releasing intrauterine device versus dydrogesterone for management of endometrial hyperplasia without atypia.

Science.gov (United States)

El Behery, Manal M; Saleh, Hend S; Ibrahiem, Moustafa A; Kamal, Ebtesam M; Kassem, Gamal A; Mohamed, Mohamed El Sayed

2015-03-01

To compare the efficacy and safety of the levonorgestrel-releasing intrauterine device (LNG-IUD) with dydrogesterone applied for the same duration in patients having endometrial hyperplasia (EH) without atypia. One hundred thirty eight women aged between 30 and 50 years with abnormal uterine bleeding and diagnosed as EH by transvaginal ultrasound were randomized to receive either LNG-IUD or dydrogesterone for 6 months. Primary outcome measures were regression of hyperplasia after 6 months of therapy. Secondary outcome measures were occurrence of side effects during treatment or recurrence of hyperplasia during follow-up period. After 6 months of treatment, regression of EH occurs in 96% of women in the levonorgestrel-releasing intrauterine system (LNG-IUS) group versus 80% of women in the oral group (P < .001). Adverse effects were relatively common with minimal differences between the 2 groups. Intermenstrual vaginal spotting and amenorrhea were more common in the LNG-IUD group (P value .01 and .0001). Patient satisfaction was significantly higher in the LNG-IUS group (P value .0001). Hysterectomy rates were lower in the LNG-IUS group than in the oral group (P = .001). Recurrence rate was 0% in the LNG-IUD group compared to 12.5% in the oral group. In management of EH without atypia, LNG-IUS achieves a higher regression and a lower hysterectomy rate than oral progesterone and could be used as a first-line therapy. © The Author(s) 2014.

Malignant neoplasms of decidual origin (deciduosarcomas) induced by estrogen-progestin-releasing intravaginal devices in rabbits.

OpenAIRE

Zook, B. C.; Spiro, I.; Hertz, R.

1987-01-01

A combination of estrogen and levonorgestrel was continuously delivered to 23 adult rabbits for up to 2 years via a Silastic ring device sutured into the vagina. Twenty-one control rabbits were given similar rings devoid of drugs. A marked decidual reaction of the endometrium occurred in 16 of 23 test rabbits. In 14 test rabbits (61%) malignant tumors developed of decidual type cells not heretofore described. The deciduosarcomas were composed of anaplastic cells that invaded the uterine walls...

Progesterone radioimmunoassay

International Nuclear Information System (INIS)

Allen, R.M.; Redshaw, M.R.

1981-01-01

This patent claims a radioimmunoassay for progesterone, which comprises contacting, in an acidic medium a sample of liquid with a predetermined amount of antibodies raised against a progesterone-protein complex, the protein being attached to the 11-position of progesterone by means of a bridging group and with a predetermined amount of a progesterone derivative having an iodinatable group attached to its 3-position by means of a bridging group, the iodinatable group being iodinated with one or more atom(s) of a radioisotope of iodine, separating the steroid bound in the resulting antibody-antigen complex from the free steroid and measuring the radioactivity of the free steroid component or of the antibody-antigen complex. Sufficient sensitivity has been achieved to enable a progesterone assay to be carried out directly on a sample of biological fluid, such as serum, plasma, urine or milk. (U.K.)

Rodent Models of Non-classical Progesterone Action Regulating Ovulation

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Melinda A. Mittelman-Smith

2017-07-01

Full Text Available It is becoming clear that steroid hormones act not only by binding to nuclear receptors that associate with specific response elements in the nucleus but also by binding to receptors on the cell membrane. In this newly discovered manner, steroid hormones can initiate intracellular signaling cascades which elicit rapid effects such as release of internal calcium stores and activation of kinases. We have learned much about the translocation and signaling of steroid hormone receptors from investigations into estrogen receptor α, which can be trafficked to, and signal from, the cell membrane. It is now clear that progesterone (P4 can also elicit effects that cannot be exclusively explained by transcriptional changes. Similar to E2 and its receptors, P4 can initiate signaling at the cell membrane, both through progesterone receptor and via a host of newly discovered membrane receptors (e.g., membrane progesterone receptors, progesterone receptor membrane components. This review discusses the parallels between neurotransmitter-like E2 action and the more recently investigated non-classical P4 signaling, in the context of reproductive behaviors in the rodent.

Roles of estrogen and progesterone in modulating renal nerve function in the rat kidney

International Nuclear Information System (INIS)

Graceli, J.B.; Cicilini, M.A.; Bissoli, N.S.; Abreu, G.R.; Moysés, M.R.

2013-01-01

The maintenance of extracellular Na + and Cl - concentrations in mammals depends, at least in part, on renal function. It has been shown that neural and endocrine mechanisms regulate extracellular fluid volume and transport of electrolytes along nephrons. Studies of sex hormones and renal nerves suggested that sex hormones modulate renal function, although this relationship is not well understood in the kidney. To better understand the role of these hormones on the effects that renal nerves have on Na + and Cl - reabsorption, we studied the effects of renal denervation and oophorectomy in female rats. Oophorectomized (OVX) rats received 17β-estradiol benzoate (OVE, 2.0 mg·kg -1 ·day -1 , sc) and progesterone (OVP, 1.7 mg·kg -1 ·day -1 , sc). We assessed Na + and Cl - fractional excretion (FE Na + and FE Cl - , respectively) and renal and plasma catecholamine release concentrations. FE Na + , FE Cl - , water intake, urinary flow, and renal and plasma catecholamine release levels increased in OVX vs control rats. These effects were reversed by 17β-estradiol benzoate but not by progesterone. Renal denervation did not alter FE Na + , FE Cl - , water intake, or urinary flow values vs controls. However, the renal catecholamine release level was decreased in the OVP (236.6±36.1 ng/g) and denervated rat groups (D: 102.1±15.7; ODE: 108.7±23.2; ODP: 101.1±22.1 ng/g). Furthermore, combining OVX + D (OD: 111.9±25.4) decreased renal catecholamine release levels compared to either treatment alone. OVE normalized and OVP reduced renal catecholamine release levels, and the effects on plasma catecholamine release levels were reversed by ODE and ODP replacement in OD. These data suggest that progesterone may influence catecholamine release levels by renal innervation and that there are complex interactions among renal nerves, estrogen, and progesterone in the modulation of renal function

Intravaginal hormonal contraception for women of reproductive age with excessive body mass

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I. B. Gridina

2015-12-01

Full Text Available There are a number of disadvantages inherent in all oral hormonal contraceptives: need for daily administration, fluctuations of hormone levels throughout the day, metabolism in the gastrointestinal tract, the effect of the first passage through the liver. All this became a prerequisite to the creation of prolonged oral hormonal methods of contraception, which would be devoid of these shortcomings. One of such method of hormonal contraception is intravaginal hormonal system. The aim was to determine the safety and efficacy of its use in women of reproductive age with overweight. 43 women were included. State of lipid metabolism, changes of the hemostatic system, blood pressure and weight fluctuations in the past 6 months of using intravaginal hormonal contraceptive system were studied. Results. It is established that hormonal intravaginal contraceptive ring gives minimal metabolic effects. Conclusion. This suggests that this ring can be used successfully in patients with excessive body mass, because there is no effect of the ring on hemostasis, lipid metabolism and body weight.

Radioimmunoassay of milk progesterone to monitor reproductive performance in smallholder dairy herds in Indonesia

International Nuclear Information System (INIS)

Mahaputra, L.; Hariadi, M.; Hardjopranjoto, S.

1990-01-01

Studies involving 260 Friesian cows from three different locations were conducted to monitor the reproductive performance in small dairy herds in Indonesia by using milk progesterone RIA. In the first study 90 post-partum cows at three locations (Surabaya, Grati and Puspo) were used to investigate post-partum ovarian function. The highest incidence of cows not showing oestrus up to 80 days post-partum, with progesterone profiles less than 0.75 ng/mL, was found in Puspo (63.3%), compared with 10% in Surabaya and 20% in Grati. The incidence of cows with silent heat and oestrus without ovulation was 13.3 and 3.3% in Surabaya, 16.7 and 6.7% in Grati, and 23.3 and 0% in Puspo. There was no significant difference (P>0.05) between the lengths of oestrous cycles at the three different locations. In the second study, using 120 cows for investigating confirmation of oestrus at AI, 69.7% of cows inseminated during the follicular phase had become pregnant, compared with 16.1% of cows inseminated during the luteal phase. The incidence of long luteal phases which included embryonic death was 13.4%. The accuracy of pregnancy diagnosis based on progesterone concentrations at day 22 was 77% and was lower than that at day 29 (88%). In the third study, cows in Subgroups 3A and 3B had cystic ovaries and were treated with prostaglandin F 2α by either intramuscular (3A) or intrauterine (3B) routes. Pregnancy rates were 50 and 40%, respectively. Cows in Subgroups 3C, 3D and 3E had inactive ovaries and were treated with intravaginal application of MPA sponges (3C), PRID (3D) or PRID followed by LH injection (3E). The pregnancy rates were 30, 40 and 60%, respectively. (author). 10 refs, 6 tabs

Engineering a segmented dual-reservoir polyurethane intravaginal ring for simultaneous prevention of HIV transmission and unwanted pregnancy.

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Justin T Clark

Full Text Available The HIV/AIDS pandemic and its impact on women prompt the investigation of prevention strategies to interrupt sexual transmission of HIV. Long-acting drug delivery systems that simultaneously protect womenfrom sexual transmission of HIV and unwanted pregnancy could be important tools in combating the pandemic. We describe the design, in silico, in vitro and in vivo evaluation of a dual-reservoir intravaginal ring that delivers the HIV-1 reverse transcriptase inhibitor tenofovir and the contraceptive levonorgestrel for 90 days. Two polyether urethanes with two different hard segment volume fractions were used to make coaxial extruded reservoir segments with a 100 µm thick rate controlling membrane and a diameter of 5.5 mm that contain 1.3 wt% levonorgestrel. A new mechanistic diffusion model accurately described the levonorgestrel burst release in early time points and pseudo-steady state behavior at later time points. As previously described, tenofovir was formulated as a glycerol paste and filled into a hydrophilic polyurethane, hollow tube reservoir that was melt-sealed by induction welding. These tenofovir-eluting segments and 2 cm long coaxially extruded levonorgestrel eluting segments were joined by induction welding to form rings that released an average of 7.5 mg tenofovir and 21 µg levonorgestrel per day in vitro for 90 days. Levonorgestrel segments placed intravaginally in rabbits resulted in sustained, dose-dependent levels of levonorgestrel in plasma and cervical tissue for 90 days. Polyurethane caps placed between segments successfully prevented diffusion of levonorgestrel into the tenofovir-releasing segment during storage.Hydrated rings endured between 152 N and 354 N tensile load before failure during uniaxial extension testing. In summary, this system represents a significant advance in vaginal drug delivery technology, and is the first in a new class of long-acting multipurpose prevention drug delivery systems.

Novel intravaginal nanomedicine for the targeted delivery of saquinavir to CD4+ immune cells

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Yang S

2013-08-01

Full Text Available Sidi Yang,1,2 Yufei Chen,1,2 Kaien Gu,1,2 Alicia Dash,1,2 Casey L Sayre,1 Neal M Davies,1 Emmanuel A Ho1,2 1Faculty of Pharmacy, 2Laboratory for Drug Delivery and Biomaterials, University of Manitoba, Winnipeg, MB, Canada Abstract: The goal of this study was to develop and characterize an intravaginal nanomedicine for the active targeted delivery of saquinavir (SQV to CD4+ immune cells as a potential strategy to prevent or reduce HIV infection. The nanomedicine was formulated into a vaginal gel to provide ease in self-administration and to enhance retention within the vaginal tract. SQV-encapsulated nanoparticles (SQV-NPs were prepared from poly(lactic-co-glycolic acid(PLGA and conjugated to antihuman anti-CD4 antibody. Antibody-conjugated SQV-NPs (Ab-SQV-NPs had an encapsulation efficiency (EE% of 74.4% ± 3.7% and an antibody conjugation efficiency (ACE% of 80.95% ± 1.10%. Over 50% of total loaded SQV was released from NPs over 3 days. NPs were rapidly taken up by Sup-T1 cells, with more than a twofold increase in the intracellular levels of SQV when delivered by Ab-SQV-NPs in comparison to controls 1 hour post-treatment. No cytotoxicity was observed when vaginal epithelial cells were treated for 24 hours with drug-free Ab-NPs (1,000 µg/mL, 1% HEC placebo gel (200 mg/mL, or 1% HEC gel loaded with drug-free Ab-NPs (5 mg NPs/g gel, 200 mg/mL of gel mixture. Overall, we described an intravaginal nanomedicine that is nontoxic and can specifically deliver SQV into CD4+ immune cells. This platform may demonstrate potential utility in its application as postexposure prophylaxis for the treatment or reduction of HIV infection, but further studies are required. Keywords: nanoparticles, saquinavir, antibody conjugation, intravaginal gel, HIV/AIDS, microbicide

Rapidly disintegrating vagina retentive cream suppositories of progesterone: development, patient satisfaction and in vitro/in vivo studies.

Science.gov (United States)

Bendas, Ehab Rasmy; Basalious, Emad B

2016-01-01

Our objective was to develop novel vagina retentive cream suppositories (VRCS) of progesterone having rapid disintegration and good vaginal retention. VRCS of progesterone were prepared using oil in water (o/w) emulsion of mineral oil or theobroma oil in hard fat and compared with conventional vaginal suppositories (CVS) prepared by hard fat. VRCS formulations were tested for content uniformity, disintegration, melting range, in vitro release and stability studies. The most stable formulation (VRCS I) was subjected to scaling-up manufacturing and patients' satisfaction test. The rapid disintegration, good retentive properties are applicable through the inclusion of emulsified theobroma oil rather than hydrophilic surfactant into the hard fat bases. The release profile of progesterone from VRCS I showed a biphasic pattern due to the formation of progesterone reservoir in the emulsified theobroma oil. All volunteers involved in patients' satisfaction test showed high satisfactory response to the tested formulation (VRCS). The in vivo pharmacokinetic study suggests that VRCS of progesterone provided higher rate and extent of absorption compared to hard fat based suppositories. Our results proposed that emulsified theobroma oil could be promising to solve the problems of poor patients' satisfaction and variability of drug absorption associated with hard fat suppositories.

Medroxyprogesterone acetate or long-acting progesterone in the biostimulation of lambs

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Luis C.O. Magalhães

2010-09-01

Full Text Available The aim of this study was to evaluate the response of prepubertal ewe lambs to exogenous administration of either medroxyprogesterone acetate (MAP or long-acting progesterone (LAP together with biostimulation. Two Pool Dorset adult males and 75 mixed-breed prepubertal ewe lambs (average of 179 days-old and 30.0kg were used. The females were randomly assigned to three different groups. In the first group the females were submitted to the insertion of intravaginal sponges containing MAP (60 mg for 12 days and were then biostimulated for eight weeks. In the second group the females were submitted to a single injection of LAP (225 mg and then to biostimulation for eight weeks. In the last group, the females were only submitted to biostimulation for eight weeks. Animals were considered cyclic when plasma progesterone (P4 concentration exceeded 1.0 ng/mL in at least one of two consecutive blood samples taken within a 7-day interval in three distinct experimental moments. After treatments 93.3% of the females disregarding their group started their cyclicity and most of them (92.0%, continued to be cyclic after 63 days of either MAP or LAP together with biostimulation under both male and female effect. We conclude that prepubertal ewe lambs when submitted to protocols of either MAP or LAP followed by biostimulation result in puberty at the 7 month of age. It can be deducted that some ewe lambs submitted to the administration of either MAP or LAP together with biostimulation promoted a multiplier effect upon the other young females that were then stimulated to start cyclicity.

Postpartum anoestrus in the suckled swamp buffalo

International Nuclear Information System (INIS)

Jainudeen, M.R.; Sharifuddin, W.; Yap, K.C.; Bakar Dahari, A.

1984-01-01

Postpartum anoestrus is a serious cause of infertility in the swamp buffalo. Our studies have revealed that it is due to a failure in the resumption of ovarian cyclicity. Parity was inversely related to the calving interval being longer in primiparous than multiparous suckled buffaloes. This effect may be partly due to the higher nutrient demands for growth as well as for lactation in the primiparous animal. The effects of suckling on ovarian and pituitary function of postpartum buffaloes were investigated with the aid of radioimmunoassays for progesterone and luteinizing hormone (LH) as well as rectal palpation and laparoscopic inspection of the ovaries. The incidence of postpartum anoestrus was higher in suckled than non-suckled buffaloes. Weaning buffalo calves at 30 d postpartum resulted in the resumption of normal ovarian cycles within 60 d postpartum. LH release in response to a single injection of a synthetic gonadotropin-releasing hormone (GnRH) indicated that pituitary responsiveness to GnRH was restored by Day 30 postpartum in suckled buffaloes whereas anoestrous buffaloes were able to release levels of LH comparable to that of the preovulatory surge. A progesterone-releasing intra-vaginal device (PRID) induced an anovulatory oestrus in the anoestrous suckled buffalo which was partially overcome by human chorionic gonadotropin (HCG) administered at the induced oestrus. However, a 72 h separation of the calf from its dam combined with PRID was the most effective substitute to weaning in initiating ovarian cycles in the suckled buffalo. Our data suggest that suckling inhibits ovarian function not by an effect on the pituitary gland but rather on GnRH release by the hypothalamus. (author)

Intravaginal insertion in KwaZulu Natal: sexual practices and preferences in the context of microbicide gel use

NARCIS (Netherlands)

Gafos, M.; Mzimela, M.; Sukazi, S.; Pool, R.; Montgomery, C.; Elford, J.

2010-01-01

Intravaginal insertion is often associated with the concept of ‘dry’ sex. All HIV-prevention microbicides tested to date have been vaginally applied lubricant-based gels. In this paper, we examine whether the use of intravaginal insertions could be in conflict with the introduction of vaginal

Posterior intravaginal slingplasty with preservation of the uterus: a modified surgical technique in a young myelomeningocele patient

NARCIS (Netherlands)

Verguts, Jasper; Roovers, Jan-Paul; de Ridder, Dirk; Coremans, Georges; Deprest, Jan

2007-01-01

We report a case of uterine prolapse in a young woman, treated by posterior intravaginal slingplasty with preservation of the uterus as a feasible and safe surgical procedure. Posterior intravaginal slingplasty is commonly used to correct vaginal vault prolapse, but may be a valuable alternative to

Progesterone resistance in endometriosis

DEFF Research Database (Denmark)

Patel, Bansari G; Rudnicki, Martin; Yu, Jie

2017-01-01

Endometriosis is a common cause of pelvic pain and affects up to 10% of women of reproductive age. Aberrant progesterone signaling in the endometrium plays a significant role in impaired decidualization and establishment of ectopic endometrial implants. Eutopic endometrial cells from women...... with endometriosis fail to downregulate genes needed for decidualization, such as those involved in cell cycle regulation, leading to unbridled proliferation. Several causes of progesterone resistance in the endometrium have been postulated, including congenital "preconditioning", whereby the in utero environment...... renders infants susceptible to neonatal uterine bleeding and endometriosis. Progesterone action is crucial to decreasing inflammation in the endometrium, and deviant progesterone signaling results in a proinflammatory phenotype. Conversely, chronic inflammation can induce a progesterone resistant state...

A Rare Cause of Scrotal Mass in a Newborn: Antenatal Intravaginal Testicular Torsion

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Ahmet Ali Tuncer

2018-04-01

Full Text Available Intravaginal testicular torsion is a very rare pathology in the neonatal period. However, it is the most common type of torsion in puberty. In this article, we present a male patient with testicular hyperemia and a mass in the testis. Ultrasonography revealed intravaginal testicular torsion and absence of testicular blood flow. This paper aims to draw attention to the importance of neonatal examination for the presence of testicular torsion which is a rare pathology in newborns with scrotal colour change or presence of an abnormal mass.

Differential effects of exogenous progesterone administration at different stages of the luteal phase on endogenous oestradiol concentration in cows.

Science.gov (United States)

Starbuck, G R; Mann, G E

2010-04-01

We have investigated the effects administering exogenous progesterone, via insertion of a controlled internal drug release (CIDR) for 4 days, from either day 5 or day 12 of the oestrous cycle on plasma oestradiol concentrations. In study 1, in which progesterone was administered from day 5, measurement of plasma oestradiol in daily samples revealed a significant (p < 0.001) decrease in peripheral oestradiol concentration. In contrast, in study 2, similar administration of progesterone from day 12 had no effect on plasma oestradiol concentration. In study 3, collection of hourly samples following progesterone treatment on day 5 revealed peak progesterone concentrations within 1 h of CIDR insertion and nadir oestradiol concentrations within 4 h. The results demonstrate that treatment with progesterone early in the luteal phase causes a rapid inhibition of oestradiol secretion, while later treatment does not. While improvements in pregnancy rate following progesterone treatment at this time have traditionally been attributed to increases in progesterone, the potential involvement of decreased oestradiol secretion has often been overlooked.

Concentrations of progesterone and insulin in serum of nonlactating dairy cows in response to carbohydrate source and processing.

Science.gov (United States)

Moriel, P; Scatena, T S; Sá Filho, O G; Cooke, R F; Vasconcelos, J L M

2008-12-01

Two experiments were conducted to investigate the effects of carbohydrate source and processing on serum progesterone (P4) and insulin concentrations of nonlactating dairy cows. In experiment 1, 12 ovariectomized grazing Gir x Holstein cows were stratified by body weight and body condition score, and randomly assigned to receive a supplement containing either finely ground corn or citrus pulp in a Latin square crossover design. Diets were fed individually, twice daily at a rate of 10.9 kg of dry matter per cow. Cows received a controlled intravaginal P4-releasing insert before the beginning of the study, and inserts were replaced every 7 d. During the first experimental period, cows were adapted to treatments from d 0 to 13 and blood was collected on d 14, whereas during the second experimental period cows were adapted to treatments from d 0 to 6 and blood samples were collected on d 7. In both periods, blood samples were collected immediately before and at 1, 2, 3, 4, 5, and 6 h after the first supplement feeding of the collection day. In experiment 2, the cows utilized in experiment 1 were randomly assigned to receive a supplement based on finely ground corn, coarsely ground corn, or high-moisture corn in a Latin square crossover design. Cows were fed and received the controlled intravaginal P4-releasing insert as in experiment 1. Within each of the 3 experimental periods, cows were adapted to diets from d 0 to 6, and blood samples were collected on d 7 as in experiment 1. Time effects were detected in experiments 1 and 2 because insulin concentrations increased by 1 h (4.6 +/- 0.90 vs. 7.4 +/- 0.91 microIU/mL for 0 and 1 h, respectively) and P4 concentrations decreased by 3 h (1.8 +/- 0.12 vs. 1.2 +/- 0.11 ng/mL for 0 and 3 h, respectively) after supplements were offered. In experiment 2, insulin concentrations were greater in cows fed high-moisture corn compared with those fed coarsely or finely ground corn (8.8 +/- 1.05, 5.7 +/- 1.05, and 6.1 +/- 1.05 micro

Segmented polyurethane intravaginal rings for the sustained combined delivery of antiretroviral agents dapivirine and tenofovir.

Science.gov (United States)

Johnson, Todd J; Gupta, Kavita M; Fabian, Judit; Albright, Theodore H; Kiser, Patrick F

2010-02-19

Dual segment polyurethane intravaginal rings (IVRs) were fabricated to enable sustained release of antiretroviral agents dapivirine and tenofovir to prevent the male to female sexual transmission of the human immunodeficiency virus. Due to the contrasting hydrophilicity of the two drugs, dapivirine and tenofovir were separately formulated into polymers with matching hydrophilicity via solvent casting and hot melt extrusion. The resultant drug loaded rods were then joined together to form dual segment IVRs. Compression testing of the IVRs revealed that they are mechanically comparable to the widely accepted NuvaRing IVR. Physical characterization of the individual IVR segments using wide angle X-ray scattering and differential scanning calorimetry determined that dapivirine and tenofovir are amorphous and crystalline within their polymeric segments, respectively. In vitro release of tenofovir from the dual segment IVR was sustained over 30 days while dapivirine exhibited linear release over the time period. A 90 day accelerated stability study confirmed that dapivirine and tenofovir are stable in the IVR formulation. Altogether, these results suggest that multisegment polyurethane IVRs are an attractive formulation for the sustained vaginal delivery of drugs with contrasting hydrophilicity such as dapivirine and tenofovir. 2009 Elsevier B.V. All rights reserved.

Nanoscale architectural tuning of parylene patch devices to control therapeutic release rates

International Nuclear Information System (INIS)

Pierstorff, Erik; Lam, Robert; Ho, Dean

2008-01-01

The advent of therapeutic functionalized implant coatings has significantly impacted the medical device field by enabling prolonged device functionality for enhanced patient treatment. Incorporation of drug release from a stable, biocompatible surface is instrumental in decreasing systemic application of toxic therapeutics and increasing the lifespan of implants by the incorporation of antibiotics and anti-inflammatories. In this study, we have developed a parylene C-based device for controlled release of Doxorubicin, an anti-cancer chemotherapy and definitive read-out for preserved drug functionality, and further characterized the parylene deposition condition-dependent tunability of drug release. Drug release is controlled by the deposition of a layer of 20-200 nm thick parylene over the drug layer. This places a porous layer above the Doxorubicin, limiting drug elution based on drug accessibility to solvent and the solvent used. An increase in the thickness of the porous top layer prolongs the elution of active drug from the device from, in the conditions tested, the order of 10 min to the order of 2 d in water and from the order of 10 min to no elution in PBS. Thus, the controlled release of an anti-cancer therapeutic has been achieved via scalably fabricated, parylene C-encapsulated drug delivery devices.

Prodigiosin release from an implantable biomedical device: kinetics of localized cancer drug release

International Nuclear Information System (INIS)

Danyuo, Y.; Obayemi, J.D.; Dozie-Nwachukwu, S.; Ani, C.J.; Odusanya, O.S.; Oni, Y.; Anuku, N.; Malatesta, K.; Soboyejo, W.O.

2014-01-01

This paper presents an implantable encapsulated structure that can deliver localized heating (hyperthermia) and controlled concentrations of prodigiosin (a cancer drug) synthesized by bacteria (Serratia marcesce (subsp. marcescens)). Prototypical Poly-di-methyl-siloxane (PDMS) packages, containing well-controlled micro-channels and drug storage compartments, were fabricated along with a drug-storing polymer produced by free radical polymerization of Poly(N-isopropylacrylamide)(PNIPA) co-monomers of Acrylamide (AM) and Butyl-methacrylate (BMA). The mechanisms of drug diffusion of PNIPA-base gels were elucidated. Scanning Electron Microscopy (SEM) was also used to study the heterogeneous porous structure of the PNIPA-based gels. The release exponents, n, of the gels were found to between 0.5 and 0.7. This is in the range expected for Fickian (n = 0.5). Deviation from Fickian diffusion was also observed (n > 0.5) diffusion. The gel diffusion coefficients were shown to vary between 2.1 × 10 −12 m 2 /s and 4.8 × 10 −6 m 2 /s. The implications of the results are then discussed for the localized treatment of cancer via hyperthermia and the controlled delivery of prodigiosin from encapsulated PNIPA-based devices. - Highlights: • Fabricated thermo-sensitive hydrogels for localized drug release from an implantable biomedical device. • Determined the cancer drug diffusion mechanisms of PNIPA-co-AM copolymer hydrogel. • Encapsulated PNIPA-based hydrogels in PDMS capsules for controlled drug delivery. • Established the kinetics of drug release from gels and channels in an implantable biomedical device. • Demonstrated the potential for the controlled release of prodigiosin (PG) as an anticancer drug

Prodigiosin release from an implantable biomedical device: kinetics of localized cancer drug release

Energy Technology Data Exchange (ETDEWEB)

Danyuo, Y.; Obayemi, J.D.; Dozie-Nwachukwu, S. [Department of Materials Science and Engineering, African University of Science and Technology (AUST), Abuja, Federal Capital Territory (Nigeria); Ani, C.J. [Department of Theoretical Physics, African University of Science and Technology (AUST), Abuja, Federal Capital Territory (Nigeria); Odusanya, O.S. [Biotechnology and Genetic Engineering Advanced Laboratory, Sheda Science and Technology Complex (SHESTCO), Abuja, Federal Capital Territory (Nigeria); Oni, Y. [Department of Chemistry, Bronx Community College, New York, NY (United States); Anuku, N. [Department of Chemistry, Bronx Community College, New York, NY (United States); Princeton Institute for the Science and Technology of Materials (PRISM), 70 Prospect Street, Princeton, NJ 08544 (United States); Malatesta, K. [Department of Chemistry, Bronx Community College, New York, NY (United States); Soboyejo, W.O., E-mail: soboyejo@princeton.edu [Department of Materials Science and Engineering, African University of Science and Technology (AUST), Abuja, Federal Capital Territory (Nigeria); Princeton Institute for the Science and Technology of Materials (PRISM), 70 Prospect Street, Princeton, NJ 08544 (United States); Department of Mechanical and Aerospace Engineering 1 Olden Street, Princeton, NJ 08544 (United States)

2014-09-01

This paper presents an implantable encapsulated structure that can deliver localized heating (hyperthermia) and controlled concentrations of prodigiosin (a cancer drug) synthesized by bacteria (Serratia marcesce (subsp. marcescens)). Prototypical Poly-di-methyl-siloxane (PDMS) packages, containing well-controlled micro-channels and drug storage compartments, were fabricated along with a drug-storing polymer produced by free radical polymerization of Poly(N-isopropylacrylamide)(PNIPA) co-monomers of Acrylamide (AM) and Butyl-methacrylate (BMA). The mechanisms of drug diffusion of PNIPA-base gels were elucidated. Scanning Electron Microscopy (SEM) was also used to study the heterogeneous porous structure of the PNIPA-based gels. The release exponents, n, of the gels were found to between 0.5 and 0.7. This is in the range expected for Fickian (n = 0.5). Deviation from Fickian diffusion was also observed (n > 0.5) diffusion. The gel diffusion coefficients were shown to vary between 2.1 × 10{sup −12} m{sup 2}/s and 4.8 × 10{sup −6} m{sup 2}/s. The implications of the results are then discussed for the localized treatment of cancer via hyperthermia and the controlled delivery of prodigiosin from encapsulated PNIPA-based devices. - Highlights: • Fabricated thermo-sensitive hydrogels for localized drug release from an implantable biomedical device. • Determined the cancer drug diffusion mechanisms of PNIPA-co-AM copolymer hydrogel. • Encapsulated PNIPA-based hydrogels in PDMS capsules for controlled drug delivery. • Established the kinetics of drug release from gels and channels in an implantable biomedical device. • Demonstrated the potential for the controlled release of prodigiosin (PG) as an anticancer drug.

Pregnancy outcome of home intravaginal insemination in couples with unconsummated marriage

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Kaberi Banerjee

2017-01-01

Full Text Available Unconsummated marriage are mainly due to vaginismus or erectile dysfunction. They contribute to about 5% of couples in an infertility clinic. Their incidence is increasing in the metropolitan cities because of stressful lifestyles. Many of couples are advised intrauterine insemination as fertility treatment. However, home insemination is a simple, inexpensive and effective way of achieving pregnancy in such couples. We present the first study to document pregnancy rates of artificial home intravaginal insemination in couples with unconsummated marriage. Aim: To assess the pregnancy rates (PR with intravaginal insemination (IVI by couples with nonconsummation of marriage. Setting: Infertility outpatient clinic, New Delhi. Design: Retrospective analysis. Material and Methods: 55 couples of unconsummated marriage were evaluated in a period of two years. Group 1 contains 29 patients aged between 20 to 33 years; group 2 includes 14 patients aged between 33 to 36 years and group 3 includes 12 patients aged more than 36 years. Result(s: Unconsummated marriage was caused by vaginismus in 67% of the cases, erectile dysfunction in 22% and premature ejaculation in 11%. Clinical pregnancy rate was 69% in group 1; 43% in group 2 and 25% in group 3 after 6 cycles of AI. Conclusion(s: Intravaginal insemination is a simple, short, economical, effective and painless procedure for conception in nonconsummation of marriage.

Pregnancy Outcome of Home Intravaginal Insemination in Couples with Unconsummated Marriage

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Banerjee, Kaberi; Singla, Bhavana

2017-01-01

Unconsummated marriage are mainly due to vaginismus or erectile dysfunction. They contribute to about 5% of couples in an infertility clinic. Their incidence is increasing in the metropolitan cities because of stressful lifestyles. Many of couples are advised intrauterine insemination as fertility treatment. However, home insemination is a simple, inexpensive and effective way of achieving pregnancy in such couples. We present the first study to document pregnancy rates of artificial home intravaginal insemination in couples with unconsummated marriage. Aim: To assess the pregnancy rates (PR) with intravaginal insemination (IVI) by couples with nonconsummation of marriage. Setting: Infertility outpatient clinic, New Delhi. Design: Retrospective analysis. Material and Methods: 55 couples of unconsummated marriage were evaluated in a period of two years. Group 1 contains 29 patients aged between 20 to 33 years; group 2 includes 14 patients aged between 33 to 36 years and group 3 includes 12 patients aged more than 36 years. Result(s): Unconsummated marriage was caused by vaginismus in 67% of the cases, erectile dysfunction in 22% and premature ejaculation in 11%. Clinical pregnancy rate was 69% in group 1; 43% in group 2 and 25% in group 3 after 6 cycles of AI. Conclusion(s): Intravaginal insemination is a simple, short, economical, effective and painless procedure for conception in nonconsummation of marriage. PMID:29430157

Antibody against progesterone in local rabbit following low dose of progesterone injection

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Suyadi Suyadi

2012-03-01

Full Text Available ABSTRACT: Antibody against progesgerone was produced from serum of local rabbit following low dose of progesterone injection: While a control group (Control; n=5 was injected with Freund's adjuvant solution in aquadest, the treatment groups were either firstly injected with progesterone conjugated to Freund's Adjuvant (P--CFA, 150 p.l : 150 pl or progesterone conjugated to Freund's Adjuvant and bovine serum albumin (P-CFA-BSA; 135 p;l : 150 tt1 : 15 gl. Twice boostering injections were adminstered using incomplete Freund's Adjuvant on day 14 and 52 after first immunization. Weekly bleeding for serum collection were done from 1 week following first booster immunization to week 10, Using ELISA technique it was shown that the antibody titer to progesterone after first and second booster immunization in the P-CFA groug was higher than Control- and P-CFA-BSA groups. The antibody titer in the P-CFA-BSA remained low similar in the Control group: Key words: antibody; progesterone; rabbit

Progesterone increases nitric oxide synthesis in human vascular endothelial cells through activation of membrane progesterone receptor-α.

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Pang, Yefei; Dong, Jing; Thomas, Peter

2015-05-15

Progesterone exerts beneficial effects on the human cardiovascular system by inducing rapid increases in nitric oxide (NO) production in vascular endothelial cells, but the receptors mediating these nongenomic progesterone actions remain unclear. Using human umbilical vein endothelial cells (HUVECs) as a model, we show that progesterone binds to plasma membranes of HUVECs with the characteristics of membrane progesterone receptors (mPRs). The selective mPR agonist Org OD 02-0 had high binding affinity for the progesterone receptor on HUVEC membranes, whereas nuclear PR (nPR) agonists R5020 and medroxyprogesterone acetate displayed low binding affinities. Immunocytochemical and Western blot analyses confirmed that mPRs are expressed in HUVECs and are localized on their plasma membranes. NO levels increased rapidly after treatment with 20 nM progesterone, Org OD 02-0, and a progesterone-BSA conjugate but not with R5020, suggesting that this progesterone action is at the cell surface and initiated through mPRs. Progesterone and Org OD 02-0 (20 nM) also significantly increased endothelial nitric oxide synthase (eNOS) activity and eNOS phosphorylation. Knockdown of mPRα expression by treatment with small-interfering RNA (siRNA) blocked the stimulatory effects of 20 nM progesterone on NO production and eNOS phosphorylation, whereas knockdown of nPR was ineffective. Treatment with PI3K/Akt and MAP kinase inhibitors blocked the stimulatory effects of progesterone, Org OD 02-0, and progesterone-BSA on NO production and eNOS phosphorylation and also prevented progesterone- and Org OD 02-0-induced increases in Akt and ERK phosphorylation. The results suggest that progesterone stimulation of NO production in HUVECs is mediated by mPRα and involves signaling through PI3K/Akt and MAP kinase pathways. Copyright © 2015 the American Physiological Society.

Predicting patient exposure to nickel released from cardiovascular devices using multi-scale modeling.

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Saylor, David M; Craven, Brent A; Chandrasekar, Vaishnavi; Simon, David D; Brown, Ronald P; Sussman, Eric M

2018-04-01

Many cardiovascular device alloys contain nickel, which if released in sufficient quantities, can lead to adverse health effects. However, in-vivo nickel release from implanted devices and subsequent biodistribution of nickel ions to local tissues and systemic circulation are not well understood. To address this uncertainty, we have developed a multi-scale (material, tissue, and system) biokinetic model. The model links nickel release from an implanted cardiovascular device to concentrations in peri-implant tissue, as well as in serum and urine, which can be readily monitored. The model was parameterized for a specific cardiovascular implant, nitinol septal occluders, using in-vitro nickel release test results, studies of ex-vivo uptake into heart tissue, and in-vivo and clinical measurements from the literature. Our results show that the model accurately predicts nickel concentrations in peri-implant tissue in an animal model and in serum and urine of septal occluder patients. The congruity of the model with these data suggests it may provide useful insight to establish nickel exposure limits and interpret biomonitoring data. Finally, we use the model to predict local and systemic nickel exposure due to passive release from nitinol devices produced using a wide range of manufacturing processes, as well as general relationships between release rate and exposure. These relationships suggest that peri-implant tissue and serum levels of nickel will remain below 5 μg/g and 10 μg/l, respectively, in patients who have received implanted nitinol cardiovascular devices provided the rate of nickel release per device surface area does not exceed 0.074 μg/(cm 2  d) and is less than 32 μg/d in total. The uncertainty in whether in-vitro tests used to evaluate metal ion release from medical products are representative of clinical environments is one of the largest roadblocks to establishing the associated patient risk. We have developed and validated a multi

Comparison between two forms of vaginally administered progesterone for luteal phase support in assisted reproduction cycles.

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Geber, Selmo; Moreira, Ana Carolina Ferreira; de Paula, Sálua Oliveira Calil; Sampaio, Marcos

2007-02-01

The use of progesterone for luteal phase support has been demonstrated to be beneficial in assisted reproduction cycles using gonadotrophin-releasing hormone analogues (GnRHa). Two micronized progesterone preparations are available for vaginal administration: capsules and gel. The objective of this study was to compare the efficacy of these two forms for luteal phase support in assisted reproduction cycles. A total of 244 couples undergoing IVF/intracytoplasmic sperm injection cycles were included in the study and were randomly allocated (sealed envelopes) into two groups: group 1 (122) received vaginal capsules of 200 mg of micronized progesterone (Utrogestan), 3 times daily, and group 2 (122) received micronized progesterone in gel (Crinone 8%), once daily. Both groups received progesterone for 13 days beginning day 1 after oocyte retrieval, continuing until the pregnancy test was performed and until 12 weeks of pregnancy. Groups were compared by clinical data and assisted reproduction results and had similar ages and causes of infertility. Although the pregnancy rate was higher for those receiving progesterone gel than capsules (44.26 and 36.06% respectively), this difference was not statistically significant. The study showed that vaginal progesterone gel and capsules used for luteal phase support in assisted reproduction cycles with long protocol GnRHa result in similar pregnancy rates.

Progesterone for preterm birth prevention

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Miha Lucovnik

2015-10-01

Full Text Available Background: Progesterone is important in maintaining pregnancy. Progesterone supplementation may reduce risk of preterm birth in certain populations of pregnant women. The objective of this review was to develop evidence-based clinical recommendation for progesterone treatment in the prevention of preterm birth.Methods: A search in the Medline database was performed using keywords: progesterone, pregnancy, preterm birth, preterm labour, preterm delivery, randomized trial, and randomized controlled trial. We only included studies of vaginal progesterone treatments for the prevention of preterm birth and excluded studies on 17-α-hydroksiprogesterone caproate.Results: We report findings from twelve randomized trials conducted since 2003. These trials differ regarding inclusion criteria, progesterone dose, vehicle used, and duration of treatment. Inclusion criteria were: short uterine cervix (two trials, history of previous preterm birth (two trials, signs and symptoms of preterm labour (three trials, twin pregnancies (three trials, and multiple risk factors (among these history of previous preterm birth was the most common (two trials. Six of these twelve trials showed a significant reduction in preterm birth in the progesterone groups.Conclusions: Based on current evidence we recommend treatment with 200 mg of micronized progesterone daily, administered vaginally, in pregnant women found to have a short cervix (≤ 25 mm at 19-24 weeks. The treatment should be continued until 37 weeks.

Production of Monoclonal Antibodies specific for Progesterone

OpenAIRE

YÜCEL, Fatıma

2014-01-01

Progesterone levels in milk and serum are indicators of pregnancy in cattle. The progesterone level reaches a peak on the 21 st and 22 nd days of pregnancy. Monoclonal antibodies specific to progesterone could be used for the immunodetection of milk and serum progesterone levels. We report here the development of hybrid cells prdoducing monoclonal antibodies specific for progesterone using hybridoma technology. Hybridoma cells secreting monoclonal antibodies against progesterone (MAM 2H1...

Progesterone modulates the LPS-induced nitric oxide production by a progesterone-receptor independent mechanism.

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Wolfson, Manuel Luis; Schander, Julieta Aylen; Bariani, María Victoria; Correa, Fernando; Franchi, Ana María

2015-12-15

Genital tract infections caused by Gram-negative bacteria induce miscarriage and are one of the most common complications of human pregnancy. LPS administration to 7-day pregnant mice induces embryo resorption after 24h, with nitric oxide playing a fundamental role in this process. We have previously shown that progesterone exerts protective effects on the embryo by modulating the inflammatory reaction triggered by LPS. Here we sought to investigate whether the in vivo administration of progesterone modulated the LPS-induced nitric oxide production from peripheral blood mononuclear cells from pregnant and non-pregnant mice. We found that progesterone downregulated LPS-induced nitric oxide production by a progesterone receptor-independent mechanism. Moreover, our results suggest a possible participation of glucocorticoid receptors in at least some of the anti-inflammatory effects of progesterone. Copyright © 2015 Elsevier B.V. All rights reserved.

Progesterone impairs social recognition in male rats.

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Bychowski, Meaghan E; Auger, Catherine J

2012-04-01

The influence of progesterone in the brain and on the behavior of females is fairly well understood. However, less is known about the effect of progesterone in the male system. In male rats, receptors for progesterone are present in virtually all vasopressin (AVP) immunoreactive cells in the bed nucleus of the stria terminalis (BST) and the medial amygdala (MeA). This colocalization functions to regulate AVP expression, as progesterone and/or progestin receptors (PR)s suppress AVP expression in these same extrahypothalamic regions in the brain. These data suggest that progesterone may influence AVP-dependent behavior. While AVP is implicated in numerous behavioral and physiological functions in rodents, AVP appears essential for social recognition of conspecifics. Therefore, we examined the effects of progesterone on social recognition. We report that progesterone plays an important role in modulating social recognition in the male brain, as progesterone treatment leads to a significant impairment of social recognition in male rats. Moreover, progesterone appears to act on PRs to impair social recognition, as progesterone impairment of social recognition is blocked by a PR antagonist, RU-486. Social recognition is also impaired by a specific progestin agonist, R5020. Interestingly, we show that progesterone does not interfere with either general memory or olfactory processes, suggesting that progesterone seems critically important to social recognition memory. These data provide strong evidence that physiological levels of progesterone can have an important impact on social behavior in male rats. Copyright © 2012 Elsevier Inc. All rights reserved.

Radioimmunoassay of plasma progesterone

Energy Technology Data Exchange (ETDEWEB)

Langer, L; Veleminsky, J [Institute of Clinical Endocrinology, Lubochna (Czechoslovakia); Hampl, R; Starka, L [Vyzkumny Ustav Endokrinologicky, Prague (Czechoslovakia); Holan, J [Comenius Univ., School of Medicine, Martin (Czechoslovakia). Dept. of Physics and Nuclear Medicine

1978-06-30

A simple modification of plasma progesterone radioimmunoassay is described. 11..cap alpha..-Hydroxyprogesterone hemisuccinate - BSA conjugate was used as an immunogen. (1,2,6,7-H-3) Progesterone specific radioactivity 82 Ci.mmol/sup -1/ was purchased from Radiochemical Centre Amersham (England). The method has been applied for the analysis of more than 2000 plasma samples. The typical fluctuation of progesterone in plasma during the menstrual cycle, using data obtained with this method is illustrated. The reliability criteria of the method are given.

Progesterone radioimmunoassay with the use of progesterone derivative substituted at 12α position

International Nuclear Information System (INIS)

Kula, E.; Stupnicka, R.

1981-01-01

A direct (non-extraction) radioimmunoassay method for progesterone determination in blood plasma has been presented. A new progesterone derivative substituted at 12α position was used as antigen for production of antibody. Cheap and easily accessible substrate -deoxycholic acid - was used as starting material for 9 step degradation procedure yielding 12α-hydroxy-progesterone. The latter compound was subsequently esterified with succinic anhydrine and conjugated with bovine serum albumin. The conjugate was then used for the immunization of rabbits to obtain immune antisera. After the detailed characterization, the obtained antibodies have been used for the determination of progesterone in human and cattle blood plasma. Transcortin present in samples used for the determinations was saturated with the excess of cortisol. The sensitivity of the method was found to be 5 pg in a sample, which corresponds to the concentration of about 0.25 ng/ml in blood plasma, in as much as the volume of plasma used for analysis was 20 ml. The within-series error was 7% when progesterone concentration in plasma samples was higher than 2.5 ng/ml. (author)

Progesterone as a bone-trophic hormone.

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Prior, J C

1990-05-01

Experimental, epidemiological, and clinical data indicate that progesterone is active in bone metabolism. Progesterone appears to act directly on bone by engaging an osteoblast receptor or indirectly through competition for a glucocorticoid osteoblast receptor. Progesterone seems to promote bone formation and/or increase bone turnover. It is possible, through estrogen-stimulated increased progesterone binding to the osteoblast receptor, that progesterone plays a role in the coupling of bone resorption with bone formation. A model of the interdependent actions of progesterone and estrogen on appropriately-"ready" cells in each bone multicellular unit can be tied into the integrated secretions of these hormones within the ovulatory cycle. Figure 5 is an illustration of this concept. It shows the phases of the bone remodeling cycle in parallel with temporal changes in gonadal steroids across a stylized ovulatory cycle. Increasing estrogen production before ovulation may reverse the resorption occurring in a "sensitive" bone multicellular unit while gonadal steroid levels are low at the time of menstrual flow. The bone remodeling unit would then be ready to begin a phase of formation as progesterone levels peaked in the midluteal phase. From this perspective, the normal ovulatory cycle looks like a natural bone-activating, coherence cycle. Critical analysis of the reviewed data indicate that progesterone meets the necessary criteria to play a causal role in mineral metabolism. This review provides the preliminary basis for further molecular, genetic, experimental, and clinical investigation of the role(s) of progesterone in bone remodeling. Much further data are needed about the interrelationships between gonadal steroids and the "life cycle" of bone. Feldman et al., however, may have been prophetic when he commented; "If this anti-glucocorticoid effect of progesterone also holds true in bone, then postmenopausal osteoporosis may be, in part, a progesterone deficiency

Progesterone for premenstrual syndrome

NARCIS (Netherlands)

Ford, Olive; Lethaby, Anne; Roberts, Helen; Mol, Ben Willem J.

2009-01-01

BACKGROUND: About 5% of women experience severe symptoms called premenstrual syndrome (PMS), only in the two weeks before their menstrual periods. Treatment with progesterone may restore a deficiency, balance menstrual hormone levels or reduce effects of falling progesterone levels on the brain or

Use of fluorogestone acetate sponges or controlled internal drug release for estrus synchronization in ewes: Effects of hormonal profiles and reproductive performance.

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Swelum, Ayman Abdel-Aziz; Alowaimer, Abdullah Nasser; Abouheif, Mohamed Ahmed

2015-09-01

This study was carried out using 300 multiparous Najdi ewes during breeding season to compare the effects of fluorogestone acetate (FGA) sponges and controlled internal drug release (CIDR) dispensers to synchronize estrus on reproductive performance and hormonal profiles. Ewes were equally and randomly allotted into group A (FGA) and group B (CIDR); intravaginal progestagen was administered for 14-day period with intramuscular administration of 600-IU eCG at withdrawal time. Estrus was detected using a vasectomized ram starting 12 hours after progestagen withdrawal and repeated every 12 hours up to 84 hours. Blood samples were collected at the time of progestagen withdrawal (0 hour), 24 hours, and 48 hours. Follicle-stimulating hormone, LH, estradiol, and progesterone serum concentrations were measured using commercial ELISA kits and microtitrimetric plates. Timed laparoscopic insemination was performed 48 hours after progestagen withdrawal. Pregnancy and the number of fetuses were diagnosed by ultrasonography on Day 23 after insemination and confirmed on Days 35 and 60. The results revealed that the retention, vaginal discharge, and drawstring breakage rates after progestagen removal were significantly (P ≤ 0.05) higher in the FGA group (94.00, 98.58, and 9.22, respectively) than those in the CIDR group. On the other hand, pregnancy, fertility, twinning rates, and fecundity were significantly (P ≤ 0.05) higher in the CIDR group (77.86, 75.57, 34.34, and 1.02, respectively) than in the FGA group. Estrus responses in FGA and CIDR groups increased gradually to attain their significantly (P ≤ 0.05) higher percentages after 48 hours of progestagen withdrawal (91.49 and 92.37, respectively); thereafter, they decreased. The overall estrus responses and prolificacy did not differ between the FGA and CIDR groups. Follicle-stimulating hormone was significantly higher in the FGA group at 24 and 48 hours after progestagen withdrawal, whereas LH was significantly higher

Sulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive drug delivery system for vaginal administration of protein therapeutics: improved stability, mucin-dependent release and effective intravaginal placement.

Science.gov (United States)

Li, ChunYan; Huang, ZhiGang; Liu, ZheShuo; Ci, LiQian; Liu, ZhePeng; Liu, Yu; Yan, XueYing; Lu, WeiYue

Effective interaction between mucoadhesive drug delivery systems and mucin is the basis of effective local placement of drugs to play its therapeutic role after mucosal administration including vaginal use, which especially requires prolonged drug presence for the treatment of gynecological infectious diseases. Our previous report on phenylboronic acid-rich nanoparticles (PBNPs) demonstrated their strong interaction with mucin and mucin-sensitive release profiles of the model protein therapeutics interferon (IFN) in vitro, but their poor stability and obvious tendency to aggregate over time severely limited future application. In this study, sulfonate-modified PBNPs (PBNP-S) were designed as a stable mucoadhesive drug delivery system where the negative charges conferred by sulfonate groups prevented aggregation of nanoparticles and the phenylboronic acid groups ensured effective interaction with mucin over a wide pH range. Results suggested that PBNP-S were of spherical morphology with narrow size distribution (123.5 nm, polydispersity index 0.050), good stability over a wide pH range and 3-month storage and considerable in vitro mucoadhesion capability at vaginal pH as shown by mucin adsorption determination. IFN could be loaded to PBNP-S by physical adsorption with high encapsulation efficiency and released in a mucin-dependent manner in vitro. In vivo near-infrared fluorescent whole animal imaging and quantitative vaginal lavage followed by enzyme-linked immunosorbent assay (ELISA) assay of IFN demonstrated that PBNP-S could stay in the vagina and maintain intravaginal IFN level for much longer time than IFN solution (24 hours vs several hours) without obvious histological irritation to vaginal mucosa after vaginal administration to mice. In summary, good stability, easy loading and controllable release of protein therapeutics, in vitro and in vivo mucoadhesive properties and local safety of PBNP-S suggested it as a promising nanoscale mucoadhesive drug delivery

Progesterone for premenstrual syndrome

NARCIS (Netherlands)

Ford, Olive; Lethaby, Anne; Roberts, Helen; Mol, Ben Willem J.

2012-01-01

Background About 5% of women experience severe symptoms called premenstrual syndrome (PMS), only in the two weeks before their menstrual periods. Treatment with progesterone may restore a deficiency, balance menstrual hormone levels or reduce effects of falling progesterone levels on the brain or on

Chemical Kinetics of Progesterone Radioimmunoassay System

International Nuclear Information System (INIS)

Abdel-Fattah, A.A.; Moustsfs, K.A.; El-Kolally, M.T.

2004-01-01

Progesterone is one of the steroids secreted by the corpus Iuteum in females during the menstrual cycle, and in a much higher amount by the placenta during pregnancy. It is also secreted in a minor quantities by the adrenal cortex in both males and females. Measurement of serum progesterone represents one of diagnostic values in menstrual disorders and infertility. The progesterone radioimmunoassay is based on the competition between unlabelled progesterone and a fixed quantity of 125 I-labeled progesterone for a limited number of binding sites on progesterone specific antibody. Allowing for a fixed amount of magnetizable immunosorbent to react, the antigen-antibody complex is bound on solid particles which are then separated by magnetic rack, and the radioactivity of the solid phase was counted using gamma counter. In this work, the chemical kinetics of the assay was followed, where the specific rate constant (K) was calculated at 4 degree and 37 degree and the activation energy (E act ) were calculated and the reaction rate was deduced

Preparation and characterization of 125I labeled progesterone derivatives for the development of a radioimmunoassay for progesterone

International Nuclear Information System (INIS)

Kothari, K.; Pillai, M.R.A.

1994-01-01

Preparation and purification of radioiodinated progesterone derivatives for the development of a radioimmunoassay of progesterone is described. Two procedures have been standardized for preparing radioiodinated progesterone conjugate. In the first procedure 125 I labeled histamine was conjugated to progesterone 11 α hemisuccinate by the mixed anhydride method. In the second procedure, tyrosyl methyl ester was conjugated to progesterone 11 α hemisuccinate and iodination of the conjugate was carried out. Purification of the iodinated products was carried out by solvent extraction and thin layer chromatography techniques. The radiochemical purity of the tracers prepared by both methods were more than 95%. Labeled progesterone derivatives prepared were used for developing a radioimmunoassay procedure. The non-specific binding of the tracer was about 2-3%, while up to 80% binding could be obtained in the presence of excess antibody. The radioiodinated tracer could be used up to four months in the assay. (author) 12 refs.; 2 figs.; 2 tabs

The benefits of progesterone therapy in imminent abortion

Directory of Open Access Journals (Sweden)

A. Abadi

2005-12-01

Full Text Available The causes of imminent abortion are multi-factorial. The biggest causal factor is the low level of serum progesterone level. The lowest critical level of serum progesterone for survivability of pregnancy is 10 ng/ml. Eighty percent of patients experiencing abortion showed that their progesterone level was < 10 ng/ml. Patients who realized that their pregnancy would experience hemorrhage generally would suffer from depression. Stress was one of the factors responsible for the occurence of abortion. Administration of natural progesterone substitution (not  progestogen accelerates the disappearance of uterine contractions, and speeds up the stoppage of bleeding. In addition, progesterone has the effect of anti-anxiety. Adminstration of oral progesterone would result in metabolism in the intestine and liver, such that physiological level of serum progesterone could not be reached, while administration of suppositoria progesterone would result in physiological level of serum, such that it was effective to prevent imminent abortion. (Med J Indones 2005; 14:258-62Keywords: progesterone, imminent abortion

Altrenogest and progesterone therapy during pregnancy in bottlenose dolphins (Tursiops truncatus) with progesterone insufficiency.

Science.gov (United States)

Robeck, Todd R; Gill, Claudia; Doescher, Bethany M; Sweeney, Jay; De Laender, Piet; Van Elk, Cornelis E; O'Brien, Justine K

2012-06-01

Progesterone production is essential for growth and development of the conceptus during pregnancy. Abnormal development of the corpus luteum (CL) after conception can result in early embryonic loss or fetal abortion. Routine monitoring of bottlenose dolphin (Tursiops truncatus) pregnancy after artificial insemination or natural conception with ultrasonography and serum progesterone determination has allowed for the establishment of expected fetal growth rates and hormone concentrations. Using these monitoring techniques, we revealed four pregnant dolphins (12-24 yr old) with abnormally low progesterone production indicative of luteal insufficiency. Once diagnosed, animals were placed on altrenogest (0.044-0.088 mg/kg once daily) alone or with oral progesterone (50-200 mg twice daily). Doses of hormone were increased or decreased in each animal based on how fetal skull biparietal and thoracic growth rates compared with published normal values. Hormones were withdrawn starting from day 358 of gestation in animals 1 and 2, with labor occurring 6 and 7 days after withdrawal and at 376 and 373 days of gestation, respectively. Both deliveries were dystocic, with each calf requiring manual extraction and fetotomy for calf 1. The fetuses in animals 3 and 4 died at 348 and 390 days of gestation, respectively. Induction of labor was attempted in both animals, after fetal death, by using a combination of rapid progesterone withdrawal and steroid and prostaglandin F2alpha administration. The calf of animal 4 had to be removed with manual cervical dilation and fetotomy All adult females survived the procedures. These data provide the first in vivo evidence that the CL is the primary source of progesterone throughout pregnancy in the bottlenose dolphin. Until further characterization of hormones required during pregnancy and at parturition has been accomplished, the exogenous progestagen supplementation protocol described here cannot be recommended for treatment of progesterone

Microfluidic Device for Controllable Chemical Release via Field-Actuated Membrane Incorporating Nanoparticles

Directory of Open Access Journals (Sweden)

Xiang Wang

2013-01-01

Full Text Available We report a robust magnetic-membrane-based microfluidic platform for controllable chemical release. The magnetic membrane was prepared by mixing polydimethylsiloxane (PDMS and carbonyl-iron nanoparticles together to obtain a flexible thin film. With combined, simultaneous regulation of magnetic stimulus and mechanical pumping, the desired chemical release rate can easily be realized. For example, the dose release experimental data was well fitted by a mathematical sigmoidal model, exhibiting a typical dose-response relationship, which shows promise in providing significant guidance for on-demand drug delivery. To test the platform’s feasibility, our microfluidic device was employed in an experiment involving Escherichia coli culture under controlled antibiotic ciprofloxacin exposure, and the expected outcomes were successfully obtained. Our experimental results indicate that such a microfluidic device, with high accuracy and easy manipulation properties, can legitimately be characterized as active chemical release system.

Microfluidic Device for Controllable Chemical Release via Field-Actuated Membrane Incorporating Nanoparticles

KAUST Repository

Wang, Xiang; Li, Shunbo; Wang, Limu; Yi, Xin; Hui, Yu Sanna; Qin, Jianhua; Wen, Weijia

2013-01-01

We report a robust magnetic-membrane-based microfluidic platform for controllable chemical release. The magnetic membrane was prepared by mixing polydimethylsiloxane (PDMS) and carbonyl-iron nanoparticles together to obtain a flexible thin film. With combined, simultaneous regulation of magnetic stimulus and mechanical pumping, the desired chemical release rate can easily be realized. For example, the dose release experimental data was well fitted by a mathematical sigmoidal model, exhibiting a typical dose-response relationship, which shows promise in providing significant guidance for on-demand drug delivery. To test the platform’s feasibility, our microfluidic device was employed in an experiment involving Escherichia coli culture under controlled antibiotic ciprofloxacin exposure, and the expected outcomes were successfully obtained. Our experimental results indicate that such a microfluidic device, with high accuracy and easy manipulation properties, can legitimately be characterized as active chemical release system.

Microfluidic Device for Controllable Chemical Release via Field-Actuated Membrane Incorporating Nanoparticles

KAUST Repository

Wang, Xiang

2013-01-01

We report a robust magnetic-membrane-based microfluidic platform for controllable chemical release. The magnetic membrane was prepared by mixing polydimethylsiloxane (PDMS) and carbonyl-iron nanoparticles together to obtain a flexible thin film. With combined, simultaneous regulation of magnetic stimulus and mechanical pumping, the desired chemical release rate can easily be realized. For example, the dose release experimental data was well fitted by a mathematical sigmoidal model, exhibiting a typical dose-response relationship, which shows promise in providing significant guidance for on-demand drug delivery. To test the platform’s feasibility, our microfluidic device was employed in an experiment involving Escherichia coli culture under controlled antibiotic ciprofloxacin exposure, and the expected outcomes were successfully obtained. Our experimental results indicate that such a microfluidic device, with high accuracy and easy manipulation properties, can legitimately be characterized as active chemical release system.

Estradiol-induced vaginal mucus inhibits antigen penetration and CD8(+) T cell priming in response to intravaginal immunization.

Science.gov (United States)

Seavey, Matthew M; Mosmann, Tim R

2009-04-14

Although vaginal immunization has been explored as a strategy to induce mucosal immunity in the female reproductive tract, this site displays unique immunological features that probably evolved to inhibit anti-paternal T cell responses after insemination to allow successful pregnancy. We previously demonstrated that estradiol, which induces an estrus-like state, prevented CD8(+) T cell priming during intravaginal immunization of mice. We now show that estradiol prevented antigen loading of vaginal antigen presenting cells (APCs) after intravaginal immunization. Histological examination confirmed that estradiol prevented penetration of peptide antigen into the vaginal wall. Removal of the estradiol-induced mucus barrier by mucinase partially restored antigen loading of vaginal APC and CD8(+) T cell proliferation in vivo. The estradiol-induced mucus barrier may thus prevent exposure to antigens delivered intravaginally, supplementing additional estradiol-dependent mechanism(s) that inhibit CD8(+) T cell priming after insemination or vaginal vaccination.

Estradiol-induced vaginal mucus inhibits antigen penetration and CD8+ T cell priming in response to intravaginal immunization

Science.gov (United States)

Seavey, Matthew M.; Mosmann, Tim R.

2010-01-01

Although vaginal immunization has been explored as a strategy to induce mucosal immunity in the female reproductive tract, this site displays unique immunological features that probably evolved to inhibit anti-paternal T cell responses after insemination to allow successful pregnancy. We previously demonstrated that estradiol, which induces an estrus-like state, prevented CD8+ T cell priming during intravaginal immunization of mice. We now show that estradiol prevented antigen loading of vaginal antigen presenting cells (APC) after intravaginal immunization. Histological examination confirmed that estradiol prevented penetration of peptide antigen into the vaginal wall. Removal of the estradiol-induced mucus barrier by mucinase partially restored antigen loading of vaginal APC and CD8+ T cell proliferation in vivo. The estradiol-induced mucus barrier may thus prevent exposure to antigens delivered intravaginally, supplementing additional estradiol-dependent mechanism(s) that inhibit CD8+ T cell priming after insemination or vaginal vaccination. PMID:19428849

Inhibition of Progesterone Metabolism Mimics the Effect of Progesterone Withdrawal on Forced Swim Test Immobility

OpenAIRE

Beckley, Ethan H.; Finn, Deborah A.

2007-01-01

Withdrawal from high levels of progesterone in rodents has been proposed as a model for premenstrual syndrome or postpartum depression. Forced swim test (FST) immobility, used to model depression, was assessed in intact female DBA/2J mice following progesterone withdrawal (PWD) or treatment with the 5α-reductase inhibitor finasteride. Following 5 daily progesterone injections (5 mg/kg IP) FST immobility increased only in mice withdrawn for 3 days (p < .05). In another experiment, 3 days of PW...

The use of progesterone RIA to increase efficiency and quality of artificial insemination services of beef cattle in South Sulawesi, Indonesia

International Nuclear Information System (INIS)

Toleng, L.; Sonjaya, H.; Yusuf, M.; Hamid, A.

2001-01-01

The technique of artificial insemination (AI) has been used in Indonesia for several years. The fertility rate resulting from this technique, however, is still lower than that for natural mating. Therefore, two studies were conducted to evaluate the factors that might cause lower efficiency of AI in beef cattle. The first was a survey to evaluate reproductive performance and factors that affect the inefficiency of AI. A total of 652 beef cows inseminated on one large and several small farms were used. Data for farm, cow, inseminator and each insemination were recorded. Serum samples were taken at the day of insemination (day 0), and days 10-12 and 20-22 after AI, and at time of manual pregnancy diagnosis. The second study was conducted to evaluate whether the induction of first postpartum oestrus in suckling cows could be done by hormonal treatments. Two groups of suckling Brahman cows were used, with and without treatment using Controlled Intra-vaginal Drug Release devices (CIDR). CIDR were inserted into the vagina, oestradiol benzoate (OB) was injected, the CIDR were removed after 12 days and two Als were performed at 24 and 72 hr later. The studies were conducted during dry and wet seasons. Mean overall conception rate (CR) for the large and small farms were 23 and 38%, respectively. Season of the year, housing system, type of heat, time of AI, and characteristics of AI technicians (level of education and non-AI work) affected the CR. Oestrus behaviour was detected in 95 and 100% of cows respectively for the first and the second period. However, the proportions of animals showing ovulatory oestrus during the first and second periods were 22 and 48% (P<0.01), and pregnancy rates were 12 and 24%, respectively. These findings show that reproductive rate of cows served by AI in this area is low and that factors related to the cow, farm management and AI technician affect this problem. CIDR treatment can induce oestrus behaviour in suckling cows, but only few of

Reproductive performance of Karakul ewes following different ...

African Journals Online (AJOL)

SAFDARIAN

breeding season), 180 Karakul ewes were stratified based on age and body weight ... on day 12; T2 - insertion of a controlled intravaginal drug releasing device .... Due to the presence of unbalanced data, the effect of replicate was analysed ...

Progesterone and women's anxiety across the menstrual cycle.

Science.gov (United States)

Reynolds, Tania A; Makhanova, Anastasia; Marcinkowska, Urszula M; Jasienska, Grazyna; McNulty, James K; Eckel, Lisa A; Nikonova, Larissa; Maner, Jon K

2018-04-24

Animal models and a few human investigations suggest progesterone may be associated with anxiety. Progesterone naturally fluctuates across the menstrual cycle, offering an opportunity to understand how within-person increases in progesterone and average progesterone levels across the cycle correspond to women's anxiety. Across two longitudinal studies, we simultaneously modeled the between- and within-person associations between progesterone and anxiety using multilevel modeling. In Study 1, 100 Polish women provided saliva samples and reported their anxiety at three phases of the menstrual cycle: follicular, peri-ovulatory, and luteal. A significant between-person effect emerged, revealing that women with higher average progesterone levels across their cycles reported higher levels of anxiety than women with lower progesterone cycles. This effect held controlling for estradiol. In Study 2, 61 American women provided saliva samples and reported their attachment anxiety during laboratory sessions during the same three cycle phases. A significant between-person and within-person association emerged: women with higher average progesterone levels reported higher levels of attachment anxiety, and as women's progesterone levels increased across their cycles, so too did their attachment anxiety. These effects held controlling for cortisol. In sum, both studies provide support for a link between menstrual cycle progesterone levels and subjective anxiety. Copyright © 2018. Published by Elsevier Inc.

Intrahippocampal administration of Vitamin C and progesterone ...

African Journals Online (AJOL)

Vitamin C and progesterone alone improved spatial memory in comparison to lesion group. Effective doses of vitamin C + effective dose of progesterone had more improving effect on memory. Keywords: Neuroscience, Neurosteroid, Antioxidant, Demylination, Progesterone, Learning and memory impairments, Multiple ...

Physiology, production and action of progesterone.

Science.gov (United States)

Taraborrelli, Stefania

2015-11-01

The aim of this article is to review the physiology of progesterone and focus on its physiological actions on tissues such as endometrium, uterus, mammary gland, cardiovascular system, central nervous system and bones. In the last decades, the interest of researchers has focused on the role of progesterone in genomic and non-genomic receptor mechanisms. We searched PubMed up to December 2014 for publications on progesterone/steroidogenesis. A better understanding of the biological genomic and non-genomic receptor mechanisms could enable us in the near future to obtain a more comprehensive knowledge of the safety and efficacy of this agent during hormone replacement therapy (natural progesterone), in vitro fertilization (water-soluble subcutaneous progesterone), in traumatic brain injury, Alzheimer's disease and diabetic neuropathy, even though further clinical studies are needed to prove its usefulness. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

Effects of equine chorionic gonadotrophin on follicular, luteal and conceptus development of non-lactating Bos indicus beef cows subjected to a progesterone plus estradiol-based timed artificial insemination protocol

Directory of Open Access Journals (Sweden)

Paulo Pitaluga Costa e Silva Filho

2013-08-01

Full Text Available The aim of this study was to evaluate the effects of equine chorionic gonadotropin (eCG on ovarian follicular responses, corpus luteum (CL development and conceptus length on day 16 after timed artificial insemination (TAI. A total of 124 cows at day 0 (D0 received 2 mg of estradiol benzoate (EB and the insertion of a progesterone (P4 intravaginal device. Eight days later, the device was removed, and cows received 0.15 mg of prostaglandin and 0.5 mg of estradiol cypionate (EC, and were randomly assigned to 1 of 2 treatments: eCG (n=60, in which cows received 300 U of eCG; and control (n=64. Cows were TAI 48 h after P4 device removal. The diameter of the largest follicle (LF present on D8 and D10 and of CL on D15 and D26 were measured. Conceptus recovered rate, conceptus length, CL diameter and weight were determined at slaughter on D26. Plasma P4 concentration was determined on D15 and D26. Follicular growth from D8 to D10 (P=0.03, the diameter of CL at D15 (P=0.03 and D26 (P=0.003 and the CL weight at day 26 (P=0.04 were greater in the eCG group than the control. However, there was no effect of eCG treatment on oestrus occurrence, conceptus recovery rate and length, or P4 concentrations on either D15 or D26. In conclusion, although eCG increases follicular responses and the diameter of the CL, this gonadotropin treatment does not influence the length of the conceptus or the P4 concentration on the subsequent oestrus cycle.

EDC IMPACT: Chemical UV filters can affect human sperm function in a progesterone-like manner.

Science.gov (United States)

Rehfeld, A; Egeberg, D L; Almstrup, K; Petersen, J H; Dissing, S; Skakkebæk, N E

2018-01-01

Human sperm cell function must be precisely regulated to achieve natural fertilization. Progesterone released by the cumulus cells surrounding the egg induces a Ca 2+ influx into human sperm cells via the CatSper Ca 2+ -channel and thereby controls sperm function. Multiple chemical UV filters have been shown to induce a Ca 2+ influx through CatSper, thus mimicking the effect of progesterone on Ca 2+ signaling. We hypothesized that these UV filters could also mimic the effect of progesterone on sperm function. We examined 29 UV filters allowed in sunscreens in the US and/or EU for their ability to affect acrosome reaction, penetration, hyperactivation and viability in human sperm cells. We found that, similar to progesterone, the UV filters 4-MBC, 3-BC, Meradimate, Octisalate, BCSA, HMS and OD-PABA induced acrosome reaction and 3-BC increased sperm penetration into a viscous medium. The capacity of the UV filters to induce acrosome reaction and increase sperm penetration was positively associated with the ability of the UV filters to induce a Ca 2+ influx. None of the UV filters induced significant changes in the proportion of hyperactivated cells. In conclusion, chemical UV filters that mimic the effect of progesterone on Ca 2+ signaling in human sperm cells can similarly mimic the effect of progesterone on acrosome reaction and sperm penetration. Human exposure to these chemical UV filters may impair fertility by interfering with sperm function, e.g. through induction of premature acrosome reaction. Further studies are needed to confirm the results in vivo . © 2018 The authors.

EDC IMPACT: Chemical UV filters can affect human sperm function in a progesterone-like manner

Directory of Open Access Journals (Sweden)

A Rehfeld

2017-12-01

Full Text Available Human sperm cell function must be precisely regulated to achieve natural fertilization. Progesterone released by the cumulus cells surrounding the egg induces a Ca2+ influx into human sperm cells via the CatSper Ca2+-channel and thereby controls sperm function. Multiple chemical UV filters have been shown to induce a Ca2+ influx through CatSper, thus mimicking the effect of progesterone on Ca2+ signaling. We hypothesized that these UV filters could also mimic the effect of progesterone on sperm function. We examined 29 UV filters allowed in sunscreens in the US and/or EU for their ability to affect acrosome reaction, penetration, hyperactivation and viability in human sperm cells. We found that, similar to progesterone, the UV filters 4-MBC, 3-BC, Meradimate, Octisalate, BCSA, HMS and OD-PABA induced acrosome reaction and 3-BC increased sperm penetration into a viscous medium. The capacity of the UV filters to induce acrosome reaction and increase sperm penetration was positively associated with the ability of the UV filters to induce a Ca2+ influx. None of the UV filters induced significant changes in the proportion of hyperactivated cells. In conclusion, chemical UV filters that mimic the effect of progesterone on Ca2+ signaling in human sperm cells can similarly mimic the effect of progesterone on acrosome reaction and sperm penetration. Human exposure to these chemical UV filters may impair fertility by interfering with sperm function, e.g. through induction of premature acrosome reaction. Further studies are needed to confirm the results in vivo.

Externally placed vs intravaginally positioned radio frequency coils for quantitative spin-spin relaxometry of ovarian follicular fluid

International Nuclear Information System (INIS)

Sarty, G.E.; Baerwald, A.R.; Loewy, J.; Pierson, R.A.

2005-01-01

To evaluate different imaging protocols, especially with respect to radio frequency (RF) receiver coil location, for Their suitability in providing least squares derived quantitative T 2 values of ovarian follicular fluid for investigations of basic ovarian physiology. Methods: The ovaries of 10 women were imaged via magnetic resonance imaging (MRI) using externally positioned and intravaginally placed RF receiver coils. Half-Fourier acquisition with single-shot turbo spin-echo (HASTE), multiple-echo T 2 , Dixon, turbo spin-echo, and 3-dimensional (3D) fast imaging with steady-state precession (FISP) and time-reversed FISP (PSIF) sequences were used. Quantitative T 2 nuclear spin relaxation rate information from the ovarian follicles between data acquired with the external and intravaginal coils were compared. Additionally, the amount of ovarian follicle and corpora lutea structural detail visible was qualitatively assessed. Results: The T 2 computations indicated that there was no difference in the follicular fluid T 2 values or in the heterogeneity (spatial variance) of the T 2 values between data acquired with the external RF coil and date acquired with the intravaginal RF coil. The best sequences for the visualization of ovarian internal structure were the 3D PSIF sequences and the multiple-echo T 2 -weighted images, confirming our earlier imaging work on excised cow ovaries. Conclusion: It is best to use an externally placed RF coil for quantitative MRI study of ovarian physiology given the lack of difference in quantitative T 2 information and the difficulty associated with imaging the ovaries using an intravaginal RF probe. (author)

Slide release mechanism. [for space shuttle orbiter/external tank connection device

Science.gov (United States)

Bunker, J. W.; Ritchie, R. S. (Inventor)

1985-01-01

A releasable support device is described which is comprised of a hollow body with a sleeve extending transversely there-through for receiving the end of a support shank. A slider-latch, optionally lubricated, extends through side recesses in the sleeve to straddle the shank, respectively, in latched and released positions. The slider-latch is slid from its latched to its unlatched position by a pressure squib whereupon a spring or other pressure means pushes the shank out of the sleeve. At the same time, a follower element is lodged in and closed the hole in the body wall from which the shank was discharged. The mechanism was designed for the shuttle orbiter/external tank connection device.

An integrated device for magnetically-driven drug release and in situ quantitative measurements: Design, fabrication and testing

Energy Technology Data Exchange (ETDEWEB)

Bruvera, I.J. [Aragon Institute of Nanoscience (INA), University of Zaragoza, 50018 (Spain); Hernández, R.; Mijangos, C. [Instituto de Ciencia y Tecnología de Polímeros, CSIC, Juan Cierva 3, E-28006 Madrid (Spain); Goya, G.F., E-mail: goya@unizar.es [Aragon Institute of Nanoscience (INA), University of Zaragoza, 50018 (Spain); Condensed Matter Physics Department, Science Faculty, University of Zaragoza, 50009 (Spain)

2015-03-01

We have developed a device capable of remote triggering and in situ quantification of therapeutic drugs, based on magnetically-responsive hydrogels of poly (N-isopropylacrylamide) and alginate (PNiPAAm). The heating efficiency of these hydrogels measured by their specific power absorption (SPA) values showed that the values between 100 and 300 W/g of the material were high enough to reach the lower critical solution temperature (LCST) of the polymeric matrix within few minutes. The drug release through application of AC magnetic fields could be controlled by time-modulated field pulses in order to deliver the desired amount of drug. Using B12 vitamin as a concept drug, the device was calibrated to measure amounts of drug released as small as 25(2)×10{sup −9} g, demonstrating the potential of this device for very precise quantitative control of drug release. - Highlights: • A device for magnetically driven drug release was developed and constructed. • Thermally responsive PNiPAAm and Fe3O4 nanoparticles were usedas drug reservoir. • The device allowed repetitive, remote and precisely controlled drug release. • By in situ spectrometry we could detect released drug quantities as small as 25 ng. • Released drug was controlled through magnetic ac field parameters H, f and time.

An integrated device for magnetically-driven drug release and in situ quantitative measurements: Design, fabrication and testing

International Nuclear Information System (INIS)

Bruvera, I.J.; Hernández, R.; Mijangos, C.; Goya, G.F.

2015-01-01

We have developed a device capable of remote triggering and in situ quantification of therapeutic drugs, based on magnetically-responsive hydrogels of poly (N-isopropylacrylamide) and alginate (PNiPAAm). The heating efficiency of these hydrogels measured by their specific power absorption (SPA) values showed that the values between 100 and 300 W/g of the material were high enough to reach the lower critical solution temperature (LCST) of the polymeric matrix within few minutes. The drug release through application of AC magnetic fields could be controlled by time-modulated field pulses in order to deliver the desired amount of drug. Using B12 vitamin as a concept drug, the device was calibrated to measure amounts of drug released as small as 25(2)×10 −9 g, demonstrating the potential of this device for very precise quantitative control of drug release. - Highlights: • A device for magnetically driven drug release was developed and constructed. • Thermally responsive PNiPAAm and Fe3O4 nanoparticles were usedas drug reservoir. • The device allowed repetitive, remote and precisely controlled drug release. • By in situ spectrometry we could detect released drug quantities as small as 25 ng. • Released drug was controlled through magnetic ac field parameters H, f and time

Compartmental transport model of microbicide delivery by an intravaginal ring

Science.gov (United States)

Geonnotti, Anthony R.; Katz, David F.

2010-01-01

Topical antimicrobials, or microbicides, are being developed to prevent HIV transmission through local, mucosal delivery of antiviral compounds. While hydrogel vehicles deliver the majority of current microbicide products, intravaginal rings (IVRs) are an alternative microbicide modality in preclinical development. IVRs provide a long-term dosing alternative to hydrogel use, and might provide improved user adherence. IVR efficacy requires sustained delivery of antiviral compounds to the entire vaginal compartment. A two-dimensional, compartmental vaginal drug transport model was created to evaluate the delivery of drugs from an intravaginal ring. The model utilized MRI-derived ring geometry and location, experimentally defined ring fluxes and vaginal fluid velocities, and biophysically relevant transport theory. Model outputs indicated the presence of potentially inhibitory concentrations of antiviral compounds along the entire vaginal canal within 24 hours following IVR insertion. Distributions of inhibitory concentrations of antiviral compounds were substantially influenced by vaginal fluid flow and production, while showing little change due to changes in diffusion coefficients or ring fluxes. Additionally, model results were predictive of in vivo concentrations obtained in clinical trials. Overall, this analysis initiates a mechanistic computational framework, heretofore missing, to understand and evaluate the potential of IVRs for effective delivery of antiviral compounds. PMID:20222027

Autoimmune Progesterone Dermatitis Presenting as Stevens-Johnson Syndrome.

Science.gov (United States)

Drayer, Sara M; Laufer, Larry R; Farrell, Maureen E

2017-10-01

Autoimmune progesterone dermatitis is an uncommon disease presenting with cyclical skin eruptions corresponding with the menstrual cycle luteal phase. Because symptoms are precipitated by rising progesterone levels, treatment relies on hormone suppression. A 22-year-old nulligravid woman presented with symptoms mistaken for Stevens-Johnson syndrome. A cyclic recurrence of her symptoms was noted, and the diagnosis of autoimmune progesterone dermatitis was made by an intradermal progesterone challenge. After 48 months, she remained refractory to medical management and definitive surgical treatment with bilateral oophorectomy was performed. Autoimmune progesterone dermatitis is a challenging diagnosis owing to its rarity and variety of clinical presentations. Treatment centers on suppression of endogenous progesterone and avoidance of exogenous triggers. When these modalities fail, surgical management must be undertaken.

The effects of intrahippocampus injection of progesterone on passive avoidance learning and memory in adult male rats

Directory of Open Access Journals (Sweden)

Tahmoores Shahrivar

2014-10-01

Full Text Available Background: Progesterone as a reproductive hormone is studied in the brain structure. New studies are mainly about systemic injection and have shown that the progesterone has different effects on memory. But it is not clear if hippocampus is mediator of progesterone in reinforcement of memory and learning. So, the effects of intra-hippocampal injection of progesterone on passive avoidance memory and learning was studied in male Wistar rats. Material and Methods: Animals were divided in eightgroups as a control, saline, almond oil (as a vehicle and progesterone groups (0.5, 1, 1.5, 2, 3µg/Kg. body weight. All groups except the control were cannulated in left CA1 area by stereotaxic device. One week after recovery, all groups were trained by shuttle box and immediately after training different doses of progesterone in the volume of 0.5μL were injected through the cannula in CA1 of hippocampus and control groups received saline and almond oil at the same volume and condition respectively. After 48 hours passive avoidance memory and learning was evaluated. Results: Statistical analysis showed that 0.5, 1.5, 2 µg/µl progesterone groups had significantly improved passive avoidance learning and memory compared with saline group (p <0.001, but 1 and 3 µg/µl progesterone groups did not show significant effect on passive avoidance learning and memory compared with saline group. Also almond oil increased passive avoidance learning and memory compared with saline group (p <0.001. Conclusion: It seems that effects of progesterone as a neurosteroid on memory and learning depend on its dose. Also almond oil contains vitamin E, omega 3 and oleic acid that has beneficial effects on learning and memory.

Short communication: Acute but transient increase in serum insulin reduces messenger RNA expression of hepatic enzymes associated with progesterone catabolism in dairy cows.

Science.gov (United States)

Vieira, F V R; Cooke, R F; Aboin, A C; Lima, P; Vasconcelos, J L M

2013-02-01

The objective of this experiment was to evaluate the effects of glucose infusion on serum concentrations of glucose, insulin, and progesterone (P4), as well as mRNA expression of hepatic CYP2C19 and CYP3A4 in nonlactating, ovariectomized cows in adequate nutritional status. Eight Gir × Holstein cows were maintained on a low-quality Brachiaria brizantha pasture with reduced forage availability, but they individually received, on average, 3 kg/cow daily (as fed) of a corn-based concentrate from d -28 to 0 of the experiment. All cows had an intravaginal P4-releasing device inserted on d -14, which remained in cows until the end of the experiment (d 1). On d 0, cows were randomly assigned to receive, in a crossover design containing 2 periods of 24h each (d 0 and 1), (1) an intravenous glucose infusion (GLUC; 0.5 g of glucose/kg of BW, over a 3-h period) or (2) an intravenous saline infusion (SAL; 0.9%, over a 3-h period). Cows were fasted for 12h before infusions, and they remained fasted during infusion and sample collections. Blood samples were collected at 0, 3, and 6h relative to the beginning of infusions. Liver biopsies were performed concurrently with blood collections at 0 and 3h. After the last blood collection of period 1, cows received concentrate and returned to pasture. Cows gained BW (16.5 ± 3.6 kg) and BCS (0.08 ± 0.06) from d -28 to 0. Cows receiving GLUC had greater serum glucose and insulin concentrations at 3h compared with SAL cohorts. No treatment effects were detected for serum P4 concentrations, although mRNA expression of CYP2C19 and CYP3A4 after the infusion period was reduced for cows in the GLUC treatment compared with their cohorts in the SAL treatment. In conclusion, hepatic CYP3A4 and CYP2C19 mRNA expression can be promptly modulated by glucose infusion followed by acute increases in circulating insulin, which provides novel insight into the physiological mechanisms associating nutrition and reproductive function in dairy cows

In vivo evaluation of a mucoadhesive polymeric caplet for intravaginal anti-HIV-1 delivery and development of a molecular mechanistic model for thermochemical characterization.

Science.gov (United States)

Ndesendo, Valence M K; Choonara, Yahya E; Meyer, Leith C R; Kumar, Pradeep; Tomar, Lomas K; Tyagi, Charu; du Toit, Lisa C; Pillay, Viness

2015-01-01

The aim of this study was to develop, characterize and evaluate a mucoadhesive caplet resulting from a polymeric blend (polymeric caplet) for intravaginal anti-HIV-1 delivery. Poly(lactic-co-glycolic) acid, ethylcellulose, poly(vinylalcohol), polyacrylic acid and modified polyamide 6, 10 polymers were blended and compressed to a caplet-shaped device, with and without two model drugs 3'-azido-3'-deoxythymidine (AZT) and polystyrene sulfonate (PSS). Thermal analysis, infrared spectroscopy and microscopic analysis were carried out on the caplets employing temperature-modulated DSC (TMDSC), Fourier transform infra-red (FTIR) spectrometer and scanning electron microscope, respectively. In vitro and in vivo drug release analyses as well as the histopathological toxicity studies were carried out on the drug-loaded caplets. Furthermore, molecular mechanics (MM) simulations were carried out on the drug-loaded caplets to corroborate the experimental findings. There was a big deviation between the Tg of the polymeric caplet from the Tg's of the constituent polymers indicating a strong interaction between constituent polymers. FTIR spectroscopy confirmed the presence of specific ionic and non-ionic interactions within the caplet. A controlled near zero-order drug release was obtained for AZT (20 d) and PSS (28 d). In vivo results, i.e. the drug concentration in plasma ranged between 0.012-0.332 mg/mL and 0.009-0.256 mg/mL for AZT and PSS over 1-28 d. The obtained results, which were corroborated by MM simulations, attested that the developed system has the potential for effective delivery of anti-HIV-agents.

Direct effect of gonadal and contraceptive steroids on insulin release from mouse pancreatic islets in organ culture

DEFF Research Database (Denmark)

Nielsen, Jens Høiriis

1984-01-01

Sex steroids are supposed to contribute to the normal glucose homeostasis and to the altered glucose and insulin metabolism in pregnancy and during contraception. In the present study isolated mouse pancreatic islets were maintained in tissue culture medium RPMI 1640 supplemented with 0.5% newborn...... calf serum and 100 ng/ml of one of the following steroids: oestradiol, progesterone, testosterone, megestrol acetate, medroxyprogesterone, chlormadinone acetate, norethynodrel, norethindrone acetate, and ethynyloestradiol. Release of insulin to the culture medium was measured during a 2 week culture...... in the presence of oestradiol, progesterone, or testosterone were subjected to 30 min stimulation with 5.5, 11, 22 mmol/l glucose, only the progesterone-treated islets released more insulin in response to glucose than the control islets. It is concluded that progesterone and its derivatives have a direct effect...

Chemical UV Filters Mimic the Effect of Progesterone on Ca(2+) Signaling in Human Sperm Cells

DEFF Research Database (Denmark)

Rehfeld, A; Dissing, S; Skakkebæk, N E

2016-01-01

Progesterone released by cumulus cells surrounding the egg induces a Ca(2+) influx into human sperm cells via the cationic channel of sperm (CatSper) Ca(2+) channel and controls multiple Ca(2+)-dependent responses essential for fertilization. We hypothesized that chemical UV filters may mimic...

EFFECT OF POST-MATING GNRH TREATMET ON SERUM PROGESTERONE, LUTEINIZING HORMONE LEVELS, DURATION OF ESTROUS CYCLE AND PREGNANCY RATES IN COWS

Directory of Open Access Journals (Sweden)

H. YILDIZ, E. KAYGUSUZOĞLU, M. KAYA1 AND M. ÇENESIZ1

2009-07-01

Full Text Available Pregnancy rate, estrous cycle lenght, serum progesterone and luteinizing hormone (LH concentrations were determined in gonadotropin releasing hormone (GnRH; 10.5 μg synthetic gonadotrophin releasing hormone agonist, receptal administered cows on day 12 post-mating (n=9 compared to control cows (n=8. Their oestrous cycles were synchronised by intramuscular administration of prostaglandin F2 alpha (its analog, cloprostenol twice at 11 days interval. Estrous exhibited cows were mated naturally. Blood samples were collected every two days from all animals. Serum progesterone and LH concentrations were measured by ELISA method. GnRH administration significantly increased serum LH concentration which reached peak levels 2-3 h after treatment. However, serum progesterone concentration was not affected. There were no differences in mean progesterone concentrations on days 12 to 24 post-mating between GnRH administrated and control pregnant cows. However, in non pregnant animals, progesterone concentrations on days 16 in the treated group were lower than control group (P<0.01. Pregnancy diagnosis in animals made by B-mode ultrasonography between the 30th and 35th day showed that 77.7% of treated cows were pregnant compared to 50% in control group. Duration of the estrous cycle in the non-pregnant animals was not affected by the treatment (control, 21.3 ± 0.8 days; treated, 22.5 ± 0.5 days. In conclusion, this study supports the use of GnRH on day 12 post-mating as a method for enhancing pregnancy rates in lactating dairy cattle.

Decreased endogenous progesterone and ratio of progesterone to ...

African Journals Online (AJOL)

PRECIOUS

2010-02-01

Feb 1, 2010 ... 30 control subjects (15 men and 15 women) of comparable age. There were ... estrogens and progestins makes the brain more vulnerable to acute insults ... estrogen or ratio of progesterone to estrogen is different in ischemia ...

Radioimmunoassay for progesterone in bovine milk

International Nuclear Information System (INIS)

Ruiz, Miriam; Figueredo, Nancy; Castillo, Sonia; Pizarro

2002-01-01

A system for the measurement of progesterone in bovine milk by radioimmunoassay has been developed and validated. This assay includes an iodine tracer purified by HPLC, the standard prepared in fat-free milk and an antibody anti-progesterone combined with second antibody. The detection limit of the assay is at 0.2 nmol/L calculated from the maximum binding menus two standard deviations and the precision is satisfactory. In the recovery assay was used 4 milk different samples and the result was 98% of recuperation. The progesterone was determinate in milk samples from post-partum animals taking samples three times per week for 40 days. The assay is simple, rapid and possibility the progesterone measurement without sample dilution, distinguish the cyclic changes of this hormone that reflect the ovarian activity in the animals. (author)

Basal progesterone level as the main determinant of progesterone elevation on the day of hCG triggering in controlled ovarian stimulation cycles.

Science.gov (United States)

Papaleo, Enrico; Corti, Laura; Vanni, Valeria Stella; Pagliardini, Luca; Ottolina, Jessica; De Michele, Francesca; La Marca, Antonio; Viganò, Paola; Candiani, Massimo

2014-07-01

Modest increases of serum progesterone at human chorionic gonadotrophin (hCG) administration in controlled ovarian hyperstimulation (COH) cycles have been shown to have a negative impact on pregnancy outcomes. The aim of this study was to identify early predictors of progesterone elevation at hCG. Pregnancy outcome of 303 consecutive patients undergoing COH and fresh day-3 embryo transfer was analysed. Considering the non-linear relationship between progesterone at hCG triggering and pregnancy outcomes, partial area under the curve (pAUC) analysis was used to implement marker identification potential of receiver operating characteristic (ROC) curve analysis. Multivariate logistic analysis was then performed to identify predictors of progesterone rise. Pregnancy outcomes could be predicted by pAUC analysis (pAUC = 0.58, 95 % CI 0.51-0.66, p = 0.02) and a significant detrimental cut-off could be calculated (progesterone at hCG > 1.35 ng/ml). Total dose of rFSH administered, E2 level at hCG but mostly basal progesterone level (OR = 12.21, 95 % CI 1.82-81.70) were predictors of progesterone rise above the cut-off. Basal progesterone is shown to be the main prognostic factor for progesterone elevation. This observation should be taken into consideration in the clinical management of IVF/ICSI cycles to improve pregnancy outcomes.

Slow-release fluoride devices for the control of dental decay.

Science.gov (United States)

Chong, Lee-Yee; Clarkson, Jan E; Dobbyn-Ross, Lorna; Bhakta, Smriti

2018-03-01

Slow-release fluoride devices have been investigated as a potentially cost-effective method of reducing dental caries in people with high risk of disease. This is the second update of the Cochrane Review first published in 2006 and previously updated in 2014. To evaluate the effectiveness and safety of different types of slow-release fluoride devices on preventing, arresting, or reversing the progression of carious lesions on all surface types of primary (deciduous) and permanent teeth. Cochrane Oral Health's Information Specialist searched the following electronic databases: Cochrane Oral Health's Trials Register (to 23 January 2018); the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 12) in the Cochrane Library (searched 23 January 2018); MEDLINE Ovid (1946 to 23 January 2018); and Embase Ovid (1980 to 23 January 2018). The US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials (23 January 2018). We placed no restrictions on the language or date of publication when searching the electronic databases. Parallel randomised controlled trials (RCTs) comparing slow-release fluoride devices with an alternative fluoride treatment, placebo, or no intervention in all age groups. The main outcome measures sought were changes in numbers of decayed, missing, and filled teeth or surfaces (DMFT/DMFS in permanent teeth or dmft/dmfs in primary teeth), and progression of carious lesions through enamel and into dentine. We conducted data collection and analysis using standard Cochrane review methods. At least two review authors independently performed all the key steps in the review such as screening of abstracts, application of inclusion criteria, data extraction, and risk of bias assessment. We resolved discrepancies through discussions or arbitration by a third or fourth review author. We found no evidence comparing slow-release

Change of progesterone level in the uterine venous plasma of pregnant guinea-pigs and progesterone biosynthesis by the placenta in vitro

International Nuclear Information System (INIS)

Sawasaki, Toru

1977-01-01

Placental tissue slices of guinea-pigs were incubated in Krebs-Ringer phosphate buffer containing NAD and glucose using pregnenolone-4- 14 C as a substrate. The amount of progesterone converted from pregnenolone by the placenta at 50 days after mating was significantly larger than that of 64-65 days after mating (0.205 and 0.159 μg/100 mg/hr., P < 0.05). The 3 β-hydroxysteroid dehydrogenase activity of the placenta seems to decrease at the last stage of pregnancy. Progesterone levels in the systemic and uterine venous plasma of the pregnant guinea-pigs were measured. There was no significant difference between them at the middle and later stages of pregnancy. This suggested that uterine venous plasma progesterone level was not affected by the placental progesterone. The progesterone levels in both systemic and uterine venous plasma were high in middle stage and low at the end of pregnancy, but rapid decrease of progesterone reflecting initiation of parturition, as seen in many other species, was not observed. In this species, the relationship between progesterone level and initiation of parturition is seemed to be specific, being complicated by the local effect of placental progesterone on the fetus or the uterus. (auth.)

Performance of the fully automated progesterone assays on the Abbott AxSYM and the Technicon Immuno 1 Analyser compared with the radioimmunoassay progesterone MAIA

International Nuclear Information System (INIS)

Reinsberg, J.; Jost, E.; Van der Ven, H.

1997-01-01

Test performance of two automated progesterone assays available on the immunoassay analysers Abbott AxSYM and Technicon Immuno 1, respectively, was evaluated in comparison with the radioimmunoassay Progesterone MAIA. For assessment of test performance imprecision, functional sensitivity and linearity of dilution was examined. Correlation with the manual radioimmunoassay was assessed using 122 serum samples over the range 0-110 nmol/L. Imprecision studies revealed for the AxSYM Progesterone within-run CV's of 1.8-6.4% and day-to-day CV's of 3.5-9.7% (concentration range 2.3-75 nmol/L); Immuno 1 Progesterone: within-run CV's 1.0-7.3%, day-to-day CV's 2.3-7.7% (concentration range 1.2-60 nmol/L). The functional sensitivity was <1.7 nmol/L for the AxSYM Progesterone and <1.1 nmol/L for the Immuno 1 Progesterone. With the AxSYM Progesterone the mean recovery after dilution from five samples was 102% (89-107%), from one sample only 69-80% was recovered; with the Immuno 1 Progesterone the mean recovery was 95% (80-105%). Despite of a quite good overall correlation (coefficients 0.972 and 0.981) the relationship of both assays to the Progesterone MAIA significantly deviate from linearity with a considerably higher slope within the lower concentration range. The relationship between the automated assays was linear over the entire concentration range (Immuno = 1.207 * AxSYM + 1; r = 0.986). The time to first result was 20 min for the AxSYM Progesterone, 45 min for the Immuno 1 Progesterone and 90 min for the Progesterone MAIA. The evaluated progesterone assays both exhibit an excellent precision and a high degree of sensitivity. They offer a rapid and flexible method for progesterone determination which may be especially useful for the monitoring of ovarian stimulation during in-vitro fertilization. (author)

Progesterone Test

Science.gov (United States)

... replacement therapy, or help diagnose the cause of abnormal uterine bleeding When To Get Tested? At specific times during ... receiving progesterone replacement therapy; when a woman has abnormal uterine bleeding Sample Required? A blood sample drawn from a ...

Effects of progesterone and its metabolites on human granulosa cells.

Science.gov (United States)

Pietrowski, D; Gong, Y; Mairhofer, M; Gessele, R; Sator, M

2014-02-01

The corpus luteum (CL) is under control of gonadotrophic hormones and produces progesterone, which is necessary for endometrial receptivity. Recent studies have shown that progesterone and its metabolites are involved in cell proliferation and apoptosis of cancer cells. Here weanalyzed the role of progesterone and its meta-bolites on luteinized granulosa cells (LGC) by FACS analysis and quantitative Real-Time PCR. We detected the mRNA of the progesterone metabolizing genes SRD5A1, AKR1C1, and AKR1C2 in LGC. The stimulation of LGC with progesterone or progesterone metabolites did not show any effect on the mRNA expression of these genes. However, a downregulation of Fas expression was found to be accomplished by progesterone and human chorionic gonadotropin. Our findings do not support the concept of an effect of progesterone metabolites on LGCs. However, it suggests an antiapoptotic effect of hCG and progesterone during corpus luteum development by downregulation of Fas. © Georg Thieme Verlag KG Stuttgart · New York.

Radioimmunoassay of serum d-Norgestrel in women following oral and intravaginal administration

International Nuclear Information System (INIS)

Stanczyk, F.Z.; Hiroi, M.; Goebelsmann, U.; Brenner, P.F.; Lumkin, M.E.; Mishell, D.R. Jr.

1975-01-01

A radioimmunoassay (RIA) method for measuring d-Norgestrel (d-Ng) in serum has been developed utilizing petroleum ether extraction, an antiserum raised against d-Norgestrel-3-(0-carboxymethyl) oxime-epsilon-aminocaproic acid--boxine serum albumin, d-Norgestrel-3-(0-carboxymethyl) imino-[ 125 I]-iodohistamine, and dextran-coated charcoal separation. Control serum blanks were undetectable, 6 pg of d-Ng was measurable in 0.1 ml of serum with a high reliability, and intra- and interassay coefficients of variation were 4.4 and 4.9 percent, respectively. d-Ng added to control serum was quantitatively recovered. This RIA proved to be highly specific for d-Ng, cross-reacting less than 0.01 percent with 1-Ng and some 4 to 8 percent with 5α- and 5β-tetrahydro-d-Ng. Serum d-Ng levels measured in 3 women after ingestion of 75 μg of dl-Ng rose to 1.5 to 2 ng/ml within 1/2 to 2-3 hours after oral intake and fell rapidly thereafter to 0.2 to 0.4 ng/ml within 24 hours. Insertion of Silastic intravaginal rings (IVRs), containing 50 or 100 mg of dl-Ng, into 3 women for periods of 3 weeks resulted in a rapid rise of serum d-Ng after insertion. Serum d-Ng levels were highest 24 to 48 hours after the first insertion of each IVR, reaching peak levels of about 5 and 7 to 11 ng/ml, respectively, and declined gradually during the ensuing 15 to 20 days to some 30 to 40 percent of the peak serum d-Ng concentration. Serum d-Ng levels attained after IVR reinsertion remained relatively constant at 1 to 3 ng/ml during each subsequent cycle in all subjects and fell rapidly after each IVR removal. Serum estradiol and progesterone concentrations, measured about 3 times a week in these patients, indicated that ovulation was consistently inhibited

High Infection Rates for Adult Macaques after Intravaginal or Intrarectal Inoculation with Zika Virus

Science.gov (United States)

Nalca, Aysegul; Rossi, Franco D.; Miller, Lynn J.; Wiley, Michael R.; Perez-Sautu, Unai; Washington, Samuel C.; Norris, Sarah L.; Wollen-Roberts, Suzanne E.; Shamblin, Joshua D.; Kimmel, Adrienne E.; Bloomfield, Holly A.; Valdez, Stephanie M.; Sprague, Thomas R.; Principe, Lucia M.; Bellanca, Stephanie A.; Cinkovich, Stephanie S.; Lugo-Roman, Luis; Cazares, Lisa H.; Pratt, William D.; Palacios, Gustavo F.; Bavari, Sina; Pitt, M. Louise; Nasar, Farooq

2017-01-01

Unprotected sexual intercourse between persons residing in or traveling from regions with Zika virus transmission is a risk factor for infection. To model risk for infection after sexual intercourse, we inoculated rhesus and cynomolgus macaques with Zika virus by intravaginal or intrarectal routes. In macaques inoculated intravaginally, we detected viremia and virus RNA in 50% of macaques, followed by seroconversion. In macaques inoculated intrarectally, we detected viremia, virus RNA, or both, in 100% of both species, followed by seroconversion. The magnitude and duration of infectious virus in the blood of macaques suggest humans infected with Zika virus through sexual transmission will likely generate viremias sufficient to infect competent mosquito vectors. Our results indicate that transmission of Zika virus by sexual intercourse might serve as a virus maintenance mechanism in the absence of mosquito-to-human transmission and could increase the probability of establishment and spread of Zika virus in regions where this virus is not present. PMID:28548637

High Infection Rates for Adult Macaques after Intravaginal or Intrarectal Inoculation with Zika Virus.

Science.gov (United States)

Haddow, Andrew D; Nalca, Aysegul; Rossi, Franco D; Miller, Lynn J; Wiley, Michael R; Perez-Sautu, Unai; Washington, Samuel C; Norris, Sarah L; Wollen-Roberts, Suzanne E; Shamblin, Joshua D; Kimmel, Adrienne E; Bloomfield, Holly A; Valdez, Stephanie M; Sprague, Thomas R; Principe, Lucia M; Bellanca, Stephanie A; Cinkovich, Stephanie S; Lugo-Roman, Luis; Cazares, Lisa H; Pratt, William D; Palacios, Gustavo F; Bavari, Sina; Pitt, M Louise; Nasar, Farooq

2017-08-01

Unprotected sexual intercourse between persons residing in or traveling from regions with Zika virus transmission is a risk factor for infection. To model risk for infection after sexual intercourse, we inoculated rhesus and cynomolgus macaques with Zika virus by intravaginal or intrarectal routes. In macaques inoculated intravaginally, we detected viremia and virus RNA in 50% of macaques, followed by seroconversion. In macaques inoculated intrarectally, we detected viremia, virus RNA, or both, in 100% of both species, followed by seroconversion. The magnitude and duration of infectious virus in the blood of macaques suggest humans infected with Zika virus through sexual transmission will likely generate viremias sufficient to infect competent mosquito vectors. Our results indicate that transmission of Zika virus by sexual intercourse might serve as a virus maintenance mechanism in the absence of mosquito-to-human transmission and could increase the probability of establishment and spread of Zika virus in regions where this virus is not present.

Evaluation of the acceptability of intravaginal prasterone ovule administration using an applicator.

Science.gov (United States)

Montesino, Marlene; Labrie, Fernand; Archer, David F; Zerhouni, Jaâfar; Côté, Isabelle; Lavoie, Lyne; Beauregard, Adam; Martel, Céline; Vaillancourt, Mario; Moyneur, Erick; Balser, John

2016-01-01

The objective of the study is to evaluate the acceptability of the intravaginal administration of ovules/suppositories of DHEA (dehydroepiandrosterone, prasterone) for the treatment of vulvovaginal atrophy (VVA) in women with moderate to severe dyspareunia who were administered daily for 12 weeks intravaginal 0.50% (6.5 mg) DHEA or placebo. There were a total of 373 women in the per-protocol population who responded to the questionnaire for both treatment groups. While it was planned that the applicator would be evaluated as suitable if at least 80% of participants have a global score  ≤ 2 units, 99% and 100% of participants had a score  ≤ 2 units in the placebo and DHEA groups, respectively, for the global score (mean of 5 questions). When asked about like and dislike the technique of drug administration, 284 comments were positive, while 114 women gave no comment. About 92-94% of women indicated that they were very confident to be able use the applicator successfully in the future. The survey shows a high degree of satisfaction and of confidence to use the applicator successfully in the future.

Estrus synchronization and artificial insemination of hair sheep ewes in the tropics.

Science.gov (United States)

Godfrey, R W; Collins, J R; Hensley, E L; Wheaton, J E

1999-04-01

Hair sheep ewes (St. Croix White and Barbados Blackbelly) were used to evaluate 3 methods of estrus synchronization for use with transcervical artificial insemination (TAI). To synchronize estrus, ewes (n = 18) were treated with PGF2alpha (15 mg, im) 10 d apart, with controlled internal drug release (CIDR) devices containing 300 mg progesterone for 12 d (n = 18), or with intravaginal sponges containing 500 mg progesterone for 12 d (n = 18). On the day of the second PGF2alpha injection or at CIDR or sponge removal, sterile rams were placed with the ewes. Jugular blood samples were collected from the ewes at 6-h intervals until the time of ovulation, and daily for 16 d after estrus (Day 0). Plasma was harvested and stored at -20 degrees C until LH, and progesterone concentrations were determined by RIA. There was no difference (P>0.10) in time to estrus among the CIDR-, PGF2alpha- or sponge-treated ewes. All of the ewes in the CIDR group and 94.4% of the sponge treated ewes exhibited estrus by 36 h after ram introduction, while only 72.2% of PGF2alpha-treated ewes showed signs of estrus by this time (P0.10) among the CIDR-, PGF2alpha- or sponge-treated ewes. The time to the preovulatory LH surge was similar (P>0.10) among CIDR, PGF2alpha and sponge treated ewes. Progesterone levels through Day 16 after the synchronized estrus were not different (P>0.10) among treatment groups. Hair sheep ewes (n = 23) were synchronized using PGF2alpha and bred by TAI using frozen-thawed semen 48 h after the second injection. The conception rate to TAI was 2/23 (8.7%) and produced 3 ram lambs. In a subsequent trial, 17 ewes were synchronized with CIDR devices and bred by TAI using frozen-thawed semen 48 h after CIDR removal, resulting in a conception rate of 52.9% (9/17). It is possible to synchronize estrus in hair sheep using either CIDRs, sponges or PGF2alpha. Even though there were no significant differences in the timing of ovulation or the LH surge among the treatment groups, a

Effects on LOCA mass and energy release of the SIT Fluidic device for SKN 3 and 4

International Nuclear Information System (INIS)

Song, Jeung Hyo; Kim, Tae Yoon; Choi, Han Rim; Choi, Chul Jin; Seo, Jong Tae

2003-01-01

A fluidic device is employed for the control of safety injection tank flow during a large break loss of coolant accident in Shin Kori Nuclear power plant Unit 3 and 4. It is installed in the safety injection tank and provides two stages of safety injection tank flow injection, initially high flow injection and then low flow injection after the reactor vessel downcomer annulus full. This allows a more effective use of safety injection tank water inventory during a loss of coolant accident. However, the fluidic device may have an adverse impact on the mass and energy release during the accident. That is, the steam mass and energy release will be increased by a considerable amount because the safety injection tank low flow injection via fluidic device is not credited to condense the steam flows through intact cold legs. The increased mass and energy releases have an impact on the peak pressure and temperature of the containment. This effect of the fluidic device is analyzed on the mass and energy release and the peak pressure and temperature of the containment. The calculation has been done using the CEFLASH-4A, the FLOOD3 with some modifications for the fluidic device and the CONTEMPT-LT code. The results show that the mass and energy release and the peak pressure and temperature were considerably increased when compared with the case without the fluidic device. However, the results satisfy the required design margin

Effects on LOCA mass and energy release of the SIT Fluidic device for SKN 3 and 4

Energy Technology Data Exchange (ETDEWEB)

Song, Jeung Hyo; Kim, Tae Yoon; Choi, Han Rim; Choi, Chul Jin; Seo, Jong Tae [Korea Power Engineering Company, Daejon (Korea, Republic of)

2003-07-01

A fluidic device is employed for the control of safety injection tank flow during a large break loss of coolant accident in Shin Kori Nuclear power plant Unit 3 and 4. It is installed in the safety injection tank and provides two stages of safety injection tank flow injection, initially high flow injection and then low flow injection after the reactor vessel downcomer annulus full. This allows a more effective use of safety injection tank water inventory during a loss of coolant accident. However, the fluidic device may have an adverse impact on the mass and energy release during the accident. That is, the steam mass and energy release will be increased by a considerable amount because the safety injection tank low flow injection via fluidic device is not credited to condense the steam flows through intact cold legs. The increased mass and energy releases have an impact on the peak pressure and temperature of the containment. This effect of the fluidic device is analyzed on the mass and energy release and the peak pressure and temperature of the containment. The calculation has been done using the CEFLASH-4A, the FLOOD3 with some modifications for the fluidic device and the CONTEMPT-LT code. The results show that the mass and energy release and the peak pressure and temperature were considerably increased when compared with the case without the fluidic device. However, the results satisfy the required design margin.

Progesterone is essential for protecting against LPS-induced pregnancy loss. LIF as a potential mediator of the anti-inflammatory effect of progesterone.

Directory of Open Access Journals (Sweden)

Julieta Aisemberg

Full Text Available Lipopolysaccharide (LPS administration to mice on day 7 of gestation led to 100% embryonic resorption after 24 h. In this model, nitric oxide is fundamental for the resorption process. Progesterone may be responsible, at least in part, for a Th2 switch in the feto-maternal interface, inducing active immune tolerance against fetal antigens. Th2 cells promote the development of T cells, producing leukemia inhibitory factor (LIF, which seems to be important due to its immunomodulatory action during early pregnancy. Our aim was to evaluate the involvement of progesterone in the mechanism of LPS-induced embryonic resorption, and whether LIF can mediate hormonal action. Using in vivo and in vitro models, we provide evidence that circulating progesterone is an important component of the process by which infection causes embryonic resorption in mice. Also, LIF seems to be a mediator of the progesterone effect under inflammatory conditions. We found that serum progesterone fell to very low levels after 24 h of LPS exposure. Moreover, progesterone supplementation prevented embryonic resorption and LPS-induced increase of uterine nitric oxide levels in vivo. Results show that LPS diminished the expression of the nuclear progesterone receptor in the uterus after 6 and 12 h of treatment. We investigated the expression of LIF in uterine tissue from pregnant mice and found that progesterone up-regulates LIF mRNA expression in vitro. We observed that LIF was able to modulate the levels of nitric oxide induced by LPS in vitro, suggesting that it could be a potential mediator of the inflammatory action of progesterone. Our observations support the view that progesterone plays a critical role in a successful pregnancy as an anti-inflammatory agent, and that it could have possible therapeutic applications in the prevention of early reproductive failure associated with inflammatory disorders.

The history of natural progesterone, the never-ending story.

Science.gov (United States)

Piette, P

2018-05-28

The term progesterone should only be used for the natural hormone produced by the ovaries or included in a registered drug. The modern history of progesterone begins with the first book-length description of the female reproductive system including the corpus luteum and later with the Nobel Prize winner, Adolf Butenandt who took a crucial step when he succeeded in converting pregnanediol into a chemically pure form of progesterone, the corpus luteum hormone. The deficient production of progesterone was shown first to be the cause of the luteal-phase deficiency responsible for infertility and early pregnancy loss due to inadequate secretory transformation of the endometrium. Later, progesterone was confirmed to be the best and safest method of providing luteal-phase support in assisted reproductive technology. Progesterone provides adequate endometrial protection and is suggested to be the optimal progestagen in menopausal hormone therapy in terms of cardiovascular effects, venous thromboembolism, probably stroke and even breast cancer risk. Neuroprotective effects of progesterone have also been demonstrated in several of experimental models including cerebral ischemic stroke and Alzheimer's disease. Vaginal progesterone was shown to decrease the risk of preterm birth in women with a mid-trimester sonographic short cervix and to improve perinatal outcomes in singleton and twin gestations.

Sulfonate-modified phenylboronic acid-rich nanoparticles as a novel mucoadhesive drug delivery system for vaginal administration of protein therapeutics: improved stability, mucin-dependent release and effective intravaginal placement

Directory of Open Access Journals (Sweden)

Li CY

2016-11-01

IFN demonstrated that PBNP-S could stay in the vagina and maintain intravaginal IFN level for much longer time than IFN solution (24 hours vs several hours without obvious histological irritation to vaginal mucosa after vaginal administration to mice. In summary, good stability, easy loading and controllable release of protein therapeutics, in vitro and in vivo mucoadhesive properties and local safety of PBNP-S suggested it as a promising nanoscale mucoadhesive drug delivery system for vaginal administration of protein therapeutics. Keywords: mucoadhesion, phenylboronic acid, stability, controlled-release, protein therapeutics, nanoparticles

The use of the milk progesterone assay in cows

International Nuclear Information System (INIS)

Bamberg, E.; Choi, H.S.; Moestl, E.

1981-01-01

The progesterone concentration in milk-fat was determined in samples from 167 cows in 51 herds taken on day 0, 6 and 20 after artificial insemination. The rectal palpation verified pregnancy in 85% of the cows classified on their milk-progesterone concentration as ''probably pregnant''. According to the milk progesterone concentration it was possible already three weeks after artificial insemination to classify 25% of all examined cows as ''non pregnant''. Seven cows were inseminated at an inappropriate time as revealed by a high progesterone concentration in milk-fat on the day of insemination. The relevance of milk progesterone determinations as an aid for veterinary surgeons is briefly discussed. (author)

Progesterone binding nano-carriers based on hydrophobically modified hyperbranched polyglycerols

Science.gov (United States)

Alizadeh Noghani, M.; Brooks, D. E.

2016-02-01

Progesterone (Pro) is a potent neurosteroid and promotes recovery from moderate Traumatic Brain Injury but its clinical application is severely impeded by its poor water solubility. Here we demonstrate that reversibly binding Pro within hydrophobically modified hyperbranched polyglycerol (HPG-Cn-MPEG) enhances its solubility, stability and bioavailability. Synthesis, characterization and Pro loading into HPG-Cn-MPEG is described. The release kinetics are correlated with structural properties and the results of Differential Scanning Calorimetry studies of a family of HPG-Cn-MPEGs of varying molecular weight and alkylation. While the maximum amount of Pro bound correlates well with the amount of alkyl carbon per molecule contributing to its hydrophobicity, the dominant first order rate constant for Pro release correlates strongly with the amount of structured or bound water in the dendritic domain of the polymer. The results provide evidence to justify more detailed studies of interactions with biological systems, both single cells and in animal models.Progesterone (Pro) is a potent neurosteroid and promotes recovery from moderate Traumatic Brain Injury but its clinical application is severely impeded by its poor water solubility. Here we demonstrate that reversibly binding Pro within hydrophobically modified hyperbranched polyglycerol (HPG-Cn-MPEG) enhances its solubility, stability and bioavailability. Synthesis, characterization and Pro loading into HPG-Cn-MPEG is described. The release kinetics are correlated with structural properties and the results of Differential Scanning Calorimetry studies of a family of HPG-Cn-MPEGs of varying molecular weight and alkylation. While the maximum amount of Pro bound correlates well with the amount of alkyl carbon per molecule contributing to its hydrophobicity, the dominant first order rate constant for Pro release correlates strongly with the amount of structured or bound water in the dendritic domain of the polymer. The

Inhibition of progesterone metabolism mimics the effect of progesterone withdrawal on forced swim test immobility.

Science.gov (United States)

Beckley, Ethan H; Finn, Deborah A

2007-10-01

Withdrawal from high levels of progesterone in rodents has been proposed as a model for premenstrual syndrome or postpartum depression. Forced swim test (FST) immobility, used to model depression, was assessed in intact female DBA/2J mice following progesterone withdrawal (PWD) or treatment with the 5alpha-reductase inhibitor finasteride. Following 5 daily progesterone injections (5 mg/kg IP) FST immobility increased only in mice withdrawn for 3 days (pimmobility. PWD and finasteride treatment, both of which reduce allopregnanolone levels, were associated with increased FST immobility in female DBA/2J mice. These findings suggest that decreased levels of the GABAergic neurosteroid allopregnanolone contribute to symptoms of PWD. Future studies of PWD may provide information about human conditions that are associated with hormone changes such as premenstrual syndrome or postpartum depression.

New RIA kit for determination of progesterone in cow milk

International Nuclear Information System (INIS)

Byszewska-Szpocinska, E.; Markiewicz, A.

2006-01-01

The determination of progesterone concentration in whole and fat-free milk 19-24 days after conception enables to distinguish fertile and non-fertile insemination, which is important in cattle breeding. The aim of this work was to develop a simple and quick radioimmunoassay test for the determination of progesterone in cow milk. Two types of solid-phase tubes coated with specific polyclonal anti-progesterone antibody from ORION Diagnostica and BIOSOURCE International, two different progesterone derivatives viz. progesterone-3- carboxymethyl oxime (CMO) and progesterone-11α-hemisuccinate (HS) conjugated to 125 I-histamine and the HPLC system with Lichrospher RP-18 column along with 65% acetonitrile/water as eluent to purify the tracers were used to carry out this work. Progesterone-3CMO- 125 I-histamine had a retention time of 13.2 min and progesterone-11α-hemisuccinate- 125 I-histamine had a retention time of 7.8 min. Two kinds of kits (kit I and kit II) were prepared, first with progesterone-3CMO- 125 I-histamine as the tracer and coated tubes from Progesterone Veterinary RIA kit of ORION Diagnostica and the second with progesterone-11αHS- 125 I-histamine as the tracer and coated tubes from Progesterone Veterinary RIA kit from BIOSOURCE International. Progesterone from Sigma and selected fat-free cow's milk without progesterone as zero progesterone milk matrix were used for standard preparation. The optimal assay procedure was as follows: 50μL standards, controls and fat-free milk samples were pipetted into coated tubes followed by addition of 500μL of diluted tracer. The tubes were incubated for 2h in case of kit I and 3h for kit II at RT. After the incubation, the tubes were decanted and counted. The assay range was 0 to 270 nmol/L for kit I and 0 to 300 nmol/L for kit II. The sensitivity of the kit with ORION coated tubes was better (0.8 nmol/L) than that of BIOSOURCE tubes which was 1.5 nmol/L. Validation of these assays in terms of specificity, accuracy

Correlation among foetal number, corpora lutea and plasma progesterone in rockland-swiss mice. [Progesterone determination by radioimmunoassay

Energy Technology Data Exchange (ETDEWEB)

Simon, N G; Bridges, R S; Gandelmann, R [Rutgers - the State Univ., New Brunswick. NJ (USA). Dept. of Psychology; Rutgers - the State Univ., Newark, NJ (USA). Inst. of Animal Behavior)

1978-01-01

The relationship among plasma progesterone, number of corpora lutea, and foetal number was assessed in Rockland-Swiss albino mice. While number of corpora lutea and foetal number were significantly correlated, neither was related to plasma progesterone level. This finding in the mouse is similar to results reported in the rabbit.

Progesterone radioimmunoassay

International Nuclear Information System (INIS)

Stroufova, A.; Kozlova, J.

1976-01-01

RIA methods of determining progestorone using the SORIN kit made in Italy and the NEN kit made in Great Britain were compared. Plasma extraction, the initial sample size for examination and recovery, the range of calibration curves of the two kits, the variation coefficient, the values of the blank sample and the values of progesterone determined in the normal menstrual cycle are discussed in detail. Variation coefficient: Sorin (calibration curve 9 to 11%, biological material 9.2%), NEN (calibration curve 12%, biological material 27.8%); determinations of progesterone levels during a normal menstrual cycle were 10 to 15% higher with the NEN kit; tritiated samples were measured with a 30 to 37% efficiency using the SORIN kit and 15 to 18% efficiency using the NEN kit. The turbidity and later sediment which formed during the determination of steroid hormones in biological materials after the addition of the scintillation solution did not reduce the efficiency of measurement. Priority is given to the SORIN kit. (L.O.)

Progesterone in Breast Cancer Angiogenesis

OpenAIRE

Botelho, Monica C.; Soares, Raquel; Alves, Helena

2015-01-01

The involvement of steroid hormones in breast carcinogenesis is well established. Recent evidence suggests that angiogenesis can be regulated by hormones. Both oestrogen and progesterone have been implicated in the angiogenic process of hormone-dependent cancers, such as breast cancer. Vascular Endothelial Growth Factor (VEGF) is a growth factor involved in angiogenesis in breast cancer that is up-regulated by estrogens. In our study we evaluated the role of progesterone in the expression of ...

Characterization of a synthetic bacterial self-destruction device for programmed cell death and for recombinant proteins release

Directory of Open Access Journals (Sweden)

Lupotto Manuel

2011-06-01

Full Text Available Abstract Background Bacterial cell lysis is a widely studied mechanism that can be achieved through the intracellular expression of phage native lytic proteins. This mechanism can be exploited for programmed cell death and for gentle cell disruption to release recombinant proteins when in vivo secretion is not feasible. Several genetic parts for cell lysis have been developed and their quantitative characterization is an essential step to enable the engineering of synthetic lytic systems with predictable behavior. Results Here, a BioBrick™ lysis device present in the Registry of Standard Biological Parts has been quantitatively characterized. Its activity has been measured in E. coli by assembling the device under the control of a well characterized N-3-oxohexanoyl-L-homoserine lactone (HSL -inducible promoter and the transfer function, lysis dynamics, protein release capability and genotypic and phenotypic stability of the device have been evaluated. Finally, its modularity was tested by assembling the device to a different inducible promoter, which can be triggered by heat induction. Conclusions The studied device is suitable for recombinant protein release as 96% of the total amount of the intracellular proteins was successfully released into the medium. Furthermore, it has been shown that the device can be assembled to different input devices to trigger cell lysis in response to a user-defined signal. For this reason, this lysis device can be a useful tool for the rational design and construction of complex synthetic biological systems composed by biological parts with known and well characterized function. Conversely, the onset of mutants makes this device unsuitable for the programmed cell death of a bacterial population.

Progesterone treatment inhibits and dihydrotestosterone (DHT) treatment potentiates voltage-gated calcium currents in gonadotropin-releasing hormone (GnRH) neurons.

Science.gov (United States)

Sun, Jianli; Moenter, Suzanne M

2010-11-01

GnRH neurons are central regulators of fertility, and their activity is modulated by steroid feedback. In normal females, GnRH secretion is regulated by estradiol and progesterone (P). Excess androgens present in hyperandrogenemic fertility disorders may disrupt communication of negative feedback signals from P and/or independently stimulate GnRH release. Voltage-gated calcium channels (VGCCs) are important in regulating excitability and hormone release. Estradiol alters VGCCs in a time-of-day-dependent manner. To further elucidate ovarian steroid modulation of GnRH neuron VGCCs, we studied the effects of dihydrotestosterone (DHT) and P. Adult mice were ovariectomized (OVX) or OVX and treated with implants containing DHT (OVXD), estradiol (OVXE), estradiol and DHT (OVXED), estradiol and P (OVXEP), or estradiol, DHT, and P (OVXEDP). Macroscopic calcium current (I(Ca)) was recorded in the morning or afternoon 8-12 d after surgery using whole-cell voltage-clamp. I(Ca) was increased in afternoon vs. morning in GnRH neurons from OVXE mice but this increase was abolished in cells from OVXEP mice. I(Ca) in cells from OVXD mice was increased regardless of time of day; there was no additional effect in OVXED mice. P reduced N-type and DHT potentiated N- and R-type VGCCs; P blocked the DHT potentiation of N-type-mediated current. These data suggest P and DHT have opposing actions on VGCCs in GnRH neurons, but in the presence of both steroids, P dominates. VGCCs are targets of ovarian steroid feedback modulation of GnRH neuron activity and, more specifically, a potential mechanism whereby androgens could activate GnRH neuronal function.

Study of progesterone mechanisms in radio-induced apoptosis prevention; Etude des mecanismes de prevention de l'apoptose radioinduite par la progesterone

Energy Technology Data Exchange (ETDEWEB)

Vares, G.

2004-10-15

The purpose of this work was to study the modulation of radiation-induced cell death of human mammary tumoral cells by progesterone. On the one hand, we observed that progesterone protects cells against radiation-induced apoptosis and increases the proportion of surviving and proliferating damaged cells. On the other hand, a transcriptome analysis was undertaken in irradiated cells treated by progesterone, using DNA micro-arrays. This let us highlight several transcriptional dis-regulations that are likely to explain the protective effect of the hormone; in particular, we showed that progesterone regulates the expression of genes implicated in apoptosis signaling by death receptors. Knowing the crucial role of hormonal control and of apoptosis regulation in breast cancer initiation, our results may help to achieve a better understanding of the implication of progesterone in mammary carcinogenesis. (author)

COMPARISON BETWEEN ESTRADIOL CYPIONATE AND GONADOTROPIN RELEASING HORMONE AS OVULATION SYNCHRONIZATION TREATMENTS FOR FIXED-TIME ARTIFICIAL INSEMINATION PROGRAMS IN BRAHMAN-CROSS HEIFERS IN A SUBTROPICAL REGION OF NORTHEASTERN MEXICO

Directory of Open Access Journals (Sweden)

Miguel Angel Dominguez

2012-12-01

Full Text Available Synchronization protocols with intravaginal progesterone releasing devices (CIDR and PGF2α were evaluated, with GnRH or estradiol cypionate (ECP added for fixed-time artificial insemination (FTAI in five counties in Tamaulipas, Mexico. Brahman-cross heifers (≥15 months old were selected based on body condition (≥3 on a 5-point scale and confirmed ovarian activity. The six treatments (n = 320 each were: T1 (9-d CIDR, ECP on insertion, PGF2α on day 9, ECP on day 10, FTAI 54 h after removal; T2 (7-d CIDR, ECP on insertion, PGF2α on day 7, ECP on day 8, FTAI 54 h after removal; T3 (7-d CIDR, GnRH on insertion, PGF2α on day 7, FTAI and GnRH 48 h after removal; T4 (7-d CIDR, GnRH on insertion, PGF2α on day 6, FTAI and GnRH 48 h after removal; T5 (7-d CIDR, GnRH on insertion, PGF2α on day 7, FTAI and GnRH 60 h after removal; and T6 (7-d CIDR, GnRH on insertion, PGF2α on day 7, FTAI alone 48 h after removal. Pregnancy was diagnosed ultrasonically 45 days after FTAI. Analyses included pregnancy rates and treatment costs (hormones and handling. Pregnancy rates ranged from 31.6 ± 3.9 to 48.0 ± 10.6%; neither treatment nor county affected these rates (p > 0.05. In conclusion, the inclusion of treatment costs showed two more economical treatments (T2 using estradiol or T3 using GnRH under the nutritional, weather and handling conditions present in the tropical region of southeastern Tamaulipas.

The reproductive performance of dairy cows with anovulatory anoestrus that were injected with either gonadotrophin-releasing hormone or oestradiol benzoate as part of a re-treatment process after insemination

Directory of Open Access Journals (Sweden)

B.V.E. Segwagwe

2007-05-01

Full Text Available This experiment compared the reproductive performance of synchronised anoestrous dairy cows that were treated initially with a combination of progesterone and oestradiol benzoate and then with either gonadotrophin-releasing hormone (GnRH or oestradiol benzoate to resynchronise returns to service. It was hypothesised that injecting anoestrous dairy cows with GnRH 12-15 days after insemination and coinciding with the time of insertion of a controlled intravaginal progesterone-releasing (CIDR device would increase conception rates to the preceding 1st insemination compared with oestradiol benzoate treated cows; both GnRH and oestradiol benzoate would resynchronising the returns to service of those cows that did not conceive to the preceding insemination. Groups of cows in 11 herds were presented for a veterinary examination after they had not been seen in oestrus postpartum. Those cows diagnosed with anovulatory anoestrus (n = 1112 by manual rectal palpation and / or ultrasonography were enrolled in the trial. Each enrolled cow was injected with 2mg oestradiol benzoate i.m. on Day -10, (where Day 0 was the 1st day of the planned insemination concurrently with vaginal insertion of a CIDR device. The device inserted was withdrawn on Day -2 and then each cow injected i.m. with 1 mg of oestradiol benzoate on Day -1 unless it was in oestrus. Observation for oestrus preceded each insemination. Every cow that had been inseminated on Days -1,0,1 or 2 was presented for treatment for resynchrony on Day 14 (n=891. They were divided into 2 groups; those with an even number were each injected i.m. with 250 µg of a GnRH agonist (Treatment group n = 477; each of the cows with an odd number injected i.m. with 1mg of oestradiol benzoate (control group, n = 414. Each GnRH or oestradiol benzoate injection preceded reinsertion of a CIDR device previously inserted from Days -10 to -2. It was withdrawn on Day 22, 24 hours before injecting 1mg oestradiol benzoate

Radioimmunoassay for progesterone in human saliva during the menstrual cycle

Energy Technology Data Exchange (ETDEWEB)

Luisi, M.; Franchi, F.; Kicovic, P.M.; Silvestri, D.; Cossu, G.; Catarsi, A.L.; Barletta, D.; Gasperi, M. (Pisa Univ. (Italy))

1981-10-01

A sensitive, specific and accurate radioimmunoassay of progesterone in human saliva is described, using /sup 3/H. The assay had a sensitivity of 8 pg/tube and blanks were negligible. The intra- and inter-assay coefficients of variation were 5.2 and 9.4%, respectively. The mean recovery from 60 samples was 93.2 +- 6.3%. Results obtained from nine healthy, normally menstruating women showed that salivary progesterone rose from the 4th day before ovulation to a mean peak (+- SD) of 1.14 +- 0.17 ng/ml on the 8th day after ovulation, followed by a gradual decline. Correlation of salivary and simultaneously obtained plasma progesterone levels was good (r = 0.47; P < 0.001), although the maximum percent increase in salivary progesterone was more than 10 times greater than that of plasma progesterone. Salivary progesterone is thought to reflect the unbound fraction of plasma progesterone and this non-invasive technique can be used for serial investigations in which frequent samplings are required.

Manipulation of reproductive performance of lactating buffaloes using melatonin and controlled internal drug release device treatment during out-of-breeding season under tropical conditions.

Science.gov (United States)

Ramadan, T A; Sharma, R K; Phulia, S K; Balhara, A K; Ghuman, S S; Singh, I

2016-09-01

Twelve lactating Murrah buffalo, divided into control and treatment group of six animals each, were used to study the effect of melatonin and controlled internal drug release (CIDR) device treatment on the resumption of ovarian activity during out-of-breeding season (summer solstice). Treated group implanted with melatonin (18-mg melatonin/50-kg body weight) for 45 days and then animals of both groups received CIDR for 9 days. All animals received intramuscular 500 IU eCG, at day before CIDR removal, and 10-μg GnRH at day after CIDR withdrawal. All animals were subjected to estrus detection daily. Blood samples in conjunction with transrectal ultrasonography were performed once a week to determine serum concentrations of melatonin, progesterone, and antioxidant enzyme activities, as well as to monitor the ovarian activity. Melatonin treatment resulted in an increase (P Day 21 and Day 30 after artificial insemination and achieved higher percentage of conception rate than control. In conclusion, the CIDR treatment preceded by melatonin improved the reproductive performance in lactating buffaloes during out-of-breeding season under tropical conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

Radioimmunoassay kit formulation and its validation for serum progesterone using progesterone radiotracer purified by gel filtration

International Nuclear Information System (INIS)

Karir, T.; Pal, N.; Sivaprasad, N.

2003-01-01

Purification of the radioiodinated progesterone tyrosine methyl ester conjugate by gel filtration and the development, optimization and clinical validation of a direct radioimmunoassay (RIA) of progesterone using this radiotracer are described. High purity radiotracer is essential for the error free performance of any RIA. Progesterone 11α hemisuccinate was conjugated to tyrosine methyl ester (TME) by the mixed anhydride method and this conjugate was then radioiodinated by the chloramine-T method. Purification of the radioiodinated product was carried out by gel filtration. About 12 batches of the radiotracer were prepared and purified. The purification by gel filtration gave reproducible elution pattern and purity. The radiotracer thus purified was found to have consistent quality as compared to that of any other purification methods. Non-specific binding of the radiotracer was found to be 95% as checked by paper electrophoresis. The stability (retention of the immunoreactivity) of the radiotracer was two to three months. No appreciable changes in the assay characteristics were observed during this period. The assay involved 3 hours incubation of progesterone antibody with individual standards or sample and radiotracer at room temperature. The optimized assay was then validated for internal and external quality control parameters. A RIA kit was then formulated with this radiotracer for estimation of progesterone in serum. The assay kit consisted of lyophilized individual standards ranging from 0.25 to 50 ng/ml. The clinical performance of the developed kit was compared with that of a commercial ELISA kit and a correlation of 0.94 was observed. (author)

Intra-vaginal Zinc Oxide Tetrapod Nanoparticles as Novel Immunoprotective Agents against Genital Herpes

Science.gov (United States)

Antoine, Thessicar E.; Hadigal, Satvik R.; Yakoub, Abraam; Mishra, Yogendra K.; Bhattacharya, Palash; Haddad, Christine; Valyi-Nagy, Tibor; Adelung, Rainer; Prabhakar, Bellur S.; Shukla, Deepak

2016-01-01

Virtually all efforts to generate an effective protection against the life-long, recurrent genital infections caused by Herpes simplex virus-2 (HSV-2) have failed. Apart from sexual transmission, the virus can also be transmitted from mothers to neonates, and is a key facilitator of HIV co-acquisition. Here, we uncover a nanoimmunotherapy using specially designed Zinc Oxide Tetrapod Nanoparticles (ZOTEN) with engineered oxygen vacancies. We demonstrate that ZOTEN, when used intravaginally as a microbicide, is an effective suppressor of HSV-2 genital infection in female BALB/c mice. The strong HSV-2 trapping ability of ZOTEN significantly reduced the clinical signs of vaginal infection and effectively decreased animal mortality. In parallel, ZOTEN promoted the presentation of bound HSV-2 virions to mucosal antigen presenting cells, enhancing T cell- mediated and antibody-mediated responses to the infection, and thereby, suppressing a re-infection. We also found that ZOTEN exhibits strong adjuvant-like properties, which is highly comparable to alum, a commonly used adjuvant. Overall, our study provides very first evidence for the protective efficacy of an intravaginal microbicide/vaccine or microbivac platform against primary and secondary female genital herpes infections. PMID:27183601

Lysosomes are involved in induction of steroidogenic acute regulatory protein (StAR) gene expression and progesterone synthesis through low-density lipoprotein in cultured bovine granulosa cells.

Science.gov (United States)

Zhang, Jin-You; Wu, Yi; Zhao, Shuan; Liu, Zhen-Xing; Zeng, Shen-Ming; Zhang, Gui-Xue

2015-09-15

Progesterone is an important steroid hormone in the regulation of the bovine estrous cycle. The steroidogenic acute regulatory protein (StAR) is an indispensable component for transporting cholesterol to the inner mitochondrial membrane, which is one of the rate-limiting steps for progesterone synthesis. Low-density lipoprotein (LDL) supplies cholesterol precursors for progesterone formation, and the lysosomal degradation pathway of LDL is essential for progesterone biosynthesis in granulosa cells after ovulation. However, it is currently unknown how LDL and lysosomes coordinate the expression of the StAR gene and progesterone production in bovine granulosa cells. Here, we investigated the role of lysosomes in LDL-treated bovine granulosa cells. Our results reported that LDL induced expression of StAR messenger RNA and protein as well as expression of cholesterol side-chain cleavage cytochrome P-450 (CYP11A1) messenger RNA and progesterone production in cultured bovine granulosa cells. The number of lysosomes in the granulosa cells was also significantly increased by LDL; whereas the lysosomal inhibitor, chloroquine, strikingly abolished these LDL-induced effects. Our results indicate that LDL promotes StAR expression, synthesis of progesterone, and formation of lysosomes in bovine granulosa cells, and lysosomes participate in the process by releasing free cholesterol from hydrolyzed LDL. Copyright © 2015 Elsevier Inc. All rights reserved.

Study of progesterone mechanisms in radio-induced apoptosis prevention

International Nuclear Information System (INIS)

Vares, G.

2004-10-01

The purpose of this work was to study the modulation of radiation-induced cell death of human mammary tumoral cells by progesterone. On the one hand, we observed that progesterone protects cells against radiation-induced apoptosis and increases the proportion of surviving and proliferating damaged cells. On the other hand, a transcriptome analysis was undertaken in irradiated cells treated by progesterone, using DNA micro-arrays. This let us highlight several transcriptional dis-regulations that are likely to explain the protective effect of the hormone; in particular, we showed that progesterone regulates the expression of genes implicated in apoptosis signaling by death receptors. Knowing the crucial role of hormonal control and of apoptosis regulation in breast cancer initiation, our results may help to achieve a better understanding of the implication of progesterone in mammary carcinogenesis. (author)

Effect of exogenous progesterone on oestrus response of West ...

African Journals Online (AJOL)

Twenty-four (24) healthy, parous West African dwarf (WAD) does aged 2 – 3 years were used to study the effects of varying doses of progesterone on oestrus synchronization and plasma progesterone levels. The does were randomly assigned to 4 treatment groups consisting of 12.5, 25.0 and 37.5 mg progesterone ...

Hair progesterone contents during oestrus cycle and pregnancy in goats

International Nuclear Information System (INIS)

Zeng Xianyin; Guo Dazhi; Liu Xianyi

1991-01-01

Hair progesterone contents during gestasion and milk progesterone levels during oestrus cycle in Saanen(S), crosses F 1 (SXChengdu Mah) and F 2 (SX(SXChengdu Mah)) goats were determined using the RIA kit. The results showed that progesterone in goats hair could be detected using the RIA kit. In pregnant goats, hair progesterone contents was correlated with the milk progesterone profile during 1-28 days after oestrus (r=0.5458, p<0.01). In non-pregnant goats, similar correlation was observed (r=7832, p<0.01). After milk samples were collected 22 days, 3.9ng/ml of progesterone was taken as the discriminatory level, and precision of pregnancy and non-pregnancy diagnosis were 82.4% and 100% respectively. After hair samples were collected 22 days, 3.7ng/50mg of progesterone was taken as discriminatory level, and precision of pregnancy and non-pregnancy diagnosis were 77.8% and 100% respectively. During gestation, hair progesterone content increased gradually from day 30(5.67±0.98ng/50mg hair)to day 120 (9.85±1.20ng/50mg) and decreased rapidly from -8(before parturition, 7.73±1.91ng/50mg) to day 0(parturition, 4.93±0.25ng/50mg)

Protective role of melatonin in progesterone production by human luteal cells.

Science.gov (United States)

Taketani, Toshiaki; Tamura, Hiroshi; Takasaki, Akihisa; Lee, Lifa; Kizuka, Fumie; Tamura, Isao; Taniguchi, Ken; Maekawa, Ryo; Asada, Hiromi; Shimamura, Katsunori; Reiter, Russel J; Sugino, Norihiro

2011-09-01

This study investigated whether melatonin protects luteinized granulosa cells from reactive oxygen species (ROS) as an antioxidant to enhance progesterone production in the follicle during ovulation. Follicular fluid was sampled at the time of oocyte retrieval in women undergoing in vitro fertilization and embryo transfer (IVF-ET). Melatonin concentrations in the follicular fluid were positively correlated with progesterone concentrations (r = 0.342, P progesterone and 8-OHdG concentrations were negatively correlated (r = -0.246, P Progesterone production by luteinized granulosa cells was significantly inhibited by H(2)O(2). Melatonin treatment overcame the inhibitory effect of H(2) O(2) . Twenty-five patients who had luteal phase defect (serum progesterone concentrations progesterone concentrations (>10 ng/mL during the mid-luteal phase) in nine of 14 women (64.3%), whereas only two of 11 women (18.1%) showed normal serum progesterone levels in the control group. In conclusion, melatonin protects granulosa cells undergoing luteinization from ROS in the follicle and contributes to luteinization for progesterone production during ovulation. © 2011 John Wiley & Sons A/S.

Conception rates to fixed-time artificial insemination of two oestrus synchronisation programmes in dairy heifers.

Science.gov (United States)

Sahu, S K; Parkinson, T J; Laven, R A

2015-05-01

To evaluate the conception rate to fixed-time artificial insemination (FTAI) of two oestrus synchronisation programmes in dairy heifers on eight farms over 2 years. The study was conducted in 2008 and 2010 on eight farms near Palmerston North, New Zealand. Nulliparous Friesian and Friesian×Jersey heifers (13-15 months of age) were randomly allocated to one of two oestrus synchronisation programmes. Group 1 (GPG+P4; n=330), received gonadotrophin-releasing hormone (GnRH) I/M on Day 0, a progesterone (P4)-releasing intravaginal device from Days 0-7, prostaglandin F2α (PGF) I/M on Day 7 and a second dose of GnRH at the time of FTAI on Day 9. The second group (P4+PGF; n=343) received a P4-releasing intravaginal device from Days 0-7, PGF on Day 6 and FTAI on Day 9. Pregnancy was diagnosed from Days 42-52 by transrectal ultrasonography. The overall conception rate was 52.4% and 54.8% for the GPG+P4 and P4+PGF groups, respectively. The odds of conception for the two treatments were not different (OR=0.90; 95% CI=0.67-1.23), nor was there any difference between groups in different years (p=0.58). Farm affected conception rate (p=0.002), but there was no interaction with treatment (p=0.92) . This study has shown that an alternative synchronisation programme can produce similar results in terms of conception rate to the GPG+P4 treatment, currently commonly used in heifers. More research is required to establish whether other modifications to the GPG+P4 programme can produce similar results at lower costs, and to identify and quantify farm factors which affect the economic benefit of heifer synchronisation. This study indicated that synchronising heifers with P4 and PGF resulted in conception rates equivalent to those resulting from a GPG+P4 treatment, but with reduced drug costs. However, because heifers in the GPG+P4 group received the second GnRH injection at the time of AI, they needed only three yardings as opposed to the four required for the heifers treated with P4

Overview of progesterone profiles in dairy cows

DEFF Research Database (Denmark)

Blavy, P.; Derks, M.; Martin, O.

2016-01-01

The aim of this study was to gain a better understanding of the variability in shape and features of all progesterone profiles during oestrus cycles in cows, and to create templates for cycle shapes and features as a base for further research. Milk progesterone data from 1418 oestrus cycles, coming...

Systemic progesterone for modulating electrocautery-induced secondary brain injury.

Science.gov (United States)

Un, Ka Chun; Wang, Yue Chun; Wu, Wutian; Leung, Gilberto Ka Kit

2013-09-01

Bipolar electrocautery is an effective and commonly used haemostatic technique but it may also cause iatrogenic brain trauma due to thermal injury and secondary inflammatory reactions. Progesterone has anti-inflammatory and neuroprotective actions in traumatic brain injury. However, its potential use in preventing iatrogenic brain trauma has not been explored. We conducted a pilot animal study to investigate the effect of systemic progesterone on brain cellular responses to electrocautery-induced injury. Adult male Sprague-Dawley rats received standardized bipolar electrocautery (40 W for 2 seconds) over the right cerebral cortex. The treatment group received progesterone intraperitoneally 2 hours prior to surgery; the control group received the drug vehicle only. Immunohistochemical studies showed that progesterone could significantly reduce astrocytic hypertrophy on postoperative day 1, 3 and 7, as well as macrophage infiltration on day 3. The number of astrocytes, however, was unaffected. Our findings suggest that progesterone should be further explored as a neuroprotective agent against electrocautery-induced or other forms of iatrogenic trauma during routine neurosurgical procedures. Future studies may focus on different dosing regimens, neuronal survival, functional outcome, and to compare progesterone with other agents such as dexamethasone. Copyright © 2013 Elsevier Ltd. All rights reserved.

Plasma levels of progesterone in cycling and pregnant ewes

International Nuclear Information System (INIS)

Reddy, K.P.; Rao, P.N.; Reddy, B.B.; Murthy, A.S.N.

1989-01-01

The plasma progesterone profile of six cycling and three pregnant Nellore ewes was estimated by radioimmunoassay. The progesterone level of cycling ewes started rising from undetectable level on the day of oestrus to a mean peak value of 0.41 ± 0.09ng/ml during post oestrus day 10 to 14 and then declined to undetectable levels 1 to 2 days before subsequent oestrus. But the progesterone levels of pregnant ewes exhibited further raise from the post oestrus day 14 to the day 40. However, no correlation between oestrous cycle length and the total progesterone produced during the oestrous cycle was observed. (author). 9 refs., 2 figs

Ovulation following gonadotrophin treatment and determination of serum estradiol and progesterone by radioimmunoassay

International Nuclear Information System (INIS)

Vesper, B.; Lisse, K.; Ittrich, G.

1979-01-01

The use of gonadotrophins to release ovulation is indicated in women with urgent desire for children and with negative response to clomiphene therapy. 69 patients treated with 100 therapeutic gonadotrophin series were examined. Estrogens and progesterone were determined by radioimmunoassay. The treatment resulted in ovulation in 54 women, 12 patients developed an ovarian reaction with an increase of estrogen, and in 34 cases no ovarian response was detectable. 6 women became pregnant during gonadotrophin therapy and further 2 after treatment

Use Of Progesterone Radioimmunoassay for The Monitoring Reproductive status of Cows

International Nuclear Information System (INIS)

Kukuh, Ratnawati; Tjiptosumirat, Totti; Tuasikal, Boky Jeanne

2004-01-01

The artificial insemination (AI) has been widely applied for the rapid improvements of genetic and reproductive efficiency, especially in the developing countries. In Indonesia it was introduced for a long time ago, but the fertility rate of insemination cows, however, is still low. Due to the limitation or relying on visual observation and rectal palpation far determining reproductive status, monitoring milk progesterone can help to improve reproductive efficiency and economic benefits. To analyse progesterone concentration, milk samples were collected in vials containing sodium azide tablets.The milk samples were collected twice a week for about six weeks long, and stored at 4 o C in the refrigerator until analysed. Progesterone concentration in milk samples was determined by using solid phase radioimmunoassay (RIA) kit with 125 I labelled progesterone as tracer. The progesterone standards were prepared in skim milk and range from 0 to 40 nmol/I. The results of progesterone assay on samples of milk collected from five cows indicated that two cows with low progesterone, signifies that these cows had inactive ovaries (anoestrus), three other cows with post calving catalytic progesterone interpretation, and after subsequent insemination two cows getting pregnant. The accurate determination of progesterone levels can be used to confirm oestrus and diagnose non-pregnancy as well as to moriitor postpartum ovarian activity, early embryonic death and ovarian disorder

Autoimmune progesterone dermatitis: Case report with history of ...

African Journals Online (AJOL)

Autoimmune progesterone dermatitis (APD) is a rare autoimmune response to raised endogenous progesterone levels that occur during the luteal phase of the menstrual cycle. Cutaneous, mucosal lesions and other systemic manifestations develop cyclically during the luteal phase of the menstrual cycle when ...

Disturbances in production of progesterone and their implications in plant studies.

Science.gov (United States)

Janeczko, Anna; Oklestkova, Jana; Novak, Ondrej; Śniegowska-Świerk, Katarzyna; Snaczke, Zuzanna; Pociecha, Ewa

2015-04-01

Progesterone is a mammalian hormone that has also been discovered in plants but its physiological function in plants is not explained. Experiments using inhibitors of progesterone synthesis and binding would be useful in studies on the significance of this compound in plants. Until now, trilostane and mifepristone have been used in medical sciences as progesterone biosynthesis and binding inhibitors, respectively. We tested these synthetic steroids for the first time in plants and found that they reduced the content of progesterone in wheat. The aim of further experiments was to answer whether the potential disturbances in the production/binding of progesterone, influence resistance to environmental stress (drought) and the development of wheat. Inhibitors and progesterone were applied to plants via roots in a concentration of 0.25-0.5mg/l water. Both inhibitors lowered the activity of CO2 binding enzyme (Rubisco) in wheat exposed to drought stress and trilostane additionally lowered the chlorophyll content. However, trilostane-treated plants were rescued by treatment with exogenous progesterone. The inhibitors also modulated the development of winter wheat, which indicated the significance of steroid regulators and their receptors in this process. In this study, in addition to progesterone and its inhibitors, brassinosteroid (24-epibrassinolide) and an inhibitor of biosynthesis of brassinosteroids were also applied. Mifepristone inhibited the generative development of wheat (like 24-epibrassinolide), while trilostane (like progesterone and an inhibitor of biosynthesis of brassinosteroids) stimulated the development. We propose a model of steroid-induced regulation of the development of winter wheat, where brassinosteroids act as inhibitors of generative development, while progesterone or other pregnane derivatives act as stimulators. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of intravaginal dehydroepiandrosterone (DHEA) on the female sexual function in postmenopausal women: ERC-230 open-label study.

Science.gov (United States)

Bouchard, Céline; Labrie, Fernand; Derogatis, Leonard; Girard, Ginette; Ayotte, Normand; Gallagher, John; Cusan, Leonello; Archer, David F; Portman, David; Lavoie, Lyne; Beauregard, Adam; Côté, Isabelle; Martel, Céline; Vaillancourt, Mario; Balser, John; Moyneur, Erick

2016-03-01

Intravaginal DHEA (dehydroepiandrosterone, prasterone), the exclusive precursor of androgens and estrogens in postmenopausal women, has previously been shown to improve all the domains of sexual function by a strictly local action in the vagina. The well recognized female sexual function index (FSFI) questionnaire was used in the present study. The long-term effect of 52-week treatment with daily intravaginal 0.50% (6.5 mg) DHEA was evaluated on the various domains of female sexual function using the FSFI questionnaire at baseline, Week 26 and Week 52. One hundred and fifty-four postmenopausal women with at least one mild to severe symptom of vulvovaginal atrophy (VVA) and who have completed the FSFI questionnaire at baseline and at least one post-baseline timepoint were included in the analysis. The FSFI domains desire, arousal, lubrication, orgasm, satisfaction and pain were increased by 28%, 49%, 115%, 51%, 41% and 108%, respectively (p<0.0001 for all parameters) at 52 weeks vs. baseline, while the total score was increased from 13.4±0.62 at baseline to 21.5±0.82 (+60%, p<0.0001) at 52 weeks. As the serum levels of DHEA and all its metabolites, including estradiol and testosterone, show no meaningful change, the present clinical data indicate a stimulatory effect of intravaginal DHEA through a strictly local action in agreement with the preclinical data showing that the androgens made locally from DHEA in the vagina induce an increase in local nerve density.

The methoxychlor metabolite, HPTE, inhibits rat luteal cell progesterone production.

Science.gov (United States)

Akgul, Yucel; Derk, Raymond C; Meighan, Terence; Rao, K Murali Krishna; Murono, Eisuke P

2011-07-01

The methoxychlor metabolite, HPTE, was shown to inhibit P450-cholesterol side-chain cleavage (P450scc) activity resulting in decreased progesterone production by cultured ovarian follicular cells in previous studies. It is not known whether HPTE has any effect on progesterone formation by the corpus luteum. Exposure to 100 nM HPTE reduced progesterone production by luteal cells with progressive declines to progesterone formation and P450scc catalytic activity of hCG- or 8 Br-cAMP-stimulated luteal cells. However, HPTE did not alter mRNA and protein levels of P450scc. Compounds acting as estrogen (17 β-estradiol, bisphenol-A or octylphenol), antiestrogen (ICI) or antiandrogen (monobutyl phthalate, flutamide or M-2) added alone to luteal cells did not mimic the action of HPTE on progesterone and P450scc activity. These results suggest that HPTE directly inhibits P450scc catalytic activity resulting in reduced progesterone formation, and this action was not mediated through estrogen or androgen receptors. Published by Elsevier Inc.

Progesterone-induced stimulation of mammary tumorigenesis is due to the progesterone metabolite, 5α-dihydroprogesterone (5αP) and can be suppressed by the 5α-reductase inhibitor, finasteride.

Science.gov (United States)

Wiebe, John P; Rivas, Martin A; Mercogliano, Maria F; Elizalde, Patricia V; Schillaci, Roxana

2015-05-01

Progesterone has long been linked to breast cancer but its actual role as a cancer promoter has remained in dispute. Previous in vitro studies have shown that progesterone is converted to 5α-dihydroprogesterone (5αP) in breast tissue and human breast cell lines by the action of 5α-reductase, and that 5αP acts as a cancer-promoter hormone. Also studies with human breast cell lines in which the conversion of progesterone to 5αP is blocked by a 5α-reductase inhibitor, have shown that the in vitro stimulation in cell proliferation with progesterone treatments are not due to progesterone itself but to the metabolite 5αP. No similar in vivo study has been previously reported. The objective of the current studies was to determine in an in vivo mouse model if the presumptive progesterone-induced mammary tumorigenesis is due to the progesterone metabolite, 5αP. BALB/c mice were challenged with C4HD murine mammary cells, which have been shown to form tumors when treated with progesterone or the progestin, medroxyprogesterone acetate. Cells and mice were treated with various doses and combinations of progesterone, 5αP and/or the 5α-reductase inhibitor, finasteride, and the effects on cell proliferation and induction and growth of tumors were monitored. Hormone levels in serum and tumors were measured by specific RIA and ELISA tests. Proliferation of C4HD cells and induction and growth of tumors was stimulated by treatment with either progesterone or 5αP. The progesterone-induced stimulation was blocked by finasteride and reinstated by concomitant treatment with 5αP. The 5αP-induced tumors expressed high levels of ER, PR and ErbB-2. Hormone measurements showed significantly higher levels of 5αP in serum from mice with tumors than from mice without tumors, regardless of treatments, and 5αP levels were significantly higher (about 4-fold) in tumors than in respective sera, while progesterone levels did not differ between the compartments. The results indicate that

A novel intravaginal ring to prevent HIV-1, HSV-2, HPV, and unintended pregnancy.

Science.gov (United States)

Ugaonkar, Shweta R; Wesenberg, Asa; Wilk, Jolanta; Seidor, Samantha; Mizenina, Olga; Kizima, Larisa; Rodriguez, Aixa; Zhang, Shimin; Levendosky, Keith; Kenney, Jessica; Aravantinou, Meropi; Derby, Nina; Grasperge, Brooke; Gettie, Agegnehu; Blanchard, James; Kumar, Narender; Roberts, Kevin; Robbiani, Melissa; Fernández-Romero, José A; Zydowsky, Thomas M

2015-09-10

Women urgently need a self-initiated, multipurpose prevention technology (MPT) that simultaneously reduces their risk of acquiring HIV-1, HSV-2, and HPV (latter two associated with increased risk of HIV-1 acquisition) and prevents unintended pregnancy. Here, we describe a novel core-matrix intravaginal ring (IVR), the MZCL IVR, which effectively delivered the MZC combination microbicide and a contraceptive. The MZCL IVR contains four active pharmaceutical ingredients (APIs): MIV-150 (targets HIV-1), zinc acetate (ZA; targets HIV-1 and HSV-2), carrageenan (CG; targets HPV and HSV-2), and levonorgestrel (LNG; targets unintended pregnancy). The elastomeric IVR body (matrix) was produced by hot melt extrusion of the non-water swellable elastomer, ethylene vinyl acetate (EVA-28), containing the hydrophobic small molecules, MIV-150 and LNG. The solid hydrophilic core, embedded within the IVR by compression, contained the small molecule ZA and the macromolecule CG. Hydrated ZA/CG from the core was released by diffusion via a pore on the IVR while the MIV-150/LNG diffused from the matrix continuously for 94 days (d) in vitro and up to 28 d (study period) in macaques. The APIs released in vitro and in vivo were active against HIV-1ADA-M, HSV-2, and HPV16 PsV in cell-based assays. Serum LNG was at levels associated with local contraceptive effects. The results demonstrate proof-of-concept of a novel core-matrix IVR for sustained and simultaneous delivery of diverse molecules for the prevention of HIV, HSV-2 and HPV acquisition, as well as unintended pregnancy. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Neuroprotection by Progesterone Through Simulation of Mitochondrial Gene Expression

National Research Council Canada - National Science Library

Fiskum, Gary

2002-01-01

.... The most important experimental results were as follows: I Determined that low, physiological levels of plasma progesterone inhibited seizures produced by kainic acid while high levels of progesterone had no effect. 2...

Unexpected Inflammatory Effects of Intravaginal Gels (Universal Placebo Gel and Nonoxynol-9 on the Upper Female Reproductive Tract: A Randomized Crossover Study.

Directory of Open Access Journals (Sweden)

Karen Smith-McCune

Full Text Available Intravaginal anti-HIV microbicides could provide women with a self-controlled means for HIV prevention, but results from clinical trials have been largely disappointing. We postulated that unrecognized effects of intravaginal gels on the upper female reproductive tract might contribute to the lower-than-expected efficacy of HIV microbicides. Our objective was to study the effects of intravaginal gels on the immune microenvironment of the cervix and uterus. In this randomized crossover study, 27 healthy female volunteers used a nightly application of intravaginal nonoxynol-9 (N9 gel as a "failed" microbicide or the universal placebo gel (UPG as a "safe" gel (intervention cycles, or nothing (control cycle from the end of menses to the mid-luteal phase. At a specific time-point following ovulation, all participants underwent sample collection for measurements of T-cell phenotypes, gene expression, and cytokine/chemokine protein concentrations from 3 anatomic sites above the vagina: the cervical transformation zone, the endocervix and the endometrium. We used hierarchical statistical models to estimate mean (95% CI intervention effects, for N9 and UPG relative to control. Exposure to N9 gel and UPG generated a common "harm signal" that included transcriptional up-regulation of inflammatory genes chemokine (C-C motif ligand 20 (macrophage inflammatory factor-3alpha and interleukin 8 in the cervix, decreased protein concentrations of secretory leukocyte protease inhibitor, and transcriptional up-regulation of inflammatory mediators glycodelin-A and osteopontin in the endometrium. These results need to be replicated with a larger sample, but underscore the need to consider the effects of microbicide agents and gel excipients on the upper female reproductive tract in studies of vaginal microbicides.

High Levels of Inflammatory Cytokines in the Reproductive Tract of Women with BV and Engaging in Intravaginal Douching: A Cross-Sectional Study of Participants in the Women Interagency HIV Study.

Science.gov (United States)

Alcaide, Maria L; Rodriguez, Violeta J; Brown, Megan R; Pallikkuth, Suresh; Arheart, Kristopher; Martinez, Octavio; Roach, Margaret; Fichorova, Raina N; Jones, Deborah L; Pahwa, Savita; Fischl, Margaret A

2017-04-01

High levels of inflammatory cytokines in the genital tract suggest mucosal vulnerability and increased risk of HIV and sexually transmitted infection (STI) acquisition. Intravaginal douching is associated with bacterial vaginosis (BV) in women in the United States, and both douching and BV are linked to HIV and STI acquisition. This study evaluates inflammatory cytokines in the genital tract to increase understanding of the effects of both BV and intravaginal douching to the vaginal mucosa. A cross-sectional study of participants in the Miami WIHS investigated 72 reproductive age women (45 HIV + and 27 high-risk HIV - ) who completed intravaginal douching questionnaires and underwent collection of vaginal swabs and cervicovaginal lavages (CVLs). BV was assessed using the Nugent score. Inflammatory cytokines in the CVLs (interleukin [IL]-6, IL-8, IL-1α, IL-1β, soluble intracellular adhesion molecule-1 [sICAM-1], interferon [IFN]α2, chemokine C ligand 5 (CCL5), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP1), tumor necrosis factor alpha (TNFα), and secretory leukocyte protease inhibitor [SLPI]) were measured. Fourteen (19%) women reported intravaginal douching; 24 (33%) had BV. BV, intravaginal douching, and HIV were associated with higher levels of inflammatory cytokines. After controlling for demographic and risk factors and HIV status, women who had BV and douched had higher levels of inflammatory cytokines than those without BV and who did not douche, or who only had BV or only douched. These findings suggest that BV and douching are associated with greater mucosal inflammation and may facilitate HIV acquisition and transmission. Although longitudinal studies are needed to determine temporal associations and causality, interventions to decrease rates of intravaginal douching and BV could significantly decrease women's risks of acquiring STIs and HIV and limit the spread of HIV.

Progesterone modulation of alpha5 nAChR subunits influences anxiety-related behavior during estrus cycle.

Science.gov (United States)

Gangitano, D; Salas, R; Teng, Y; Perez, E; De Biasi, M

2009-06-01

Smokers often report an anxiolytic effect of cigarettes. In addition, stress-related disorders such as anxiety, post-traumatic stress syndrome and depression are often associated with chronic nicotine use. To study the role of the alpha5 nicotinic acetylcholine receptor subunit in anxiety-related responses, control and alpha5 subunit null mice (alpha5(-/-)) were subjected to the open field activity (OFA), light-dark box (LDB) and elevated plus maze (EPM) tests. In the OFA and LDB, alpha5(-/-) behaved like wild-type controls. In the EPM, female alpha5(-/-) mice displayed an anxiolytic-like phenotype, while male alpha5(-/-) mice were undistinguishable from littermate controls. We studied the hypothalamus-pituitary-adrenal axis by measuring plasma corticosterone and hypothalamic corticotropin-releasing factor. Consistent with an anxiolytic-like phenotype, female alpha5(-/-) mice displayed lower basal corticosterone levels. To test whether gonadal steroids regulate the expression of alpha5, we treated cultured NTera 2 cells with progesterone and found that alpha5 protein levels were upregulated. In addition, brain levels of alpha5 mRNA increased upon progesterone injection into ovariectomized wild-type females. Finally, we tested anxiety levels in the EPM during the estrous cycle. The estrus phase (when progesterone levels are low) is anxiolytic-like in wild-type mice, but no cycle-dependent fluctuations in anxiety levels were found in alpha5(-/-) females. Thus, alpha5-containing neuronal nicotinic acetylcholine receptors may be mediators of anxiogenic responses, and progesterone-dependent modulation of alpha5 expression may contribute to fluctuations in anxiety levels during the ovarian cycle.

Post operative high dose rate intravaginal irradiation in endometrial cancer: a safe and effective outpatient treatment

International Nuclear Information System (INIS)

Chen, Peter; Gibbons, Susan; Vicini, Frank; Weiner, Sheldon; Dmuchowski, Carl; Mele, Beth; Brabbins, Donald; Jennings, John; Gustafson, Gary; Martinez, Alvaro

1995-01-01

Purpose: We reviewed our experience with out patient high dose rate (HDR) intravaginal irradiation given post-operatively in endometrial cancer to assess local control, survival, and toxicity when used alone or in combination with external beam irradiation. Methods and Materials: From (12(88)) to (12(92)), 78 patients underwent TAH/BSO and received post-operative HDR intravaginal irradiation for endometrial cancer. Pathologic stage distribution was IB/IC: 56%, II: 22%, III: 22%. Adjuvant therapy was given in one of three schemes: HDR vaginal radiation alone (6 weekly fractions of 500 cGy prescribed 5 mm from the applicator surface treating the upper 4 cm of the vagina), pelvic irradiation with vaginal HDR (500 cGy x 4 weekly fractions) or whole abdomen/pelvic irradiation (WAPI) with vaginal HDR treatment (500 cGy x 3 weekly fractions). Prior to the first HDR vaginal treatment, a simulation with placement of vaginal apex metallic markers was performed to assure proper positioning of the intravaginal cylinders. Pelvic midline blocking was designed from the HDR intravaginal simulation films. The 55 patients who underwent combined external beam irradiation/brachytherapy received a median dose to the pelvis of 5040 cGy (range 25.2-51.6 Gy), and a median total vaginal dose of 5060 cGy (range 30.0-57.6 Gy). Results: Median follow-up is 37 months (range 6-73 months). Local control (vaginally) is 98.7%. The one vaginal failure was in the distal vagina, outside the treatment volume. All other failures (4) were distant with the vagina controlled [3 intra-abdominal and one bone/intra-abdominal]. For stages I and II, the disease free survival is 92.8%. For stage III the disease free survival is 86.5%. Median overall time to failure is 14.3 months (range 8.5-18.6 months). In terms of acute toxicity, no grade 3-4 acute toxicity of the vagina or bladder was seen. However, 9% acute GI toxicity was encountered. Chronic grade 1-2 toxicities included: vaginal 21.8% (foreshortening and

Drug release control in delivery system for biodegradable polymer drugs by γ-radiation

International Nuclear Information System (INIS)

Yoshioka, Sumie; Azo, Yukio; Kojima, Shigeo

1997-01-01

Characterizations of the drug release from microsphere and hydrogel preparation made from biodegradable polymers were investigated aiming at development of a drug delivery system which allows an optimum drug delivery and the identification of the factors which control its delivery. Poly-lactic acid microspheres containing 10% of progesterone were produced from poly DL-lactic acid and exposed to γ-ray at 5-1000 kGy. And its glass transition temperature (Tg) was determined by differential scanning calorimetry. The temperature was gradually lowered with an increase in the dose of radiation. Tg of the microsphere exposed at 1000 kGy was lower by 10degC compared with the untreated one, showing that Tg control is possible without changing the size distribution of microsphere. Then, the amount of progesterone released from microsphere was determined. The release rate of the drug linearly increased with a square root of radiation time. These results indicate that the control of drug release rate is possible through controling the microsphere's Tg by γ-ray radiation. (M.N.)

Milk progesterone on day 5 following insemination in the dairy cow ...

African Journals Online (AJOL)

Despite the importance of progesterone on the fertility of lactating dairy cows, the factors that affect post ovulatory progesterone concentration are still unclear. Thus, the aim of the present study was to identify factors associated with the post ovulatory progesterone rise following 1st insemination in lactating dairy cows.

Uso de un dispositivo intravaginal para el control del estro en yeguas

OpenAIRE

Wilde, Oscar R; de la Vega, Adolfo C; L. Cruz, María

2002-01-01

Un dispositivo intravaginal de uso bovino (PRID) conteniendo progesterona de lenta liberación, fue evaluado en once yeguas de la raza Peruano de Paso con el fin de sincronizar sus celos. El dispositivo fue instalado tal como es presentado comercialmente para bovinos y se mantuvo in situ por un lapso de doce días, al cabo de los cuales fue retirado sin mayores complicaciones. Manifestaciones de celo fueron observadas a las 24 h después del retiro del PRID, con su más alta incidencia (50%) a la...

Milk progesterone to monitor reproductive performance in Holstein Fries ian cows

International Nuclear Information System (INIS)

Lubbadeh, W.F.

1995-01-01

A study was conducted to monitor reproductive of lactating Holstein Fries ian cows by measuring milk progesterone levels. Sequential post-partum milk samples were collected weekly throughout 20 weeks after pregnancy. Progesterone concentrations were determined by solid phase RIA. Lactating cows required an average of 5.2 weeks to resume luteal activity; 48% of the cows conceived after first insemination and had significantly high progesterone concentrations during the first 5 weeks after insemination than cows which returned to heat 5-8 weeks after insemination> Results also revealed that adequate level of progesterone, which varied between 4.2 and 9.1 nmol/l, is required to maintain early pregnancy and progesterone level remains high in pregnant cows. (Author) 17 refs., 3 Tabs

Droplet trapping and fast acoustic release in a multi-height device with steady-state flow.

Science.gov (United States)

Rambach, Richard W; Linder, Kevin; Heymann, Michael; Franke, Thomas

2017-10-11

We demonstrate a novel multilayer polydimethylsiloxane (PDMS) device for selective storage and release of single emulsion droplets. Drops are captured in a microchannel cavity and can be released on-demand through a triggered surface acoustic wave pulse. The surface acoustic wave (SAW) is excited by a tapered interdigital transducer (TIDT) deposited on a piezoelectric lithium niobate (LiNbO 3 ) substrate and inverts the pressure difference across the cavity trap to push a drop out of the trap and back into the main flow channel. Droplet capture and release does not require a flow rate change, flow interruption, flow inversion or valve action and can be achieved in as fast as 20 ms. This allows both on-demand droplet capture for analysis and monitoring over arbitrary time scales, and continuous device operation with a high droplet rate of 620 drops per s. We hence decouple long-term droplet interrogation from other operations on the chip. This will ease integration with other microfluidic droplet operations and functional components.

Intravaginal testicular torsion in newborns. To fix or not to fix the contralateral testis?

Directory of Open Access Journals (Sweden)

G. Bordin

2013-10-01

Full Text Available Scrotal swelling suggesting testicular torsion is a rare urological emergency which requires a clinical urgent evaluation and most of the times must be managed surgically. In newborns it can occur in the postnatal period, usually within the twenty-eighth day of life, or more frequently in utero, during the descent of the testis into the scrotum. Usually its poor fixedness allows the testis an abnormal mobility inside the scrotum, configuring the framework of extravaginal torsion. On the contrary during the perinatal period a twist that takes place inside the tunica vaginalis, known as intravaginal torsion, is extremely uncommon and only few cases are well documented in the literature. Authors present a rare case of intravaginal testicular torsion occurred in perinatal period. In this situation only the early surgical exploration of the scrotum may allow the rescue of the gonad, although in rare cases. Timing of surgical treatment and need for contralateral testicular fixation remain controversial. However since the anatomical defect of the tunica vaginalis can be bilateral the surgical fixation even of the contralateral testis is important, now or later, in order to prevent any future torsion of this gonad. The authors also present a brief review of recent literature on the subject.

Manipulation of reproductive seasonality using melatonin implantation in Anglo-Nubian does treated with controlled internal drug release and equine chorionic gonadotropin during the nonbreeding season.

Science.gov (United States)

El-Mokadem, M Y; El-Din, A N M Nour; Ramadan, T A; Rashad, A M A; Taha, T A; Samak, M A

2017-06-01

The objective of this study was to compare the efficiency of hormonal treatments on ovarian activity and reproductive performance in anestrous Anglo-Nubian does during the nonbreeding season (February to May). A total of 48 multiparous does were divided into 2 groups (24 lactating does and 24 dry does). In each group, animals were allocated randomly into 2 equal subgroups (12 does each). In the first subgroup, does received a single 18-mg melatonin implant for 42 d followed by a controlled internal drug release (CIDR) device for 19 d in conjunction with 500 IU of equine chorionic gonadotropin (eCG) i.m. on the day of CIDR device removal. The second subgroup received CIDR combined with eCG in parallel with the first subgroup. Melatonin implantation induced a luteotrophic effect, expressed as an increasing number of corpora lutea, increased serum progesterone concentration, and reduced estradiol concentration. Regardless of treatment, dry does showed greater value of progesterone concentration. With the advancement of day of treatment, number of total follicles, small follicles, and medium follicles tended to increase to the greatest values at the day of CIDR device insertion. Furthermore, at day of mating, the numbers of large follicles reached the greatest value, which was associated with the lowest value of the number of corpora lutea. At day of mating, serum progesterone concentration achieved the lowest value, which increased until d 56 of pregnancy. The estradiol:progesterone ratio showed the opposite trend. The detrimental effect of reproductive seasonality, expressed as cessation of estrus behavior and fertile mating during the nonbreeding season, was successfully alleviated by the CIDR-eCG protocol. Furthermore, melatonin implantation in conjunction with the CIDR-eCG protocol enhanced conception rate and fecundity at d 28 of pregnancy and prolificacy at d 56 of pregnancy compared with does that were not implanted. Interestingly, does that failed to conceive

The role of progesterone in prevention of preterm birth

Directory of Open Access Journals (Sweden)

Jodie M Dodd

2009-07-01

Full Text Available Jodie M Dodd, Caroline A CrowtherDiscipline of Obstetrics and Gynaecology, The University of Adelaide, Adelaide, South Australia, AustraliaAbstract: Preterm birth continues to provide an enormous challenge in the delivery of perinatal health care, and is associated with considerable short and long-term health consequences for surviving infants. Progesterone has a role in maintaining pregnancy, by suppression of the calcium–calmodulin–myosin light chain kinase system. Additionally, progesterone has recognized anti-inflammatory properties, raising a possible link between inflammatory processes, alterations in progesterone receptor expression and the onset of preterm labor. Systematic reviews of randomized controlled trials evaluating the use of intramuscular and vaginal progesterone in women considered to be at increased risk of preterm birth have been published, with primary outcomes of perinatal death, preterm birth <34 weeks, and neurodevelopmental handicap in childhood. Eleven randomized controlled trials were included in the systematic review, involving 2714 women and 3452 infants, with results presented according to the reason women were considered to be at increased risk of preterm birth. While there is a potential beneficial effect in the use of progesterone for some women considered to be at increased risk of preterm birth, primarily in the reduction in the risk of preterm birth before 34 weeks gestation, it remains unclear if the observed prolongation of pregnancy translates into improved health outcomes for the infant.Keywords: progesterone, preterm birth, systematic review, randomized trial

Qualitative and quantitative intravaginal targeting: Key to anti-HIV-1 microbicide delivery from test tube to in vivo success

CSIR Research Space (South Africa)

Pillay, V

2012-06-01

Full Text Available employed. We hereby propose a thorough scientific qualitative and quantitative investigation of important aspects involved in HIV-1 transmission as a prerequisite for microbicide delivery. Intravaginal targeting of HIV-1 increases the chances of microbicide...

Selective suppression of endothelial cytokine production by progesterone receptor.

Science.gov (United States)

Goddard, Lauren M; Ton, Amy N; Org, Tõnis; Mikkola, Hanna K A; Iruela-Arispe, M Luisa

2013-01-01

Steroid hormones are well-recognized suppressors of the inflammatory response, however, their cell- and tissue-specific effects in the regulation of inflammation are far less understood, particularly for the sex-related steroids. To determine the contribution of progesterone in the endothelium, we have characterized and validated an in vitro culture system in which human umbilical vein endothelial cells constitutively express human progesterone receptor (PR). Using next generation RNA-sequencing, we identified a selective group of cytokines that are suppressed by progesterone both under physiological conditions and during pathological activation by lipopolysaccharide. In particular, IL-6, IL-8, CXCL2/3, and CXCL1 were found to be direct targets of PR, as determined by ChIP-sequencing. Regulation of these cytokines by progesterone was also confirmed by bead-based multiplex cytokine assays and quantitative PCR. These findings provide a novel role for PR in the direct regulation of cytokine levels secreted by the endothelium. They also suggest that progesterone-PR signaling in the endothelium directly impacts leukocyte trafficking in PR-expressing tissues. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

Intestinal tumorigenesis is not affected by progesterone signaling in rodent models.

Directory of Open Access Journals (Sweden)

Jarom Heijmans

Full Text Available Clinical data suggest that progestins have chemopreventive properties in the development of colorectal cancer. We set out to examine a potential protective effect of progestins and progesterone signaling on colon cancer development. In normal and neoplastic intestinal tissue, we found that the progesterone receptor (PR is not expressed. Expression was confined to sporadic mesenchymal cells. To analyze the influence of systemic progesterone receptor signaling, we crossed mice that lacked the progesterone receptor (PRKO to the Apc(Min/+ mouse, a model for spontaneous intestinal polyposis. PRKO-Apc(Min/+ mice exhibited no change in polyp number, size or localization compared to Apc(Min/+. To examine effects of progestins on the intestinal epithelium that are independent of the PR, we treated mice with MPA. We found no effects of either progesterone or MPA on gross intestinal morphology or epithelial proliferation. Also, in rats treated with MPA, injection with the carcinogen azoxymethane did not result in a difference in the number or size of aberrant crypt foci, a surrogate end-point for adenoma development. We conclude that expression of the progesterone receptor is limited to cells in the intestinal mesenchyme. We did not observe any effect of progesterone receptor signaling or of progestin treatment in rodent models of intestinal tumorigenesis.

Use of a levonorgestrel-releasing intrauterine device in the treatment of adenomyosis associated heavy menstrual bleeding

International Nuclear Information System (INIS)

Uysal, A.; Taner, C.E.; Mun, S.; Celimli, F.H.; Uysal, F.

2013-01-01

To evaluate the effects of a levonorgestrel-releasing intrauterine device in the treatment of adenomyosis associated with heavy menstrual bleeding. Methods: The retrospective study was conducted at a tertiary referral hospital in Izmir, Turkey, and comprised data on adenomyosis patients who were implanted with a levonorgestrel-releasing intrauterine device for heavy menstrual bleeding between December 2004 and January 2008. After the insertion of the device, all patients were followed up by transvaginal ultrasonography and serum haemoglobin levels and menstrual patterns were determined at the 6th and 12th month. Data was analysed using SPSS 10. Results: The mean age of the 42 women in the study was 43.2+-0.8 years. At the sixth month, amenorrhoea, oligomenorrhoea, spotting and regular menstrual flow were 9.5% (n=4), 7% (n=3), 19% (n=8), and 64% (n=27), respectively. At the 12th month, the same parametres were 9.5% (n=4), 7% (n=3), 12% (n=5), and 71% (n=30), respectively. Haemoglobin levels had increased and endometrial thickness had decreased, and these differences were statistically significant (p<0.001). Conclusion: The easy-to-use levonorgestrel-releasing intrauterine device can be added to the treatment options as a well-tolerated alternative in cases where a woman who has completed her fertility and does not request a hysterectomy has anaemia associated with adenomyosis. (author)

Label-Free Virus Capture and Release by a Microfluidic Device Integrated with Porous Silicon Nanowire Forest.

Science.gov (United States)

Xia, Yiqiu; Tang, Yi; Yu, Xu; Wan, Yuan; Chen, Yizhu; Lu, Huaguang; Zheng, Si-Yang

2017-02-01

Viral diseases are perpetual threats to human and animal health. Detection and characterization of viral pathogens require accurate, sensitive, and rapid diagnostic assays. For field and clinical samples, the sample preparation procedures limit the ultimate performance and utility of the overall virus diagnostic protocols. This study presents the development of a microfluidic device embedded with porous silicon nanowire (pSiNW) forest for label-free size-based point-of-care virus capture in a continuous curved flow design. The pSiNW forests with specific interwire spacing are synthesized in situ on both bottom and sidewalls of the microchannels in a batch process. With the enhancement effect of Dean flow, this study demonstrates that about 50% H5N2 avian influenza viruses are physically trapped without device clogging. A unique feature of the device is that captured viruses can be released by inducing self-degradation of the pSiNWs in physiological aqueous environment. About 60% of captured viruses can be released within 24 h for virus culture, subsequent molecular diagnosis, and other virus characterization and analyses. This device performs viable, unbiased, and label-free virus isolation and release. It has great potentials for virus discovery, virus isolation and culture, functional studies of virus pathogenicity, transmission, drug screening, and vaccine development. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Radioimmunological determination of plasma progesterone. Methods - Results - Indications

International Nuclear Information System (INIS)

Gonon-Estrangin, Chantal.

1978-10-01

The aim of this work is to describe the radioimmunological determination of plasma progesterone carried out at the hormonology Laboratory of the Grenoble University Hospital Centre (Professor E. Chambaz), to compare our results with those of the literature and to present the main clinical indications of this analysis. The measurement method has proved reproducible, specific (the steroid purification stage is unnecessary) and sensitive (detection: 10 picograms of progesterone per tube). In seven normally menstruating women our results agree with published values: (in nanograms per millilitre: ng/ml) 0.07 ng/ml to 0.9 ng/ml in the follicular phase, from the start of menstruation until ovulation, then rapid increase at ovulation with a maximum in the middle of the luteal phase (our values for this maximum range from 7.9 ng/ml to 21.7 ng/ml) and gradual drop in progesterone secretion until the next menstrual period. In gynecology the radioimmunoassay of plasma progesterone is valuable for diagnostic and therapeutic purposes: - to diagnosis the absence of corpus luteum, - to judge the effectiveness of an ovulation induction treatment [fr

Probiotics in the Prevention and Treatment of Postmenopausal Vaginal Infections: Review Article

Science.gov (United States)

Park, Yoo Jin

2017-01-01

Bacterial vaginosis (BV) and complicated vulvovaginal candidiasis (VVC) are frequently occurring vaginal infections in postmenopausal women, caused by an imbalance in vaginal microflora. Postmenopausal women suffer from decreased ovarian hormones estrogen and progesterone. A normal, healthy vaginal microflora mainly comprises Lactobacillus species (spp.), which act beneficially as a bacterial barrier in the vagina, interfering with uropathogens. During premenopausal period, estrogen promotes vaginal colonization by lactobacilli that metabolizing glycogen and producing lactic acid, and maintains intravaginal health by lowering the intravaginal pH level. A lower vaginal pH inhibits uropathogen growth, preventing vaginal infections. Decreased estrogen secretion in postmenopausal women depletes lactobacilli and increases intravaginal pH, resulting in increased vaginal colonization by harmful microorganisms (e.g., Enterobacter, Escherichia coli, Candida, and Gardnerella). Probiotics positively effects on vaginal microflora composition by promoting the proliferation of beneficial microorganisms, alters the intravaginal microbiota composition, prevents vaginal infections in postmenopausal. Probiotics also reduce the symptoms of vaginal infections (e.g., vaginal discharge, odor, etc.), and are thus helpful for the treatment and prevention of BV and VVC. In this review article, we provide information on the intravaginal mechanism of postmenopausal vaginal infections, and describes the effectiveness of probiotics in the treatment and prevention of BV and VVC. PMID:29354612

Probiotics in the Prevention and Treatment of Postmenopausal Vaginal Infections: Review Article.

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Kim, Jun-Mo; Park, Yoo Jin

2017-12-01

Bacterial vaginosis (BV) and complicated vulvovaginal candidiasis (VVC) are frequently occurring vaginal infections in postmenopausal women, caused by an imbalance in vaginal microflora. Postmenopausal women suffer from decreased ovarian hormones estrogen and progesterone. A normal, healthy vaginal microflora mainly comprises Lactobacillus species (spp.), which act beneficially as a bacterial barrier in the vagina, interfering with uropathogens. During premenopausal period, estrogen promotes vaginal colonization by lactobacilli that metabolizing glycogen and producing lactic acid, and maintains intravaginal health by lowering the intravaginal pH level. A lower vaginal pH inhibits uropathogen growth, preventing vaginal infections. Decreased estrogen secretion in postmenopausal women depletes lactobacilli and increases intravaginal pH, resulting in increased vaginal colonization by harmful microorganisms (e.g., Enterobacter , Escherichia coli , Candida , and Gardnerella ). Probiotics positively effects on vaginal microflora composition by promoting the proliferation of beneficial microorganisms, alters the intravaginal microbiota composition, prevents vaginal infections in postmenopausal. Probiotics also reduce the symptoms of vaginal infections (e.g., vaginal discharge, odor, etc.), and are thus helpful for the treatment and prevention of BV and VVC. In this review article, we provide information on the intravaginal mechanism of postmenopausal vaginal infections, and describes the effectiveness of probiotics in the treatment and prevention of BV and VVC.

Transport and Biodistribution of Dendrimers Across Human Fetal Membranes: Implications for Intravaginal Administration of Dendrimers

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Menjoge, Anupa R.; Navath, Raghavendra S.; Asad, Abbas; Kannan, Sujatha; Kim, Chong Jai; Romero, Roberto; Kannan, Rangaramanujam M.

2010-01-01

Dendrimers are emerging as promising topical antimicrobial agents, and as targeted nanoscale drug delivery vehicles. Topical intravaginal antimicrobial agents are prescribed to treat the ascending genital infections in pregnant women. The fetal membranes separate the extra-amniotic space and fetus. The purpose of the study is to determine if the dendrimers can be selectively used for local intravaginal application to pregnant women without crossing the membranes into the fetus. In the present study, the transport and permeability of PAMAM (poly(amidoamine)) dendrimers, across human fetal membrane (using a side-by-side diffusion chamber), and its biodistribution (using immunofluorescence) are evaluated ex-vivo. Transport across human fetal membranes (from the maternal side) was evaluated using Fluorescein (FITC), an established transplacental marker (positive control, size~ 400 Da) and fluorophore-tagged G4-PAMAM dendrimers (~ 16 kDa). The fluorophore-tagged G4-PAMAM dendrimers were synthesized and characterized using 1H NMR, MALDI TOF-MS and HPLC analysis. Transfer was measured across the intact fetal membrane (chorioamnion), and the separated chorion and amnion layers. Over a five hour period, the dendrimer transport across all the three membranes was less than transport of FITC was relatively fast with as much as 49% transport across the amnion. The permeability of FITC (7.9 × 10-7 cm2/s) through the chorioamnion was 7-fold higher than that of the dendrimer (5.8 × 10-8 cm2/s). The biodistribution showed that the dendrimers were largely present in interstitial spaces in the decidual stromal cells and the chorionic trophoblast cells (in 2.5 to 4 h) and surprisingly, to a smaller extent internalized in nuclei of trophoblast cells and nuclei and cytoplasm of stromal cells. Passive diffusion and paracellular transport appear to be the major route for dendrimer transport. The overall findings further suggest that entry of drugs conjugated to dendrimers would be

Expression profiles of antimicrobial peptides in the genital tract of women using progesterone intrauterine devices versus combined oral contraceptives.

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Introini, Andrea; Kaldensjö, Tove; Hirbod, Taha; Röhl, Maria; Tjernlund, Annelie; Andersson, Sonia; Broliden, Kristina

2014-11-01

Sex hormones can influence the immune defenses of the female genital tract (FGT) and its susceptibility to infections. Here we investigated the effect of different hormonal contraceptives on the production of antimicrobial peptides (AMPs) in different compartments of the female genital mucosa (FGM), secretions and tissue. Cervicovaginal secretions (CVS) and ectocervical tissue samples obtained from women using progesterone intrauterine devices (pIUD) (n = 23) and combined oral contraceptives (COC) (n = 23) were analyzed for the expression and in situ localization of HNP1-3, BD-2, LL-37, SLPI and trappin-2 by ELISA, real-time PCR and immunohistochemistry. Women using COC had significantly lower mRNA levels of BD-2 and trappin-2 in ectocervical tissue than pIUD users. The two groups showed no differences in CVS concentration, as well as similar in situ expression patterns in ectocervical tissue, of all five AMPs. The use of hormonal contraceptives influences AMP expression differently in genital secretions compared to ectocervical tissue. This suggests that the impact of sex hormones on local immune defenses varies in different compartments of the FGM, and likely in different locations across the FGT. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Progesterone to prevent spontaneous preterm birth

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Romero, Roberto; Yeo, Lami; Chaemsaithong, Piya; Chaiworapongsa, Tinnakorn; Hassan, Sonia

2014-01-01

Summary Preterm birth is the leading cause of perinatal morbidity and mortality worldwide, and its prevention is an important healthcare priority. Preterm parturition is one of the ‘great obstetrical syndromes’ and is caused by multiple etiologies. One of the mechanisms of disease is the untimely decline in progesterone action, which can be manifested by a sonographic short cervix in the midtrimester. The detection of a short cervix in the midtrimester is a powerful risk factor for preterm delivery. Vaginal progesterone can reduce the rate of preterm delivery by 45%, and the rate of neonatal morbidity (admission to neonatal intensive care unit, respiratory distress syndrome, need for mechanical ventilation, etc.). To prevent one case of spontaneous preterm birth birth in women with a short cervix both with and without a prior history of preterm birth. In patients with a prior history of preterm birth, vaginal progesterone is as effective as cervical cerclage to prevent preterm delivery. 17α-Hydroxyprogesterone caproate has not been shown to be effective in reducing the rate of spontaneous preterm birth in women with a short cervix. PMID:24315687

A three-dimensional semi-analytical solution for predicting drug release through the orifice of a spherical device.

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Simon, Laurent; Ospina, Juan

2016-07-25

Three-dimensional solute transport was investigated for a spherical device with a release hole. The governing equation was derived using the Fick's second law. A mixed Neumann-Dirichlet condition was imposed at the boundary to represent diffusion through a small region on the surface of the device. The cumulative percentage of drug released was calculated in the Laplace domain and represented by the first term of an infinite series of Legendre and modified Bessel functions of the first kind. Application of the Zakian algorithm yielded the time-domain closed-form expression. The first-order solution closely matched a numerical solution generated by Mathematica(®). The proposed method allowed computation of the characteristic time. A larger surface pore resulted in a smaller effective time constant. The agreement between the numerical solution and the semi-analytical method improved noticeably as the size of the orifice increased. It took four time constants for the device to release approximately ninety-eight of its drug content. Copyright © 2016 Elsevier B.V. All rights reserved.

The role of progesterone signaling in the pathogenesis of uterine leiomyoma

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Kim, J. Julie; Sefton, Elizabeth C.

2011-01-01

Uterine leiomyomas are benign tumors that originate from the myometrium. Evidence points to ovarian steroid hormones, in particular, progesterone as major promoters of leiomyoma development and growth. While progesterone action in leiomyomas involves the classical nuclear receptor effects on gene regulation, there is growing evidence that signaling pathways are directly activated by the progesterone receptor (PR) and that PR can interact with growth factor signaling systems to promote proliferation and survival of leiomyomas. Studies investigating the genomic and non-genomic actions of PR and its role in leiomyoma growth are summarized here. Studies testing various selective progesterone receptor modulators for the treatment of leiomyomas are also highlighted. An increased understanding of the mechanisms associated with progesterone-driven growth of leiomyomas is critical in order to develop more efficient and targeted therapies for this prevalent disease. PMID:21672608

Development of a homologous iodine-125 labelled progesterone radioimmunoassay system

International Nuclear Information System (INIS)

Elbanna, I.M.; El-Asrag, H.A.; Gado, M.S.; Gamal, M.H.

1985-01-01

Detailed procedure description of an iodinated progesterone radioimmunoassay system development is reported. Immunization regime with progesterone 11 α-hemisuccinate: BSA gave 1:6000 antibody titre within a period of 6 months. Minimal amount of the immunogen was spent to obtain a stock of the antiserum. Conjugation of progesterone 11 α-hemisuccinate to tyrosine methyl ester using the isobutyl-chloroformate reaction gave a product with less patch to patch variations in tracer characteristics. At home radioiodination with 125 I reduced the expenses drastically and resulted in extended tracer shelf life (up to 3 months). The use of the second antibody method of separating bound from free hormone proved to be more convenient and brought the progesterone radioimmunoassay system to routine work

Transport and biodistribution of dendrimers across human fetal membranes: implications for intravaginal administration of dendrimer-drug conjugates.

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Menjoge, Anupa R; Navath, Raghavendra S; Asad, Abbas; Kannan, Sujatha; Kim, Chong J; Romero, Roberto; Kannan, Rangaramanujam M

2010-06-01

Dendrimers are emerging as promising topical antimicrobial agents, and as targeted nanoscale drug delivery vehicles. Topical intravaginal antimicrobial agents are prescribed to treat the ascending genital infections in pregnant women. The fetal membranes separate the extra-amniotic space and fetus. The purpose of the study is to determine if the dendrimers can be selectively used for local intravaginal application to pregnant women without crossing the membranes into the fetus. In the present study, the transport and permeability of PAMAM (poly (amidoamine)) dendrimers, across human fetal membrane (using a side by side diffusion chamber), and its biodistribution (using immunofluorescence) are evaluated ex-vivo. Transport across human fetal membranes (from the maternal side) was evaluated using Fluorescein (FITC), an established transplacental marker (positive control, size approximately 400 Da) and fluorophore-tagged G(4)-PAMAM dendrimers (approximately 16 kDa). The fluorophore-tagged G(4)-PAMAM dendrimers were synthesized and characterized using (1)H NMR, MALDI TOF MS and HPLC analysis. Transfer was measured across the intact fetal membrane (chorioamnion), and the separated chorion and amnion layers. Over a 5 h period, the dendrimer transport across all the three membranes was less than dendrimer (5.8 x 10(-8) cm(2)/s). The biodistribution showed that the dendrimers were largely present in interstitial spaces in the decidual stromal cells and the chorionic trophoblast cells (in 2.5-4 h) and surprisingly, to a smaller extent internalized in nuclei of trophoblast cells and nuclei and cytoplasm of stromal cells. Passive diffusion and paracellular transport appear to be the major route for dendrimer transport. The overall findings further suggest that entry of drugs conjugated to dendrimers would be restricted across the human fetal membranes when administered topically by intravaginal route, suggesting new ways of selectively delivering therapeutics to the mother

Progesterone Upregulates Gene Expression in Normal Human Thyroid Follicular Cells

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Ana Paula Santin Bertoni

2015-01-01

Full Text Available Thyroid cancer and thyroid nodules are more prevalent in women than men, so female sex hormones may have an etiological role in these conditions. There are no data about direct effects of progesterone on thyroid cells, so the aim of the present study was to evaluate progesterone effects in the sodium-iodide symporter NIS, thyroglobulin TG, thyroperoxidase TPO, and KI-67 genes expression, in normal thyroid follicular cells, derived from human tissue. NIS, TG, TPO, and KI-67 mRNA expression increased significantly after TSH 20 μUI/mL, respectively: 2.08 times, P<0.0001; 2.39 times, P=0.01; 1.58 times, P=0.0003; and 1.87 times, P<0.0001. In thyroid cells treated with 20 μUI/mL TSH plus 10 nM progesterone, RNA expression of NIS, TG, and KI-67 genes increased, respectively: 1.78 times, P<0.0001; 1.75 times, P=0.037; and 1.95 times, P<0.0001, and TPO mRNA expression also increased, though not significantly (1.77 times, P=0.069. These effects were abolished by mifepristone, an antagonist of progesterone receptor, suggesting that genes involved in thyroid cell function and proliferation are upregulated by progesterone. This work provides evidence that progesterone has a direct effect on thyroid cells, upregulating genes involved in thyroid function and growth.

Metabolic level recognition of progesterone in dairy Holstein cows using probabilistic models

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Ludmila N. Turino

2014-05-01

Full Text Available Administration of exogenous progesterone is widely used in hormonal protocols for estrous (resynchronization of dairy cattle without regarding pharmacological issues for dose calculation. This happens because it is difficult to estimate the metabolic level of progesterone for each individual cow before administration. In the present contribution, progesterone pharmacokinetics has been determined in lactating Holstein cows with different milk production yields. A Bayesian approach has been implemented to build two probabilistic progesterone pharmacokinetic models for high and low yield dairy cows. Such models are based on a one-compartment Hill structure. Posterior probabilistic models have been structurally set up and parametric probability density functions have been empirically estimated. Moreover, a global sensitivity analysis has been done to know sensitivity profile of each model. Finally, posterior probabilistic models have adequately recognized cow’s progesterone metabolic level in a validation set when Kullback-Leibler based indices were used. These results suggest that milk yield may be a good index for estimating pharmacokinetic level of progesterone.

Labelling and validation of progesterone-11-α-hydroxy hemisuccinate (125I)

International Nuclear Information System (INIS)

Djajusman, Sukiyati; Andria, H.

2001-01-01

Progesteron is a steroid hormone secreted by the corpus luteum and the adrenal cortex in the hypophise gland. The hormone can be used for monitoring pregnancy and even more for the assessment of the corpus luteum in fertile woman (4). The labelling of progesterone with 125 I was carried out for tracer production in the preparation of Progesterone Kit used in the determination of the progesterone derivate has been done. The labelling was carried out in two steps reaction. First the progesterone derivate was activated using N-methyl morpholine and isobutylchloroformate. The second step was performed by conjugating the labelled 125 I Histamin to the activated progesterone derivate. The labelled compound was purified with HPLC followed with the determination of the chemical purity using electrophorosis, the immunoreactivity controlled with the maximum binding of the zerro standard and the non specific binding using the Progesterone Kit. Experimental results showed that the iodination of Progesterone -11-α-hidroxy hemisuccinate ( 125 I) yield 22.15%, chemical purity 92.30%, the radioimmunoreactivity 51% as maximum binding (for zero standard), with NSB 0.67%, and the spesific activity obtained 7.72 Ci/ g. Validation of the tracer using control (low, medium and high) shows the results as follows : (2.72 ± 0.49)nmol/L for low standard and control (1.2 - 2.5 nmol/L), (11.3 ± 1.15) nmol/L for medium standard and control (6-15 n/mol) and (15.95 ± 5.32 ) nmol/L for high standard and control (10-23 nmol/L). The sensitivity of the assay was (0.70 ± 0.024 nmol/L) for zero standard

Preparation of TPP-crosslinked chitosan microparticles by spray drying for the controlled delivery of progesterone intended for estrus synchronization in cattle.

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Helbling, Ignacio M; Busatto, Carlos A; Fioramonti, Silvana A; Pesoa, Juan I; Santiago, Liliana; Estenoz, Diana A; Luna, Julio A

2018-02-20

Planned reproduction in cattle involves regulation of estrous cycle and the use of artificial insemination. Cycle control includes the administration of exogenous progesterone during 5-8 days in a controlled manner allowing females to synchronize their ovulation. Several progesterone delivery systems are commercially available but they have several drawbacks. The aim of the present contribution was to evaluate chitosan microparticles entrapping progesterone as an alternative system. Microparticles were prepared by spray drying. The effect of formulation parameters and experimental conditions on particle features and delivery was studied. A mathematical model to predict progesterone plasma concentration in animals was developed and validated with experimental data. Microparticle size was not affected by formulation parameters but sphericity enhances as Tween 80 content increases and it impairs as TPP content rises. Z potential decreases as phosphate content rises. Particles remain stable in acidic solution but the addition of surfactant is required to stabilize dispersions in neutral medium. Encapsulation efficiencies was 69-75%. In vitro delivery studies showed burst and diffusion-controlled phases, being progesterone released faster at low pH. In addition, delivery extend in cows was affected mainly by particle size and hormone initial content, while the amount injected altered plasma concentration. Theoretical predictions with excellent accuracy were obtained. The mathematical model developed can help to find proper particle features to reach specific delivery rates in the animals. This not only save time, money and effort but also minimized experimentation with animals which is desired from an ethical point of view.

Versatile action of picomolar gradients of progesterone on different sperm subpopulations.

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Diego Rafael Uñates

Full Text Available High step concentrations of progesterone may stimulate various sperm physiological processes, such as priming and the acrosome reaction. However, approaching the egg, spermatozoa face increasing concentrations of the hormone, as it is secreted by the cumulus cells and then passively diffuses along the cumulus matrix and beyond. In this context, several questions arise: are spermatozoa sensitive to the steroid gradients as they undergo priming and the acrosome reaction? If so, what are the functional gradual concentrations of progesterone? Do spermatozoa in different physiological states respond differentially to steroid gradients? To answer these questions, spermatozoa were confronted with progesterone gradients generated by different hormone concentrations (1 pM to 100 µM. Brief exposure to a 10 pM progesterone gradient stimulated priming for the acrosome reaction in one sperm subpopulation, and simultaneously induced the acrosome reaction in a different sperm subpopulation. This effect was not observed in non-capacitated cells or when progesterone was homogeneously distributed. The results suggest a versatile role of the gradual distribution of very low doses of progesterone, which selectively stimulate the priming and the acrosome reaction in different sperm subpopulations.

Pregnancy and conception rate after two intravaginal inseminations with dog semen frozen either with 5% glycerol or 5% ethylene glycol.

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Rota, Ada; Milani, C; Romagnoli, S; Zucchini, P; Mollo, A

2010-03-01

The primary goal of this study was to compare the effects of 5% ethylene glycol (EG) and 5% glycerol (G) on fertility of frozen-thawed dog semen following intravaginal insemination. The sperm-rich fraction of the ejaculate of three male dogs was collected, pooled and divided into two aliquots, and then frozen with a Tris-glucose-egg yolk-citric acid extender containing either 5% G or 5% EG. A total of 10 bitches were inseminated twice, five with G-frozen-thawed semen and five with EG-frozen-thawed semen; intravaginal inseminations were performed the 4th and the 5th day after the estimated LH peak; four straws, thawed in a 37 degrees C water bath for 1 min and diluted in a Tris buffer, were used for insemination (200 x 10(6) spermatozoa); the insemination dose was introduced in the cranial vagina of the bitch using a sterile plastic catheter. Ovariohysterectomy was performed in all bitches between days 29 and 31 after the calculated LH surge, and pregnancy status, and the number of conceptuses and corpora lutea were recorded. All bitches were pregnant. Neither the number of conceptuses, nor the ratio of conceptuses to corpora lutea (conception rate) was significantly different between groups. In this first screening, with a limited number of bitches, EG-frozen semen did not show a higher fertility than G-frozen semen when used for two intravaginal inseminations. Irrespective of the semen used, conception rate was 0.50.

Effects of metformin treatment on luteal phase progesterone concentration in polycystic ovary syndrome

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Meenakumari K.J.

2004-01-01

Full Text Available The causes of luteal phase progesterone deficiency in polycystic ovary syndrome (PCOS are not known. To determine the possible involvement of hyperinsulinemia in luteal phase progesterone deficiency in women with PCOS, we examined the relationship between progesterone, luteinizing hormone (LH and insulin during the luteal phase and studied the effect of metformin on luteal progesterone levels in PCOS. Patients with PCOS (19 women aged 18-35 years were treated with metformin (500 mg three times daily for 4 weeks prior to the test cycle and throughout the study period, and submitted to ovulation induction with clomiphene citrate. Blood samples were collected from control (N = 5, same age range as PCOS women and PCOS women during the late follicular (one sample and luteal (3 samples phases and LH, insulin and progesterone concentrations were determined. Results were analyzed by one-way analysis of variance (ANOVA, Duncan's test and Karl Pearson's coefficient of correlation (r. The endocrine study showed low progesterone level (4.9 ng/ml during luteal phase in the PCOS women as compared with control (21.6 ng/ml. A significant negative correlation was observed between insulin and progesterone (r = -0.60; P < 0.01 and between progesterone and LH (r = -0.56; P < 0.05 concentrations, and a positive correlation (r = 0.83; P < 0.001 was observed between LH and insulin. The study further demonstrated a significant enhancement in luteal progesterone concentration (16.97 ng/ml in PCOS women treated with metformin. The results suggest that hyperinsulinemia/insulin resistance may be responsible for low progesterone levels during the luteal phase in PCOS. The luteal progesterone level may be enhanced in PCOS by decreasing insulin secretion with metformin.

Intravaginal lactic Acid bacteria modulated local and systemic immune responses and lowered the incidence of uterine infections in periparturient dairy cows.

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Qilan Deng

Full Text Available The objective of this investigation was to evaluate whether intravaginal infusion of a lactic acid bacteria (LAB cocktail around parturition could influence the immune response, incidence rate of uterine infections, and the overall health status of periparturient dairy cows. One hundred pregnant Holstein dairy cows were assigned to 1 of the 3 experimental groups as follows: 1 one dose of LAB on wk -2 and -1, and one dose of carrier (sterile skim milk on wk +1 relative to the expected day of parturition (TRT1; 2 one dose of LAB on wk -2, -1, and +1 (TRT2, and 3 one dose of carrier on wk -2, -1, and +1 (CTR. The LAB were a lyophilized culture mixture composed of Lactobacillus sakei FUA3089, Pediococcus acidilactici FUA3138, and Pediococcus acidilactici FUA3140 with a cell count of 108-109 cfu/dose. Blood samples and vaginal mucus were collected once a week from wk -2 to +3 and analyzed for content of serum total immunoglobulin G (IgG, lipopolysaccharide-binding protein (LBP, serum amyloid A (SAA, haptoglobin (Hp, tumor necrosis factor (TNF, interleukin (IL-1, IL-6, and vaginal mucus secretory IgA (sIgA. Clinical observations including rectal temperature, vaginal discharges, retained placenta, displaced abomasum, and laminitis were monitored from wk -2 to +8 relative to calving. Results showed that intravaginal LAB lowered the incidence of metritis and total uterine infections. Intravaginal LAB also were associated with lower concentrations of systemic LBP, an overall tendency for lower SAA, and greater vaginal mucus sIgA. No differences were observed for serum concentrations of Hp, TNF, IL-1, IL-6 and total IgG among the treatment groups. Administration with LAB had no effect on the incidence rates of other transition cow diseases. Overall intravaginal LAB lowered uterine infections and improved local and systemic immune responses in the treated transition dairy cows.

Progesterone Enhanced Remyelination in the Mouse Corpus Callosum After Cuprizone Induced Demyelination

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Iraj Ragerdi Kashani

2015-11-01

Full Text Available Background: Progesterone as a sex steroid hormone is thought to affect and prevent demyelination, but its role in promoting myelin repair is far less investigated. In this study, remyelinating potential of progesterone in corpus callosum was evaluated on an experimental model of MS. Methods: In this experimental study, adult male C57BL/6 mice were fed with 0.2% (w/w cuprizone in ground breeder chow ad libitum for 6 weeks. At day zero, after cuprizone removal, mice were divided randomly into two groups: (a placebo group, which received saline pellet implant, (b progesterone group, which received progesterone pellet implant. Some mice of the same age were fed with their normal diet to serve as the healthy control group. Two weeks after progesterone administration, Myelin content was assessed by Luxol-fast blue staining. The myelin basic protein (MBP and proteolipid protein (PLP expression were assessed using Western blot analysis and the changes in the number of oligodendrocytes and oligodendroglial progenitor cells were assessed by immunohistochemistry (IHC and flow cytometry. Results: Luxol-fast blue staining revealed enhanced remyelination in the progesterone group when compared with the placebo group. Densitometry measurements of immunoblots demonstrated that MBP and PLP proteins contents were significantly increased in the progesterone group compared with the placebo group. Flow cytometry and IHC analysis showed increases in Olig2 and O4 cells in the progesterone group compared with the placebo group. Conclusion: Overall, our results indicate that progesterone treatment can stimulate myelin production and that it may provide a feasible and practical way for remyelination in diseases such as multiple sclerosis.

Prenatal Exposure to Progesterone Affects Sexual Orientation in Humans.

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Reinisch, June M; Mortensen, Erik Lykke; Sanders, Stephanie A

2017-07-01

Prenatal sex hormone levels affect physical and behavioral sexual differentiation in animals and humans. Although prenatal hormones are theorized to influence sexual orientation in humans, evidence is sparse. Sexual orientation variables for 34 prenatally progesterone-exposed subjects (17 males and 17 females) were compared to matched controls (M age = 23.2 years). A case-control double-blind design was used drawing on existing data from the US/Denmark Prenatal Development Project. Index cases were exposed to lutocyclin (bioidentical progesterone = C 21 H 30 O 2 ; M W : 314.46) and no other hormonal preparation. Controls were matched on 14 physical, medical, and socioeconomic variables. A structured interview conducted by a psychologist and self-administered questionnaires were used to collect data on sexual orientation, self-identification, attraction to the same and other sex, and history of sexual behavior with each sex. Compared to the unexposed, fewer exposed males and females identified as heterosexual and more of them reported histories of same-sex sexual behavior, attraction to the same or both sexes, and scored higher on attraction to males. Measures of heterosexual behavior and scores on attraction to females did not differ significantly by exposure. We conclude that, regardless of sex, exposure appeared to be associated with higher rates of bisexuality. Prenatal progesterone may be an underappreciated epigenetic factor in human sexual and psychosexual development and, in light of the current prevalence of progesterone treatment during pregnancy for a variety of pregnancy complications, warrants further investigation. These data on the effects of prenatal exposure to exogenous progesterone also suggest a potential role for natural early perturbations in progesterone levels in the development of sexual orientation.

Inseminação artificial em tempo fixo e diagnóstico precoce de gestação em vacas leiteiras mestiças Timed artificial insemination and early pregnancy diagnosis in crossbred dairy cows

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Cláudio França Barbosa

2011-01-01

Full Text Available Avaliou-se, durante um ano, o desempenho reprodutivo de 94 vacas leiteiras mestiças Bos taurus x Bos indicus submetidas a um programa de reprodução assistida. Um protocolo de inseminação artificial em tempo fixo (IATF foi executado por meio de dispositivo intravaginal contendo progesterona e das injeções de prostaglandina F2α e de cipionato de estradiol. Por meio de ultrassonografia, entre 7 e 14 dias após as inseminações ou montas controladas, realizou-se a detecção de corpo lúteo nos ovários a fim de determinar a taxa de ovulação e, no 28º dia, fez-se o diagnóstico de gestação para cálculo da taxa de concepção. Respeitou-se um período mínimo de 34 dias após o parto antes do tratamento. Não houve influência do escore de condição corporal e da presença de corpo lúteo no início do protocolo, nem da reutilização do dispositivo intravaginal e da monta controlada ou inseminação artificial, sobre as taxas de ovulação, concepção e concepção das vacas ovuladas. As taxas de concepção e de concepção das vacas ovuladas foram afetadas negativamente pelo elevado número de dias pós-parto (DPP, ou dias em lactação e pela época quente do ano, primavera/verão. A resposta ao protocolo de inseminação artificial em tempo fixo baseado no uso de progesterona, PGF2α e cipionato de estradiol é prejudicada pelo aumento dos dias em lactação e pela época quente do ano. A condição corporal não afeta a resposta ao protocolo de inseminação artificial, desde que as vacas tratadas apresentem escore acima de 2,25 pontos.It was evaluated, during a period of one year, the reproductive performance of 94 Bos taurus x Bos indicus crossbred dairy cows submitted to an assisted reproduction program. A timed artificial insemination (TAI protocol was carried out by using an intra-vaginal progesterone device containing progesterone and through injections with Prostaglandin F2α and estradiol cypionate. By using ultrasound

Effect of copper intrauterine device vs. injectable contraceptive on serum hormone levels and cell mitotic activity in endometrium

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Ebtesam Moustafa Kamal

2013-09-01

Conclusion: Either copper intrauterine device or injectable contraceptive usage for more than 9 months results in significant decrease in endometrial proliferative or cell mitotic activity. While copper IUD has no effect on serum estradiol or progesterone levels, DMPA usage increased serum progesterone level with no effect on serum estradiol.

Effectiveness of melatonin and controlled internal drug release device treatment on reproductive performance of buffalo heifers during out-of-breeding season under tropical conditions.

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Ramadan, T A; Sharma, R K; Phulia, S K; Balhara, A K; Ghuman, S S; Singh, I

2014-12-01

Sixteen Murrah buffalo heifers, divided into control and treatment groups of eight animals each, were used to study the effect of melatonin and controlled internal drug release (CIDR) device treatment on the resumption of ovarian activity during out-of-breeding season (summer solstice). Treated group was implanted with melatonin (18 mg of melatonin per 50 kg of body weight) for 45 days and then heifers of both groups received CIDR for 9 days. All heifers received intramuscular 500 IU eCG on the day before CIDR removal and 10 μg GnRH on the day after CIDR withdrawal. All animals were subjected to estrus detection daily. Blood sampling in conjunction with transrectal ultrasonography were performed twice weekly to determine serum concentrations of melatonin, progesterone, LH, and antioxidant enzyme activities, as well as to monitor the ovarian follicular activity. Melatonin treatment resulted in an increase (P Days 0 and 35 of melatonin treatment. However, melatonin exhibited superior ability to maintain CL at 21 days after artificial insemenation (AI) and increased the percentage of conception to threefold higher than control. In conclusion, melatonin implantation successfully improved the diameter of largest follicles and the ability to maintain CL at 21 days after AI in buffalo heifers during out-of-breeding season under tropical conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

Synthesis of copolymers suitable for the storage and slow release of reactants. Cases of copper salts for intra-uterine devices

International Nuclear Information System (INIS)

Gaussens, Gilbert; Duchemin-Berthet, Jeanne.

1976-01-01

This research has been carried out to determine whether a grafted poly(ethylene-vinyl acetate) matrix could be prepared which would release useful amounts of copper salts when used in intra-uterine devices. Intra-uterine devices were prepared by grafting hydroxyethyl acrylate onto ethylene-vinylacetate copolymers (EVA). The kinetics of the grafting reaction were studied. The grafting reaction was initiated by cobalt 60 gamma rays using the simultaneous method. The conditions of copper salts absorption by the grafted copolymers were selected. The average quantity of copper salts released daily from the intra-uterine device was meaured as a function of grafting ratio and the amount of copper salt initially incorporated in the grafted polymeric matrix. In vitro experiments samples showed constant release rates during a period of 18 months

α-Estrogen and Progesterone Receptors Modulate Kisspeptin Effects on Prolactin: Role in Estradiol-Induced Prolactin Surge in Female Rats.

Science.gov (United States)

Aquino, Nayara S S; Araujo-Lopes, Roberta; Henriques, Patricia C; Lopes, Felipe E F; Gusmao, Daniela O; Coimbra, Candido C; Franci, Celso R; Reis, Adelina M; Szawka, Raphael E

2017-06-01

Kisspeptin (Kp) regulates prolactin (PRL) in an estradiol-dependent manner. We investigated the interaction between ovarian steroid receptors and Kp in the control of PRL secretion. Intracerebroventricular injections of Kp-10 or Kp-234 were performed in ovariectomized (OVX) rats under different hormonal treatments. Kp-10 increased PRL release and decreased 3,4-dihydroxyphenylacetic acid levels in the median eminence (ME) of OVX rats treated with estradiol (OVX+E), which was prevented by tamoxifen. Whereas these effects of Kp-10 were absent in OVX rats, they were replicated in OVX rats treated with selective agonist of estrogen receptor (ER)α, propylpyrazole triol, but not of ERβ, diarylpropionitrile. Furthermore, the Kp-10-induced increase in PRL was two times higher in OVX+E rats also treated with progesterone (OVX+EP), which was associated with a reduced expression of both tyrosine hydroxylase (TH) and Ser40-phosphorylated TH in the ME. Kp-10 also reduced dopamine levels in the ME of OVX+EP rats, an effect blocked by the progesterone receptor (PR) antagonist RU486. We also determined the effect of Kp antagonism with Kp-234 on the estradiol-induced surges of PRL and luteinizing hormone (LH), using tail-tip blood sampling combined with ultrasensitive enzyme-linked immunosorbent assay. Kp-234 impaired the early phase of the PRL surge and prevented the LH surge in OVX+E rats. Thus, we provide evidence that Kp stimulation of PRL release requires ERα and is potentiated by progesterone via PR activation. Moreover, alongside its essential role in the LH surge, Kp seems to play a role in the peak phase of the estradiol-induced PRL surge. Copyright © 2017 Endocrine Society.

Design Project on Controlled-Release Drug Delivery Devices: Implementation, Management, and Learning Experiences

Science.gov (United States)

Xu, Qingxing; Liang, Youyun; Tong, Yen Wah; Wang, Chi-Hwa

2010-01-01

A design project that focuses on the subject of controlled-release drug delivery devices is presented for use in an undergraduate course on mass transfer. The purpose of the project is to introduce students to the various technologies used in the fabrication of drug delivery systems and provide a practical design exercise for understanding the…

Endometrial cancer treated with levonorgestrel-releasing intrauterine device for almost three years in an elderly woman with comorbidity

DEFF Research Database (Denmark)

Andreasen, Lisbeth Anita; Antonsen, Sofie Leisby; Settnes, Annette

2016-01-01

but with a minimum of symptoms and side effects. At the final examination there were no signs of extra uterine disease. The levonorgestrel-releasing intrauterine device may be an acceptable alternative to surgery in severely comorbid patients, or if the patient refuses surgical treatment. © 2016, Springer......In this case report we describe the treatment of a 95-year-old woman with endometrioid adenocarcinoma. She suffered from cardiovascular comorbidity and did not want surgical treatment. Instead a levonorgestrel-releasing intrauterine device (Mirena) was inserted. She had progression of the tumor...

Administration of progesterone after trauma and hemorrhagic shock prevents hepatocellular injury.

Science.gov (United States)

Kuebler, Joachim F; Yokoyama, Yukihiro; Jarrar, Doraid; Toth, Balazs; Rue, Loring W; Bland, Kirby I; Wang, Ping; Chaudry, Irshad H

2003-07-01

Administration of a single dose of progesterone following trauma and hemorrhage in progesterone-deficient rats would ameliorate the inflammatory response and hepatocellular damage. A university laboratory. Ovariectomized female Sprague-Dawley rats (250-350 g; Charles River Laboratories, Wilmington, Mass) underwent a 5-cm midline laparotomy (ie, induction of soft tissue trauma), were bled to a mean arterial blood pressure of 35 mm Hg for about 90 minutes, and then were resuscitated using Ringer lactate solution. Progesterone (25 mg/kg of body weight) or vehicle was administered subcutaneously at the end of resuscitation. In additional animals, Kupffer cells were isolated following trauma, hemorrhage, and resuscitation and treated in vitro with progesterone, lipopolysaccharide, or both. Six hours following resuscitation, plasma tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) levels and liver myeloperoxidase activity were determined. Hepatocellular function (maximum velocity of indocyanine green clearance [Vmax] and the efficiency of the active transport or Michaelis-Menten constant [Km]) and plasma levels of transaminases were measured 20 hours after resuscitation. Kupffer cell IL-6 and TNF-alpha production were assessed. Plasma levels of TNF-alpha, IL-6, aspartate aminotransferase, and alanine aminotransferase, as well as hepatic myeloperoxidase activity were increased, whereas indocyanine green clearance was depressed in vehicle-treated rats following trauma-hemorrhage. Animals treated with progesterone showed significantly reduced levels of the TNF-alpha, IL-6, and transaminases as well as reduced myeloperoxidase activity in the liver. Progesterone-treated animals showed increased Vmax and Kmax values for indocyanine green. In vitro treatment of Kupffer cells with progesterone decreased TNF-alpha production but did not affect the production of IL-6. Progesterone administration following trauma-hemorrhage ameliorates the proinflammatory response

Elevated progesterone during ovarian stimulation for IVF

DEFF Research Database (Denmark)

Al-Azemi, M; Kyrou, D; Kolibianakis, E M

2012-01-01

of Medline and PubMed were searched to identify relevant publications. Good-quality evidence supports the negative impact on endometrial receptivity of elevated progesterone concentrations at the end of the follicular phase in ovarian stimulation. Future trials should document the cause and origin...... phase in ovarian stimulation. The databases of Medline and PubMed were searched to identify relevant publications. Good-quality evidence supports the negative impact on endometrial receptivity of elevated progesterone concentrations at the end of follicular phase in ovarian stimulation. Future trials...

Flash release an alternative for releasing complex MEMS devices

NARCIS (Netherlands)

Deladi, S.; Krijnen, Gijsbertus J.M.; Elwenspoek, Michael Curt

2004-01-01

A novel time-saving and cost-effective release technique has been developed and is described. The physical nature of the process is explained in combination with experimental observations. The results of the flash release process are compared with those of freeze-drying and supercritical CO2

Effect Of Exogenous Progesterone On Blood Chemistry Of Large ...

African Journals Online (AJOL)

Exogenous hormones are major economic factors in swine production. This study evaluate the effects of exogenous administration of progesterone on the blood chemistry of pigs.Experiment involved weekly injections of progesterone to 24 pigs (12 males and 12 females)from day old to 24 weeks and only corn oil to another ...

A multinational population survey of intravaginal ejaculation latency time.

Science.gov (United States)

Waldinger, Marcel D; Quinn, Paul; Dilleen, Maria; Mundayat, Rajiv; Schweitzer, Dave H; Boolell, Mitradev

2005-07-01

Intravaginal ejaculation latency time (IELT), defined as the time between the start of vaginal intromission and the start of intravaginal ejaculation, is increasingly used in clinical trials to assess the amount of selective serotonin reuptake inhibitor-induced ejaculation delay in men with premature ejaculation. Prospectively, stopwatch assessment of IELTs has superior accuracy compared with retrospective questionnaire and spontaneous reported latency. However, the IELT distribution in the general male population has not been previously assessed. To determine the stopwatch assessed-IELT distribution in large random male cohorts of different countries. A total of 500 couples were recruited from five countries: the Netherlands, United Kingdom, Spain, Turkey, and the United States. Enrolled men were aged 18 years or older, had a stable heterosexual relationship for at least 6 months, with regular sexual intercourse. The surveyed population were not included or excluded by their ejaculatory status and comorbidities. This survey was performed on a "normal" general population. Sexual events and stopwatch-timed IELTs during a 4-week period were recorded, as well as circumcision status and condom use. The IELT, circumcision status, and condom use. The distribution of the IELT in all the five countries was positively skewed, with a median IELT of 5.4 minutes (range, 0.55-44.1 minutes). The median IELT decreased significantly with age, from 6.5 minutes in the 18-30 years group, to 4.3 minutes in the group older than 51 years (PIELT varied between countries, with the median value for Turkey being the lowest, i.e., 3.7 minutes (0.9-30.4 minutes), which was significantly different from each of the other countries. Comparison of circumcised (N=98) and not-circumcised (N=261) men in countries excluding Turkey resulted in median IELT values of 6.7 minutes (0.7-44.1 minutes) in circumcised compared with 6.0 minutes (0.5-37.4 minutes) in not-circumcised men (not significant). The

Progesterone receptor antagonist CDB-4124 increases depression-like behavior in mice without affecting locomotor ability.

Science.gov (United States)

Beckley, Ethan H; Scibelli, Angela C; Finn, Deborah A

2011-07-01

Progesterone withdrawal has been proposed as an underlying factor in premenstrual syndrome and postpartum depression. Progesterone withdrawal induces forced swim test (FST) immobility in mice, a depression-like behavior, but the contribution of specific receptors to this effect is unclear. The role of progesterone's GABA(A) receptor-modulating metabolite allopregnanolone in depression- and anxiety-related behaviors has been extensively documented, but little attention has been paid to the role of progesterone receptors. We administered the classic progesterone receptor antagonist mifepristone (RU-38486) and the specific progesterone receptor antagonist CDB-4124 to mice that had been primed with progesterone for five days, and found that both compounds induced FST immobility reliably, robustly, and in a dose-dependent fashion. Although CDB-4124 increased FST immobility, it did not suppress initial activity in a locomotor test. These findings suggest that decreased progesterone receptor activity contributes to depression-like behavior in mice, consistent with the hypothesis that progesterone withdrawal may contribute to the symptoms of premenstrual syndrome or postpartum depression. Copyright © 2010 Elsevier Ltd. All rights reserved.

Gluteo-vaginal fistula after posterior intravaginal slingplasty: a case report.

Science.gov (United States)

Grynberg, Michael; Teyssedre, Jacques; Staerman, Frederic

2009-07-01

In patients with posthysterectomy prolapse of the vaginal vault, the posterior intravaginal slingplasty (posterior IVS, Tyco Healthcare, USA) has been suggested as an alternative to traditional vaginal vault suspensions. The goal of this technique is to recreate the uterosacral ligaments and to reinforce the rectovaginal fascia with the use of prosthetic material. We report the case of a 53-year-old woman with a history of 27 months of perineal suppurative discharge after she underwent a vaginal vault prolapse and rectocele repair using a posterior IVS (Tyco Healthcare, USA). The IVS tape was reinforced by interposing a rectovaginal monofilament polypropylene mesh (Parietex, Sofradim, France). Imaging studies and surgical exploration confirmed infection of the IVS mesh with the formation of a gluteo-vaginal fistula while the rectovaginal mesh was intact.

Randomized, Placebo-Controlled Phase 2 Trial of a Lactobacillus crispatus Probiotic Given Intravaginally for Prevention of Recurrent Urinary Tract Infection

OpenAIRE

Stapleton, Ann E.; Au-Yeung, Melissa; Hooton, Thomas M.; Fredricks, David N.; Roberts, Pacita L.; Czaja, Christopher A.; Yarova-Yarovaya, Yuliya; Fiedler, Tina; Cox, Marsha; Stamm, Walter E.

2011-01-01

In a double-blind placebo-controlled trial of a Lactobacillus crispatus intravaginal suppository probiotic (LACTIN-VÜ, Osel, Inc.) for prevention of recurrent UTI (rUTI) in pre-menopausal women, LACTIN-V was safe, well tolerated, and associated with a reduction in rUTI.

Expression of estrogen and progesterone receptors in astrocytomas: a literature review

Directory of Open Access Journals (Sweden)

Cléciton Braga Tavares

Full Text Available Gliomas are the most common type of primary central nervous system neoplasm. Astrocytomas are the most prevalent type of glioma and these tumors may be influenced by sex steroid hormones. A literature review for the presence of estrogen and progesterone receptors in astrocytomas was conducted in the PubMed database using the following MeSH terms: “estrogen receptor beta” OR “estrogen receptor alpha” OR “estrogen receptor antagonists” OR “progesterone receptors” OR “astrocytoma” OR “glioma” OR “glioblastoma”. Among the 111 articles identified, 13 studies met our inclusion criteria. The majority of reports showed the presence of estrogen and progesterone receptors in astrocytomas. Overall, higher tumor grades were associated with decreased estrogen receptor expression and increased progesterone receptor expression.

Expression of estrogen and progesterone receptors in astrocytomas: a literature review

Science.gov (United States)

Tavares, Cléciton Braga; Gomes-Braga, Francisca das Chagas Sheyla Almeida; Costa-Silva, Danylo Rafhael; Escórcio-Dourado, Carla Solange; Borges, Umbelina Soares; Conde, Airton Mendes; da Conceição Barros-Oliveira, Maria; Sousa, Emerson Brandão; da Rocha Barros, Lorena; Martins, Luana Mota; Facina, Gil; da-Silva, Benedito Borges

2016-01-01

Gliomas are the most common type of primary central nervous system neoplasm. Astrocytomas are the most prevalent type of glioma and these tumors may be influenced by sex steroid hormones. A literature review for the presence of estrogen and progesterone receptors in astrocytomas was conducted in the PubMed database using the following MeSH terms: “estrogen receptor beta” OR “estrogen receptor alpha” OR “estrogen receptor antagonists” OR “progesterone receptors” OR “astrocytoma” OR “glioma” OR “glioblastoma”. Among the 111 articles identified, 13 studies met our inclusion criteria. The majority of reports showed the presence of estrogen and progesterone receptors in astrocytomas. Overall, higher tumor grades were associated with decreased estrogen receptor expression and increased progesterone receptor expression. PMID:27626480

The 5-HT₁A receptor CG polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation

NARCIS (Netherlands)

Janssen, Paddy K C; van Schaik, R; Zwinderman, Aeilko H; Olivier, Berend|info:eu-repo/dai/nl/073067199; Waldinger, Marcel D|info:eu-repo/dai/nl/163958564

INTRODUCTION: Lifelong premature ejaculation (LPE) is characterized by persistent intravaginal ejaculation latency times (IELTs) of less than 1 min, and has been postulated as a neurobiological dysfunction related to diminished serotonergic neurotransmission with 5-HT₁A receptor hyperfunction and

Evaluation of Progesterone Utilization and Birth Outcomes in a State Medicaid Plan.

Science.gov (United States)

Hydery, Tasmina; Price, Mylissa K; Greenwood, Bonnie C; Takeshita, Mito; Kunte, Parag S; Mauro, Rose P; Lenz, Kimberly; Jeffrey, Paul L

2017-10-01

Progesterone (hydroxyprogesterone caproate injection and vaginal progesterone) has been shown to reduce preterm birth (PTB) rates by a third among pregnant women at high risk. The purpose of this analysis is to report birth outcomes and medication adherence among Massachusetts Medicaid (MassHealth) members receiving progesterone, evaluate the association between member characteristics and birth outcomes and medication adherence, and compare cost of care with a prior preterm pregnancy. This retrospective cohort study used medical claims, pharmacy claims, and prior authorization (PA) request data for MassHealth members who had a PA submitted for progesterone between January 1, 2011, and March 31, 2015. Members were excluded due to breaks in coverage, progesterone was not indicated for prevention of PTB, and if current gestational week or date of delivery was unavailable. A total of 418 members were screened for inclusion of whom 190 met criteria and 169 filled progesterone. Mean age was 29.2 years (SD = 5.23), and clinical comorbidities were identified in 90.5% of members. Consistent with clinical trials on progesterone effectiveness, 62.1% of members had a term delivery (37 wks of gestation). Among members with prior gestational age at delivery available, the average difference in gestational age between pregnancies was 8.25 weeks (SD = 6.11). In addition, 66.3% of members were adherent to progesterone based on proportion of days covered (PDC) of 0.8 or higher. The overall mean PDC was 0.79 (SD = 0.26). Despite similar birth outcomes in clinical trials and national trends, medication adherence is low in this state Medicaid program. Therefore, members may benefit from adherence support. © 2017 Pharmacotherapy Publications, Inc.

Regulation of uterine progesterone receptors by the nonsteroidal anti-androgen hydroxyflutamide

International Nuclear Information System (INIS)

Chandrasekhar, Y.; Armstrong, D.T.

1991-01-01

The authors have recently reported that the anti-androgen hydroxyflutamide causes delayed implantation and exhibits antideciduogenic activity in the rat. The present experiments were conducted to examine whether hydroxyflutamide binds to the uterine progesterone receptors and/or alters the progesterone binding sites in the uterus. Cytosol and nuclear fractions from decidualized rat uterus were incubated with [3H]-R5020 without or with increasing concentrations of radioinert R5020, RU486, dihydrotestosterone, or hydroxyflutamide. From the log-dose inhibition curves, the relative binding affinity of both hydroxyflutamide and dihydrotestosterone was less than 0.1% and 2%, compared with R5020 (100%) for displacing [3H]-R5020 bound to uterine cytosol and nuclear fractions, respectively. Injection of estradiol-17 beta (1 microgram/rat) to ovariectomized prepubertal rats induced a 1.85-fold increase in uterine weight by 24 h. Hydroxyflutamide at 2.5 or 5.0 mg did not significantly alter the estrogen-induced increase in uterine weight. Compared to vehicle alone, estrogen induced an approximately 5-fold increase in uterine cytosolic progesterone binding sites. Hydroxyflutamide at both 2.5- and 5.0-mg doses significantly attenuated the estrogen-induced elevation in uterine progesterone binding sites. These studies demonstrate that hydroxyflutamide does not bind with high affinity to progesterone receptors, but suppresses the estrogen-induced elevation in progesterone receptor levels in the uterus

The 5-HT₁A receptor CG polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation

NARCIS (Netherlands)

Janssen, Paddy K. C.; van Schaik, R.; Zwinderman, Aeilko H.; Olivier, Berend; Waldinger, Marcel D.

2014-01-01

Lifelong premature ejaculation (LPE) is characterized by persistent intravaginal ejaculation latency times (IELTs) of less than 1 min, and has been postulated as a neurobiological dysfunction related to diminished serotonergic neurotransmission with 5-HT₁A receptor hyperfunction and 5-HT₂C

Evaluation of reproductive performance using milk progesterone assay

International Nuclear Information System (INIS)

Reimers, T.J.

1990-01-01

Dairy herds (472) in the northeastern United States of America were surveyed to evaluate reproductive performance. Error of oestrus detection (>> 1 ng/mL of milk progesterone) on the day of insemination was 5.1% for 4558 cows. 'Standing' and 'riding other cows' were the most accurate signs of oestrus. Of cows in or near oestrus when inseminated, 28.1% were open three weeks later, 12.9% were probably open, and 59% were probably pregnant according to milk progesterone analysis. Post-partum days to first insemination and conception rates showed positive correlation. Concentrations of progesterone in milk samples collected 21 to 24 days after service allowed prediction with 88.6% accuracy that a cow was pregnant and with 93.9% accuracy that she was not. By rectal palpation, veterinarians predicted with 92.5% accuracy that a cow was pregnant. (author). 12 refs, 4 tabs

Childhood conditions influence adult progesterone levels.

Directory of Open Access Journals (Sweden)

Alejandra Núñez-de la Mora

2007-05-01

Full Text Available Average profiles of salivary progesterone in women vary significantly at the inter- and intrapopulation level as a function of age and acute energetic conditions related to energy intake, energy expenditure, or a combination of both. In addition to acute stressors, baseline progesterone levels differ among populations. The causes of such chronic differences are not well understood, but it has been hypothesised that they may result from varying tempos of growth and maturation and, by implication, from diverse environmental conditions encountered during childhood and adolescence.To test this hypothesis, we conducted a migrant study among first- and second-generation Bangladeshi women aged 19-39 who migrated to London, UK at different points in the life-course, women still resident in Bangladesh, and women of European descent living in neighbourhoods similar to those of the migrants in London (total n = 227. Data collected included saliva samples for radioimmunoassay of progesterone, anthropometrics, and information from questionnaires on diet, lifestyle, and health. Results from multiple linear regression, controlled for anthropometric and reproductive variables, show that women who spend their childhood in conditions of low energy expenditure, stable energy intake, good sanitation, low immune challenges, and good health care in the UK have up to 103% higher levels of salivary progesterone and an earlier maturation than women who develop in less optimal conditions in Sylhet, Bangladesh (F9,178 = 5.05, p < 0.001, standard error of the mean = 0.32; adjusted R(2 = 0.16. Our results point to the period prior to puberty as a sensitive phase when changes in environmental conditions positively impact developmental tempos such as menarcheal age (F2,81 = 3.21, p = 0.03 and patterns of ovarian function as measured using salivary progesterone (F2,81 = 3.14, p = 0.04.This research demonstrates that human females use an extended period of the life cycle prior

The multifaceted nature of access to compounded progesterone: a cross-sectional study from Australia.

Science.gov (United States)

Spark, M Joy; Willis, Jon; Byrne, Graeme; Iacono, Teresa

2014-02-01

To explore the influences on accessibility of compounded progesterone therapy for Australian women. A cross-sectional survey of a stratified sample of Australian women who use progesterone only products using the 'Perspectives on Progesterone' questionnaire. Principle components analysis (PCA) to determine components of access to progesterone treatment and multi-way analysis of variance to compare groups. Women using compounded progesterone were likely to have made at least one lifestyle adaptation (73%), and to have tried and stopped using at least one complementary and alternative medicine therapy (63%) or conventional hormone therapy (41%). PCA revealed six components of access to progesterone treatment: affordable, values natural treatments and is concerned about other treatments, conventionally available, perceived knowledge, values information gathered from a variety of sources, and rural & disadvantaged. The multifaceted nature of progesterone use illustrates that there are multiple aspects to use of non-conventional medicines. Women looking for non-conventional treatment are neither stupid nor uninformed, their understandings, based on experience and research, need to be addressed by health professionals while assessing their condition prior to discussing the risks and benefits of non-conventional medicines. Access to compounded progesterone is multifaceted, and many of the women who use it have tried other treatments first. Despite the clinical ambivalence towards progesterone as an alternative for women who may have tried and rejected other treatments, including conventional hormone therapy, the women described in this paper are using it. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Direct 125I-radioligand assays for serum progesterone compared with assays involving extraction of serum

International Nuclear Information System (INIS)

Ratcliffe, W.A.; Corrie, J.E.T.; Dalziel, A.H.; Macpherson, J.S.

1982-01-01

Two direct radioimmunoassays for progesterone in 50 μL of unextracted serum or plasma with assays involving extraction of serum were compared. The direct assays include the use of either danazol at pH 7.4 or 8-anilino-1-naphthalenesulfonic acid at pH 4.0 to displace progesterone from serum binding-proteins. Progesterone is then assayed by using an antiserum to a progesterone 11α-hemisuccinyl conjugate and the radioligand 125 I-labeled progesterone 11α-glucuronyl tyramine, with separation by double-antibody techniques. Direct assays with either displacing agent gave good analytical recovery of progesterone added to human serum, and progesterone values for patients' specimens correlated well (r > 0.96) with results of assays involving extraction of serum. Precision was similar with each displacing agent over the working range 2.5-100 nmol/L and superior to that of extraction assays. We conclude that these direct assays of progesterone are analytically valid and more robust, precise, and technically convenient than many conventional methods involving extraction of serum

Progesterone receptor antagonist CDB-4124 increases depression-like behavior in mice without affecting locomotor ability

Science.gov (United States)

Beckley, Ethan H.; Scibelli, Angela C.; Finn, Deborah A.

2010-01-01

Progesterone withdrawal has been proposed as an underlying factor in premenstrual syndrome and postpartum depression. Progesterone withdrawal induces forced swim test (FST) immobility in mice, a depression-like behavior, but the contribution of specific receptors to this effect is unclear. The role of progesterone’s GABAA receptor-modulating metabolite allopregnanolone in depression- and anxiety-related behaviors has been extensively documented, but little attention has been paid to the role of progesterone receptors. We administered the classic progesterone receptor antagonist mifepristone (RU-38486) and the specific progesterone receptor antagonist CDB-4124 to mice that had been primed with progesterone for five days, and found that both compounds induced FST immobility reliably, robustly, and in a dose-dependent fashion. Although CDB-4124 increased FST immobility, it did not suppress initial activity in a locomotor test. These findings suggest that decreased progesterone receptor activity contributes to depression-like behavior in mice, consistent with the hypothesis that progesterone withdrawal may contribute to the symptoms of premenstrual syndrome or postpartum depression. PMID:21163582

The Determinations of Estrogen and Progesterone Receptor in Breast Cancer Cell by Radioimmunoassay Method

International Nuclear Information System (INIS)

Kim, Chi Yeul

1981-01-01

The estrogen and progesterone receptors which are bound to the cytoplasmic protein of cancer cells were measured in 20 patients with the early breast cancer by means of radioimmunoassay using charcoal. 1) The patients with estrogen receptor positive were 13 (65%) of 20 cases and with progestrone receptor positive were 7 cases (35%) in the early breast cancer. 2) Coexistence of estrogen and progesterone receptor positive was noted in 7 cases (35%). The cases of estrogen receptor positive and progesterone receptor negative were 6 cases (33.3%), while there were no cases of estrogen receptor negative with progesterone receptor positive. 3) Coincidence of estrogen and progesterone negative was noticed in 7 cases (35%). Conclusively it is considered that the measurement of estrogen and progesterone receptors has relevance as predictive value, in the response to hormonal manipulations and chemotherapy for breast cancer patients.

Serum progesterone levels using radioimmunoassay during the oestrous cycle of indigenous Damascus does

International Nuclear Information System (INIS)

Zarkawi, M.

2000-11-01

An experiment was conducted on Damascus does to characterize the oestrous cycle, the activity of the corpus luteum and to determine normal progesterone profiles during different phases of the oestrous cycle using radioimmunoassay. Fifteen indigenous cycling Damascus does were used during the normal breeding season for two consecutive oestrous cycles. Average length of the oestrous cycles was 21.2 ± 1.5 days (range: 19 - 26 days), divided into: 2.9 ± 0.8 days (2 - 5 days), where progesterone level was low averaging 0.69 ± 0.85 nmol l -1 (range: 0.00 - 3.08 nmol l -1 , followed by a sharp increase in progesterone secretion, i.e. presence of active corpora lutea, lasted on average for 15.3 ± 1.4 days (range: 13 - 20 days), with an average progesterone level of 13.4 nmol l -1 (range: 3.26 - 27.98 nmol l -1 ), followed by a sharp decline in progesterone level, i.e. inactive corpora lutea, lasted on average for 3.1 ± 0.6 days (range: 2 - 5 days), with an average progesterone level of 0.68 nmol l -1 (range: 0.00 - 2.81 nmol l -1 ). Maximum progesterone level during the luteal phase averaged 18.67 ± 3.15 nmol l -1 (range: 14.00 - 27.98 nmol l -1 ), occurred on average on 12.2 ± 3.2 days of the oestrous cycle. It was possible, for the first time, to characterize the oestrous cycle of the Damascus doe, and to determine normal progesterone profiles during different phases of oestrous cycle. Based on the results reported above, it is also concluded that progesterone levels under 3.18 nmol l -1 were found on average during 2.9 days at the start of the oestrous cycle and during 3.1 days at the end of the oestrous cycle (follicular phase), and that progesterone levels above 3.18 nmol l -1 were found during the luteal phase lasting on average 15.3 days. (Author)

Nonenzymatic electrochemical sensor based on imidazole-functionalized graphene oxide for progesterone detection.

Science.gov (United States)

Gevaerd, Ava; Blaskievicz, Sirlon F; Zarbin, Aldo J G; Orth, Elisa S; Bergamini, Márcio F; Marcolino-Junior, Luiz H

2018-07-30

The modification of electrode surfaces has been the target of study for many researchers in order to improve the analytical performance of electrochemical sensors. Herein, the use of an imidazole-functionalized graphene oxide (GO-IMZ) as an artificial enzymatic active site for voltammetric determination of progesterone (P4) is described for the first time. The morphology and electrochemical performance of electrode modified with GO-IMZ were characterized by scanning electron microscopy and cyclic voltammetry, respectively. Under optimized conditions, the proposed sensor showed a synergistic effect of the GO sheets and the imidazole groups anchored on its backbone, which promoted a significant enhancement on electrochemical reduction of P4. Figures of merits such as linear dynamic response for P4 concentration ranging from 0.22 to 14.0 μmol L -1 , limit of detection of 68 nmol L -1 and limit of quantification and 210 nmol L -1 were found. In addition, presented a higher sensitivity, 426 nA L µmol -1 , when compared to the unmodified electrode. Overall, the proposed device showed to be a promising platform for a simple, rapid, and direct analysis of progesterone. Copyright © 2018 Elsevier B.V. All rights reserved.

Blood periovulatory progesterone quantification using different techniques in the dog.

Science.gov (United States)

Gloria, Alessia; Contri, Alberto; Carluccio, Augusto; Robbe, Domenico

2018-05-01

Blood progesterone concentration is used in several procedures related to the reproduction in the bitch, such as ovulation monitoring, estimating time of parturition, or hypo-luteoidism management. Several techniques are available to evaluate blood progesterone concentration, such as the radioimmunoassay (RIA), the chemiluminescent immunoassay (CLIA), and the enzyme-linked immunosorbent assay (ELISA). The aim of this study was to compare the blood progesterone concentration using these three methods during the periovulatory period of 23 bitches. Vaginal cytology was used to classify cytologic estrus (CE) and cytologic diestrus (CD), and blood samples were collected once during proestrus and every other day between CE and CD. The samples were retrospectively classified in the different phases of the estrus based on CD. Pregnancy rate and gestational length were also recorded. A significant increase of the circulating progesterone during the progression of the estrus was recorded, and there were significant differences in the values when using the different methods, with lesser, intermediate, and greatest values with use of the RIA, CLIA, and ELISA, respectively. There was a high correlation (Pearson's correlation coefficient = 0.978) and substantial strength-of-agreement (Lin's concordance correlation coefficient = 0.966) between values obtained when using CLIA and RIA, while there was a high correlation (Pearson's correlation coefficient = 0.955) but poor strength-of-agreement (Lin's concordance correlation coefficient = 0.866) with use of the ELISA and RIA. The data reported in this study provide evidence that the method used for measuring the blood progesterone concentration during the periovulatory phase of the bitch significantly affected the progesterone values. Copyright © 2018 Elsevier B.V. All rights reserved.

Blastocyst transfer does not improve cycle outcome as compared to D3 transfer in antagonist cycles with an elevated progesterone level on the day of hCG.

Science.gov (United States)

Demirel, Cem; Aydoğdu, Serkan; Özdemir, Arzu İlknur; Keskin, Gülşah; Baştu, Ercan; Buyru, Faruk

2017-09-01

To evaluate the association between progesterone elevation on the day of human chorionic gonadotropin (hCG) administration and clinical pregnancy rates of gonadotropin-releasing hormone (GnRH) antagonist in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles with the transfer of embryos at different developmental stages (day-3 versus day-5 ETs). This is a retrospective analysis of fresh IVF/ICSI; 194 cycles out of 2676 conducted in a single center. A total of 2676 cycles were analyzed, of which 386 had no progesterone measurements available. Two hundred eighteen cycles had progesterone elevation (p>1.5 ng/mL) giving an overall incidence of 9.5%. Twenty-four cycles were excluded from further analysis. Of the remaining 194 cycles, 151 had day-3 transfers and 43 had blastocyst transfers. There was no statistically significant difference in pregnancy and clinical pregnancy rates per transfer between the D3-ET and D5-ET groups (46% vs. 49%, and 39% vs. 35%, respectively). The results of this study suggest that blastocyst transfer does not improve cycle outcomes compared with D3 transfer in GnRH antagonist cycles with an elevated progesterone level on the day of hCG.

Enhancing of progesterone transformation by cochliobolus spicifer fungus using different environmental conditions and gamma irradiation

International Nuclear Information System (INIS)

Moussa, L.A.A.

2005-01-01

Five isolates belonging to five species of the genus Cochliobolus were tested for their ability to transform progesterone. Two species namely C. australiensis and C. tuberculates failed to transform progesterone, C. pallescens produced 11B-hydroxy and 6 (3, 11a-dihydroxy progesterone, while the isolate of C. lunatus produced 11B-hydroxy and 17a-hydroxy progesterone. The isolate of C. spicifer produced four mono hydroxylated products (11a-, 11B- -17a dihydroxy progesterone and dihydro-xylated product 11 a, 17a-dihydroxy progesterone) with the addition of two trihydroxy products namely 11 a, 17a,21-trihydroxy progesterone (epicortisol) and 11/3, 17a, 21-trihydroxy progesterone (cortisol). The transformation pattern of progesterone by C. spicifer was markedly affected by the composition of culture medium, pH value of culture medium and gamma irradiation of the tested isolate. The different transformation products were resolved chromatographically. The identity of each product was established through the determination of m.p, optical rotation and ultraviolet as well as infrared absorption spectra. A comparison of the Rf -values of each product with that of the corresponding reference, using different solvent systems as well as their colours with two spray reagents, was used as a further proof for the identity of the isolated products

Progesterone reduces erectile dysfunction in sleep-deprived spontaneously hypertensive rats

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Tufik Sergio

2007-03-01

Full Text Available Abstract Background Paradoxical sleep deprivation (PSD associated with cocaine has been shown to enhance genital reflexes (penile erection-PE and ejaculation-EJ in Wistar rats. Since hypertension predisposes males to erectile dysfunction, the aim of the present study was to investigate the effects of PSD on genital reflexes in the spontaneously hypertensive rat (SHR compared to the Wistar strain. We also extended our study to examine how PSD affect steroid hormone concentrations involved in genital events in both experimental models. Methods The first experiment investigated the effects of PSD on genital reflexes of Wistar and SHR rats challenged by saline and cocaine (n = 10/group. To further examine the impact of the PSD on concentrations of sexual hormones, we performed a hormonal analysis of testosterone and progesterone in the Wistar and in SHR strains. Since after PSD progesterone concentrations decreased in the SHR compared to the Wistar PSD group we extended our study by investigating whether progesterone (25 mg/kg or 50 mg/kg or testosterone (0.5 mg/kg or 1.0 mg/kg administration during PSD would have a facilitator effect on the occurrence of genital reflexes in this hypertensive strain. Results A 4-day period of PSD induced PE in 50% of the Wistar rats against 10% for the SHR. These genital reflexes was potentiated by cocaine in Wistar rats whereas this scenario did not promote significant enhancement in PE and EJ in hypertensive rats, and the percentage of SHR displaying genital reflexes still figured significantly lower than that of the Wistar strain. As for hormone concentrations, both sleep-deprived Wistar and SHR showed lower testosterone concentrations than their respective controls. Sleep deprivation promoted an increase in concentrations of progesterone in Wistar rats, whereas no significant alterations were found after PSD in the SHR strain, which did not present enhancement in erectile responses. In order to explore the role

Dose dependent effect of progesterone on hypoxic ventilatory response in newborn rats.

Science.gov (United States)

Hichri, Oubeidallah; Laurin, Jean-C; Julien, Cécile A; Joseph, Vincent; Bairam, Aida

2012-01-01

The effect of progesterone as a respiratory stimulant in newborn subjects is less known than that in adults. This study investigated the dose-response curve (0, 2, 4, and 8 mg/kg, ip) of progesterone on ventilation in non-anesthetized newborn rats at 4- and 12-days old using plethysmography. Progesterone had no effects in the regulation of normoxic ventilation. However, it enhanced the response to moderate hypoxia (FiO(2) 12%, 20 min) in 4- but not in 12-days old pups. This response was similar between the dose of 4 and 8 mg/kg. These observations suggested that progesterone enhances in age- and dose-dependent manner the hypoxic ventilatory response in newborn rats.

Diagnosis of pregnancy in dairy cows based on the progesterone ...

African Journals Online (AJOL)

Diagnosis of pregnancy in dairy cows based on the progesterone content of milk. Part 1. ... best overall classification of dairy cows into pregnant and non-pregnant groups (confirmed by rectal palpation). Progesterone levels ... Teen 'n diskriminante progesteroonwaarde van 5 ng/ml melk het hierdie funksie 98,0% van alle ...

A Gata2-Dependent Transcription Network Regulates Uterine Progesterone Responsiveness and Endometrial Function

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Cory A. Rubel

2016-10-01

Full Text Available Altered progesterone responsiveness leads to female infertility and cancer, but underlying mechanisms remain unclear. Mice with uterine-specific ablation of GATA binding protein 2 (Gata2 are infertile, showing failures in embryo implantation, endometrial decidualization, and uninhibited estrogen signaling. Gata2 deficiency results in reduced progesterone receptor (PGR expression and attenuated progesterone signaling, as evidenced by genome-wide expression profiling and chromatin immunoprecipitation. GATA2 not only occupies at and promotes expression of the Pgr gene but also regulates downstream progesterone responsive genes in conjunction with the PGR. Additionally, Gata2 knockout uteri exhibit abnormal luminal epithelia with ectopic TRP63 expressing squamous cells and a cancer-related molecular profile in a progesterone-independent manner. Lastly, we found a conserved GATA2-PGR regulatory network in both human and mice based on gene signature and path analyses using gene expression profiles of human endometrial tissues. In conclusion, uterine Gata2 regulates a key regulatory network of gene expression for progesterone signaling at the early pregnancy stage.

Anti-inflammatory effects of progesterone in lipopolysaccharide-stimulated BV-2 microglia.

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Beilei Lei

Full Text Available Female sex is associated with improved outcome in experimental brain injury models, such as traumatic brain injury, ischemic stroke, and intracerebral hemorrhage. This implies female gonadal steroids may be neuroprotective. A mechanism for this may involve modulation of post-injury neuroinflammation. As the resident immunomodulatory cells in central nervous system, microglia are activated during acute brain injury and produce inflammatory mediators which contribute to secondary injury including proinflammatory cytokines, and nitric oxide (NO and prostaglandin E2 (PGE2, mediated by inducible NO synthase (iNOS and cyclooxygenase-2 (COX-2, respectively. We hypothesized that female gonadal steroids reduce microglia mediated neuroinflammation. In this study, the progesterone's effects on tumor necrosis factor alpha (TNF-α, iNOS, and COX-2 expression were investigated in lipopolysaccharide (LPS-stimulated BV-2 microglia. Further, investigation included nuclear factor kappa B (NF-κB and mitogen activated protein kinase (MAPK pathways. LPS (30 ng/ml upregulated TNF-α, iNOS, and COX-2 protein expression in BV-2 cells. Progesterone pretreatment attenuated LPS-stimulated TNF-α, iNOS, and COX-2 expression in a dose-dependent fashion. Progesterone suppressed LPS-induced NF-κB activation by decreasing inhibitory κBα and NF-κB p65 phosphorylation and p65 nuclear translocation. Progesterone decreased LPS-mediated phosphorylation of p38, c-Jun N-terminal kinase and extracellular regulated kinase MAPKs. These progesterone effects were inhibited by its antagonist mifepristone. In conclusion, progesterone exhibits pleiotropic anti-inflammatory effects in LPS-stimulated BV-2 microglia by down-regulating proinflammatory mediators corresponding to suppression of NF-κB and MAPK activation. This suggests progesterone may be used as a potential neurotherapeutic to treat inflammatory components of acute brain injury.

A label-free colorimetric progesterone aptasensor based on the aggregation of gold nanoparticles

International Nuclear Information System (INIS)

Du, Gaoshang; Xu, Lurong; Zhan, Shenshan; Ni, Xuan; Zhou, Xiaotong; Wang, Lumei; Zhang, Dongwei; Xia, Bing; Wu, Shijian

2016-01-01

The authors describe an aptasensor for the detection of the gonadal hormone progesterone (P4) in aqueous solution. Gold nanoparticles (AuNPs) were coated with a P4-specific aptamer, and such particles do not aggregate in presence of NaCl due to the presence of the aptamer coating. If, however, progesterone is added, it will bind to the aptamer and release it from the surface. The uncoated AuNPs, on addition of NaCl, will aggregate and a color change from red (520 nm) to blue (650 nm) can be visually detected or photometrically quantified. The ratio of the absorbances at 650 and 520 nm is linearly related to the P4 concentration in the range from 2.6 to 800 nM. The complete detection range extends from 2.6 to 1400 nM, and the detection limit is 2.6 nM. Water containing various potential interferents, as well as tap water and urine, were spiked with P4 and the recoveries of P4 are in the range of 89.7–117.5%, 84.4–115.0% and 94.7–118.8%, respectively. This assay has a large potential with respect to the visual and instrumental determination of P4 in aquatic environment and urine. (author)

Intravaginal boric acid: is it an alternative therapeutic option for vaginal trichomoniasis?

Science.gov (United States)

Thorley, Nicola; Ross, Jonathan

2017-12-09

Trichomoniasis, caused by Trichomonas vaginalis (TV), is the most common curable sexually transmitted infection worldwide. Current guidance in the UK is to treat TV with a nitroimidazole antibiotic. The high prevalence of TV, high rate of antibiotic resistance and limited tolerability to nitroimidazoles suggest that alternative treatment regimens are needed. Intravaginal boric acid (BA) has been used safely for the treatment of candida vulvovaginitis and bacterial vaginosis, and in vitro studies suggest BA is active against TV. We review the evidence for the efficacy of BA in patients with TV. MEDLINE, EMBASE, CINAHL, AMED, HMIC and BNI and Grey literature databases, The Cochrane Library, Trial Registers, conference abstracts and proceedings were searched. Inclusion criteria were women aged 16 years or over with microbiological confirmation of TV infection and using BA as treatment. There were no restrictions on language, publication date or study design. The in vitro evidence for BA activity against TV was also reviewed. No randomised controlled trials or case series were found. Four case reports demonstrated TV clearance with BA using a variety of dose regimens (dose 600 mg alternate nights to 600 mg two times per day; duration 1-5 months). In vitro studies suggest that BA has activity against TV which is independent of its effect on pH. Further evaluation of BA for the treatment of uncomplicated TV is required, but it may be useful when therapeutic options are limited. If shown to be safe and effective, intravaginal BA might provide a well-tolerated alternative anti-infective treatment which reduces community exposure to systemic antibiotics. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Testosterone stimulates progesterone production and STAR, P450 cholesterol side-chain cleavage and LH receptor mRNAs expression in hen (Gallus domesticus) granulosa cells.

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Rangel, P L; Rodríguez, A; Rojas, S; Sharp, P J; Gutierrez, C G

2009-12-01

The chicken ovary is organized into a hierarchy of yellow yolky follicles that ovulate on successive days. Active or passive immunization of laying hens against testosterone blocks ovulation without affecting follicle development. Testosterone may play a role in pre-ovulatory follicle maturation by stimulating granulosa progesterone production. We assessed whether this stimulus is dose-related and depends on the maturity of the donor follicle, and if it does so by stimulating granulosa cell STAR, P450 cholesterol side-chain cleavage (P450scc), and LH receptor (LHCGR) mRNAs expression. Progesterone production by granulosa cells from F1, F3, and F4 follicles, cultured for 3 h without testosterone was greater in cells collected 11-14 h than 1-4 h after ovulation. These differences in progesterone production were less pronounced after granulosa cells had been cultured for 24 h. Culture of granulosa cells for 3 or 24 h with testosterone (1-100 ng/ml) stimulated progesterone production in cells collected from F4, F3, or F1 follicles 1-4, or 11-14 h after ovulation. Testosterone (0-4000 ng/ml) alone or in combination with LH (0-100 ng/ml) increased progesterone production by F1 granulosa cells, collected 1-4 and 11-14 h after ovulation and cultured for 3 h. Finally, testosterone (10 or 100 ng/ml) increased STAR, P450scc, and LHCGR mRNAs, when added to 3 h cultures of F1 granulosa cells. In conclusion, testosterone stimulates granulosa cell progesterone production in hen pre-ovulatory hierarchical follicles irrespective of maturational state, acting alone or additively with LH. We propose that testosterone promotes granulosa cell maturation to facilitate the pre-ovulatory release of LH.

Novel atmospheric pressure plasma device releasing atomic hydrogen: reduction of microbial-contaminants and OH radicals in the air

International Nuclear Information System (INIS)

Nojima, Hideo; Park, Rae-Eun; Kwon, Jun-Hyoun; Suh, Inseon; Jeon, Junsang; Ha, Eunju; On, Hyeon-Ki; Kim, Hye-Ryung; Choi, KyoungHui; Lee, Kwang-Hee; Seong, Baik-Lin; Jung, Hoon; Kang, Shin Jung; Namba, Shinichi; Takiyama, Ken

2007-01-01

A novel atmospheric pressure plasma device releasing atomic hydrogen has been developed. This device has specific properties such as (1) deactivation of airborne microbial-contaminants, (2) neutralization of indoor OH radicals and (3) being harmless to the human body. It consists of a ceramic plate as a positive ion generation electrode and a needle-shaped electrode as an electron emission electrode. Release of atomic hydrogen from the device has been investigated by the spectroscopic method. Optical emission of atomic hydrogen probably due to recombination of positive ions, H + (H 2 O)n, generated from the ceramic plate electrode and electrons emitted from the needle-shaped electrode have been clearly observed in the He gas (including water vapour) environment. The efficacy of the device to reduce airborne concentrations of influenza virus, bacteria, mould fungi and allergens has been evaluated. 99.6% of airborne influenza virus has been deactivated with the operation of the device compared with the control test in a 1 m 3 chamber after 60 min. The neutralization of the OH radical has been investigated by spectroscopic and biological methods. A remarkable reduction of the OH radical in the air by operation of the device has been observed by laser-induced fluorescence spectroscopy. The cell protection effects of the device against OH radicals in the air have been observed. Furthermore, the side effects have been checked by animal experiments. The harmlessness of the device has been confirmed

Serotonin Transporter Promoter Region (5-HTTLPR) Polymorphism is Associated with the Intravaginal Ejaculation Latency Time in Dutch Men with Lifelong Premature Ejaculation

NARCIS (Netherlands)

Janssen, Paddy K. C.; Bakker, Steven C.; Réthelyi, Janos; Zwinderman, Aeilko H.; Touw, Daan J.; Olivier, Berend; Waldinger, Marcel D.

2009-01-01

Introduction. Lifelong premature ejaculation (LPE) is characterized by persistent intravaginal ejaculation latency times (IELTs) of less than 1 minute, and has been postulated as a neurobiological dysfunction with genetic vulnerability for the short IELTs, related to disturbances of central

Serotonin transporter promoter region (5-HTTLPR) polymorphism is associated with the intravaginal ejaculation latency time in Dutch men with lifelong premature ejaculation

NARCIS (Netherlands)

Janssen, Paddy K C; Bakker, Steven C; Réthelyi, Janos; Zwinderman, Aeilko H; Touw, Daan J; Olivier, Berend; Waldinger, Marcel D

INTRODUCTION: Lifelong premature ejaculation (LPE) is characterized by persistent intravaginal ejaculation latency times (IELTs) of less than 1 minute, and has been postulated as a neurobiological dysfunction with genetic vulnerability for the short IELTs, related to disturbances of central

Amphiregulin mediates hCG-induced StAR expression and progesterone production in human granulosa cells.

Science.gov (United States)

Fang, Lanlan; Yu, Yiping; Zhang, Ruizhe; He, Jingyan; Sun, Ying-Pu

2016-04-26

Progesterone plays critical roles in maintaining a successful pregnancy at the early embryonic stage. Human chorionic gonadotropin (hCG) rapidly induces amphiregulin (AREG) expression. However, it remains unknown whether AREG mediates hCG-induced progesterone production. Thus, the objective of this study was to investigate the role of AREG in hCG-induced progesterone production and the underlying molecular mechanism in human granulosa cells; primary cells were used as the experimental model. We demonstrated that the inhibition of EGFR and the knockdown of AREG abolished hCG-induced steroidogenic acute regulatory protein (StAR) expression and progesterone production. Importantly, follicular fluid AREG levels were positively correlated with progesterone levels in the follicular fluid and serum. Treatment with AREG increased StAR expression and progesterone production, and these stimulatory effects were abolished by EGFR inhibition. Moreover, activation of ERK1/2, but not PI3K/Akt, signaling was required for the AREG-induced up-regulation of StAR expression and progesterone production. Our results demonstrate that AREG mediates hCG-induced StAR expression and progesterone production in human granulosa cells, providing novel evidence for the role of AREG in the regulation of steroidogenesis.

Targeting progesterone metabolism in breast cancer with l-proline derived new 14-azasteroids.

Science.gov (United States)

Singh, Jyotsana; Singh, Ritesh; Gupta, Preeti; Rai, Smita; Ganesher, Asha; Badrinarayan, Preethi; Sastry, G Narahari; Konwar, Rituraj; Panda, Gautam

2017-08-15

Breast cancer cell proliferation is promoted by a variety of mitogenic signals. Classically estrogen is considered as most predominant mitogenic signal in hormone-dependent breast cancer and progesterone is primarily considered to have protective effect. However, it is suggested that some progesterone metabolite may promote breast cancer and progesterone metabolites like 5α-pregnane and 4-pregnene could serve as regulators of estrogen-responsiveness of breast cancer cells. Here, we estimated the potential of alternate targeting of breast cancer via progesterone signalling. l-Proline derived novel 14-azasteroid compounds were screened against MCF-7 and MDA-MB-231 cell lines using MTT assay. In silico studies, cell cycle, Annexin-V-FITC/PI, JC-1 mitochondrial assay, ROS analysis were performed to analyse the impact of hit compound 3b on breast cancer cells. Further, we analysed the impact of hit 3b on the progesterone, its metabolites and enzymes responsible for the conversion of progesterone and its metabolites using ELISA. Data suggests that compound 3b binds and down regulates of 5α-reductase by specifically inhibiting production of progesterone metabolites that are capable of promoting breast cancer proliferation, epithelial mesenchymal transition and migration. This study establishes the proof of concept and generation of new leads for additional targeting of breast cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Selective suppression of endothelial cytokine production by progesterone receptor

OpenAIRE

Goddard, Lauren M.; Ton, Amy N.; Org, Tõnis; Mikkola, Hanna K.A.; Iruela-Arispe, M. Luisa

2013-01-01

Steroid hormones are well-recognized suppressors of the inflammatory response, however, their cell- and tissue-specific effects in the regulation of inflammation are far less understood, particularly for the sex-related steroids. To determine the contribution of progesterone in the endothelium, we have characterized and validated an in vitro culture system in which human umbilical vein endothelial cells constitutively express human progesterone receptor (PR). Using next generation RNA-sequenc...

Estrogen, Progesterone and Epithelial Ovarian Cancer

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Ho Shuk-Mei

2003-10-01

Full Text Available Abstract Ovarian carcinoma (OCa continues to be the leading cause of death due to gynecologic malignancies and the vast majority of OCa is derived from the ovarian surface epithelium (OSE and its cystic derivatives. Epidemiological evidence strongly suggests that steroid hormones, primarily estrogens and progesterone, are implicated in ovarian carcinogenesis. However, it has proved difficult to fully understand their mechanisms of action on the tumorigenic process. New convincing data have indicated that estrogens favor neoplastic transformation of the OSE while progesterone offers protection against OCa development. Specifically, estrogens, particularly those present in ovulatory follicles, are both genotoxic and mitogenic to OSE cells. In contrast, pregnancy-equivalent levels progesterone are highly effective as apoptosis inducers for OSE and OCa cells. In this regard, high-dose progestin may exert an exfoliation effect and rid an aged OSE of pre-malignant cells. A limited number of clinical studies has demonstrated efficacies of antiestrogens, aromatase inhibitors, and progestins alone or in combination with chemotherapeutic drugs in the treatment of OCa. As a result of increased life expectancy in most countries, the number of women taking hormone replacement therapies (HRT continues to grow. Thus, knowledge of the mechanism of action of steroid hormones on the OSE and OCa is of paramount significance to HRT risk assessment and to the development of novel therapies for the prevention and treatment of OCa.

Milk samples collected with filter paper for progesterone radioimmunoassay

Energy Technology Data Exchange (ETDEWEB)

Jiahua, Zhang; Guoxia, Geng; Huaiyu, Zhang

1985-09-01

The cow milk was collected with filter paper treated with ethanol during eastrus-day (0 day) and 22th and 24th day after mating. Then it was dried and stored in room temprature until analysis for progesterone by means of radioimmunoassay. The sensitivity is 13.62 pg/bule (n = 4), the coefficients of variation within a group and between groups are 8.8% (n = 10) and 16.65% (n = 8) respectively, and the recovery is 91.23% (n = 4). The average progesterone level for 22th and 24th day in the pregnant cows (6.28 +- 1.28 ng/ml) was much higher than that in the non-pregnant cow (2.00 +- 1.18 ng/ml), the difference being significant (P < 0.001). The judgement based on progesterone level (5 pregnant and 5 non-pregnant cows) faily agreed with the clinical diagnosis.

Sex-related differences in effects of progesterone following neonatal hypoxic brain injury.

Science.gov (United States)

Peterson, Bethany L; Won, Soonmi; Geddes, Rastafa I; Sayeed, Iqbal; Stein, Donald G

2015-06-01

There is no satisfactory therapeutic intervention for neonatal hypoxic-ischemic (HI) encephalopathy. Progesterone is known to be effective in treating traumatic brain injury in adult animals but its effects in neonatal brains have not been reported. Brain injuries were induced by a unilateral common carotid artery ligation plus hypoxia exposure. Progesterone was administered immediately after hypoxia and daily for 5 days at 8 mg/kg, followed by a tapered dose for two days. At six weeks post-injury, lesion size and inflammatory factors were evaluated. Progesterone-treated, HI-injured male animals, but not females, showed significant long-term tissue protection compared to vehicle, suggesting an important sex difference in neuroprotection. Progesterone-treated, HI-injured male rats had fewer activated microglia in the cortex and hippocampus compared to controls. The rats were tested for neurological reflexes, motor asymmetry, and cognitive performance at multiple time points. The injured animals exhibited few detectable motor deficits, suggesting a high level of age- and injury-related neuroplasticity. There were substantial sex differences on several behavioral tests, indicating that immature males and females should be analyzed separately. Progesterone-treated animals showed modest beneficial effects in both sexes compared to vehicle-treated injured animals. Sham animals given progesterone did not behave differently from vehicle-treated sham animals on any measures. Copyright © 2015 Elsevier B.V. All rights reserved.

Immunohistochemical Expression of Estrogen and Progesterone Receptors in Epulis Fissuratum

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Maryam Seyedmajidi

2013-01-01

Full Text Available Background: Epulis Fissuratum (Epulis Fissuratum (EF or Denture Epulis or inflammatory fibrous hyperplasia is a common hyperplastic tumor-like lesion with reactive nature, related to loose and ill-fitting, full or partial removable dentures and it is more common in women than men. For this reason, hormonal influences may also play role in its creation. The effect of steroid hormones especially sex hormones (Estrogen and progesterone on oral mucosa is identified in some studies. In the present study, the distribution pattern and presence of estrogen and progesterone receptors in epithelial, stromal, endothelial and inflammatory cells in Epulis Fissuratum was investigated. Materials and Methods: This cross-sectional study was carried out on 30 samples of paraffin blocks with Epulis Fissuratum diagnosis and 30 samples of normal mucosal tissues as a control group who have had surgery as a margin beside the above lesions and had been obtained from the oral and maxillofacial pathology departement of Babol Dental School since 2003 up to 2010. Intensity of staining and immunoreactivity were evaluated using subjective index and considering the positive control group (breast carcinoma.Results: Epithelial, stromal, endothelial and inflammatory cells didn’t show reaction with monoclonal antibodies against estrogen and progesterone in none of the samples. Conclusion: It seems that the hypothesis of the existence of estrogen and progesterone receptors in epulis fissuratum and normal oral mucosa is ruled out. The possibility of direct effect of estrogen and progesterone in occurring of epulis fissuratum is rejected.

Role of sex steroids in progesterone and corticosterone response to acute restraint stress in rats: sex differences.

Science.gov (United States)

Kalil, B; Leite, C M; Carvalho-Lima, M; Anselmo-Franci, J A

2013-07-01

Adrenal progesterone secretion increases along with corticosterone in response to stress in male and female rats to modulate some stress responses. Here we investigated the role of sex steroids in sex differences in the progesterone response to 60 min of restraint stress in adult male and female rats. Comparisons between males and females in the progesterone response were evaluated in parallel with corticosterone responses. From day 5 to 7 after gonadectomy, female and male rats were treated with estradiol or testosterone, respectively (OVX-E and ORCH-T groups), or oil (OVX and ORCH groups). Female rats in proestrus, intact and 7 d adrenalectomized (ADX) male rats were also studied. At 10:00 h, blood samples were withdrawn via an implanted jugular cannula before (-5 min), during (15, 30, 45, 60 min) and after (90 and 120 min) restraint stress to measure plasma progesterone and corticosterone concentrations by radioimmunoassay. Intact male and proestrus female rats exhibited similar progesterone responses to stress. Gonadectomy did not alter the amount of progesterone secreted during stress in female rats but decreased secretion in male rats. Unlike corticosterone, the progesterone response to stress in females was not influenced by estradiol. In males, testosterone replacement attenuated the progesterone and corticosterone responses to stress. Basal secretion of progesterone among intact, ORCH and ADX males was similar, but ADX-stressed rats secreted little progesterone. Hence, the gonads differently modulate adrenal progesterone and corticosterone responses to stress in female and male rats. The ovaries enhance corticosterone but not progesterone secretion, while the testes stimulate progesterone but not corticosterone secretion.

A new approach to enhance reproductive performance in sheep using royal jelly in comparison with equine chorionic gonadotropin.

Science.gov (United States)

Husein, M Q; Haddad, S G

2006-06-01

The objective was to compare the effects of royal jelly (RJ) and eCG treatments on reproductive performance of ewes synchronized using intravaginal progesterone-releasing devices. Forty-two cycling Awassi ewes were treated intramuscularly (i.m.) with 15 mg PGF2alpha. On the following day, all ewes were administered with CIDR-G for 12 days and were randomly allocated to three (RJ, eCG and control) groups of 14 ewes each. Ewes in the RJ-treated group received daily i.m. treatments of 400mg RJ during the period of CIDR-treatment. Each ewe in the eCG-treated group received an i.m. treatment of 500 IU eCG at the time of CIDR-G removal (day 0) and no further treatment was given to ewes in the control group. Ewes were exposed to four fertile rams for 72 h, from the time of CIDR-G removal, and checked for breeding marks at 6-h intervals. Blood samples were collected from day -13 until day 0 and thereafter until day 19 for progesterone analysis. Royal jelly treatment resulted in a greater rate of decline and lower (Pprogesterone concentrations between days -10 and 0 than eCG-treated and control ewes. Expression of estrus was similar among the three groups and intervals to onset of estrus were shorter (P<0.01) in RJ-treated (31.3h) and eCG-treated (29.8h) than control (41.3h) ewes. First-cycle pregnancy and lambing rates were greater (P<0.05) in RJ-treated (71.4 and 71.4%) and eCG-treated (85.7 and 78.6%) than in control (42.9 and 35.7%) ewes, respectively. Results demonstrate that the treatments of RJ and eCG in conjunction with CIDR-G were similarly effective in induction of estrus and improvement of pregnancy and lambing rates.

Results of applications of DISKOT system and of RIA determination of progesterone

International Nuclear Information System (INIS)

Beranek, J.

1989-01-01

Milk for progesterone determination was taken from cows picked out for insemination, cows following insemination and cows with reproduction disorders. The samples were taken in test tubes containing potassium dichromate. Progesterone was determined by RIA of skimmed milk and the results were transmitted to the DISKOT system in the data processing centre. The use of the DISKOT system output and the monitoring of progesterone in milk by the RIA laboratory improved reproduction indexes of the herd under study. (E.J.). 2 tabs

Micro-dose hCG as luteal phase support without exogenous progesterone administration

DEFF Research Database (Denmark)

Andersen, C Yding; Fischer, R; Giorgione, V

2016-01-01

RHa trigger to induce ovulation showed that exogenous progesterone administration without hCG supplementation was insufficient to obtain satisfactory pregnancy rates. This has prompted development of alternative strategies for LPS. Augmenting the local endogenous production of progesterone by the multiple......For the last two decades, exogenous progesterone administration has been used as luteal phase support (LPS) in connection with controlled ovarian stimulation combined with use of the human chorionic gonadotropin (hCG) trigger for the final maturation of follicles. The introduction of the Gn...... corpora lutea has been one focus with emphasis on one hand to avoid development of ovarian hyper-stimulation syndrome and, on the other hand, to provide adequate levels of progesterone to sustain implantation. The present study evaluates the use of micro-dose hCG for LPS support and examines the potential...

Low glucose availability stimulates progesterone production by mouse ovaries in vitro.

Science.gov (United States)

Wilsterman, Kathryn; Pepper, Aimee; Bentley, George E

2017-12-15

Steroid production by the ovary is primarily stimulated by gonadotropins but can also be affected by biological cues that provide information about energy status and environmental stress. To further understand which metabolic cues the ovary can respond to, we exposed gonadotropin-stimulated mouse ovaries in vitro to glucose metabolism inhibitors and measured steroid accumulation in media. Gonadotropin-stimulated ovaries exposed to 2-deoxy-d-glucose increased progesterone production and steroidogenic acute regulatory protein mRNA levels. However, oocytes and granulosa cells in antral follicles do not independently mediate this response because targeted treatment of these cell types with a different inhibitor of glucose metabolism (bromopyruvic acid) did not affect progesterone production. Elevated progesterone production is consistent with the homeostatic role of progesterone in glucose regulation in mammals. It also may regulate follicle growth and/or atresia within the ovary. These results suggest that ovaries can regulate glucose homeostasis in addition to their primary role in reproductive activity. © 2017. Published by The Company of Biologists Ltd.

Transition Metal Chelator Induces Progesterone Production in Mouse Cumulus-Oocyte Complexes and Corpora Lutea.

Science.gov (United States)

Tian, X; Anthony, K; Diaz, Francisco J

2017-04-01

Progesterone production is upregulated in granulosa cells (cumulus and mural) after the LH surge, but the intra-follicular mechanisms regulating this transition are not completely known. Recent findings show that the transition metal chelator, N,N,N',N'-tetrakis-(2-pyridylmethyl)-ethylenediamine (TPEN), impairs ovarian function. In this study, we provide evidence that chelating transition metals, including zinc, enhances progesterone production. The findings show that TPEN (transition metal chelator) increases abundance of Cyp11a1 and Star messenger RNA (mRNA) between 8- and 20-fold and progesterone production more than 3-fold in cultured cumulus-oocyte complexes (COC). Feeding a zinc-deficient diet for 10 days, but not 3 days, increased Star, Hsd3b, and prostaglandin F2 alpha receptor (Ptgfr) mRNA ~2.5-fold, suggesting that the effect of TPEN is through modulation of zinc availability. Progesterone from cumulus cells promotes oocyte developmental potential. Blocking progesterone production with epostane during maturation reduced subsequent blastocyst formation from 89 % in control to 18 % in epostane-treated complexes, but supplementation with progesterone restored blastocyst developmental potential to 94 %. Feeding a zinc-deficient diet for 5 days before ovulation did not affect the number of CL, STAR protein, or serum progesterone. However, incubating luteal tissue with TPEN increased abundance of Star, Hsd3b, and Ptgfr mRNA 2-3-fold and increased progesterone production 3-fold. TPEN is known to abolish SMAD2/3 signaling in cumulus cells. However, treatment of COC with the SMAD2/3 phosphorylation inhibitor, SB421542, did not by itself induce steroidogenic transcripts but did potentiate EGF-induced Star mRNA expression. Collectively, the results show that depletion of transition metals with TPEN acutely enhances progesterone biosynthesis in COC and luteal tissue.

Diurnal rhythms in gonadotropins and progesterone in lactating and photoperiod induced acyclic hamsters

International Nuclear Information System (INIS)

Bridges, R.S.; Goldman, B.D.

1975-01-01

Levels of LH, FSH, and progesterone in serum were measured in lactating hamsters and in hamsters in which acyclicity was induced with altered photoperiod. Lactating hamsters were found to have low titers of LH, FSH, and progesterone in serum at 0900 (lights on 0500--1900) on Days 4, 9, 14, and 19 of lactation and increased levels of these hormones at 1600. Levels of LH and FSH in serum at both 0900 and 1600 remained relatively constant throughout lactation. In contrast, levels of progesterone in serum obtained at both 0900 and 1600 sampling times increased as lactation progressed. Ovariectomy on Day 9 of lactation reduced serum levels of progesterone at both 0900 and 1600 and eliminated the afternoon surge in progesterone in animals bled 5 days after surgery. The levels and pattern of LH in serum remained unchanged after ovariectomy in lactating hamsters. However, serum FSH levels in the ovariectomized, lactating animals were elevated at both 0900 and 1600 when compared to levels present in intact, lactating hamsters bled at the same times. Females which were acyclic due to altered photoperiod displayed similar patterns of LH, FSH, and progesterone in serum. Levels of LH, FSH, and progesterone in serum were low at 1000 (lights on 0500--1500) and were increased 2 to 10 fold at 1500. Ovariectomy was followed by lower progesterone levels in serum at 1000 and 1500 and eliminated the afternoon rise of this hormone. Serum levels of LH were unaffected by ovariectomy. As in lactating hamsters, levels of FSH in serum were elevated 3--4 days following ovariectomy at both bleeding times, but the levels were higher at 1500. These results indicate that acyclicity induced by lactation or exposure to a short photoperiod is characterized by similar diurnal patterns of circulating hormones in the hamster

Determination of progesterone for reproduction control in cows using a 3H radioimmunoassay. 1

International Nuclear Information System (INIS)

Taubert, H.; Barth, T.; Hempel, G.; Graeser, K.

1984-01-01

For verification of cow fertility a 3 H radioimmunoassay of progesterone in milk and blood plasma was developed. It is of high specificity and accuracy as well. Extraction of progesterone from milk was facilitated by application of alcohol. Suggested differences in milk and plasma progesterone levels between pregnant and nonpregnant cows could be revealed

Preovulatory progesterone concentration associates significantly to follicle number and LH concentration but not to pregnancy rate

DEFF Research Database (Denmark)

Yding Andersen, Claus; Bungum, Leif; Nyboe Andersen, Anders

2011-01-01

Using data from a large prospective randomized controlled trial that evaluated the effect of recombinant LH (rLH)co-administration for ovarian stimulation, the present study assessed whether progesterone concentration on the day of human chorionic gonadotrophin (HCG) administration was associated...... with or without rLH administration from day 6 of stimulation. There was no significant association between the late-follicular-phase progesterone concentration and the clinical pregnancy rate. However, progesterone concentration was strongly associated with the number of follicles and retrieved oocytes. Late......-follicular-phase LH concentration also showed a significant positive association with progesterone concentration (P = 0.018). Administration of rLH during ovarian stimulation did not affect progesterone concentration. The present study does not support an association between progesterone concentration on the day...

Effect of triptolide on progesterone production from cultured rat granulosa cells.

Science.gov (United States)

Zhang, J; Jiang, Z; Mu, X; Wen, J; Su, Y; Zhang, L

2012-06-01

Triptolide(CAS 38748-32-2), a major active component of Tripterygium wilfordii Hook F (TWHF), is known to have multiple pharmacological activities. However, studies have also shown that triptolide is highly disrupt to the reproductive system by disrupting normal steroid hormone signaling. In the present study, we investigated the effect of triptolide (5, 10, or 20 nM for 24 h) on progesterone production by rat granulosa cells. Triptolide inhibited both basal and human chorionic gonadotropin (HCG)- and 8-bromo-cAMP-stimulated progesterone production as revealed by RIA assay. Furthermore, the HCG-evoked increase in cellular cAMP content was also inhibited by triptolide, indicating that disruption of the cAMP/PKA signaling pathway may mediate the deleterious effects of triptolide on progesterone regulation. In addition, triptolide inhibited 25-OH-cholesterol-stimulated progesterone production, suggesting that activity of the P450 side chain cleavage (P450scc) enzyme was also be inhibited by triptolide. Western blot and quantitative real-time PCR (qRT-PCR) assays further revealed that triptolide decreased mRNA and protein expression of P450scc and the steroidogenic regulatory (StAR) protein in granulosa cells. In contrast, cell viability tests using 3-(4,5-dimethyl-thiazol-2-yl)-2,5- diphenyl-tetrazolium bromide (MTT) indicated that triptolide did not cause measurable cell death at doses that suppressed steroidogenesis. The reproductive toxicity of triptolide may be caused by disruption of cAMP/PKA-mediated expression of a number of progesterone synthesis enzymes or regulatory proteins, leading to reduced progesterone synthesis and reproductive dysfunction. © Georg Thieme Verlag KG Stuttgart · New York.

Use of progesterone, measurement to monitor artificial insemination, reproductive functions and pregnancy in Tunisian cattle

International Nuclear Information System (INIS)

Slimane, Naceur; Haffar, M.A.; Chetoui, C.; Bahri, M.

2005-01-01

Use of progesterone, measurement to monitor artificial insemination, reproductive functions and pregnancy in tunisian and pregnancy in tunisian cattle Results saved during field application in four Tunisian farms from 924 dairy cows. A total of 2830 milk samples were collected from these cows at 3 fixed intervals to evaluate the level of Progesterone: at Artificial Insemination (AI) time (1034), 12th day (948) and at 22nd to 24th days after AI (848). Progesterone concentrations in samples done at AI moment (n=1034) revealed that 10.1% of cows was inseminated at improper moment (progesterone level higher or equal to 1nmol/l). In the second category (samples collected 12 days after AI, n=948), allowed distinguishing between two different situations: (1)- Cycling cows: progesterone concentration was higher or equal to 3nmol/l (69.4%). (2)- Non cycling cows: progesterone level was strictly lower than 3nmol/l (30.6%). The aim of progesterone assay of samples collected in the third category (22 to 24 days after AI) is to establish the Early Non Pregnancy Diagnosis (ENPD). Recorded data allow distinguishing: (1)- Non pregnant females: progesterone concentration is strictly less than 2nmol/l. The confirmation of this situation was carried out by rectal palpation. The gathered information indicated that ENPD accuracy is equal to 96.6%. (2)- Pregnant females: progesterone level is to be higher than or equal to 3.5nmol/l. The ENPD accuracy is 73.3% after confirmation using rectal palpation. (3)- Doubtful females: progesterone concentration is to be between (2 and 3.5nmol/l). Fertility and fecundity criteria were determined by using AIDA software, the analysis considered some variation factors such as cow parity, body score condition, number of services, inseminator, and milk production

Inhibition effects of perfluoroalkyl acids on progesterone production in mLTC-1.

Science.gov (United States)

Zhao, Wei; Cui, Ruina; Wang, Jianshe; Dai, Jiayin

2017-06-01

Perfluoroalkyl substances (PFASs) are a class of fluorine substituted carboxylic acid, sulfonic acid and alcohol, structurally similar to their corresponding parent compounds. Previous study demonstrated the potential endocrine disruption and reproductive toxicity of perfluorooctane sulfonic acid and perfluorooctanoic acid, two dominant PFASs in animals and humans. We explored the relationship between eleven perfluoroalkyl acids (PFAAs) with different carbon chain length and their ability to inhibit progesterone production in mouse Leydig tumor cells (mLTC-1). We found an obvious dose-response relationship between progesterone inhibition rate and PFAA exposure concentration in mLTC-1. The relative inhibition rate of progesterone by PFAAs was linearly related to the carbon chain length and molar refractivity of PFAAs. Mitochondrial membrane potential (MMP) decreased after PFAA exposure at the half-maximal inhibitory effect concentration (IC 50 ) of progesterone production in mLTC-1, while the reactive oxygen species (ROS) content increased significantly. These results imply that the inhibition effect of PFAAs on progesterone production might be due, in part, to ROS damage and the decrease in MMP in mLTC-1. Copyright © 2016. Published by Elsevier B.V.

Progesterone-specific stimulation of triglyceride biosynthesis in a breast cancer cell line (T-47D)

International Nuclear Information System (INIS)

Judge, S.M.; Chatterton, R.T. Jr.

1983-01-01

The purpose of this study was to examine the lactogenic response of human mammary cancer cell lines to hormones in vitro. Progesterone was found to stimulate the incorporation of 14C from [14C]acetate into triglycerides (TG) and to promote accumulation of TG with a fatty acid composition similar to that of human milk fat in T-47D cells. Lipid droplets were observed in larger numbers without concomitant accumulation of casein granules in cells incubated with progesterone, but secretion of lipid into the medium did not occur. An effect of progesterone on TG accumulation was detectable after 12 hr and was maximal at 72 hr. Increasing doses of progesterone (10(-9) to 10(-5) M) caused a progressive increase in TG accumulation. The presence of cortisol and/or prolactin did not alter TG formation nor the dose response of the cells to progesterone. The growth rate of T-47D cells was not altered by the presence of progesterone in the medium. Neither of the human mammary cancer cell lines, MCF-7 and HBL-100, nor the human fibroblast cell lines, 28 and 857, responded to progesterone. The data indicate that, while the normally lactogenic hormones do not stimulate milk product biosynthesis in the cell lines tested, progesterone specifically stimulated synthesis and accumulation of TG in the T-47D cells

Progesterone modulation of transmembrane helix-helix interactions between the α-subunit of Na/K-ATPase and phospholipid N-methyltransferase in the oocyte plasma membrane

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Askari Amir

2010-05-01

Full Text Available Abstract Background Progesterone binding to the surface of the amphibian oocyte initiates the meiotic divisions. Our previous studies with Rana pipiens oocytes indicate that progesterone binds to a plasma membrane site within the external loop between the M1 and M2 helices of the α-subunit of Na/K-ATPase, triggering a cascade of lipid second messengers and the release of the block at meiotic prophase. We have characterized this site, using a low affinity ouabain binding isoform of the α1-subunit. Results Preparations of isolated plasma membranes from Rana oocytes demonstrate that physiological levels of progesterone (or the non-metabolizable progestin R5020 successively activate phosphatidylethanolamine-N-methyltransferase (PE-NMT and sphingomyelin synthase within seconds. Inhibition of PE-NMT blocks the progesterone induction of meiosis in intact oocytes, whereas its initial product, phosphatidylmonomethylethanolamine (PME, can itself initiate meiosis in the presence of the inhibitor. Published X-ray crystallographic data on Na/K-ATPase, computer-generated 3D projections, heptad repeat analysis and hydrophobic cluster analysis of the transmembrane helices predict that hydrophobic residues L, V, V, I, F and Y of helix M2 of the α1-subunit interact with F, L, G, L, L and F, respectively, of helix M3 of PE-NMT. Conclusion We propose that progesterone binding to the first external loop of the α1-subunit facilitates specific helix-helix interactions between integral membrane proteins to up-regulate PE-NMT, and, that successive interactions between two or more integral plasma membrane proteins induce the signaling cascades which result in completion of the meiotic divisions.

A prospective randomized multicentre study comparing vaginal progesterone gel and vaginal micronized progesterone tablets for luteal support after in vitro fertilization/intracytoplasmic sperm injection

DEFF Research Database (Denmark)

Bergh, Christina; Lindenberg, Svend; Al Humaidan, Peter Samir Heskjær

2012-01-01

fertility centres in Denmark and Sweden between March 2006 and January 2010. A web-based randomization program was used with concealed allocation of patients. Patients were randomized to one of two groups: vaginal progesterone gel or vaginal micronized progesterone tablets. There was no blinding of patients....... PARTICIPANTS AND SETTING: A total of 2057 women ≤ 40 years of age were included and down-regulated, using the long agonist protocol and rFSH for stimulation. Luteal support was given for 19 days after embryo transfer or until a negative pregnancy test Day 14 after embryo transfer. Patient convenience...... (pregnancy) is robust, blinding would have been unlikely to affect the results. Unfortunately, owing to an error in the randomization, the intended age distribution allocated older women to the micronized progesterone tablet group. In the analysis of results, adjustments were made for age and number...

Possibilities of implementing progesterone EIA test in the control of reproduction in dairy cows

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Barna S. Tomislav,

2013-09-01

Full Text Available The aim of this study was to implement the progesterone EIA test, developed in our laboratory by using an anti-progesterone antibody (Yamaguchi University, Japan, in order to determine the optimal moment for artificial insemination (AI and to detect pregnancy in Holstein-Friesian cows according to the progesterone concentration in the whole milk. Also, the influence of β-carotene, applied at the day of insemination and human chorionic gonadotrophin applied on day 7 after AI on the progesterone level and the pregnancy rate were evaluated.For the accuracy of oestrus detection, the milk samples from 70 cows were collected on the day of insemination. Milk samples from 148 cows were collected 19-22 days following insemination for pregnancy check.After detection of naturally occurring oestrus (day 0 and AI, cows were divided into the following groups: group A (n = 19 was treated with 200 mg β-carotene (20 ml Carofertin® i.m. Alvetra u. Werfft Gmbh, Austria, group B (n = 17 was treated with 1 500 IU hCG i.m. (Schering-Plough, the Netherlands and control (non treated group C (n = 18. The milk samples for EIA progesterone concentration analysis were collected on the day of AI, the 14th and the 20th day of the oestrus cycle. Oestrus detection errors and inappropriate moments of insemination according to the progesterone concentration were detected in 22.86% animals (16/70. The test accuracy for non-pregnant cows was 90.48% (76/84. The accuracy of the progesterone test in pregnant cows was 75% (48/64. False positive results (high progesterone level, but the cows were not pregnant was detected in 25% of cows (16/64 as a result of a prolonged oestrus cycles, embrional mortality and endomethritis (10/16 cases. The treatment of cows with 1500 IU of hCG, on the day 7 of the oestrus cycle, resulted in statistically significant increase of progesterone concentration in the dioestrus (P 0.05.The EIA test developed in our laboratory could be used for accurate

[Progesterone Promotes Human Bone Marrow Mesenchymal Stem Cells to Synthesize Fibronectin via ERK Pathway].

Science.gov (United States)

Wu, Zhen-Yong; Chen, Jing-Li; Huang, Shu; Zhang, Hui; Wang, Fang; Wang, Yan; Bi, Xiao-Yun; Guo, Zi-Kuan

2015-12-01

To investigate whether the progesterone can promote fibronection (FN) synthesis by human bone marrow mesenchymal stem cells (MSCs) and to explore the potential underlying mechanism. The human bone marrow MSCs were cultured in a serum-free medium with progesterone for 72 hours, the MTT test was performed to observe the proliferation status and adhension ability of the treated cells. Western blot was used to detect the content of FN in MSDs with GAPDH as the internal reference, the phosphorylation of ERK1/2, as well as the FN content in MSC treated by PD98059, a specific inhibitor of ERK1/2. The progesterone at a range of certain doses not effect on the proliferation of human bone marrow MSCs. Progesterone (25 µg/L) treatment enhanced the FN expression and adherent ability of marrow MSCs. Progesterone could induce prompt phosphorylation of ERK 1/2 and its promoting effects on FN synthesis was reversed by PD98059. The progesterone can promote FN synthesis by human bone marrow MSCs via ERK 1/2 pathway, and it might be used to culture MSCs in serum-free medium.

Changes of progesterone levels in the milk of dairy cows in post-partum

Energy Technology Data Exchange (ETDEWEB)

Yongpeng, Li

1985-06-01

Progesterone levels were measured by radioimmunoassay in the last milk of seven dairy cows in 5-75 days post-partum. The progesterone levels were from 0.1 to 1.5 ng/ml and averaged 0.4 +- 0.2 ng/ml for the last milk of the seven cows. A range of 0.3 to 0.7 ng/ml for average progesterone levels of the seven cows can be estimated. Two ovarian cycle activities in post-partum of cow No. 43 were observed and a ovulation on 15-20 days post-partum was revealed. The peak value after 20 days post-partum was 3.0 ng/ml. The progesterone level after peak value was declined, and reached to about 0.2 ng/ml on 35 days post-partum. The changes of ovarian activities were exhibited again in 35-55 days post-partum. The progesterone levels of cow No. 43 were lower in luteal phase oestrous cycles post-partum than that from the other cows in normal luteal phase oestrous cycles.

Progesterone production requires activation of caspase-3 in preovulatory granulosa cells in a serum starvation model.

Science.gov (United States)

An, Li-Sha; Yuan, Xiao-Hua; Hu, Ying; Shi, Zi-Yun; Liu, Xiao-Qin; Qin, Li; Wu, Gui-Qing; Han, Wei; Wang, Ya-Qin; Ma, Xu

2012-11-01

Granulosa cells proliferate, differentiate, and undergo apoptosis throughout follicular development. Previous studies have demonstrated that stimulation of progesterone production is accompanied by caspase-3 activation. Moreover, we previously reported that arsenic enhanced caspase-3 activity coupled with progesterone production. Inhibition of caspase-3 activity can significantly inhibit progesterone production induced by arsenic or follicle-stimulating hormone (FSH). Here, we report that serum starvation induces caspase-3 activation coupled with augmentation of progesterone production. Serum starvation also increased the levels of cytochrome P450 cholesterol side chain cleavage enzyme (P450scc) and steroidogenic acute regulatory (StAR) protein, both of which may contribute to progesterone synthesis in preovulatory granulosa cells. Inhibition of caspase-3 activity resulted in a decrease in progesterone production. Deactivation of caspase-3 activity by caspase-3 specific inhibitor also resulted in decreases in P450scc and StAR expression, which may partly contribute to the observed decrease in progesterone production. Our study demonstrates for the first time that progesterone production in preovulatory granulosa cells is required for caspase-3 activation in a serum starvation model. Inhibition of caspase-3 activity can result in decreased expression of the steroidogenic proteins P450scc and StAR. Our work provides further details on the relationship between caspase-3 activation and steroidogenesis and indicates that caspase-3 plays a critical role in progesterone production by granulosa cells. Copyright © 2012 Elsevier Inc. All rights reserved.

Progesterone for Acute Traumatic Brain Injury: A Systematic Review of Randomized Controlled Trials.

Directory of Open Access Journals (Sweden)

Yunhui Zeng

Full Text Available To evaluate the efficacy and safety of progesterone administrated in patients with acute traumatic brain injury (TBI.PubMed/MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials (CENTRAL, Clinicaltrials.gov, ISRCTN registry and WHO International Clinical Trials Registry Platform (ICTRP were searched for randomized controlled trials (RCTs comparing progesterone and placebo administrated in acute TBI patients. The primary outcome was mortality and the secondary outcomes were unfavorable outcomes and adverse events. A meta-analysis was conducted to evaluate the efficacy and safety of progesterone administrated in patients with acute TBI.A total of 6 studies met inclusion criteria, involving 2,476 patients. The risk of bias was considered to be low in 4 studies but high in the other 2 studies. The results of meta-analysis indicated progesterone did not reduce the mortality (RR = 0.83, 95% CI = 0.57-1.20 or unfavorable outcomes (RR = 0.89, 95% CI = 0.78-1.02 of acute TBI patients in comparison with placebo. Sensitivity analysis yielded consistent results. Progesterone was basically safe and well tolerated in TBI patients with the exception of increased risk of phlebitis or thrombophlebitis (RR = 3.03, 95% CI = 1.96-4.66.Despite some modest bias, present evidence demonstrated that progesterone was well tolerated but did not reduce the mortality or unfavorable outcomes of adult patients with acute TBI.

Long-term effects of prenatal progesterone exposure

DEFF Research Database (Denmark)

Vedel, C.; Larsen, H.; Holmskov, Anni

2016-01-01

children from 498 twin pregnancies, were followed-up. PREDICT was a placebo-controlled randomized clinical trial examining the effect of progesterone for prevention of preterm delivery in unselected twin pregnancies. Medical histories of the children were reviewed and neurophysiological development...... does not seem to have long-term harmful effects during childhood, but future studies should focus on cardiac disease in the child. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.......OBJECTIVES: To perform a neurophysiological follow-up at 48 or 60 months of age in children exposed prenatally to progesterone compared with a placebo and evaluate their medical histories up to 8 years of age. METHODS: In this study, Danish participants of the PREDICT study, including 989 surviving...

Effects of the 3β-hydroxysteroid dehydrogenase inhibitor trilostane on luteal progesterone production in the dog

NARCIS (Netherlands)

de Gier, J.; Wolthers, C.H.; Galac, S.; Schaefers-Okkens, A.C.; Kooistra, H.S.

2011-01-01

Abstract Interference with the pregnancy-maintaining influence of progesterone is the basis of most methods for termination of unwanted pregnancy in dogs. The currently available methods are based on induction of luteolysis or blocking of the progesterone receptor. Inhibition of progesterone

Long-term exposure to electromagnetic radiation from mobile phones and Wi-Fi devices decreases plasma prolactin, progesterone, and estrogen levels but increases uterine oxidative stress in pregnant rats and their offspring.

Science.gov (United States)

Yüksel, Murat; Nazıroğlu, Mustafa; Özkaya, Mehmet Okan

2016-05-01

Wi-Fi devices. It is likely that TRPV1-mediated Ca(2+) entry in the uterus of pregnant rats involves accumulation of oxidative stress and opening of mitochondrial membrane pores that consequently leads to mitochondrial dysfunction, substantial swelling of the mitochondria with rupture of the outer membrane and release of oxidants such as superoxide (O2 (-)) and hydrogen peroxide (H2O2). The superoxide radical is converted to H2O2 by superoxide dismutase (SOD) enzyme. Glutathione peroxidase (GSH-Px) is an important antioxidant enzyme for removing lipid hydroperoxides and hydrogen peroxide and it catalyzes the reduction of H2O2 to water.

Progesterone attenuates airway remodeling and glucocorticoid resistance in a murine model of exposing to ozone.

Science.gov (United States)

Zhang, Xue; Bao, Wuping; Fei, Xia; Zhang, Yingying; Zhang, Guoqing; Zhou, Xin; Zhang, Min

2018-04-01

Airway remodeling is a vital component of chronic obstructive pulmonary disease (COPD). Despite the broad anti-inflammation effects of glucocorticoids, they exhibit relatively little therapeutic benefit in COPD, indicating the accelerating demands of new agents for COPD. We aim to explore the effect of progesterone on airway remodeling in a murine modeling of exposing to ozone and to further examine the potential effect of progesterone on glucocorticoid insensitivity. C57/BL6 mice were exposed to ozone for 12 times over 6 weeks, and were administered with progesterone alone or combined with budesonide (BUD) after each exposure until the 10th week. The peribronchial collagen deposition was measured. The protein levels of MMP8 and MMP9 in bronchoalveolar lavage fluid (BALF) and lungs were assessed. Western blot analysis was used to detect the levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), a-smooth muscle actin (α-SMA), glycogen synthase kinase-3β (GSK-3β). The expression of VEGF and histone deacetylase 2 (HDAC2) in the lung were determined by Immunohistochemical analyses. We observe that progesterone attenuates the peribronchial collagen deposition, as well as the expression of MMP8, MMP9, HIF-1α, VEGF, α-SMA, and GSK-3β in BALF or lung tissues. Progesterone or BUD monotherapy has no effect on HDAC2 production. Progesterone combines with BUD induce dramatically enhanced effects. Thus, these results demonstrate novel roles of progesterone for the pathogenesis and airway remodeling in COPD. Progesterone plus BUD administration exerts more significant inhibition on airway remodeling with dose-independent. Additionally, progesterone may, to some extent, improve the glucocorticoid insensitivity. Copyright © 2018. Published by Elsevier Ltd.

PLASMA PROGESTERONE LEVELS TN LACTATING EWES AFTER ...

African Journals Online (AJOL)

Oestrus, ovulation and perrpheral plasma progesterone concentrations were recorded in ... progestagen and PMS were srmilar to those reported for spontaneous oesttous cycles in ..... involved could perhaps cast some light on the problem.

A functional polymorphism in the promoter of the progesterone receptor gene associated with endometrial cancer risk

NARCIS (Netherlands)

De Vivo, Immaculata; Huggins, Gordon S; Hankinson, Susan E; Lescault, Pamela J; Boezen, Hendrika; Colditz, Graham A; Hunter, David J

2002-01-01

Excessive estrogen stimulation unopposed by progesterone strongly predisposes to endometrial cancer. Because the antiproliferative effect of progesterone requires the progesterone receptor (PR), which exists in two isoforms, PR-A and -B, we reasoned that variants in the PR gene may predispose to

Use of Progesterone Treatment for the Prevention of Recurrent Preterm Birth: Identification of Obstacles to Change

NARCIS (Netherlands)

Lim, Arianne C.; Goossens, Astrid; Ravelli, Anita C. J.; Boer, Kees; Bruinse, Hein W.; Mol, Ben Willem J.

2010-01-01

Progesterone treatment has proven to be effective in preventing recurrent preterm birth. The use of progesterone varies widely between different obstetric clinics in the Netherlands. The study aimed to identify factors that hamper or facilitate the use of progesterone to create an implementation

Milk progesterone profiles and the effect of the buck during the anoestrous period in goats

International Nuclear Information System (INIS)

Guo Dazhi; Liu Xianyi; Chen Faju; Song Xuehua; Wang Kairong; Liu Xiangmo; Xu Gongyi

1991-01-01

Milk progesterone profiles in Chengdu Mah (CM), Saanen (S) and crossbred (CM x S, F1) goats were determined using radioimmunoassay throughout the period from kidding to the beginning of the next breeding season. Different patterns of progesterone profiles were recorded in these does. When milk progesterone concentrations were elevated above 6 ng/mL for at least 6 days they were regarded as signs of ovarian activity. The frequencies of such rises during anoestrus were 4.0, 1.8 and 2.5 per animal in CM, S and F1 goats respectively. The frequencies of progesterone rise were higher than that of behavioural oestrus in the does. After exposing the does to the buck three times during the anoestrus period, no significant 'male effect' was observed on the milk progesterone level or behavioural oestrus during the first six months after kidding. The male effect on behavioural oestrus became apparent only in the seventh month after kidding, while milk progesterone levels did not change markedly compared with those of the control does. (author). 9 refs, 4 figs

Relationships between the conception rate of estrus synchronization using estradiol benzoate and CIDR (progesterone) and other parameters in holstein lactating dairy cows.

Science.gov (United States)

Miura, Hiroshi; Kotani, Satoko; Kohiruimaki, Masayuki; Ohtsuka, Hiromichi; Kikuchi, Motohiro; Ohnami, Yoji

2008-06-01

The purpose of this study was to determine the relationships between conception rate and other parameters before estrus synchronization with a Controlled Internal Drug Release Device (CIDR) and estradiol benzoate (EB). In the estrus synchronization program, animals were injected with 2 mg EB and then received a CIDR. Seven days later, the CIDR was removed and the animals were given an injection of Prostaglandin F(2alpha). Twenty-four hours later, they received an injection of 1 mg EB, and they were artificially inseminated 24 h after that. This program was applied to 258 Holstein cows in Tohoku-machi (Aomori, Japan). Blood was collected at the beginning of the program, and the conception rate was determined about 40 days after insemination. The relationships among conception rate, blood biochemical values, age, body condition score and days in milk were statistically analyzed to determine better conditions for cow conception. The conception rate of the cows in the high progesterone group (more than 1 ng/ml, P(4)+) was significantly higher than that of the low progesterone group (less than 1 ng/ml, P(4)-; 47.9% vs. 28.6% Pconception group than in the non-conception group, and the same tendency was seen in the P(4)+ groups. Blood urea nitrogen (BUN), albumin (Alb), and total cholesterol (TChol) were significantly higher in the conception group compared with the non-conception group, but no with P(4) was observed. We concluded that 1) the conception rate of the P(4)- group was remarkably low, that 2) the low conception rate and low P(4) level was related to a low PL level and that 3) BUN, Alb and TChol were higher in the conception group, although no relation with P(4) was found.

Immunolocalization of progesterone receptors in binucleate trophoblast cells of the buffalo placenta (Bubalus bubalis

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Carlos Eduardo Ambrósio

2007-06-01

Full Text Available The binucleate trophoblast cells (CTBs of the water buffalo placenta (Bubalus bubalis were studied with emphasis on the presence of progesterone receptor. Placentomal tissues from 27 buffalos (2-10 months of pregnancy were processed and embedded in paraplast (Paraplast Embedding Media – Paraplast Plus to locate the progesterone receptors using the immunohistochemistry technique. The immunohistochemical reaction for progesterone receptor through monoclonal antibody PgR Ab2 showed staining of CTBs, caruncular epithelial and estromal cells and blood vessel estromal pericitos present in the placentome throughout the entire gestational period analyzed. These results indicate the production of progesterone with autocrine and paracrine action in the placentome growth, differentiation and functional regulation.

A Role of Endogenous Progesterone in Stroke Cerebroprotection Revealed by the Neural-Specific Deletion of Its Intracellular Receptors.

Science.gov (United States)

Zhu, Xiaoyan; Fréchou, Magalie; Liere, Philippe; Zhang, Shaodong; Pianos, Antoine; Fernandez, Neïké; Denier, Christian; Mattern, Claudia; Schumacher, Michael; Guennoun, Rachida

2017-11-08

Treatment with progesterone protects the male and female brain against damage after middle cerebral artery occlusion (MCAO). However, in both sexes, the brain contains significant amounts of endogenous progesterone. It is not known whether endogenously produced progesterone enhances the resistance of the brain to ischemic insult. Here, we used steroid profiling by gas chromatography-tandem mass spectrometry (GC-MS/MS) for exploring adaptive and sex-specific changes in brain levels of progesterone and its metabolites after MCAO. We show that, in the male mouse brain, progesterone is mainly metabolized via 5α-reduction leading to 5α-dihydroprogesterone (5α-DHP), also a progesterone receptor (PR) agonist ligand in neural cells, then to 3α,5α-tetrahydroprogesterone (3α,5α-THP). In the female mouse brain, levels of 5α-DHP and 3α,5α-THP are lower and levels of 20α-DHP are higher than in males. After MCAO, levels of progesterone and 5α-DHP are upregulated rapidly to pregnancy-like levels in the male but not in the female brain. To assess whether endogenous progesterone and 5α-DHP contribute to the resistance of neural cells to ischemic damage, we inactivated PR selectively in the CNS. Deletion of PR in the brain reduced its resistance to MCAO, resulting in increased infarct volumes and neurological deficits in both sexes. Importantly, endogenous PR ligands continue to protect the brain of aging mice. These results uncover the unexpected importance of endogenous progesterone and its metabolites in cerebroprotection. They also reveal that the female reproductive hormone progesterone is an endogenous cerebroprotective neurosteroid in both sexes. SIGNIFICANCE STATEMENT The brain responds to injury with protective signaling and has a remarkable capacity to protect itself. We show here that, in response to ischemic stroke, levels of progesterone and its neuroactive metabolite 5α-dihydroprogesterone are upregulated rapidly in the male mouse brain but not in the

Implications of progesterone metabolism in MA-10 cells for accurate measurement of the rate of steroidogenesis

NARCIS (Netherlands)

F.F.G. Rommerts (Focko); S.R. King (Steven); P.N. Span (Paul)

2001-01-01

textabstractIn virtually all studies with MA-10 cells, progesterone RIAs have been used to measure steroid synthesis. To test whether progesterone is a stable end product, we investigated the metabolism of added tritiated progesterone and pregnenolone in MA-10 cells over a period

Synthesis of hydrogels of alginate for system controlled release of progesterone

International Nuclear Information System (INIS)

Abreu, Marlon de F.; Rodriguez, Ruben J.S.; Silva, Ester C.C. da; Barreto, Gabriela N.S.

2015-01-01

The chemical modifications of natural polymers like alginate, has allowed the development of new formulations for controlled release systems. In this work we report the synthesis of a derivative of the amidic alginate with alkyl chain. The polymer was characterized by spectroscopic techniques: Nuclear Magnetic Resonance and Fourier Transform Infrared. (author)

The nonnucleoside reverse transcription inhibitor MIV-160 delivered from an intravaginal ring, but not from a carrageenan gel, protects against simian/human immunodeficiency virus-RT Infection.

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Aravantinou, Meropi; Singer, Rachel; Derby, Nina; Calenda, Giulia; Mawson, Paul; Abraham, Ciby J; Menon, Radhika; Seidor, Samantha; Goldman, Daniel; Kenney, Jessica; Villegas, Guillermo; Gettie, Agegnehu; Blanchard, James; Lifson, Jeffrey D; Piatak, Michael; Fernández-Romero, José A; Zydowsky, Thomas M; Teleshova, Natalia; Robbiani, Melissa

2012-11-01

We previously showed that a carrageenan (CG) gel containing 50 μM MIV-150 (MIV-150/CG) reduced vaginal simian/human immunodeficiency virus (SHIV)-RT infection of macaques (56%, p>0.05) when administered daily for 2 weeks with the last dose given 8 h before challenge. Additionally, when 100 mg of MIV-150 was loaded into an intravaginal ring (IVR) inserted 24 h before challenge and removed 2 weeks after challenge, >80% protection was observed (p<0.03). MIV-160 is a related NNRTI with a similar IC(50), greater aqueous solubility, and a shorter synthesis. To objectively compare MIV-160 with MIV-150, herein we evaluated the antiviral effects of unformulated MIV-160 in vitro as well as the in vivo protection afforded by MIV-160 delivered in CG (MIV-160/CG gel) and in an IVR under regimens used with MIV-150 in earlier studies. Like MIV-150, MIV-160 exhibited potent antiviral activity against SHIV-RT in macaque vaginal explants. However, formulated MIV-160 exhibited divergent effects in vivo. The MIV-160/CG gel offered no protection compared to CG alone, whereas the MIV-160 IVRs protected significantly. Importantly, the results of in vitro release studies of the MIV-160/CG gel and the MIV-160 IVR suggested that in vivo efficacy paralleled the amount of MIV-160 released in vitro. Hundreds of micrograms of MIV-160 were released daily from IVRs while undetectable amounts of MIV-160 were released from the CG gel. Our findings highlight the importance of testing different modalities of microbicide delivery to identify the optimal formulation for efficacy in vivo.

FAILURE OF PROGESTERONE TO PRODUCE HIGH BLOOD-PRESSURE IN RABBITS AND RATS

NARCIS (Netherlands)

Winter, M.; Veldhuyzen, B.; Dorhout Mees, E.J.

1972-01-01

Contrary to earlier claims, daily Summary administration of 50 mg. progesterone over ten days did not increase the blood-pressure of 6 rabbits. Daily injection of 10 mg. progesterone had no influence on the blood-pressure of rats. The weight-gain of female rats was significantly increased by this

Progesterone inhibits epithelial-to-mesenchymal transition in endometrial cancer.

Directory of Open Access Journals (Sweden)

Paul H van der Horst

Full Text Available BACKGROUND: Every year approximately 74,000 women die of endometrial cancer, mainly due to recurrent or metastatic disease. The presence of tumor infiltrating lymphocytes (TILs as well as progesterone receptor (PR positivity has been correlated with improved prognosis. This study describes two mechanisms by which progesterone inhibits metastatic spread of endometrial cancer: by stimulating T-cell infiltration and by inhibiting epithelial-to-mesenchymal cell transition (EMT. METHODOLOGY AND PRINCIPAL FINDINGS: Paraffin sections from patients with (n = 9 or without (n = 9 progressive endometrial cancer (recurrent or metastatic disease were assessed for the presence of CD4+ (helper, CD8+ (cytotoxic and Foxp3+ (regulatory T-lymphocytes and PR expression. Progressive disease was observed to be associated with significant loss of TILs and loss of PR expression. Frozen tumor samples, used for genome-wide expression analysis, showed significant regulation of pathways involved in immunesurveillance, EMT and metastasis. For a number of genes, such as CXCL14, DKK1, DKK4, PEG10 and WIF1, quantitive RT-PCR was performed to verify up- or downregulation in progressive disease. To corroborate the role of progesterone in regulating invasion, Ishikawa (IK endometrial cancer cell lines stably transfected with PRA (IKPRA, PRB (IKPRB and PRA+PRB (IKPRAB were cultured in presence/absence of progesterone (MPA and used for genome-wide expression analysis, Boyden- and wound healing migration assays, and IHC for known EMT markers. IKPRB and IKPRAB cell lines showed MPA induced inhibition of migration and loss of the mesenchymal marker vimentin at the invasive front of the wound healing assay. Furthermore, pathway analysis of significantly MPA regulated genes showed significant down regulation of important pathways involved in EMT, immunesuppression and metastasis: such as IL6-, TGF-β and Wnt/β-catenin signaling. CONCLUSION: Intact progesterone signaling in non

Production of antiserum and development of radioimmunoassay for progesterone measurement in serum

International Nuclear Information System (INIS)

Abdalla, O.M; Abbas, S.H.

2004-03-01

The anti progesterone antibody was obtained by injection of local sudanese sheep (bevies arias) intramuscularly and subcutaneously using 11-a-hydroxy progesterone conjugated with bovine serum albumin and emulsified in friend's adjuvant. The blood samples collected one week after the 3 rd injection was tested for anti-progesterone antibodies. Different dilutions of antisera in Pbs containing 0.0.1 % BSA and 0.1 % Na N 3 (Ph 7.4) were made. Using these dilutions, polystyrene balls of 6.4 mm diameter were coated with a coating volume of 500 μ1/bead.The antibody dilution of 1/200000 was selected and used for assembling a kit to measure progesterone level in serum. Optimization of the assay condition resulted in the following recipes: Fifty μ1 of standard or Qc (Low, normal and high) from Bio Rad for 2 hours. The reaction medium aspirated, washed twice and read for 100 seconds in gamma counter. Assay validation tests including Linearity, recovery, reproducibility and comparability were done. In regards to linearity, the measured concentrations of progesterone in serum samples were plotted against the expected values. The correlation coefficient was 0.997 and a linear regression equation was Y=1.1019+0.9895 X. The mean recovery was 96.86% of the sample replicates ranged from 0.2% to 6%. between assay reproducibility was assessed fro the results obtained from 3 samples which were used for quality control in different assays. The results obtained were in the reference range and were close to each other. Comparison between local and American Dpc reagents for progesterone determination in serum showed high correlation high correlation where r 0.9492.(Author)

A Potential Role for Endoplasmic Reticulum Stress in Progesterone Deficiency in Obese Women.

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Takahashi, Nozomi; Harada, Miyuki; Hirota, Yasushi; Zhao, Lin; Azhary, Jerilee M K; Yoshino, Osamu; Izumi, Gentaro; Hirata, Tetsuya; Koga, Kaori; Wada-Hiraike, Osamu; Fujii, Tomoyuki; Osuga, Yutaka

2017-01-01

Obesity in reproductive-aged women is associated with a shorter luteal phase and lower progesterone levels. Lipid accumulation in follicles of obese women compromises endoplasmic reticulum (ER) function, activating ER stress in granulosa cells. We hypothesized that ER stress activation in granulosa-lutein cells (GLCs) would modulate progesterone production and contribute to obesity-associated progesterone deficiency. Pretreatment with an ER stress inducer, tunicamycin or thapsigargin, inhibited human chorionic gonadotropin (hCG)-stimulated progesterone production in cultured human GLCs. Pretreatment of human GLCs with tunicamycin inhibited hCG-stimulated expression of steroidogenic acute regulatory protein (StAR) and 3β-hydroxysteroid dehydrogenase (3β-HSD) messenger RNAs (mRNAs) without affecting expression of cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), as determined by real-time quantitative polymerase chain reaction. Pretreatment with tunicamycin also inhibited hCG-stimulated expression of StAR protein and 3β-HSD enzyme activity in cultured human GLCs, as determined by Western blot analysis and an enzyme immunoassay, respectively, but did not affect hCG-induced intracellular 3',5'-cyclic adenosine monophosphate accumulation. Furthermore, tunicamycin attenuated hCG-induced protein kinase A and extracellular signal-regulated kinase activation, as determined by Western blot analysis. In vivo administration of tunicamycin to pregnant mare serum gonadotropin-treated immature mice prior to hCG treatment inhibited the hCG-stimulated increase in serum progesterone levels and hCG-induced expression of StAR and 3β-HSD mRNA in the ovary without affecting serum estradiol levels or the number of corpora lutea. Our findings indicate that ER stress in the follicles of obese women contributes to progesterone deficiency by inhibiting hCG-induced progesterone production in granulosa cells. Copyright © 2017 by the Endocrine Society.

Milk and hair progesterone contents during the oestrous cycle and gestation in goats

International Nuclear Information System (INIS)

Guo Dazhi; Zeng Xianyin; Liu Xianyi; Chen Faju; Song Xuehua

1991-01-01

Milk and hair progesterone contents were determined during the oestrous cycle and gestation in Saanen, F1 crosses (Saanen x Chengdu Mah) and F2 (Saanen x (Saanen x Chengdu Mah)) goats using the radioimmunoassay kits provided by the IAEA. Hair samples were collected from the back of the goats every day from day 1 (after oestrus) to day 28 and every 5 days from day 30 to parturition. Foremilk samples were also collected daily from day 1 to day 20. The results showed that there were significant differences in milk progesterone concentration between pregnant and non-pregnant goats during days 19 to 22 after oestrus. Progesterone in goat hair could be detected using the RIA kits. Hair progesterone content was correlated with the milk progesterone profile during the first 20 days of pregnancy in non-pregnant goats; a similar correlation was observed during the oestrous cycle. When milk samples were collected on day 22 post-oestrus and 3.9 ng/mL was taken as the discriminatory level, the accuracy of pregnancy and non-pregnancy diagnosis was 82.4% and 100% respectively. When hair samples were collected on day 22 and 3.7 ng/50 mg hair was taken as the discriminatory level, the accuracy of pregnancy and non-pregnancy diagnosis was 77.8% and 100% respectively. During gestation, hair progesterone contents increased gradually from day 30 to day 120 and decreased rapidly from day -8 before parturition to parturition. 6 refs, 3 figs, 2 tabs

Intravaginal administration of metformin hydrochloride loaded cationic niosomes amalgamated with thermosensitive gel for the treatment of polycystic ovary syndrome: In vitro and in vivo studies.

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Saini, Neetu; Sodhi, Rupinder Kaur; Bajaj, Lotika; Pandey, Ravi Shankar; Jain, Upendra Kumar; Katare, Om Prakash; Madan, Jitender

2016-08-01

Metformin hydrochloride (MTF-HCl) is extensively recommended by physicians for the treatment of polycystic ovary syndrome (PCOS). Mechanistically, MTF-HCl activates AMP-dependent kinase-α (AMPK-α) pathway to decrease the glucose production, enhances fatty acid oxidation and elevates the uptake of glucose in tissues. However, despite favourable physicochemical properties, oral administration of MTF-HCl is associated with impaired bioavailability (50-60%), lactic-acidosis and frequent dosing (500mg 2-3 times a day) in PCOS that ultimately influence the patient compliance. Therefore, in present investigation, MTF-HCl loaded unmodified and cationic small unilamellar niosomes were separately amalgamated with thermosensitive gel (MTF-HCl-SUNs-Gel and MTF-HCl-C-SUNs-Gel) for the treatment of PCOS through vaginal route of administration. MTF-HCl-SUNs and MTF-HCl-C-SUNs were separately prepared by reverse phase evaporation method. The nanovesicle size and zeta-potential of MTF-HCl-C-SUNs were measured to be 210.3±14.8-nm (Ptreatment of PCOS rats under scheduled dose-dosage regimen with oral MTF-HCl solution, intravaginal MTF-HCl-SUNs-Gel and intravaginal MTF-HCl-C-SUNs-gel exhibited remarkable alterations, recruitment and development of normal follicles in addition to normalization of level of various hormones in PCOS. In conclusion, MTF-C-SUNs-Gel has paved the way for developing intravaginal dosage form of MTF-HCl for the treatment of PCOS. Copyright © 2016 Elsevier B.V. All rights reserved.

Biotransformation of Progesterone by the Ascomycete Aspergillus niger N402.

Science.gov (United States)

Savinova, O S; Solyev, P N; Vasina, D V; Tyazhelova, T V; Fedorova, T V; Savinova, T S

2018-01-01

The ability of the ascomycete Aspergillus niger N402 to transform exogenous progesterone was investigated. We found that this strain has steroid-hydroxylating activity and can introduce a hydroxyl group into the progesterone molecule mainly at positions C11(α) and C21 with predominant formation of 21-hydroxyprogesterone (deoxycortone). In addition, formation of 6β,11α-dihydroxyprogesterone was also observed. Studying the effects of the growth medium composition and temperature on progesterone conversion by A. niger N402 showed that the most intense accumulation of 21-hydroxyprogesterone occurred in minimal synthetic medium at 28°C. Increasing the cultivation temperature to 37°C resulted in almost complete inhibition of the hydroxylase activity in the minimal medium. In the complete medium, a similar increase in temperature inhibited 11α-hydroxylase activity and completely suppressed 6β-hydroxylase activity, but it produced no effect on 21-hydroxylating activity.

Effect of radiofrequency radiation from Wi-Fi devices on mercury release from amalgam restorations.

Science.gov (United States)

Paknahad, Maryam; Mortazavi, S M J; Shahidi, Shoaleh; Mortazavi, Ghazal; Haghani, Masoud

2016-01-01

Dental amalgam is composed of approximately 50% elemental mercury. Despite concerns over the toxicity of mercury, amalgam is still the most widely used restorative material. Wi-Fi is a rapidly using local area wireless computer networking technology. To the best of our knowledge, this is the first study that evaluates the effect of exposure to Wi-Fi signals on mercury release from amalgam restorations. Standard class V cavities were prepared on the buccal surfaces of 20 non-carious extracted human premolars. The teeth were randomly divided into 2 groups (n = 10). The control group was stored in non-environment. The specimens in the experimental groups were exposed to a radiofrequency radiation emitted from standard Wi Fi devices at 2.4 GHz for 20 min. The distance between the Wi-Fi router and samples was 30 cm and the router was exchanging data with a laptop computer that was placed 20 m away from the router. The concentration of mercury in the artificial saliva in the groups was evaluated by using a cold-vapor atomic absorption Mercury Analyzer System. The independent t test was used to evaluate any significant differences in mercury release between the two groups. The mean (±SD) concentration of mercury in the artificial saliva of the Wi-Fi exposed teeth samples was 0.056 ± .025 mg/L, while it was only 0.026 ± .008 mg/L in the non-exposed control samples. This difference was statistically significant (P =0.009). Exposure of patients with amalgam restorations to radiofrequency radiation emitted from conventional Wi-Fi devices can increase mercury release from amalgam restorations.

Implications of progesterone metabolism in MA-10 cells for accurate measurement of the rate of steroidogenesis.

NARCIS (Netherlands)

Rommerts, F.F.; King, S.R.; Span, P.N.

2001-01-01

In virtually all studies with MA-10 cells, progesterone RIAs have been used to measure steroid synthesis. To test whether progesterone is a stable end product, we investigated the metabolism of added tritiated progesterone and pregnenolone in MA-10 cells over a period of 3 h. Steroids were then

The Effects of Sugammadex on Progesterone Levels in Pregnant Rats

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Tayfun Et

2015-06-01

Full Text Available Background: Sugammadex has been shown to decrease the efficiency of progesterone-containing oral contraceptive drugs which possess a steroid structure. Aims: The aim of the present study was to evaluate the effects of sugammadex on progesterone levels in pregnant rats as well as on the physiological course of the pregnancy. Study Design: Animal experiment. Methods: This study was approved by the Selçuk University Ethical Committee for Experimental Animal Research. Pregnant Winster Albino rats (n=26 were divided into three groups and administered with various intravenous injections on the 7th day of pregnancy. The control group (Group K, n=6 received 1.5 mL serum physiologic, the sugammadex group (Group S, n=10 received 30 mg/kg sugammadex and the sugammadex + rocuronium group (Group SR, n=10 received 30 mg/kg sugammadex and 3.5 mg/kg rocuronium. Progesterone levels were measured and the offspring were monitored for morphologic status. Results: Mean progesterone levels were 94.16±15.54 ng/mL in Group K, 87.86±12.48 ng/mL in Group S, and 94.53±16.10 ng/mL in Group SR (p>0.05. No stillbirth or miscarriage was observed in the rats. The mean number of offspring was 6.8±1.47 in Group K, 6.5±1.35 in Group S, and 6.4±1.17 in Group SR. The offspring appeared macroscopically normal. Conclusion: Sugammadex does not appear to affect the progesterone levels in pregnant rats in the first trimester and the clinical course. Successful completion of pregnancy and the absence of stillbirth or miscarriage will guide future studies about the use of sugammadex, particularly in the first trimester of the pregnancy.

Transcriptional regulation of genes related to progesterone production.

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Mizutani, Tetsuya; Ishikane, Shin; Kawabe, Shinya; Umezawa, Akihiro; Miyamoto, Kaoru

2015-01-01

Steroid hormones are synthesized from cholesterol in various tissues, mainly in the adrenal glands and gonads. Because these lipid-soluble steroid hormones immediately diffuse through the cells in which they are produced, their secretion directly reflects the activity of the genes related to their production. Progesterone is important not only for luteinization and maintenance of pregnancy, but also as a substrate for most other steroids. Steroidogenic acute regulatory protein (STAR), cytochrome P450 cholesterol side-chain cleavage enzyme (P450scc), and 3β-hydroxysteroid dehydrogenase/Δ(5)-Δ(4) isomerase (3β-HSD) are well-known proteins essential for progesterone production. In addition to them, glutathione S-transferase A1-1 and A3-3 are shown to exert Δ(5)-Δ(4) isomerization activity to produce progesterone in a cooperative fashion with 3β-HSD. 5-Aminolevulinic acid synthase 1, ferredoxin 1, and ferredoxin reductase also play a role in steroidogenesis as accessory factors. Members of the nuclear receptor 5A (NR5A) family (steroidogenic factor 1 and liver receptor homolog 1) play a crucial role in the transcriptional regulation of these genes. The NR5A family activates these genes by binding to NR5A responsive elements present within their promoter regions, as well as to the elements far from their promoters. In addition, various NR5A-interacting proteins including peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), nuclear receptor subfamily 0, group B, member 1 (DAX-1), and CCAAT/enhancer-binding proteins (C/EBP) are involved in the transcription of NR5A target genes and regulate the transcription either positively or negatively under both basal and tropic hormone-stimulated conditions. In this review, we describe the transcriptional regulation of genes related to progesterone production.

Effect and mechanism of cadmium on the progesterone synthesis of ovaries

International Nuclear Information System (INIS)

Zhang Wenchang; Jia Haimei

2007-01-01

The paper presents results of the effect of cadmium on the progesterone synthesis of ovaries. In the current study, we investigated whether Cd also disrupts progesterone synthesis via steroidogenic acute regulatory protein (StAR) and P450 cholesterol side-chain cleavage (P450scc), which play important roles in progesterone synthesis. The Wistar rats were exposed to cadmium in vivo (at 2.5, 5, 7.5 mg/kg, as a single s.c. dose). We showed that the serum P 4 and granule cells P 4 of rats were significantly lower than control group. Ovaries granule cells were incubated in Dulbecco-modified Eagle medium +15% fetal bovine serum with 0, 10, 20, or 40 μM CdCl 2 in vitro, progesterone levels were declined in a dose-dependent manner. Our data showed that the expression of StAR and P450scc in vivo or in vitro were inhibited when treated with CdCl 2 (p 2 treatment; the expression of StAR mRNA and P450scc mRNA in 8-Br-cAMP + 40 μM CdCl 2 were significantly higher than 40 μM CdCl 2 , and were lower than control group. We concluded that StAR, which delivers cholesterol to the inner mitochondrial membrane, is one site at which Cd interferes with progesterone production in cultured rats ovarian granule cells; P450scc, which conveys cholesterol to pregnenolone, is anther site. The mechanisms were mainly controlled by the cAMP-dependent pathway

Development of solid phase radioimmunoassay using antibody coupled magnetizable particles for measurement of progesterone in human serum

International Nuclear Information System (INIS)

Mehany, N.L.

2007-01-01

The aim of the present study was to prepare solid phase radioimmunoassay (RIA) reagents. Development as well as optimization and validation of RIA system using solid phase magnetic particles for the measurement of progesterone in human serum are described. The production of polyclonal antibodies was carried out by immunizing five white New-Zealand rabbits subcutaneously. Low density magnetizable cellulose iron oxide particles have been used to couple covalently to the IgG fraction of polyclonal anti-progesterone using carbonyl diimidazole activation method and applied as a solid phase separating agent for RIA of serum progesterone. 125 I-progesterone tracer was prepared using chloramine-T and iodogen oxidation methods and purified using high performance liquid chromatography. The progesterone standards were prepared using highly purified progesterone powder with hormone free serum as standard matrix. Optimization and validation of the assay were carried out. The results obtained provide a low cost, simple, sensitive, specific and accurate RIA system of progesterone based on magnetizable solid phase separation. This may be extremely helpful in diagnosis and proper management of ovulation during childbearing years

Detection of estrus in dairy cows by electrical measurements of vaginal mucus and by milk progesterone.

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Gartland, P; Schiavo, J; Hall, C E; Foote, R H; Scott, N R

1976-05-01

Electrical resistance (ohms) of mucus were analyzed in 20 postpartum Holstein cows by use of a probe inserted into the anterior vagina every other day for 30 days. Composite milk samples were taken on the same day, and progesterone was determined by radioimmunoassay. Cows were observed twice daily for standing estrus and reproductive organs palpated weekly per rectum (rectal palpation). Fifteen cows which were cycling showed increasing progesterone 6 to 7 days after the onset of estrus with values of 8.1 to 10.0 ng progesterone/ml milk on days 10 to 17. Concentrations had declined rapidly 2 days before onset of the next estrus. Progesterone in milk was affected by cow and by day of the cycle. Electrical resistance followed a similar cyclical pattern, but variability was large and only cows differed. The correlation between milk progesterone and mucus resistance was .22. Progesterone concentrations for four cows with follicular cysts fluctuated randomly with a mean of 2.6 ng/ml. Mean resistance of vaginal mucus was 44 omega for both cycling and cystic cows, indicating that a single measurement of electrical resistance every 2nd day was unreliable in distinguishing physiological states. One cow had high progesterone in milk on days 19 to 25 and was diagnosed pregnant by rectal palpation 3 wk later. Cows were not seen in estrus 28% of the time when milk progesterone and rectal palpation indicated they were in the follicular phase of the estrous cycle and were cycling.

Binding of (/sup 3/H) progesterone to normal and neoplastic tissue samples from tumour bearing breasts

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Pollow, K; Sinnecker, R; Schmidt-Gollwitzer, M; Boquoi, E; Pollow, B [Institut fuer Molekularbiologie und Biochemie, Frauenklinik Charlottenburg der Freien Universitat, Berlin (G.F.R.)

1977-01-01

Macromolecular components of normal human mammary cytosol (obtained from 'non-malignant tissue samples' from cancer bearing breasts) which bind (/sup 3/H)progesterone in vitro were characterized by sucrose gradient centrifugation, gel filtration on Agarose, ion exchange chromatography, isoelectric focusing, competition studies and kinetic parameters. The size of the cytoplasmic binding components vary with the concentration of KCl. In the absence of KCl, the major components are characterized by sedimentation coefficients of about 4 S and 8 S. In solutions containing 0.3M KCl, the cytoplasmic components sediment at 4 S in sucrose gradient. The corticosteroid-binding component of normal human mammary cytosol both sediment at about the same rate in the presence of 0.3M KCl and chromatograph as a single component on Agarose. The isoelectric point of the progesterone-binding component of normal human mammary cytosol was located around pH 5.0. The progesterone-binding component was more thermo-labile than serum CBG. CBG was inactivated at temperatures above 45 deg C but temperature above 20 deg C destroyed specific progesterone receptor binding. Progesterone receptor concentrations in normal mammary cytosol of premenopausal women depended on the menstrual cycle. The binding of progesterone was highest around the time of ovulation. In breast tumor tissue samples the progesterone receptor concentration was lower than in the normal mammary cytosol (obtained in each case from the same tumor-bearing breast). In 5 out of 37 breast tumor samples progesterone binding activity could not be detected.

Liquid phase radioimmunoassay system for determination of progesterone in human serum using different radiolabeled tracers

International Nuclear Information System (INIS)

Mehany, N.L.; El-Kolaly, M.T.; Sallam, Kh.M.; EI-Hashash, M.A.

2007-01-01

The preparation and development of primary reagents of progesterone radioimmunoassay (R1A) technique with low cost is considered to be the main objective of the present study . The preparation of 125 l-progesterone radiotracers was carried out using chloramine-T, iodogen and lactoperoxidase oxidation methods and they were purified using high perfomance liquid chromatography (HPLC). Tyramine hydrochloride was conjugated with activated progesterone 11α-hemisuccinate and then iodinated using Na 125 I.The tracers obtained were investigated in terms of radiochemical purity, radiochemical yield and immunoreactivity. The production of polyclonal antibodies was undertaken by immunizing six New-Zealand rabbits subcutaneously through primary injection and four booster doses.The preparation of progesterone standards were carried out by preparing stock standard solution of progesterone in ethanol. After evaporation of ethanol, the steroid assay buffer was used as a standard matrix to prepare the working standards required. Optimization and validation of the assay were carried out. The results obtained provide a highly sensitive, specific and accurate RIA system of progesterone based on liquid phase separation. In conclusion, this assay could be used in evaluating corpus luteum insufficiency among women in child bearing period

Antibody bond to the microcrystalline cellulose in progesterone radioimmunoassay

International Nuclear Information System (INIS)

Krnavek, B.

1992-01-01

A suspension of microcrystalline cellulose with bonded globulin fraction of the polyclonal antibody against progesterone was prepared and applied to the radioimmunoanalysis of progesterone in full milk and in blood serum. The results were compared with those obtained using RETRO-test kits; the comparison gave evidence that the novel technique can fully replace the RETRO-test, the elimination of the separating medium (activated carbon, polyethylene glycol) being an asset. The obtained correlation coefficient and regression equation for a simultaneous determination of 120 samples by the two methods were r = 0.964 and y = 1.113x - 0.939, respectively

Abnormal regulation for progesterone production in placenta with prenatal cocaine exposure in rats.

Science.gov (United States)

Wu, L; Yan, J; Qu, S C; Feng, Y Q; Jiang, X L

2012-12-01

Cocaine abuse in pregnant women is currently a significant public hygiene problem and is tightly associated with elevated risk for preterm delivery. Placental steroidogenesis especially progesterone production was essential for success and maintenance of pregnancy in humans and rodents. In the present study, we determined the impact of prenatal cocaine exposure on pathways of placental progesterone synthesis in rats. Pregnant rats were treated cocaine twice daily (15 mg/kg/day) during the third trimester, and the maternal and fetal plasma progesterone and pregnenolone concentrations were detected. We also examined both the protein and mRNA expression of some key enzymes and regulators for progesterone production in placenta. Results showed that, after maternal cocaine use during pregnancy, progesterone and pregnenolone concentrations in both maternal and fetal rats were significantly decreased. Although prenatal cocaine exposure had no effects on placental 3β-hydroxysteroid dehydrogenase type 1 (3βHSD1) expression, protein and mRNA expression of the cholesterol side-chain cleavage enzyme (P450scc/CYP11a) in placenta was significantly inhibited. Moreover, protein and mRNA expressions of MLN64 that regulating cholesterol transport and activating protein 2γ (AP2γ/Tfap2c) that controlling P450scc/CYP11a gene expression in placenta were both decreased following maternal cocaine use in pregnancy. Collectively, this study suggested that prenatal cocaine exposure could insult the placental progesterone production in rats possibly associated with the high risk for preterm delivery. Copyright © 2012 Elsevier Ltd. All rights reserved.

Selectivity in progesterone and androgen receptor binding of progestagens used in oral contraceptives

International Nuclear Information System (INIS)

Kloosterboer, H.J.; Vonk-Noordegraaf, C.A.; Turpijn, E.W.

1988-01-01

The relative binding affinities (RBAs) of four progestational compounds (norethisterone, levonorgestrel, 3-keto-desogestrel and gestodene) for the human progesterone and androgen receptors were measured in MCF-7 cytosol and intact MCF-7 cells. For the binding to the progesterone receptor, both Org 2058 and Org 3236 (or 3-keto-desogestrel) were used as labelled ligands. The following ranking (low to high) for the RBA of the nuclear (intact cells) progesterone receptor irrespective of the ligand used is found: norethisterone much less than levonorgestrel less than 3-keto-destogestrel less than gestodene. The difference between the various progestagens is significant with the exception of that between 3-keto-desogestrel and gestodene, when Org 2058 is used as ligand. For the cytosolic progesterone receptor, the same order is found with the exception that similar RBAs are found for gestodene and 3-keto-desogestrel. The four progestagens clearly differ with respect to binding to the androgen receptor using dihydrotestosterone as labelled ligand in intact cells; the ranking (low to high) is: norethisterone less than 3 keto-desogestrel less than levonorgestrel and gestodene. The difference between 3-keto-desogestrel and levonorgestrel or gestodene is significant. The selectivity indices (ratio of the mean RBA for the progesterone receptor to that of androgen receptor) in intact cells are significantly higher for 3-keto-desogestrel and gestodene than for levonorgestrel and norethisterone. From these results we conclude that the introduction of the 18-methyl in norethisterone (levonorgestel) increases both the binding to the progesterone and androgen receptors

A critical period of progesterone withdrawal precedes menstruation in macaques

Science.gov (United States)

Slayden, Ov D; Brenner, Robert M

2006-01-01

Macaques are menstruating nonhuman primates that provide important animal models for studies of hormonal regulation in the uterus. In women and macaques the decline of progesterone (P) at the end of the cycle triggers endometrial expression of a variety of matrix metalloproteinase (MMP) enzymes that participate in tissue breakdown and menstrual sloughing. To determine the minimal duration of P withdrawal required to induce menses, we assessed the effects of adding P back at various time points after P withdrawal on both frank bleeding patterns and endometrial MMP expression. Artificial menstrual cycles were induced by treating the animals sequentially with implants releasing estradiol (E2) and progesterone (P). To assess bleeding patterns, P implants were removed at the end of a cycle and then added back at 12, 24, 30, 36, 40, 48, 60, or 72 hours (h) after the initial P withdrawal. Observational analysis of frank bleeding patterns showed that P replacement at 12 and 24 h blocked menses, replacement at 36 h reduced menses but replacement after 36 h failed to block menses. These data indicate that in macaques, a critical period of P withdrawal exists and lasts approximately 36 h. In other similarly cycled animals, we withdrew P and then added P back either during (12–24 h) or after (48 h) the critical period, removed the uterus 24 h after P add back and evaluated endometrial MMP expression. Immunocytochemistry showed that replacement of P during the critical period suppressed MMP-1, -2 and -3 expression along with menses, but replacement of P at 48 h, which failed to suppress mense, suppressed MMP-1 and MMP-3 but did not block MMP-2. We concluded that upregulation of MMPs is essential to menses induction, but that after the critical period, menses will occur even if some MMPs are experimentally blocked. PMID:17118170

Release from Xenopus oocyte prophase I meiotic arrest is independent of a decrease in cAMP levels or PKA activity.

Science.gov (United States)

Nader, Nancy; Courjaret, Raphael; Dib, Maya; Kulkarni, Rashmi P; Machaca, Khaled

2016-06-01

Vertebrate oocytes arrest at prophase of meiosis I as a result of high levels of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) activity. In Xenopus, progesterone is believed to release meiotic arrest by inhibiting adenylate cyclase, lowering cAMP levels and repressing PKA. However, the exact timing and extent of the cAMP decrease is unclear, with conflicting reports in the literature. Using various in vivo reporters for cAMP and PKA at the single-cell level in real time, we fail to detect any significant changes in cAMP or PKA in response to progesterone. More interestingly, there was no correlation between the levels of PKA inhibition and the release of meiotic arrest. Furthermore, we devised conditions whereby meiotic arrest could be released in the presence of sustained high levels of cAMP. Consistently, lowering endogenous cAMP levels by >65% for prolonged time periods failed to induce spontaneous maturation. These results argue that the release of oocyte meiotic arrest in Xenopus is independent of a reduction in either cAMP levels or PKA activity, but rather proceeds through a parallel cAMP/PKA-independent pathway. © 2016. Published by The Company of Biologists Ltd.

Vasopressin infusion into the lateral septum of adult male rats rescues progesterone induced impairment in social recognition

Science.gov (United States)

Bychowski, Meaghan E.; Mena, Jesus D.; Auger, Catherine J.

2013-01-01

It is well established that social recognition memory is mediated, in part, by arginine vasopressin (AVP). AVP cells within the bed nucleus of the stria terminalis (BST) and medial amygdala (MeA) send AVP-ergic projections to the lateral septum (LS). We have demonstrated that progesterone treatment decreases AVP immunoreactivity within the BST, the MeA and the LS, and that progesterone treatment impairs social recognition. These data suggested that progesterone may impair social recognition memory by decreasing AVP. In the present experiment, we hypothesized that infusions of AVP into the LS would rescue the progesterone induced impairment in social recognition within adult male rats. One week after adult male rats underwent cannula surgery, they were given systemic injections of either a physiological dose of progesterone or oil control for three days. Four hours after the last injection, we tested social recognition memory using the social discrimination paradigm, a two-trial test that is based on the natural propensity for rats to be highly motivated to investigate novel conspecifics. Immediately after the first exposure to a juvenile, each animal received bilateral infusions of either AVP or artificial CSF (aCSF) into the LS. Our results show that, as expected, control animals exhibited normal social discrimination. In corroboration with our previous results, animals given progesterone have impaired social discrimination. Interestingly, animals treated with progesterone and AVP exhibited normal social discrimination, suggesting that AVP treatment rescued the impairment in social recognition caused by progesterone. These data also further support a role for progesterone in modulating vasopressin dependent behavior within the male brain. PMID:23639881

The role of adrenergic activation on murine luteal cell viability and progesterone production.

Science.gov (United States)

Wang, Jing; Tang, Min; Jiang, Huaide; Wu, Bing; Cai, Wei; Hu, Chuan; Bao, Riqiang; Dong, Qiming; Xiao, Li; Li, Gang; Zhang, Chunping

2016-09-15

Sympathetic innervations exist in mammalian CL. The action of catecholaminergic system on luteal cells has been the focus of a variety of studies. Norepinephrine (NE) increased progesterone secretion of cattle luteal cells by activating β-adrenoceptors. In this study, murine luteal cells were treated with NE and isoprenaline (ISO). We found that NE increased the viability of murine luteal cells and ISO decreased the viability of luteal cells. Both NE and ISO promoted the progesterone production. Nonselective β-adrenergic antagonist, propranolol reversed the effect of ISO on cell viability but did not reverse the effect of NE on cell viability. Propranolol blocked the influence of NE and ISO on progesterone production. These results reveal that the increase of luteal cell viability induced by NE is not dependent on β-adrenergic activation. α-Adrenergic activation possibly contributes to it. Both NE and ISO increased progesterone production through activating β-adrenergic receptor. Further study showed that CyclinD2 is involved in the increase of luteal cell induced by NE. 3β-Hydroxysteroid dehydrogenase, LHR, steroidogenic acute regulatory protein (StAR), and PGF2α contribute to the progesterone production induced by NE and ISO. Copyright © 2016 Elsevier Inc. All rights reserved.

Autoimmune Progesterone Dermatitis: A Diagnosis to Consider in a Patient With Cyclical Cutaneous Eruptions.

Science.gov (United States)

Steuer, Alexa B; Scherl, Sharon; Ashinoff, Robin

2017-10-01

Autoimmune progesterone dermatitis (APD) is a cyclical cutaneous reaction to progesterone, with symptoms that typically begin 3-10 days before the onset of menstrual flow and end 1-2 days into menses. The symptoms vary in severity from barely visible to anaphylaxis, but most often include an eczematous eruption, erythema multiforme, urticaria, folliculitis, and angioedema. This is a rare disorder with only a handful of documented cases. The pathogenesis of this condition remains unknown and significant variations in the presentation and severity of symptoms complicates its diagnosis. Treatment seeks to inhibit progesterone secretion through suppression of ovulation, but it may be unsuccessful. We present a case of autoimmune progesterone dermatitis that eluded diagnosis for several years, and subsequently the patient was completely controlled with oral contraceptive pills. J Drugs Dermatol. 2017;16(10):1040-1042..

Loss of Progesterone Receptor-Mediated Actions Induce Preterm Cellular and Structural Remodeling of the Cervix and Premature Birth

Science.gov (United States)

Yellon, Steven M.; Dobyns, Abigail E.; Beck, Hailey L.; Kurtzman, James T.; Garfield, Robert E.; Kirby, Michael A.

2013-01-01

A decline in serum progesterone or antagonism of progesterone receptor function results in preterm labor and birth. Whether characteristics of premature remodeling of the cervix after antiprogestins or ovariectomy are similar to that at term was the focus of the present study. Groups of pregnant rats were treated with vehicle, a progesterone receptor antagonist (onapristone or mifepristone), or ovariectomized on day 17 postbreeding. As expected, controls given vehicle delivered at term while rats delivered preterm after progesterone receptor antagonist treatment or ovariectomy. Similar to the cervix before term, the preterm cervix of progesterone receptor antagonist-treated rats was characterized by reduced cell nuclei density, decreased collagen content and structure, as well as a greater presence of macrophages per unit area. Thus, loss of nuclear progesterone receptor-mediated actions promoted structural remodeling of the cervix, increased census of resident macrophages, and preterm birth much like that found in the cervix at term. In contrast to the progesterone receptor antagonist-induced advance in characteristics associated with remodeling, ovariectomy-induced loss of systemic progesterone did not affect hypertrophy, extracellular collagen, or macrophage numbers in the cervix. Thus, the structure and macrophage census in the cervix appear sufficient for premature ripening and birth to occur well before term. With progesterone receptors predominantly localized on cells other than macrophages, the findings suggest that interactions between cells may facilitate the loss of progesterone receptor-mediated actions as part of a final common mechanism that remodels the cervix in certain etiologies of preterm and with parturition at term. PMID:24339918

Levonorgestrel-releasing intrauterine device in the treatment of abnormal uterine bleeding: a 6- and 12-month morphological and clinical follow-up.

Science.gov (United States)

Palmara, Vittorio; Sturlese, Emanuele; Villari, Daniela; Giacobbe, Valentina; Retto, Annalisa; Santoro, Giuseppe

2013-08-01

Abnormal uterine bleeding is defined as any alteration in the pattern or volume of menstrual blood flow, and it is preferably treated using hysterectomy, endometrial destruction or the levonorgestrel-releasing intrauterine system (Mirena(®) ). Recently, it has been demonstrated that studies of Mirena(®) were generally small and consequently imprecise. Our study was aimed at assessing the effects of a slow-release levonorgestrel (20 μg/day) intrauterine device in fertile and postmenopausal women experiencing abnormal uterine bleeding that did not respond to traditional medical management. A total of 40 women, of whom 24 were of reproductive capacity and 16 were postmenopausal, were enrolled in the trial. Removal of the intrauterine device was required for only 2 of the 24 fertile women and for only 3 of the 16 postmenopausal women. After 6 and 12 months of treatment, the remaining women were clinically evaluated and underwent ultrasound and hysteroscopy using biopsy specimens as a control. The EuroQol Group EQ-5D questionnaire was used for evaluation of quality of life. The device showed good tolerability and efficacy. It resulted in a reduction in the endometrial mucosal thickness with a regression of bleeding and collateral effects, which were more evident after 12 months of treatment. A positive effect of the device on the woman's quality of life was demonstrated. The slow-release levonorgestrel intrauterine device may be a valid therapeutic tool for treating basic symptomatology and increasing quality of life in women with abnormal uterine bleeding. © 2013 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Correlation analysis of the progesterone-induced sperm acrosome reaction rate and the fertilisation rate in vitro.

Science.gov (United States)

Jiang, T; Qin, Y; Ye, T; Wang, Y; Pan, J; Zhu, Y; Duan, L; Li, K; Teng, X

2015-10-01

In this study, we aimed to investigate whether progesterone-induced acrosome reaction (AR) rate could be an indicator for fertilisation rate in vitro. Twenty-six couples with unexplained infertility and undergoing in vitro fertilisation (IVF) treatment were involved. On the oocytes retrieval day after routine IVF, residual sperm samples were collected to receive progesterone induction (progesterone group) or not (control group). AR rate was calculated and fertilisation rate was recorded. The correlation between progesterone-induced AR and fertilisation rate and between sperm normal morphology and 3PN (tripronuclear) were analysed using the Spearman correlation analysis. The AR rate of progesterone group was statistically higher than that of the control group (15.6 ± 5.88% versus 9.66 ± 5.771%, P rate (r = -0.053, P > 0.01) or rate of high-quality embryo development (r = -0.055, P > 0.01). Normal sperm morphology also showed no significant correlation with the amount of 3PN zygotes (r = 0.029, P > 0.01), rate of 3PN zygotes production (r = 0.20, P > 0.01), rate of 3PN embryo development (r = -0.406, P > 0.01), fertilisation rate (r = -0.148, P > 0.01) or progesterone-induced AR rate (r = 0.214, P > 0.01). Progesterone can induce AR in vitro significantly; however, the progesterone-induced AR may not be used to indicate fertilisation rate. © 2014 Blackwell Verlag GmbH.

Ischiorectal abscess and ischiorectal-vaginal fistula as delayed complications of posterior intravaginal slingplasty: a case report.

Science.gov (United States)

Chen, Heidi Wen-Chu; Guess, Marsha K; Connell, Kathleen A; Bercik, Richard S

2009-10-01

Synthetic meshes have been used extensively to augment surgical management of pelvic organ prolapses. Posterior intravaginal sling (IVS) is a technique used for correcting vaginal vault/apical prolapse, posterior vaginal prolapse or rectocele. There are limited data on long-term safety of this procedure. In a subanalysis of the IVS tapes from the SUSPEND trial performed secondary to the large number of patients with complications of suburethral sling erosions after IVS, it was noted that the sling erosion tended to have a delayed presentation secondary to poor incorporation of the mesh. A 48-year-old woman with cystocele, uterine prolapse and rectocele had undergone total vaginal hysterectomy, mesh-augmented anterior repair, posterior colporrhaphy and posterior intravaginal slingplasty (IVS) in July 2005. Thirty months after the surgery, she presented with gradual symptoms of copious vaginal discharge for several weeks followed by constant right buttock pain and swelling. Examination was notable for intact mesh with no signs of erosion and a 3-cm induration deep within the right buttock. Computed tomography suggested a pelvic abscess. Magnetic resonance imaging confirmed a right ischiorectal fossa abscess and a vaginal fistula. The patient underwent sling excision, right ischiorectal fossa exploration and vaginal fistula repair. A fistulous tract was found to extend along the intact sling from the vaginal epithelium toward the right ischiorectal fossa. At 2 months' followup, there were no recurrences or other complications. This is the first report of a delayed complication of an ischiorectal abscess associated with an ischiorectal-vaginal fistula that presented 30 months after the placement of a posterior IVS.

Effects of estradiol and progesterone on the variability of the micronucleus assay

International Nuclear Information System (INIS)

Baeyens, Ans; Vandersickel, Veerle; Thierens, Hubert; Ridder, Leo De; Vral, Anne

2005-01-01

To investigate chromosomal radiosensitivity of lymphocytes the micronucleus (MN) assay has been used for many years. The results of these studies suggest the use of the MN assay as a biomarker for cancer predisposition. However, the MN assay has still some limitations associated with the reproducibility and sensitivity. Especially a high intra-individual variability has been observed. An explanation for this high intra-individual variability is not yet available. In literature it is suggested that the high variability among females is attributable to hormonal status. In this study we investigated if the high intra-individual variability in micronucleus formation in lymphocytes of females after in vitro exposure to ionising radiation is caused by variations in hormone levels of estradiol (E2) and progesterone (PROG). For this, the MN assay was performed on blood samples of 18 healthy women during 7 consecutive weeks while the estradiol and progesterone levels were determined at the same time. The MN assay was also examined in cultures of isolated blood lymphocytes with estradiol or progesterone levels added in vitro. The results demonstrated that estradiol and progesterone levels have no influence on the variations in radiation-induced MN yields observed in blood samples of healthy women. These conclusions were confirmed by the 'in vitro' experiments as no correlation between the MN yields and the concentrations of hormones (estradiol or progesterone) added in vitro to isolated lymphocytes cultures was observed

Selective progesterone receptor modulators 3: use in oncology, endocrinology and psychiatry.

Science.gov (United States)

Benagiano, Giuseppe; Bastianelli, Carlo; Farris, Manuela

2008-10-01

A number of synthetic steroids are capable of modulating progesterone receptors with a spectrum of activities ranging from pure antagonism to a mixture of agonism and antagonism. The best known of these are mifepristone (RU 486), asoprisnil (J 867), onapristone (ZK 98299), ulipristal (CDB 2914), Proellex() (CDB 4124), ORG 33628 and ORG 31710. Outside reproduction selective modulators of progesterone receptors have been under investigation for a large variety of indications, for example in oncology as adjuvants in breast, cervical, endometrial, ovarian and prostate cancer, as well as inoperable meningioma and leiomyosarcoma. In addition, they have been used as antiglucocorticoids. It is therefore useful to review the results obtained in these conditions. A careful evaluation of existing major review papers and of recently published articles was carried out for the indications under review, focusing not only on mifepristone but also on those other selective modulators of progesterone receptors for which data are available. In preliminary studies selective modulators of progesterone receptors had some activity on a number of neoplasias. Their antiglucocorticoid activity has been tested with some success in Cushing's syndrome, several psychiatric conditions (e.g., mood disorders and Alzheimer's disease) and acute renal failure. Finally they are being used in a gene regulator system.

The past, present, and future of selective progesterone receptor modulators in the management of uterine fibroids.

Science.gov (United States)

Singh, Sukhbir S; Belland, Liane; Leyland, Nicholas; von Riedemann, Sarah; Murji, Ally

2017-12-21

Uterine fibroids are common in women of reproductive age and can have a significant impact on quality of life and fertility. Although a number of international obstetrics/gynecology societies have issued evidence-based clinical practice guidelines for the management of symptomatic uterine fibroids, many of these guidelines do not yet reflect the most recent clinical evidence and approved indication for one of the key medical management options: the selective progesterone receptor modulator class. This article aims to share the clinical experience gained with selective progesterone receptor modulators in Europe and Canada by reviewing the historical development of selective progesterone receptor modulators, current best practices for selective progesterone receptor modulator use based on available data, and potential future uses for selective progesterone receptor modulators in uterine fibroids and other gynecologic conditions. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Production of progesterone antibodies and their use in studying reproductive functions in sheep and goats

International Nuclear Information System (INIS)

Seren, E.; Bacci, M.L.

1988-01-01

The characteristics of antisera raised in six rabbits by immunization with progesterone-3-0-carboxymethyloxime-BSA are described. The performance of a progesterone RIA involving the use of the best antiserum is described. This progesterone RIA, carried out in sheep and goat plasma samples collected throughout the different stages of the reproductive life cycle turned out to be a reliable method to monitor ovarian activity. (author). 8 refs, 1 fig., 3 tabs

Amphiregulin mediates hCG-induced StAR expression and progesterone production in human granulosa cells

OpenAIRE

Fang, Lanlan; Yu, Yiping; Zhang, Ruizhe; He, Jingyan; Sun, Ying-Pu

2016-01-01

Progesterone plays critical roles in maintaining a successful pregnancy at the early embryonic stage. Human chorionic gonadotropin (hCG) rapidly induces amphiregulin (AREG) expression. However, it remains unknown whether AREG mediates hCG-induced progesterone production. Thus, the objective of this study was to investigate the role of AREG in hCG-induced progesterone production and the underlying molecular mechanism in human granulosa cells; primary cells were used as the experimental model. ...

Progesterone inserts may help to improve breeding readiness in beef heifers

OpenAIRE

Favetto, Pedro H; Hoar, Bruce R; Myers, Dan M; Tindall, Justin

2010-01-01

The accurate determination of pubertal status in yearling beef heifers, possibly combined with the use of exogenous progesterone, allows females to produce the maximum number of calves over their lifetimes. This study aimed to determine the reliability of a reproductive tract scoring (RTS) system that combines manual palpation with ultrasound as a measure of pubertal status, and whether the treatment of heifers with progesterone-containing vaginal inserts — followed by breeding on the second ...

Plasma progesterone levels and corpus luteum morphology in the female prairie dog (Cynomys ludovicianus).

Science.gov (United States)

Foreman, D; Garris, D

1984-08-01

Plasma progesterone levels in female prairie dogs were determined by a radioimmunoassay specific for progesterone. Plasma progesterone levels were determined in samples taken before estrus, at estrus, during the luteal phase, and during anestrus from females maintained all year in the laboratory. Progesterone levels were also determined in plasma samples taken in the laboratory from two pregnant and three postparturient females captured in the field. Progesterone levels were low before estrus and continued low during estrus. They rose on the first week after estrus to 0.8 ng/ml or above and continued at or above this level for 9-14 weeks following estrus. Gestation in prairie dogs is 35 days in this species. Progesterone levels of three postparturient females were above 1.0 ng/ml for 7 weeks after their arrival in the laboratory. These females all had uterine scars showing that they had delivered their litters before they were captured. Two females were determined to be pregnant at the time of their capture. These females later reabsorbed their fetuses (determined by laparotomy). Progesterone values of samples from these females were all above 1.0 ng/ml except for one low value in one female which occurred 3 weeks after her capture and after reabsorption of her fetuses was in progress. The cells of the corpus lutea (CL) of nonpregnant, pregnant, and postparturient females had well-developed rings of cytoplasmic basophilia but as the CL regressed this pattern became disorganized and disappeared. The function of this basophilia is not known. The long luteal phase found in female prairie dogs is compared to those found in other species of mammals. This is the first annually breeding rodent reported to have a longer luteal phase that the period of gestation.

Nanostructured progesterone immunosensor using a tyrosinase-colloidal gold-graphite-Teflon biosensor as amperometric transducer

International Nuclear Information System (INIS)

Carralero, Veronica; Gonzalez-Cortes, Araceli; Yanez-Sedeno, Paloma; Pingarron, Jose M.

2007-01-01

A novel progesterone immunosensor using a colloidal gold-graphite-Teflon-tyrosinase composite biosensor as amperometric transducer is reported. A sequential competitive configuration between the analyte and progesterone labelled with alkaline phosphatase (AP) was used. Phenyl phosphate was employed as the AP-substrate and the enzyme reaction product, phenol, was oxidized by tyrosinase to o-quinone, which is subsequently reduced at -0.1 V at the biocomposite electrode. Variables such as the concentration of phenyl phosphate, the amount of antibody attached to the electrode surface, immersion time in a 2% BSA solution, working pH and incubation times in progesterone and AP conjugate were optimized. A linear calibration graph for progesterone was obtained between 0 and 40 ng mL -1 with a slope value of -82.3 nA ng -1 mL, and a detection limit of 0.43 ng mL -1 . The time needed to reach the steady-state current from the addition of phenyl phosphate was 30-40 s. These analytical characteristics improve substantially those reported for other progesterone immunosensors. A lifetime of 14 days with no need to apply any regeneration procedure was also achieved. The usefulness of the immunosensor was evaluated by determining progesterone in milk samples spiked with the analyte at 5.0 and 1.5 ng mL -1 concentration levels. Following a very simple procedure, involving only sample dilution, mean recoveries (n = 7) of 98 ± 3% and 99 ± 3%, respectively, were obtained

Nanostructured progesterone immunosensor using a tyrosinase-colloidal gold-graphite-Teflon biosensor as amperometric transducer

Energy Technology Data Exchange (ETDEWEB)

Carralero, Veronica [Department of Analytical Chemistry, Faculty of Chemistry, University Complutense of Madrid, 28040 Madrid (Spain); Gonzalez-Cortes, Araceli [Department of Analytical Chemistry, Faculty of Chemistry, University Complutense of Madrid, 28040 Madrid (Spain); Yanez-Sedeno, Paloma [Department of Analytical Chemistry, Faculty of Chemistry, University Complutense of Madrid, 28040 Madrid (Spain)]. E-mail: yseo@quim.ucm.es; Pingarron, Jose M. [Department of Analytical Chemistry, Faculty of Chemistry, University Complutense of Madrid, 28040 Madrid (Spain)

2007-07-16

A novel progesterone immunosensor using a colloidal gold-graphite-Teflon-tyrosinase composite biosensor as amperometric transducer is reported. A sequential competitive configuration between the analyte and progesterone labelled with alkaline phosphatase (AP) was used. Phenyl phosphate was employed as the AP-substrate and the enzyme reaction product, phenol, was oxidized by tyrosinase to o-quinone, which is subsequently reduced at -0.1 V at the biocomposite electrode. Variables such as the concentration of phenyl phosphate, the amount of antibody attached to the electrode surface, immersion time in a 2% BSA solution, working pH and incubation times in progesterone and AP conjugate were optimized. A linear calibration graph for progesterone was obtained between 0 and 40 ng mL{sup -1} with a slope value of -82.3 nA ng{sup -1} mL, and a detection limit of 0.43 ng mL{sup -1}. The time needed to reach the steady-state current from the addition of phenyl phosphate was 30-40 s. These analytical characteristics improve substantially those reported for other progesterone immunosensors. A lifetime of 14 days with no need to apply any regeneration procedure was also achieved. The usefulness of the immunosensor was evaluated by determining progesterone in milk samples spiked with the analyte at 5.0 and 1.5 ng mL{sup -1} concentration levels. Following a very simple procedure, involving only sample dilution, mean recoveries (n = 7) of 98 {+-} 3% and 99 {+-} 3%, respectively, were obtained.

Estradiol and Progesterone Strongly Inhibit the Innate Immune Response of Mononuclear Cells in Newborns ▿

Science.gov (United States)

Giannoni, Eric; Guignard, Laurence; Knaup Reymond, Marlies; Perreau, Matthieu; Roth-Kleiner, Matthias; Calandra, Thierry; Roger, Thierry

2011-01-01

Newborns are particularly susceptible to bacterial infections due to qualitative and quantitative deficiencies of the neonatal innate immune system. However, the mechanisms underlying these deficiencies are poorly understood. Given that fetuses are exposed to high concentrations of estradiol and progesterone during gestation and at time of delivery, we analyzed the effects of these hormones on the response of neonatal innate immune cells to endotoxin, bacterial lipopeptide, and Escherichia coli and group B Streptococcus, the two most common causes of early-onset neonatal sepsis. Here we show that at concentrations present in umbilical cord blood, estradiol and progesterone are as powerful as hydrocortisone for inhibition of cytokine production by cord blood mononuclear cells (CBMCs) and newborn monocytes. Interestingly, CBMCs and newborn monocytes are more sensitive to the effects of estradiol and progesterone than adult peripheral blood mononuclear cells and monocytes. This increased sensitivity is associated with higher expression levels of estrogen and membrane progesterone receptors but is independent of a downregulation of Toll-like receptor 2 (TLR2), TLR4, and myeloid differentiation primary response gene 88 in newborn cells. Estradiol and progesterone mediate their anti-inflammatory activity through inhibition of the NF-κB pathway but not the mitogen-activated protein kinase pathway in CBMCs. Altogether, these results suggest that elevated umbilical cord blood concentrations of estradiol and progesterone acting on mononuclear cells expressing high levels of steroid receptors contribute to impair innate immune responses in newborns. Therefore, intrauterine exposure to estradiol and progesterone may participate in increasing susceptibility to infection during the neonatal period. PMID:21518785

Organotin compounds cause structure-dependent induction of progesterone in human choriocarcinoma Jar cells.

Science.gov (United States)

Hiromori, Youhei; Yui, Hiroki; Nishikawa, Jun-ichi; Nagase, Hisamitsu; Nakanishi, Tsuyoshi

2016-01-01

Organotin compounds, such as tributyltin (TBT) and triphenyltin (TPT), are typical environmental contaminants and suspected endocrine-disrupting chemicals because they cause masculinization in female mollusks. In addition, previous studies have suggested that the endocrine disruption by organotin compounds leads to activation of peroxisome proliferator-activated receptor (PPAR)γ and retinoid X receptor (RXR). However, whether organotin compounds cause crucial toxicities in human development and reproduction is unclear. We here investigated the structure-dependent effect of 12 tin compounds on mRNA transcription of 3β-hydroxysteroid dehydrogenase type I (3β-HSD I) and progesterone production in human choriocarcinoma Jar cells. TBT, TPT, dibutyltin, monophenyltin, tripropyltin, and tricyclohexyltin enhanced progesterone production in a dose-dependent fashion. Although tetraalkyltin compounds such as tetrabutyltin increased progesterone production, the concentrations necessary for activation were 30-100 times greater than those for trialkyltins. All tested active organotins increased 3β-HSD I mRNA transcription. We further investigated the correlation between the agonistic activity of organotin compounds on PPARγ and their ability to promote progesterone production. Except for DBTCl2, the active organotins significantly induced the transactivation function of PPARγ. In addition, PPARγ knockdown significantly suppressed the induction of mRNA transcription of 3β-HSD I by all active organotins except DBTCl2. These results suggest that some organotin compounds promote progesterone biosynthesis in vitro by inducing 3β-HSD I mRNA transcription via the PPARγ signaling pathway. The placenta represents a potential target organ for these compounds, whose endocrine-disrupting effects might cause local changes in progesterone concentration in pregnant women. Copyright © 2014 Elsevier Ltd. All rights reserved.

Vasopressin infusion into the lateral septum of adult male rats rescues progesterone-induced impairment in social recognition.

Science.gov (United States)

Bychowski, M E; Mena, J D; Auger, C J

2013-08-29

It is well established that social recognition memory is mediated, in part, by arginine vasopressin (AVP). AVP cells within the bed nucleus of the stria terminalis (BST) and medial amygdala (MeA) send AVP-ergic projections to the lateral septum (LS). We have demonstrated that progesterone treatment decreases AVP immunoreactivity within the BST, the MeA and the LS, and that progesterone treatment impairs social recognition. These data suggested that progesterone may impair social recognition memory by decreasing AVP. In the present experiment, we hypothesized that infusions of AVP into the LS would rescue the progesterone-induced impairment in social recognition within adult male rats. One week after adult male rats underwent cannula surgery, they were given systemic injections of either a physiological dose of progesterone or oil control for 3 days. Four hours after the last injection, we tested social recognition memory using the social discrimination paradigm, a two-trial test that is based on the natural propensity for rats to be highly motivated to investigate novel conspecifics. Immediately after the first exposure to a juvenile, each animal received bilateral infusions of either AVP or artificial cerebrospinal fluid into the LS. Our results show that, as expected, control animals exhibited normal social discrimination. In corroboration with our previous results, animals given progesterone have impaired social discrimination. Interestingly, animals treated with progesterone and AVP exhibited normal social discrimination, suggesting that AVP treatment rescued the impairment in social recognition caused by progesterone. These data also further support a role for progesterone in modulating vasopressin-dependent behavior within the male brain. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Gonadorelin at the outset and/or end of an ovulation synchronization progesterone estradiol benzoate-based protocol in Nellore females

Directory of Open Access Journals (Sweden)

Carla Cristian Campos

2016-02-01

Full Text Available This study aimed to evaluate the effects of gonadorelin (GnRH, used both at the outset of a timed artificial insemination (TAI protocol to synchronize follicular wave recruitment and at the end to synchronize ovulation, on the conception rate (CR in Nellore cows. The experiment was conducted on two beef cattle farms in the Vale do Araguaia, MT. The body condition score (BCS evaluation and ultrasound examination to determine ovarian status [follicle diameter < 10 mm, ? 10 mm or presence of corpus luteum (CL] were performed at the beginning (Day 0 of the TAI protocol. Multiparous cows (n = 494 were subjected to the following protocol: Day 0 – insertion of intravaginal progesterone device (P4 DIB®, MSD previously used for 8 or 16 days and IM administration of 2.0 mg of estradiol benzoate (EB, Gonadiol®, MSD; Day 8 – P4 device withdrawal, IM injection of 300 IU of equine chorionic gonadotropin (eCG, Folligon®, MSD, 1.0 mg of estradiol cypionate (ECP®, Zoetis and 0.265 mg of Sodium cloprostenol (PGF2?, Ciosin®, MSD; Day 10 – TAI, performed by a single inseminator. Animals were randomly assigned to one of four groups: control (n = 126, GnRH D0 (n = 123, GnRH D10 (n = 123 and GnRH D0 + D10 (n = 122. Animals treated with GnRH received 50 mcg of gonadorelin (GnRH, Cystorelin®, Merial. Pregnancy was diagnosed by ultrasound 39 ± 10 days after TAI. Data were analyzed using the GLIMMIX procedure of SAS program (P < 0.05. The overall CR was 42.71%. Effect of treatment was not detected (P = 0.2482 on CR, which was 36.89% ± 0.19 (47/126 for the control group, 46.08% ± 0.19 (56/123 for GnRH D0, 48.30% ± 0.18 (61/123 for GnRH D10 and 38.48% ± 0.19 (47/122 for GnRH D0 + D10. An effect of farm was detected; the CR was 47.32% ± 0.13 at Farm A and was 38.24% ± 0.13 at Farm B (P = 0.0249. No effects of the interaction between farm and treatment were observed (P = 0.7662, nor of those among ovarian condition and treatment (P = 0.1225 on CR. Cows with

Chronic potassium depletion increases adrenal progesterone production that is necessary for efficient renal retention of potassium.

Science.gov (United States)

Elabida, Boutaïna; Edwards, Aurélie; Salhi, Amel; Azroyan, Anie; Fodstad, Heidi; Meneton, Pierre; Doucet, Alain; Bloch-Faure, May; Crambert, Gilles

2011-08-01

Modern dietary habits are characterized by high-sodium and low-potassium intakes, each of which was correlated with a higher risk for hypertension. In this study, we examined whether long-term variations in the intake of sodium and potassium induce lasting changes in the plasma concentration of circulating steroids by developing a mathematical model of steroidogenesis in mice. One finding of this model was that mice increase their plasma progesterone levels specifically in response to potassium depletion. This prediction was confirmed by measurements in both male mice and men. Further investigation showed that progesterone regulates renal potassium handling both in males and females under potassium restriction, independent of its role in reproduction. The increase in progesterone production by male mice was time dependent and correlated with decreased urinary potassium content. The progesterone-dependent ability to efficiently retain potassium was because of an RU486 (a progesterone receptor antagonist)-sensitive stimulation of the colonic hydrogen, potassium-ATPase (known as the non-gastric or hydrogen, potassium-ATPase type 2) in the kidney. Thus, in males, a specific progesterone concentration profile induced by chronic potassium restriction regulates potassium balance.

Progesterone profiles and post-partum fertility in dairy cattle in southern Chile

International Nuclear Information System (INIS)

Correa, J.E.; Gatica, R.; Tapia, P.

1990-01-01

Milk samples were taken at weekly intervals from 77 dairy cows on days 23, 30, 37, 43 and 50 post-partum (pp) in order to monitor ovarian activity through progesterone concentration measurement. Skim milk samples were assayed for progesterone by radioimmunoassay using kits provided through the FAO and IAEA. Oestrus, clinical examinations, treatments, artificial insemination and pregnancy diagnosis were recorded. The profiles of progesterone concentration and oestrus occurrence combined with behavioural and clinical data indicated that the study cows were in the following reproductive states: I - normal, 38%; II - 'silent' oestrus, 12%; III - prolonged luteal activity, 13%; IV - irregular cyclic activity, 23%; and V - anoestrus, 13%. After artificial insemination, 89% (25/28) of normal, 77% (7/9) of silent oestrus, 50% (5/10) of prolonged luteal activity, 82% (14/17) of irregular cyclic activity and 80% (8/10) of anoestrous cows eventually became pregnant either with or without hormone treatment. With the exception of the anoestrous group, these results seem to support the idea that once a week sampling for progesterone over a seven week period pp is sufficient to monitor the ovarian activity and predict the fertility of a dairy herd. (author). 16 refs, 6 figs, 3 tabs

Short communication: estrus synchronization using progestogens or cloprostenol in tropical hair sheep.

Science.gov (United States)

Alavez Ramírez, Alejandro; Arroyo Ledezma, Jaime; Montes Pérez, Ruben; Zamora Bustillos, Roberto; Navarrete Sierra, Luis Fernando; Magaña Sevilla, Hector

2014-12-01

The objective of the experiment was to compare the use of a PGF2α analogue (Cloprostenol) IM, with an intravaginal progestagen sponge, flurogestone acetate (FGA), and equine chorionic gonadotropin (eCG) IM application protocol. A total of 30 cyclical hair ewes (54.07 ± 0.5 kg live weight, body condition score 3.5 ± 0.5, and age 3 ± 1 years) were used. For the control group ewes (n = 15), intravaginal sponges (IS) impregnated with 20 mg of FGA were inserted for 12 days with 500 IU of eCG IM at sponges withdrawal. For the PG group ewes (Treatment group n = 15), two injections of Cloprostenol (75 mcg) were given 12 days apart. The presence of estrus was detected using two rams with 8 h interval beginning at the end of the treatment. Progesterone concentrations in blood were measured by solid phase radioimmunoassay. A student's t test was performed to analyze the duration of estrus and the interval between the ends of the treatment and the onset of estrus (ET-OE) presentation. Progesterone levels were compared with two-way ANOVA, with treatment, and day of menstrual cycle as fixed factors. Treatment costs ratio was calculated by dividing the total costs of FGA IS application between total costs of Cloprostenol application. Significant differences (P Progesterone levels in both treatments. Treatment costs of Cloprostenol protocol were 2.63 cheaper than FGA including disposable material, biological products, and labor. It was concluded that Cloprostenol could be an effective tool in estrus synchronization in hair sheep in tropical areas.

Evaluation of a seasonal-breeding artificial insemination programme in Uruguay using milk progesterone radioimmunoassay

International Nuclear Information System (INIS)

Cavestany, D.; Juanbeltz, R.; Canclini, E.; ElHordoy, D.; Lanzzeri, S.; Gama, S.; Martinez, E.; Galina, C.S.

2001-01-01

synchronised with a combination of gonadotrophin releasing hormone (GnRH) + medroxyprogesterone acetate (MAP) on Day 0 and prostaglandin F 2α (PGF) + MAP removal on Day 7, followed by oestrus detection and AI. In Farm A, besides the traditional twice per day (AM/PM) oestrus detection, a third period of observation was included at noon. Progesterone was measured in milk samples to monitor treatment response and to evaluate oestrus detection precision. Interval from PGF to heat was reduced in the farm with three times per day oestrus detection system (6.1 vs. 13.2 days). It was concluded that losses in reproductive efficiency in dairy farms of Uruguay in a seasonal AI programme were mainly due to failure rather than incorrect oestrus detection. More oestrus observation periods improved the response to the synchronisation treatment. (author)

Cellular Mechanics of Primary Human Cervical Fibroblasts: Influence of Progesterone and a Pro-inflammatory Cytokine.

Science.gov (United States)

Shukla, Vasudha; Barnhouse, Victoria; Ackerman, William E; Summerfield, Taryn L; Powell, Heather M; Leight, Jennifer L; Kniss, Douglas A; Ghadiali, Samir N

2018-01-01

The leading cause of neonatal mortality, pre-term birth, is often caused by pre-mature ripening/opening of the uterine cervix. Although cervical fibroblasts play an important role in modulating the cervix's extracellular matrix (ECM) and mechanical properties, it is not known how hormones, i.e., progesterone, and pro-inflammatory insults alter fibroblast mechanics, fibroblast-ECM interactions and the resulting changes in tissue mechanics. Here we investigate how progesterone and a pro-inflammatory cytokine, IL-1β, alter the biomechanical properties of human cervical fibroblasts and the fibroblast-ECM interactions that govern tissue-scale mechanics. Primary human fibroblasts were isolated from non-pregnant cervix and treated with estrogen/progesterone, IL-1β or both. The resulting changes in ECM gene expression, matrix remodeling, traction force generation, cell-ECM adhesion and tissue contractility were monitored. Results indicate that IL-1β induces a significant reduction in traction force and ECM adhesion independent of pre-treatment with progesterone. These cell level effects altered tissue-scale mechanics where IL-1β inhibited the contraction of a collagen gel over 6 days. Interestingly, progesterone treatment alone did not modulate traction forces or gel contraction but did result in a dramatic increase in cell-ECM adhesion. Therefore, the protective effect of progesterone may be due to altered adhesion dynamics as opposed to altered ECM remodeling.

Use of radioimmunoassay for quantitative determination of progesterone in milk samples from dairy cows in Zimbabwe

International Nuclear Information System (INIS)

Freymark, P.J.; McCabe, C.T.

1986-01-01

A maximum 90-day service interval is an important economic factor in dairying. The determination of pregnancy at 21 to 26 days post-insemination can ensure that particular attention is paid to non-pregnant cows at subsequent heats, and thus help reduce this interval. In Zimbabwe a radioimmunoassay for milk progesterone using an iodinated tracer was developed in 1982 from a previously established assay for plasma progesterone. Progesterone antiserum is produced locally and the assay is used as an early pregnancy diagnosis test in dairy cattle. During 1983 two pilot schemes were instituted to investigate breed differences, logistics, and feasibility under the local conditions, and to identify constraints. Milk samples taken 24 days post-insemination were found to differentiate best between pregnant and non-pregnant cows for both major breeds in the country (Friesian/Holstein and Jersey). Pregnant cows had an average of 13.76 ng/mL (+-1.06) progesterone on day 24 while non-pregnant cows averaged 0.34 ng/mL (+-0.13) of progesterone. Apparently 12.2% of cows subsequently lost their embryos after day 24, and these cows averaged 9.98 ng/mL (+-1.52). Milk samples were also taken on the day of insemination; the results showed that 11% of cows were incorrectly inseminated when progesterone concentrations were high (2.59 ng/mL+-0.80). A National Early Pregnancy Diagnosis Scheme using milk progesterone was implemented in December 1984 and results to date are discussed in the paper. (author)

Follicle vascularity coordinates corpus luteum blood flow and progesterone production.

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de Tarso, S G S; Gastal, G D A; Bashir, S T; Gastal, M O; Apgar, G A; Gastal, E L

2017-03-01

Colour Doppler ultrasonography was used to compare the ability of preovulatory follicle (POF) blood flow and its dimensions to predict the size, blood flow and progesterone production capability of the subsequent corpus luteum (CL). Cows (n=30) were submitted to a synchronisation protocol. Follicles ≥7mm were measured and follicular wall blood flow evaluated every 12h for approximately 3.5 days until ovulation. After ovulation, cows were scanned daily for 8 days and similar parameters were evaluated for the CL. Blood samples were collected and plasma progesterone concentrations quantified. All parameters were positively correlated. Correlation values ranged from 0.26 to 0.74 on data normalised to ovulation and from 0.31 to 0.74 on data normalised to maximum values. Correlations between calculated ratios of both POF and CL in data normalised to ovulation and to maximum values ranged from moderate (0.57) to strong (0.87). Significant (Pprogesterone concentrations of the resultant CL. These findings indicate that follicle vascularity coordinates CL blood flow and progesterone production in synchronised beef cows.

Vaginal microbial communities from synchronized heifers and cows with reproductive disorders.

Science.gov (United States)

Gonzalez Moreno, C; Fontana, C; Cocconcelli, P S; Callegari, M L; Otero, M C

2016-11-01

To evaluate changes in the resident microbial population in the cranial vaginal mucosa induced by a progesterone-releasing intravaginal device (PRID) compared to the vaginal microbiota of cows with reproductive disorders. Vaginal discharge was evaluated by clinical examination and a Vaginitis Diagnosis Score was performed by exfoliative cytology. All samples classified as positive and some classified as negative by clinical evaluation were later diagnosed as positive for vaginitis by cytological analysis. Bacterial diversity profiles were performed by PCR-DGGE and clustered according to the reproductive health status of the specimens, revealing a correspondence between the structures of the communities in the vagina and the clinical profile. Representative bands from each group were sequenced and identified as Ruminococcus sp., Dialister sp., Escherichia sp./Shigella sp., Virgibacillus sp., Campylobacter sp., Helcoccoccus sp., Staphylococcus sp., Bacillus sp., Actinopolymorpha sp., Exiguobacterium sp., Haemophilus sp./Histophilus sp., Aeribacillus sp., Porphyromonas sp., Lactobacillus sp. and Clostridium sp. Our results contribute to the knowledge of the vaginal microbiome in synchronized heifers showing positive or negative clinical vaginitis. This study contributes to the understanding of a dynamic vaginal colonization by bacterial consortiums during the synchronization with a widely used PRID protocol. Also, the results reveal the presence of well-known metritis-related pathogens as well as emerging uterine opportunistic pathogens. The provided information will allow to carry out further studies to elucidate functional roles of these native micro-organisms in the bovine reproductive tract. © 2016 The Society for Applied Microbiology.

Progesterone Induces Mucosal Immunity in a Rodent Model of Human Taeniosis by Taenia solium

Science.gov (United States)

Escobedo, Galileo; Camacho-Arroyo, Ignacio; Nava-Luna, Paul; Olivos, Alfonso; Pérez-Torres, Armando; Leon-Cabrera, Sonia; Carrero, J.C.; Morales-Montor, Jorge

2011-01-01

More than one quarter of human world's population is exposed to intestinal helminth parasites. The Taenia solium tapeworm carrier is the main risk factor in the transmission of both human neurocysticercosis and porcine cysticercosis. Sex steroids play an important role during T. solium infection, particularly progesterone has been proposed as a key immunomodulatory hormone involved in susceptibility to human taeniosis in woman and cysticercosis in pregnant pigs. Thus, we evaluated the effect of progesterone administration upon the experimental taeniosis in golden hamsters (Mesocricetus auratus). Intact female adult hamsters were randomly divided into 3 groups: progesterone-subcutaneously treated; olive oil-treated as the vehicle group; and untreated controls. Animals were treated every other day during 4 weeks. After 2 weeks of treatment, all hamsters were orally infected with 4 viable T. solium cysticerci. After 2 weeks post infection, progesterone-treated hamsters showed reduction in adult worm recovery by 80%, compared to both vehicle-treated and non-manipulated infected animals. In contrast to control and vehicle groups, progesterone treatment diminished tapeworm length by 75% and increased proliferation rate of leukocytes from spleen and mesenteric lymph nodes of infected hamsters by 5-fold. The latter exhibited high expression levels of IL-4, IL-6 and TNF-α at the duodenal mucosa, accompanied with polymorphonuclear leukocytes infiltration. These results support that progesterone protects hamsters from the T. solium adult tapeworm establishment by improving the intestinal mucosal immunity, suggesting a potential use of analogues of this hormone as novel inductors of the gut immune response against intestinal helminth infections and probably other bowel-related disorders. PMID:22110394

Progesterone induces mucosal immunity in a rodent model of human taeniosis by Taenia solium.

Science.gov (United States)

Escobedo, Galileo; Camacho-Arroyo, Ignacio; Nava-Luna, Paul; Olivos, Alfonso; Pérez-Torres, Armando; Leon-Cabrera, Sonia; Carrero, J C; Morales-Montor, Jorge

2011-01-01

More than one quarter of human world's population is exposed to intestinal helminth parasites. The Taenia solium tapeworm carrier is the main risk factor in the transmission of both human neurocysticercosis and porcine cysticercosis. Sex steroids play an important role during T. solium infection, particularly progesterone has been proposed as a key immunomodulatory hormone involved in susceptibility to human taeniosis in woman and cysticercosis in pregnant pigs. Thus, we evaluated the effect of progesterone administration upon the experimental taeniosis in golden hamsters (Mesocricetus auratus). Intact female adult hamsters were randomly divided into 3 groups: progesterone-subcutaneously treated; olive oil-treated as the vehicle group; and untreated controls. Animals were treated every other day during 4 weeks. After 2 weeks of treatment, all hamsters were orally infected with 4 viable T. solium cysticerci. After 2 weeks post infection, progesterone-treated hamsters showed reduction in adult worm recovery by 80%, compared to both vehicle-treated and non-manipulated infected animals. In contrast to control and vehicle groups, progesterone treatment diminished tapeworm length by 75% and increased proliferation rate of leukocytes from spleen and mesenteric lymph nodes of infected hamsters by 5-fold. The latter exhibited high expression levels of IL-4, IL-6 and TNF-α at the duodenal mucosa, accompanied with polymorphonuclear leukocytes infiltration. These results support that progesterone protects hamsters from the T. solium adult tapeworm establishment by improving the intestinal mucosal immunity, suggesting a potential use of analogues of this hormone as novel inductors of the gut immune response against intestinal helminth infections and probably other bowel-related disorders.

Simultaneous effects of endocrine disruptor bisphenol A and flavonoid fisetin on progesterone production by granulosa cells.

Science.gov (United States)

Bujnakova Mlynarcikova, Alzbeta; Scsukova, Sona

2018-04-01

In the present study, we aimed to examine effects of different concentrations of the endocrine disruptor Bisphenol A (BPA; 1 nM, 1 μM, 100 μM) and the flavonoid fisetin (1, 10, 25, 50 μM), individually and in combinations, on steroidogenic function of porcine ovarian granulosa cells (GCs) represented by progesterone production. We confirmed that BPA inhibited progesterone production by GCs at the highest concentration. Fisetin reduced gonadotropin-stimulated progesterone synthesis dose-dependently, and in this manner, fisetin impaired progesterone production when added to BPA-treated GCs. The mechanisms of the inhibitory effects of the combinations included a significant down-regulation of the key steroidogenesis-related genes (STAR, CYP11A1, HSD3B). Our findings suggest for the first time that fisetin might interfere with ovarian steroidogenesis, and might not have beneficial but rather aggravating effects in terms of modulating progesterone synthesis altered by high concentrations of BPA. Copyright © 2018 Elsevier B.V. All rights reserved.

Increasing vaginal progesterone gel supplementation after frozen-thawed embryo transfer significantly increases the delivery rate

DEFF Research Database (Denmark)

Alsbjerg, Birgit; Polyzos, Nikolaos P; Elbaek, Helle Olesen

2013-01-01

The aim of this study was to evaluate the reproductive outcome in patients receiving frozen-thawed embryo transfer before and after doubling of the vaginal progesterone gel supplementation. The study was a retrospective study performed in The Fertility Clinic, Skive Regional Hospital, Denmark....... A total of 346 infertility patients with oligoamenorrhoea undergoing frozen-thawed embryo transfer after priming with oestradiol and vaginal progesterone gel were included. The vaginal progesterone dose was changed from 90mg (Crinone) once a day to twice a day and the reproductive outcome during the two...... rate (8.7% versus 20.5%, respectively; P=0.002). Doubling of the vaginal progesterone gel supplementation during frozen-thawed embryo transfer cycles decreased the early pregnancy loss rate, resulting in a significantly higher delivery rate. This study evaluated the reproductive outcome of 346 women...

Expression of Estrogen and Progesterone Receptors among ...

African Journals Online (AJOL)

Study design: This is a descriptive study to detect the level of Estrogen (ER) and Progesterone (PR) receptors in a sample of biopsies from Sudanese women with breast cancer presented at Khartoum teaching Hospital Material and Methods: Forty biopsies from breast cancer patients were examined with immunostaining

Plasma progesterone levels following breeding in goats

International Nuclear Information System (INIS)

Jain, G.C.; Arora, R.C.; Pahwa, G.S.; Batra, S.K.; Pandey, R.S.

1980-01-01

Progesterone concentration in the peripheral blood plasma of ten lactating goats of mixed breeds following breeding were determined by radioimmunoassay to diagnose early pregnancy. The mean concentration was very low (0.25 +- 0.15 ng/ml) on the day of oestrus and reached at peak level on day 13 (1.30 +- 0.07 ng/ml) and on day 19 (2.77 +- 1.18 ng/ml) in non-pregnant and pregnant goats, respectively. The level sharply declined on day 19 (0.40 +- 0.07 ng/ml) of oestrous cycle in non-pregnant goats. However, the level remained below 1.5 ng/ml on day 9, 13, 15 and 17 and 3 ng/ml on day 9, 13, 15, 17, 19, 21 and 23 in nonpregnant and pregnant goats, respectively. The progesterone concentration continued to increase to 2.94 +- 0.70, 4.42 +- 0.92 and 6.2 +- 0.61 ng/ml on day 45, 60 and 75 of gestation, respectively. (auth.)

The progesterone receptor antagonist, onapristone has differential effects on the timing and control of the luteolytic mechanism depending on timing of administration in sheep.

Science.gov (United States)

Mann, G E; Wathes, D C; Robinson, R S

2013-08-25

Cyclic ewes were treated with control vehicle or progesterone receptor antagonist (onapristone; 100mg i.m. twice daily) during either early (day 3-5) or late (day 12-14) luteal phase and plasma samples collected for hormone analysis and to determine endogenous and oxytocin induced PGF2α release. On day 14 and 17, ewes were euthanised and reproductive tracts collected for ovarian morphology and endometrium for oxytoxin and steroid hormone receptor analysis. Early treatment increased LH, but not progesterone or oestradiol, while late treatment elevated all three hormones. Early treatment delayed the up-regulation of endometrial oxytocin receptors and responsiveness to oxytocin challenge, delaying luteolysis. Late treatment advanced development of oxytocin receptors and responsiveness to oxytocin though not timing of luteolysis. Patterns of hormone receptor mRNA were differentially disrupted by treatments. Results provide mechanistic insight into hormonal control of the oestrous cycle and identify the ability of the luteolytic mechanism to dissociate from functional luteolysis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Use of milk progesterone for determining the reproductive status of cross-bred swamp buffaloes and cattle

International Nuclear Information System (INIS)

Cuong Le Xuan; Tan Luu Van; Trieu Cao Van; Dung Chung Anh; Canh Tran Tich; Quynh Vuong Dac

1990-01-01

Eighteen cross-bred buffaloes (F 1 , local breed x Murrah) and 19 cross-bred cows (F 1 , local breed x Holstein Friesian), 4-6 years of age, were used in the study to determine the potential of milk progesterone measurement as an aid in characterizing the onset of postpartum ovarian activity and for early pregnancy diagnosis. The first oestrous cycle, based on milk progesterone, commenced between days 40-50 postpartum in 17% of the buffaloes but between days 25-35 postpartum in 21% of the cows. At days 61-100 postpartum, 33% of the buffaloes had cycling ovaries with progesterone concentrations of 3.23-4.02 ng/mL, while 53% of the cows had cycling ovaries during the same period with progesterone concentrations of 3.52-4.16 ng/mL. During the oestrous cycle, the progesterone level showed peak elevations on day 15 in buffaloes and on day 9 in cows. The milk progesterone profiles of the buffalo took longer to reach peak levels, but declined faster than those in the cow. The accuracy of positive pregnancy diagnosis was 78% in buffaloes and 83.3% in cows, but the accuracy of diagnosing non-pregnancy was 100% in both species. (author). 4 refs, 2 figs, 1 tab

Progesterone receptor isoform A may regulate the effects of neoadjuvant aglepristone in canine mammary carcinoma

DEFF Research Database (Denmark)

Guil-Luna, Silvia; Stenvang, Jan; Brünner, Nils

2014-01-01

RNA expression of progesterone receptor isoforms A and B in mammary carcinomas in dogs treated with 20 mg/Kg of aglepristone (n¿=¿22) or vehicle (n¿=¿5) twice before surgery.ResultsFormalin-fixed, paraffin-embedded tissue samples taken before and after treatment were used to analyse total progesterone receptor......-receptor positive and isoform-A positive tumours in aglepristone-treated dogs.ConclusionsThese findings suggest that the antiproliferative effects of aglepristone in canine mammary carcinomas are mediated by progesterone receptor isoform A....

Effects of progesterone stimulated allopregnanolone on craving and stress response in cocaine dependent men and women.

Science.gov (United States)

Milivojevic, Verica; Fox, Helen C; Sofuoglu, Mehmet; Covault, Jonathan; Sinha, Rajita

2016-03-01

Fluctuations in progesterone levels during the menstrual cycle have been shown to affect physiological and subjective effects of cocaine. Furthermore, our laboratory has demonstrated that following drug-cue exposure, cocaine dependent women with high levels of circulating progesterone display lower diastolic and systolic blood pressure responses and report lower levels of anxiety and drug craving compared to cocaine dependent women with low levels of progesterone. In the current study we examined the role of the progesterone derived neuroactive steroid allopregnanolone (ALLO) on stress arousal, inhibitory control and drug craving in cocaine dependent subjects. Plasma levels of ALLO were measured using GC/MS in 46 treatment-seeking cocaine dependent men and women on day 5 of a 7-day treatment regimen of micronized progesterone (15M/8F) (400mg/day) or placebo (14M/9F) administered in a double blind, randomized manner. As a control, levels of the testosterone derived neurosteroid androstanediol (ADIOL) were also measured. All subjects participated in laboratory sessions on days 5-7 of progesterone/placebo administration in which they were exposed to a series of 5-min personalized guided imagery of either a stressful situation, cocaine use or of a neutral setting and dependent variables including subjective craving, mood, Stroop task as a measure of inhibitory control performance and plasma cortisol were assessed. Participants were grouped by high or low ALLO level and levels of dependent variables compared between ALLO groups. Progesterone relative to placebo significantly increased ALLO levels with no sex differences. There were no effects of micronized progesterone on the testosterone derived ADIOL. Individuals in the high versus the low ALLO group showed decreased levels of cortisol at baseline, and a higher cortisol response to stress; higher positive mood scores at baseline and improved Stroop performance in the drug-cue and stress conditions, and reduced cocaine

Arsenic induced progesterone production in a caspase-3-dependent manner and changed redox status in preovulatory granulosa cells.

Science.gov (United States)

Yuan, Xiao-Hua; Lu, Cai-Ling; Yao, Nan; An, Li-Sha; Yang, Bai-Qing; Zhang, Chuan-Ling; Ma, Xu

2012-01-01

Arsenic contamination is a principal environmental health threat throughout the world. However, little is known about the effect of arsenic on steroidogenesis in granulosa cells (GCs). We found that the treatment of preovulatory GCs with arsenite stimulated progesterone production. A significant increase in serum level of progesterone was observed in female Sprague-Dawley rats following arsenite treatment at a dose of 10 mg/L/rat/day for 7 days. Further experiments demonstrated that arsenite treatment did not change the level of intracellular cyclic AMP (cAMP) or phosphorylated ERK1/2 in preovulatory GCs; however, progesterone production was significantly decreased when cAMP-dependent protein kinase (PKA) or ERK1/2 pathway was inhibited. This implied that the effect of arsenite on progesterone production may require cAMP/PKA and ERK1/2 signaling but not depend on them. Furthermore, we found that arsenite decreased intracellular reactive oxygen species (ROS) but increased the antioxidant glutathione (GSH) levels and mitochondrial membrane potential (ΔΨm) in parallel to the changes in progesterone production. Progesterone antagonist blocked the arsenic-stimulated increase of GSH levels. Arsenite treatment induced caspase-3 activation, although no apoptosis was observed. Inhibition of caspase-3 activity significantly decreased progesterone production stimulated by arsenite or follicle-stimulating hormone (FSH). GSH depletion with buthionine sulfoximine led to cell apoptosis in response to arsenite treatment. Collectively, this study demonstrated for the first time that arsenite stimulates progesterone production through cleaved/active caspase-3-dependent pathway, and the increase of GSH level promoted by progesterone production may protect GCs against apoptosis and maintain the steroidogenesis of GCs in response to arsenite treatment. Copyright © 2011 Wiley Periodicals, Inc.

Intravaginal rings as delivery systems for microbicides and multipurpose prevention technologies

Directory of Open Access Journals (Sweden)

Thurman AR

2013-10-01

Full Text Available Andrea Ries Thurman, Meredith R Clark, Jennifer Hurlburt, Gustavo F Doncel CONRAD, Department of Obstetrics and Gynecology, Eastern Virginia Medical School, Norfolk, VA, USA Abstract: There is a renewed interest in delivering pharmaceutical products via intravaginal rings (IVRs. IVRs are flexible torus-shaped drug delivery systems that can be easily inserted and removed by the woman and that provide both sustained and controlled drug release, lasting for several weeks to several months. In terms of women's health care products, it has been established that IVRs effectively deliver contraceptive steroids and steroids for the treatment of postmenopausal vaginal atrophy. A novel application for IVRs is the delivery of antiretroviral drugs for the prevention of human immunodeficiency virus (HIV genital infection. Microbicides are antiviral drugs delivered topically for HIV prevention. Recent reviews of microbicide IVRs have focused on technologies in development and optimizing ring design. IVRs have several advantages, including the ability to deliver sustained drug doses for long periods of time while bypassing first pass metabolism in the gut. IVRs are discreet, woman-controlled, and do not require a trained provider for placement or fitting. Previous data support that women and their male sexual partners find IVRs highly acceptable. Multipurpose prevention technology (MPT products provide protection against unintended/mistimed pregnancy and reproductive tract infections, including HIV. Several MPT IVRs are currently in development. Early clinical testing of new microbicide and MPT IVRs will require a focus on safety, pharmacokinetics and pharmacodynamics. Specifically, IVRs will have to deliver tissue concentrations of drugs that are pharmacodynamically active, do not cause mucosal alterations or inflammation, and do not change the resident microbiota. The emergence of resistance to antiretrovirals will need to be investigated. IVRs should not

Treatment of Women With an Endometrial Polyp and Heavy Menstrual Bleeding: A Levonorgestrel-Releasing Intrauterine Device or Hysteroscopic Polypectomy?

NARCIS (Netherlands)

van Dijk, Myrthe M.; van Hanegem, Nehalennia; de Lange, Maria E.; Timmermans, Anne

2015-01-01

We performed a literature review of reports comparing a levonorgestrel-releasing intrauterine device (LNG-IUD) with transcervical polyp resection (TCRP) as a treatment for heavy menstrual bleeding (HMB). Our second objective was to investigate the effectiveness of LNG-IUD and TCRP in reducing

COUP-TFII mediates progesterone regulation of uterine implantation by controlling ER activity.

Directory of Open Access Journals (Sweden)

Isao Kurihara

2007-06-01

Full Text Available Progesterone and estrogen are critical regulators of uterine receptivity. To facilitate uterine remodeling for embryo attachment, estrogen activity in the uterine epithelia is attenuated by progesterone; however, the molecular mechanism by which this occurs is poorly defined. COUP-TFII (chicken ovalbumin upstream promoter transcription factor II; also known as NR2F2, a member of the nuclear receptor superfamily, is highly expressed in the uterine stroma and its expression is regulated by the progesterone-Indian hedgehog-Patched signaling axis that emanates from the epithelium. To further assess COUP-TFII uterine function, a conditional COUP-TFII knockout mouse was generated. This mutant mouse is infertile due to implantation failure, in which both embryo attachment and uterine decidualization are impaired. Using this animal model, we have identified a novel genetic pathway in which BMP2 lies downstream of COUP-TFII. Epithelial progesterone-induced Indian hedgehog regulates stromal COUP-TFII, which in turn controls BMP2 to allow decidualization to manifest in vivo. Interestingly, enhanced epithelial estrogen activity, which impedes maturation of the receptive uterus, was clearly observed in the absence of stromal-derived COUP-TFII. This finding is consistent with the notion that progesterone exerts its control of implantation through uterine epithelial-stromal cross-talk and reveals that stromal-derived COUP-TFII is an essential mediator of this complex cross-communication pathway. This finding also provides a new signaling paradigm for steroid hormone regulation in female reproductive biology, with attendant implications for furthering our understanding of the molecular mechanisms that underlie dysregulation of hormonal signaling in such human reproductive disorders as endometriosis and endometrial cancer.

Quantification of fecal estradiol and progesterone metabolites in Syrian hamsters (Mesocricetus auratus

Directory of Open Access Journals (Sweden)

Chelini M.O.M.

2005-01-01

Full Text Available Alternative methods to the utilization of laboratory animal blood and its by-products are particularly attractive, especially regarding hamsters due to their small size and difficulties in obtaining serial blood samples. Steroid hormone metabolite quantification in feces, widely used in studies of free-ranging or intractable animals, is a non-invasive, non-stressor, economical, and animal saving technique which allows longitudinal studies by permitting frequent sampling of the same individual. The present study was undertaken to determine the suitability of this method for laboratory animals. Estradiol and progesterone metabolites were quantified by radioimmunoassay in feces of intact, sexually mature female Syrian hamsters during the estrous cycle (control and in feces of superovulated females. Metabolites were extracted by fecal dilution in ethanol and quantified by solid phase radioimmunoassay. Median estrogen and progesterone concentrations were 9.703 and 180.74 ng/g feces in the control group, respectively. Peaks of estrogen (22.44 ± 4.54 ng/g feces and progesterone (655.95 ± 129.93 ng/g feces mean fecal concentrations respectively occurred 12 h before and immediately after ovulation, which is easily detected in this species by observation of a characteristic vaginal postovulatory discharge. Median estrogen and progesterone concentrations (28.159 and 586.57 ng/g feces, respectively were significantly higher in superovulated animal feces (P < 0.0001. The present study demonstrated that it is possible to monitor ovarian activity in Syrian hamsters non-invasively by measuring fecal estradiol and progesterone metabolites. This technique appears to be a quite encouraging method for the development of new endocrinologic studies on laboratory animals.

Processes for multi-layer devices utilizing layer transfer

Science.gov (United States)

Nielson, Gregory N; Sanchez, Carlos Anthony; Tauke-Pedretti, Anna; Kim, Bongsang; Cederberg, Jeffrey; Okandan, Murat; Cruz-Campa, Jose Luis; Resnick, Paul J

2015-02-03

A method includes forming a release layer over a donor substrate. A plurality of devices made of a first semiconductor material are formed over the release layer. A first dielectric layer is formed over the plurality of devices such that all exposed surfaces of the plurality of devices are covered by the first dielectric layer. The plurality of devices are chemically attached to a receiving device made of a second semiconductor material different than the first semiconductor material, the receiving device having a receiving substrate attached to a surface of the receiving device opposite the plurality of devices. The release layer is etched to release the donor substrate from the plurality of devices. A second dielectric layer is applied over the plurality of devices and the receiving device to mechanically attach the plurality of devices to the receiving device.

The Effect of Progesterone on Lipid Peroxidation and in Rat Alzheimer Model by Local Injection of Streptozotocin

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M Mozafari

2016-10-01

Full Text Available Introduction: Alzheimer’s disease is one of the most prevalent brain neurodegenerative diseases and the most common cognitive deficits are memory dysfunction and spatial perception impairment. Progesterone has a neorostroid action in hippocampal neurogenesis, synaptic stability and spatial learning and memory and has antioxidant effect. Since oxidative stress is involved in the pathogenesis of Alzheimer's disease, and conflicting results were reported about the effects of progesterone on therefore in Alzheimer’s, the present study investigated the effect of microinjection of three doses of progesterone on the process of spatial memory and lipid peroxidation and total peroxidation in the hippocampus in the experimental model of AD. Methods: 42 adult male Wistar rats weighting 250±50 g were randomly divided into six main groups (n=7: control group, sham group, Alzheimer’s model (intracerebroventricular injection of streptozotocin, Alzheimer model + progesterone (0.5, 1.5, 2µg/kg. 2 weeks after injection of streptozotocin (3 mg/kg, Alzheimer's was induced then progesterone injected in different doses. After termination of behavioral testing days, the hippocampus was removed to measure the levels of oxidative stress parameter to measure levels of oxidative stress parameters. Statistical analysis was performed using analysis of variance (ANOVA. Results: Results showed that intraventricular injection of STZ decreased spatial memory in comparison to control group (P<0.001. Administration progesterone significantly improved spatial memory in experimental models of Alzheimer's rats (P<0.001. MDA and SOD in all doses of progesterone showed a significant reduction compared to the AD animals (P<0.001. Conclusion: Progesterone can prevent a decrease in spatial learning and memory by reducing oxidative stress in the hippocampus of rats with Alzheimer's.

Determination of serum progesterone by radioimmunoassay (RIA) on fertility control and early pregnancy diagnosis in angora goats

International Nuclear Information System (INIS)

Ozsar, S.; Guven, B.; Ozekin, N.; Noyan, A.

1984-01-01

This study was undertaken to provide information on diagnosis of cyclicity, confirmation of estrus so that mating timing and confirmation of return on non-return (pregnancy diagnosis) in Angora goats by using progesterone radioimmunoassay (RIA) in serum as well as observing the sexual behaviours of the goats. The cyclic reproductive activity of 20 mature Angora goat does with normal previous reproductive function, 5 does which had never become pregnant in the previous breeding seasons, and 10 does which were old for breeding was investigated. Circulating progesterone was relatively low (0.45 ng/ml) at estrus (day 0) and increased progressively to 3.45 ng/ml during the subsequent luteal phase. This high level was maintained until day-3 of the succeding estrus cycle, when it decreased abruptly. Pregnancy diagnosis based on the levels of progesterone in serum was confirmed by kidding. 1.5 ng/ml or more progesterone was used as an indication of pregnancy (within 21 days after mating). The accuracy of pregnancy by progesterone assay was 100%. It was concluded that the use of progesterone RIA in serum is a reliable and convenient means of monitoring ovarian activity and early pregnancy. (author)

The 5-HT2C receptor gene Cys23Ser polymorphism influences the intravaginal ejaculation latency time in Dutch Caucasian men with lifelong premature ejaculation

NARCIS (Netherlands)

Janssen, Paddy Kc; Schaik, Ron van; Olivier, Berend|info:eu-repo/dai/nl/073067199; Waldinger, Marcel D|info:eu-repo/dai/nl/163958564

2014-01-01

It has been postulated that the persistent short intravaginal ejaculation latency time (IELT) of men with lifelong premature ejaculation (LPE) is related to 5-hydroxytryptamine (HT)2C receptor functioning. The aim of this study was to investigate the relationship of Cys23Ser 5-HT2C receptor gene

Recent advances on synchronization of ovulation in goats, out of season, for a more sustainable production

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J. Simões

2015-06-01

Full Text Available Goats show marked progressive seasonal reproduction at latitude > 25° and reproductive management should be adapted to market demands. The present review aimed to discuss the synchronization of ovulation for timed artificial insemination concerning new insights regarding a clean, green and ethical meat and milk production. Today, the induction of ovulation during breeding season or transitions periods is mainly based on progestagens/ progesterone (P4 devices intravaginally inserted on females, at least during 11 days, plus equine chorionic gonadotropin (eCG and prostaglandin F2 alfa administration. In last years a reduction to 20 mg of fluorogestone acetate was made and the successful reutilization of devices containing 0.3 g of P4 indicates a possible reduction of their levels. Shortening the period of exogenous progestagens/P4 priming (5 to 7 days is critical for a rational use of hormones. Moreover, the eCG exchange by socio-sexual cues (male effect seems to see a great advance, even if a previous photoperiod treatment, or equivalent method, being necessary in high latitudes. Research trends on these subjects are expected in future using different goats breeds in distinct regions of world.

The Role of Progesterone and a Novel Progesterone Receptor, Progesterone Receptor Membrane Component 1, in the Inflammatory Response of Fetal Membranes to Ureaplasma parvum Infection.

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Liping Feng

Full Text Available Ureaplasma parvum (U. parvum is gaining recognition as an important pathogen for chorioamnionitis and preterm premature rupture of membranes. We aimed to investigate the roles of progesterone (P4 and a novel progesterone receptor, progesterone receptor membrane component 1 (PGRMC1, in the response of fetal membranes to U. parvum. Fetal membrane cells (amnion, chorion and decidua were isolated and confirmed to be free of Mycoplasmataceae. Cells were treated with U. parvum (5x106 CFU, and adherence was quantified by qPCR. Amnion and chorion cells were transfected with scrambled siRNA or validated PGRMC1 siRNA for 72h. Cells were then treated with U. parvum for 4h with or without pretreatment with P4 (10-7 M or ethanol for 1h. Interleukin-8 (IL-8, matrix metalloproteinase 9 (MMP9 and cyclooxygenase (COX-2 mRNA expression were quantified by qRT-PCR. Culture medium was harvested and analyzed for IL-8 and prostaglandin (PGE2 secretion by ELISA and MMP9 activity by zymography. U. parvum had a mean adherence of 15.0±0.6%, 16.9± 3.7% and 4.7±0.3% in cultured amnion, chorion and decidua cells, respectively. Exposure to U. parvum elicited significant inflammatory responses including induction of IL-8, COX-2, PGE2 and MMP9. A possible role of PGRMC1 was identified in the inhibition of U. parvum-stimulated COX-2 and MMP9 mRNA expression in chorion cells and MMP9 activity in amnion cells. On the other hand, it might enhance the U. parvum-stimulated IL-8 protein secretion in amnion cells. P4, mediated through PGRMC1, significantly inhibited U. Parvum-induced MMP9 mRNA and COX-2 mRNA expression in chorion cells. P4 appeared to attenuate U. parvum induced IL-8 mRNA expression in chorion cells, but this P4 effect might not mediated through PGRMC1. In summary, U. parvum preferentially adheres to and induces inflammatory responses in chorion and amnion cells. P4 and PGRMC1 appear to differentially modulate the inflammatory responses induced by U. parvum among

Synergistic effect of DDT and its metabolites in lipopolysaccharide-mediated TNF-α production is inhibited by progesterone in peripheral blood mononuclear cells.

Science.gov (United States)

Dominguez-Lopez, Pablo; Diaz-Cueto, Laura; Aguilar-Rojas, Arturo; Arechavaleta-Velasco, Fabian

2017-07-01

Increased TNF-α levels have been associated with adverse pregnancy outcomes. Lipopolysaccharide (LPS), 1,1,1-trichloro-2,2-bis-(chlorophenyl)ethane (DDT), 1,1-bis-(chlorophenyl)-2,2-dichloroethene (DDE), and 1,1-dichloro-2,2-bis(chlorophenyl)ethane (DDD) induce TNF-α release in peripheral blood mononuclear cells (PBMC). Conversely, progesterone (P4) inhibits TNF-α secretion. Pregnant women in malaria endemic areas may be co-exposure to these compounds. Thus, this study was to investigate the synergistic effect of LPS and these pesticides in PBMC and to assess P4 influence on this synergy. Cultured PBMC were exposed to each pesticide in the presence of LPS, P4, or their combination. TNF-α was measured by ELISA. All pesticides enhanced TNF-α synthesis in PBMC. Co-exposure with LPS synergizes TNF-α production, which is blocked by progesterone. These results indicate that these organochlorines act synergistically with LPS to induce TNF-α secretion in PBMC. This effect is blocked by P4. © 2017 Wiley Periodicals, Inc.

49 CFR 236.790 - Release, time.

Science.gov (United States)

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Release, time. 236.790 Section 236.790... Release, time. A device used to prevent the operation of an operative unit until after the expiration of a predetermined time interval after the device has been actuated. ...

Effect of Progesterone Therapy versus Diet Modification on ...

African Journals Online (AJOL)

progesterone therapy) compared to Group A (diet modification) (54% [154/281] and 62.98% [177/281] vs. 89.76% [614/684] and 91.08% [623/684], respectively) (P = 0.04 and 0.03, respectively). Straining during defecation and manual maneuvers ...

Progesterone Metabolites Produced by Cytochrome P450 3A Modulate Uterine Contractility in a Murine Model

Science.gov (United States)

Patil, Avinash S.; Swamy, Geeta K.; Murtha, Amy P.; Heine, R. Phillips; Zheng, Xiaomei; Grotegut, Chad A.

2015-01-01

Objective: We seek to characterize the effect of progesterone metabolites on spontaneous and oxytocin-induced uterine contractility. Study Design: Spontaneous contractility was studied in mouse uterine horns after treatment with progesterone, 2α-hydroxyprogesterone, 6β-hydroxyprogesterone (6β-OHP), 16α-hydroxyprogesterone (16α-OHP), or 17-hydroxyprogesterone caproate (17-OHPC) at 10−9 to 10−6 mol/L. Uterine horns were exposed to progestins (10−6 mol/L), followed by increasing concentrations of oxytocin (1-100 nmol/L) to study oxytocin-induced contractility. Contraction parameters were compared for each progestin and matched vehicle control using repeated measures 2-way analysis of variance. In vitro metabolism of progesterone by recombinant cytochrome P450 3A (CYP3A) microsomes (3A5, 3A5, and 3A7) identified major metabolites. Results: Oxytocin-induced contractile frequency was decreased by 16α-OHP (P = .03) and increased by 6β-OHP (P = .05). Progesterone and 17-OHPC decreased oxytocin-induced contractile force (P = .02 and P = .04, respectively) and frequency (P = .02 and P = .03, respectively). Only progesterone decreased spontaneous contractile force (P = .02). Production of 16α-OHP and 6β-OHP metabolites were confirmed in all CYP3A isoforms tested. Conclusion: Progesterone metabolites produced by maternal or fetal CYP3A enzymes influence uterine contractility. PMID:26037300

Progesterone metabolism by the hypothalamus, pituitary, and uterus of the rat during pregnancy

International Nuclear Information System (INIS)

Marrone, B.L.; Karavolas, H.J.

1981-01-01

Metabolites of [ 3 H]progesterone were quantitated from incubations of hypothalamus, pituitary, and uterus of rats during different stages of pregnancy. The hypothalamus, anterior pituitary, and a section of uterus from five rats on Days 1, 8, 15, and 21 of pregnancy were incubated individually with [3H]progesterone and analyzed for metabolite formation by reverse isotopic dilution analysis. The radioactive metabolites present were 5 alpha-pregnane-3,20-dione (5 alpha-DHP), 3 alpha-hydroxy-5 alpha-pregnan-20-one, 20 alpha-hydroxy-4-pregnen-3-one, 20 alpha-hydroxy-5 alpha-pregnan-3-one, and 5 alpha-pregnane-3 alpha, 20 alpha-diol. The major metabolite formed by the hypothalamus and pituitary was 5 alpha-DHP. In the pituitary samples, formation of 5 alpha-DHP was decreased on Days 15 and 21 of pregnancy compared to Day 1, and formation of 20 alpha-hydroxy-5 alpha-pregnan-3-one was decreased on Day 21 compared to Day 1. In the uterine samples, 3 alpha-hydroxy-5 alpha-pregnan-20-one was the major metabolite formed at all stages of pregnancy. The formation of all metabolic products of progesterone by the uterus was increased on Day 21 compared to Days 1, 8, and 15 of pregnancy. No changes in the formation of progesterone metabolites were observed in the hypothalamic samples during pregnancy. It is concluded that there are different profiles in the in vitro metabolism of [3H]progesterone by the hypothalamus, pituitary, and uterus of the rat during the course of pregnancy

HIV Protease Inhibitor Use During Pregnancy Is Associated With Decreased Progesterone Levels, Suggesting a Potential Mechanism Contributing to Fetal Growth Restriction

Science.gov (United States)

Papp, Eszter; Mohammadi, Hakimeh; Loutfy, Mona R.; Yudin, Mark H.; Murphy, Kellie E.; Walmsley, Sharon L.; Shah, Rajiv; MacGillivray, Jay; Silverman, Michael; Serghides, Lena

2015-01-01

Background. Protease inhibitor (PI)–based combination antiretroviral therapy (cART) is administered during pregnancy to prevent perinatal human immunodeficiency virus (HIV) transmission. However, PI use has been associated with adverse birth outcomes, including preterm delivery and small-for-gestational-age (SGA) births. The mechanisms underlying these outcomes are unknown. We hypothesized that PIs contribute to these adverse events by altering progesterone levels. Methods. PI effects on trophoblast progesterone production were assessed in vitro. A mouse pregnancy model was used to assess the impact of PI-based cART on pregnancy outcomes and progesterone levels in vivo. Progesterone levels were assessed in plasma specimens from 27 HIV-infected and 17 HIV-uninfected pregnant women. Results. PIs (ritonavir, lopinavir, and atazanavir) but not nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors reduced trophoblast progesterone production in vitro. In pregnant mice, PI-based cART but not dual-NRTI therapy was associated with significantly lower progesterone levels that directly correlated with fetal weight. Progesterone supplementation resulted in a significant improvement in fetal weight. We observed lower progesterone levels and smaller infants in HIV-infected women receiving PI-based cART, compared with the control group. In HIV-infected women, progesterone levels correlated significantly with birth weight percentile. Conclusions. Our data suggest that PI use in pregnancy may lead to lower progesterone levels that could contribute to adverse birth outcomes. PMID:25030058

HIV protease inhibitor use during pregnancy is associated with decreased progesterone levels, suggesting a potential mechanism contributing to fetal growth restriction.

Science.gov (United States)

Papp, Eszter; Mohammadi, Hakimeh; Loutfy, Mona R; Yudin, Mark H; Murphy, Kellie E; Walmsley, Sharon L; Shah, Rajiv; MacGillivray, Jay; Silverman, Michael; Serghides, Lena

2015-01-01

Protease inhibitor (PI)-based combination antiretroviral therapy (cART) is administered during pregnancy to prevent perinatal human immunodeficiency virus (HIV) transmission. However, PI use has been associated with adverse birth outcomes, including preterm delivery and small-for-gestational-age (SGA) births. The mechanisms underlying these outcomes are unknown. We hypothesized that PIs contribute to these adverse events by altering progesterone levels. PI effects on trophoblast progesterone production were assessed in vitro. A mouse pregnancy model was used to assess the impact of PI-based cART on pregnancy outcomes and progesterone levels in vivo. Progesterone levels were assessed in plasma specimens from 27 HIV-infected and 17 HIV-uninfected pregnant women. PIs (ritonavir, lopinavir, and atazanavir) but not nucleoside reverse transcriptase inhibitors (NRTIs) or nonnucleoside reverse transcriptase inhibitors reduced trophoblast progesterone production in vitro. In pregnant mice, PI-based cART but not dual-NRTI therapy was associated with significantly lower progesterone levels that directly correlated with fetal weight. Progesterone supplementation resulted in a significant improvement in fetal weight. We observed lower progesterone levels and smaller infants in HIV-infected women receiving PI-based cART, compared with the control group. In HIV-infected women, progesterone levels correlated significantly with birth weight percentile. Our data suggest that PI use in pregnancy may lead to lower progesterone levels that could contribute to adverse birth outcomes. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

Energy Technology Data Exchange (ETDEWEB)

Souza, M.F. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Couto-Pereira, N.S. [Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Bioquímica, Porto Alegre, RS, Brasil, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Freese, L.; Costa, P.A.; Caletti, G.; Bisognin, K.M. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Nin, M.S. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil); Instituto Porto Alegre, Centro Metodista do Sul, Curso de Farmácia, Porto Alegre, RS, Brasil, Curso de Farmácia, Centro Metodista do Sul, Instituto Porto Alegre, Porto Alegre, RS (Brazil); Gomez, R. [Universidade Federal do Rio Grande do Sul, Instituto de Ciências Básicas da Saúde, Departamento de Farmacologia, Porto Alegre, RS, Brasil, Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS (Brazil); Barros, H.M.T. [Universidade Federal de Ciências da Saúde de Porto Alegre, Laboratório de Neurociência Comportamental, Porto Alegre, RS, Brasil, Laboratório de Neurociência Comportamental, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS (Brazil)

2014-05-09

Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.

Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

International Nuclear Information System (INIS)

Souza, M.F.; Couto-Pereira, N.S.; Freese, L.; Costa, P.A.; Caletti, G.; Bisognin, K.M.; Nin, M.S.; Gomez, R.; Barros, H.M.T.

2014-01-01

Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL), estradiol (0.05 mg/mL), progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip) for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy) to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse

Thyroxin and progesterone concentrations in pregnant, nonpregnant bitches, and bitches during abortion.

Science.gov (United States)

Thuróczy, Julianna; Müller, Linda; Kollár, Eszter; Balogh, Lajos

2016-04-01

Serum progesterone and thyroxin concentrations were measured weekly until 61 to 62 days after ovulation in 24 pregnant bitches and in the control group of nine nonpregnant bitches in the luteal phase. Fourteen of the 24 dogs had a normal pregnancy and parturition. Ten of the 24 dogs showed mucinous or colored vaginal discharge, decreased appetite, or lethargy. These initial signs of abortion or fetal resorption were noted during the fourth week of pregnancy, and the process occurred over the next 2 weeks. Progesterone and thyroxin concentrations were measured by quantitative ELISAs validated to dog serum. The serum progesterone concentrations of the group going through abortions differed significantly from the third week until the end of the eighth week. The mean serum thyroxin concentrations of healthy pregnant and nonpregnant groups significantly exceeded the reference range (20-45 nmol/L). The serum thyroxin concentrations in the abortion group were between 16.15 ± 3.17 and 40.78 ± 8.97 nmol/L. The values in this group were significantly different from the other two groups at the third week of the luteal phase. Clinical signs of abortion or fetus resorption manifested in midpregnancy. The clinical signs of abortion coincided in each case with a low serum progesterone concentration (<10 ng/mL). This phenomenon indicated, in contrast with other studies, that the decrease of serum progesterone below 10 ng/mL at the fourth week of pregnancy may signal impending abortion. In the second half of pregnancy, the thyroid gland was not able to respond adequately to the elevated requirement in thyroid hormone, although in other periods of the ovarian cycle, there were no clinical signs of hypothyroidism. Copyright © 2016 Elsevier Inc. All rights reserved.

A dynamical systems model of progesterone receptor interactions with inflammation in human parturition.

Science.gov (United States)

Brubaker, Douglas; Barbaro, Alethea; R Chance, Mark; Mesiano, Sam

2016-08-19

Progesterone promotes uterine relaxation and is essential for the maintenance of pregnancy. Withdrawal of progesterone activity and increased inflammation within the uterine tissues are key triggers for parturition. Progesterone actions in myometrial cells are mediated by two progesterone receptor (PR) isoforms, PR-A and PR-B, that function as ligand-activated transcription factors. PR-B mediates relaxatory actions of progesterone, in part, by decreasing myometrial cell responsiveness to pro-inflammatory stimuli. These same pro-inflammatory stimuli promote the expression of PR-A which inhibits the anti-inflammatory activity of PR-B. Competitive interaction between the progesterone receptors then augments myometrial responsiveness to pro-inflammatory stimuli. The interaction between PR-B transcriptional activity and inflammation in the pregnancy myometrium is examined using a dynamical systems model in which quiescence and labor are represented as phase-space equilibrium points. Our model shows that PR-B transcriptional activity and the inflammatory load determine the stability of the quiescent and laboring phenotypes. The model is tested using published transcriptome datasets describing the mRNA abundances in the myometrium before and after the onset of labor at term. Surrogate transcripts were selected to reflect PR-B transcriptional activity and inflammation status. The model coupling PR-B activity and inflammation predicts contractile status (i.e., laboring or quiescent) with high precision and recall and outperforms uncoupled single and two-gene classifiers. Linear stability analysis shows that phase space bifurcations exist in our model that may reflect the phenotypic states of the pregnancy uterus. The model describes a possible tipping point for the transition of the quiescent to the contractile laboring phenotype. Our model describes the functional interaction between the PR-A:PR-B hypothesis and tissue level inflammation in the pregnancy uterus and is a

Endometrial changes from short-term therapy with CDB-4124, a selective progesterone receptor modulator.

Science.gov (United States)

Ioffe, Olga B; Zaino, Richard J; Mutter, George L

2009-03-01

Selective progesterone receptor modulators are a class of drugs with progesterone antagonist activity that may confer therapeutic benefit for reproductive disorders in premenopausal women. Endometrial structure, which is dynamically controlled by circulating sex hormones, is likely to be perturbed by progesterone receptor modulators through their progesterone antagonist properties. We examined endometrial histology in 58 premenopausal women treated with the progesterone receptor modulator CDB-4124 (also known as Proellex) for endometriosis or uterine leiomyomata in two clinical trials. Endometrial biopsies obtained after 3 or 6 months with doses of 12.5, 25, or 50 mg daily oral CDB-4124 were reviewed independently by three pathologists. Consensus diagnoses using the World Health Organization hyperplasia scoring system, comments on specific histologic features, and clinical annotation were collected and analyzed. The majority of the endometrial biopsies (103 of 174 biopsies) contained histologic changes that are not seen during normal menstrual cycles. The histology of CDB-4124-treated patients was generally inactive or atrophic, and less frequently, proliferative or secretory, superimposed upon which were novel changes including formation of cystically dilated glands, and secretory changes coexisting with mitoses and apoptotic bodies. With increasing treatment dose and duration, the cysts became predominant and their lining inactive or atrophic. Cystic glands in the CDB-4124-treated subjects correlated with increased endometrial thickness by ultrasound. None of the CDB-4124-treated patients developed endometrial carcinoma or hyperplasia while on therapy. CDB-4124 therapy for 3-6 months produces histologic changes that are sufficiently novel that they might easily be misinterpreted by pathologists, particularly as disordered proliferative or hyperplastic endometrium. Knowledge of the constellation of endometrial changes associated with this agent and other

Role of 11. beta. -hydroxyprogesterone in biosynthesis of corticosterone from progesterone in guinea pig adrenals

Energy Technology Data Exchange (ETDEWEB)

Yudaev, N A; Afinogenova, S A [Institute of Experimental Endocrinology and Hormone Chemistry, Moscow (USSR)

1975-06-01

Slices of male guinea pig adrenals were incubated with a trace amount of /sup 3/H-7..cap alpha..-progesterone and the proportion of /sup 3/H incorporation various steroids at various intervals was measured. It was found that /sup 3/H accumulated predominantly in 11..beta..-hydroxyprogesterone as compared to DOC. This indicated that in guinea pig adrenals 11..beta..-hydroxyprogesterone plays a predominant role in the formation of corticosterone from progesterone. The observed sequence of changes in progesterone label accumulation in 17-hydroxycompounds indicated the pathway of cortisol synthesis through the intermediate formation of 17-hydroxyprogesterone and 11-deoxycortisol.

Progesterone promotes maternal–fetal tolerance by reducing human maternal T‐cell polyfunctionality and inducing a specific cytokine profile

Science.gov (United States)

Eldershaw, Suzy A.; Inman, Charlotte F.; Coomarasamy, Aravinthan; Moss, Paul A. H.; Kilby, Mark D.

2015-01-01

Progesterone is a steroid hormone essential for the maintenance of human pregnancy, and its actions are thought to include promoting maternal immune tolerance of the semiallogenic fetus. We report that exposure of maternal T cells to progesterone at physiological doses induced a unique skewing of the cytokine production profile of CD4+ and CD8+ T cells, with reductions not only in potentially deleterious IFN‐γ and TNF‐α production but also in IL‐10 and IL‐5. Conversely, production of IL‐4 was increased. Maternal T cells also became less polyfunctional, focussing cytokine production toward profiles including IL‐4. This was accompanied by reduced T‐cell proliferation. Using fetal and viral antigen‐specific CD8+ T‐cell clones, we confirmed that this as a direct, nonantigen‐specific effect. Yet human T cells lacked conventional nuclear progesterone receptors, implicating a membrane progesterone receptor. CD4+ and CD8+ T cells responded to progesterone in a dose‐dependent manner, with subtle effects at concentrations comparable to those in maternal blood, but profound effects at concentrations similar to those at the maternal–fetal interface. This characterization of how progesterone modulates T‐cell function is important in understanding the normal biology of pregnancy and informing the rational use of progesterone therapy in pregnancies at risk of fetal loss. PMID:26249148

The interaction between vaginal microbiota, cervical length, and vaginal progesterone treatment for preterm birth risk.

Science.gov (United States)

Kindinger, Lindsay M; Bennett, Phillip R; Lee, Yun S; Marchesi, Julian R; Smith, Ann; Cacciatore, Stefano; Holmes, Elaine; Nicholson, Jeremy K; Teoh, T G; MacIntyre, David A

2017-01-19

Preterm birth is the primary cause of infant death worldwide. A short cervix in the second trimester of pregnancy is a risk factor for preterm birth. In specific patient cohorts, vaginal progesterone reduces this risk. Using 16S rRNA gene sequencing, we undertook a prospective study in women at risk of preterm birth (n = 161) to assess (1) the relationship between vaginal microbiota and cervical length in the second trimester and preterm birth risk and (2) the impact of vaginal progesterone on vaginal bacterial communities in women with a short cervix. Lactobacillus iners dominance at 16 weeks of gestation was significantly associated with both a short cervix vaginal dysbiosis. A longitudinal characterization of vaginal microbiota (vaginal progesterone (400 mg/OD, n = 25) versus controls (n = 42). Progesterone did not alter vaginal bacterial community structure nor reduce L. iners-associated preterm birth (vaginal microbiota at 16 weeks of gestation is a risk factor for preterm birth, whereas L. crispatus dominance is protective against preterm birth. Vaginal progesterone does not appear to impact the pregnancy vaginal microbiota. Patients and clinicians who may be concerned about "infection risk" associated with the use of a vaginal pessary during high-risk pregnancy can be reassured.

Progesterone treatment shows benefit in a pediatric model of moderate to severe bilateral brain injury.

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Rastafa I Geddes

Full Text Available Controlled cortical impact (CCI models in adult and aged Sprague-Dawley (SD rats have been used extensively to study medial prefrontal cortex (mPFC injury and the effects of post-injury progesterone treatment, but the hormone's effects after traumatic brain injury (TBI in juvenile animals have not been determined. In the present proof-of-concept study we investigated whether progesterone had neuroprotective effects in a pediatric model of moderate to severe bilateral brain injury.Twenty-eight-day old (PND 28 male Sprague Dawley rats received sham (n = 24 or CCI (n = 47 injury and were given progesterone (4, 8, or 16 mg/kg per 100 g body weight or vehicle injections on post-injury days (PID 1-7, subjected to behavioral testing from PID 9-27, and analyzed for lesion size at PID 28.The 8 and 16 mg/kg doses of progesterone were observed to be most beneficial in reducing the effect of CCI on lesion size and behavior in PND 28 male SD rats.Our findings suggest that a midline CCI injury to the frontal cortex will reliably produce a moderate TBI comparable to what is seen in the adult male rat and that progesterone can ameliorate the injury-induced deficits.

Systematic review of progesterone for the prevention of preterm birth in singleton pregnancies

DEFF Research Database (Denmark)

Rode, Line; Langhoff-Roos, Jens; Andersson, Charlotte

2009-01-01

. SEARCH STRATEGY: A search in the PubMed, Embase, and Cochrane database was performed using the keywords: pregnancy, progesterone, preterm birth/preterm delivery, preterm labor, controlled trial, and randomized controlled trial. SELECTION CRITERIA: Studies on singleton pregnancies. DATA COLLECTION...... AND ANALYSIS: A meta-analysis was performed on randomized trials including singleton pregnancies with previous preterm birth. MAIN RESULTS: Two new randomized controlled trials of women with previous preterm birth were added to the four analyzed in the Cochrane review, and the meta-analysis of all six studies......BACKGROUND: A Cochrane review in 2006 concluded that further knowledge is required before recommendation can be made with regard to progesterone in the prevention of preterm birth. OBJECTIVE: To provide an update on the preventive effect of progesterone on preterm birth in singleton pregnancies...

Efficacy of intravaginal dehydroepiandrosterone (DHEA) on moderate to severe dyspareunia and vaginal dryness, symptoms of vulvovaginal atrophy, and of the genitourinary syndrome of menopause.

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Labrie, Fernand; Archer, David F; Koltun, William; Vachon, Andrée; Young, Douglas; Frenette, Louise; Portman, David; Montesino, Marlene; Côté, Isabelle; Parent, Julie; Lavoie, Lyne; Beauregard, Adam; Martel, Céline; Vaillancourt, Mario; Balser, John; Moyneur, Érick

2016-03-01

The aim of this study is to confirm the local beneficial effects of intravaginal dehydroepiandrosterone (DHEA, Prasterone) on moderate to severe dyspareunia or pain at sexual activity, the most frequent symptom of vulvovaginal atrophy due to menopause or genitourinary syndrome of menopause (GSM). In a prospective, randomized, double-blind, and placebo-controlled phase III clinical trial, the effect of daily intravaginal 0.50% DHEA (6.5 mg) (Prasterone, EndoCeutics) was examined on four coprimary objectives, namely percentage of parabasal cells, percentage or superficial cells, vaginal pH, and moderate to severe pain at sexual activity (dyspareunia) identified by the women as their most bothersome vulvovaginal atrophy symptom. The intent-to-treat population included 157 and 325 women in the placebo and DHEA-treated groups, respectively. After daily intravaginal administration of 0.50% DHEA for 12 weeks, when compared to baseline by the analysis of covariance test, the percentage of parabasal cells decreased by 27.7% over placebo (P < 0.0001), whereas the percentage of superficial cells increased by 8.44% over placebo (P < 0.0001), vaginal pH decreased by 0.66 pH unit over placebo (P < 0.0001), and pain at sexual activity decreased by 1.42 severity score unit from baseline or 0.36 unit over placebo (P = 0.0002). On the other hand, moderate to severe vaginal dryness present in 84.0% of women improved at 12 weeks by 1.44 severity score unit compared to baseline, or 0.27 unit over placebo (P = 0.004). At gynecological evaluation, vaginal secretions, epithelial integrity, epithelial surface thickness, and color all improved by 86% to 121% over the placebo effect (P < 0.0001 for all comparisons with placebo). Serum steroid levels remained well within the normal postmenopausal values according to the involved mechanisms of intracrinology. The only side effect reasonably related to treatment is vaginal discharge due to melting of the vehicle at

Effects of 17β-estradiol and progesterone on the production of adipokines in differentiating 3T3-L1 adipocytes: Role of Rho-kinase.

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Pektaş, Mehtap; Kurt, Akif Hakan; Ün, İsmail; Tiftik, Rukiye Nalan; Büyükafşar, Kansu

2015-04-01

Effect of female sex hormones on the production/release of adipocyte-derived cytokines has been debatable. Furthermore, whether the cellular signaling triggered by these hormones involve Rho-kinase has not been investigated yet. Therefore, in this study, effects of 17β-estradiol and progesterone as well as the Rho-kinase inhibitor, Y-27632 on the level of adipokines such as resistin, adiponectin, leptin, TNF-α and IL-6 were investigated in 3T3-L1-derived adipocytes. Differentiation was induced in the post-confluent preadipocytes by the standard differentiation medium (Dulbecco's modified Eagle's medium with 10% fetal bovine serum together with the mixture of isobutylmethylxanthine, dexamethasone and insulin) in the presence of 17β-estradiol (10(-8)-10(-7)M), progesterone (10(-6)-10(-5)M), the Rho-kinase inhibitor, Y-27632 (10(-5)M) and their combination for 8days. Measurements of the adipokines were performed in the culturing medium by ELISA kits using specific monoclonal antibodies. 17β-estradiol elevated resistin but decreased adiponectin and IL-6 levels; however, it did not alter the concentration of leptin and TNF-α. Y-27632 pretreatment inhibited the rise of resistin and the fall of adiponectin by 17β-estradiol without any effects by its own. Progesterone did not change resistin, leptin and TNF-α level; however, it elevated adiponectin and decreased IL-6 production. Neither 17β-estradiol nor Y-27632 was able to antagonize the increase of adiponectin and the reduction of IL-6 levels by progesterone. While Y-27632 alone lowered IL-6 level, it increased leptin and TNF-α concentration without altering resistin and adiponectin. In conclusion, 17β-estradiol could modify adipokine production in 3T3-L1 adipocytes with the actions some of which involve Rho-kinase mediation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Preovulatory progesterone concentration associates significantly to follicle number and LH concentration but not to pregnancy rate

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Yding Andersen, Claus; Bungum, Leif; Nyboe Andersen, Anders

2011-01-01

Using data from a large prospective randomized controlled trial that evaluated the effect of recombinant LH (rLH)co-administration for ovarian stimulation, the present study assessed whether progesterone concentration on the day of human chorionic gonadotrophin (HCG) administration was associated...... with or without rLH administration from day 6 of stimulation. There was no significant association between the late-follicular-phase progesterone concentration and the clinical pregnancy rate. However, progesterone concentration was strongly associated with the number of follicles and retrieved oocytes. Late...

Progesterone receptor modulators in breast cancer

OpenAIRE

WIEHLE, Ronald D.

2015-01-01

Breast cancer has been treated successfully with selective estrogen receptor antagonists (SERMs) such as tamoxifen, receptor-depleting agents such as fulvestrant, and aromatase inhibitors such as anastrozole. Selective progesterone receptor modulators (SPRMs or PRMs) have not been studied as much and are currently under investigation for inhibition of mammary carcinogenesis in animal models and breast cancer prevention trials in women. They might follow tamoxifen and aromatase inhibitors in t...

Analytical Method Validation of High-Performance Liquid Chromatography and Stability-Indicating Study of Medroxyprogesterone Acetate Intravaginal Sponges

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Nidal Batrawi

2017-02-01

Full Text Available Medroxyprogesterone acetate is widely used in veterinary medicine as intravaginal dosage for the synchronization of breeding cycle in ewes and goats. The main goal of this study was to develop reverse-phase high-performance liquid chromatography method for the quantification of medroxyprogesterone acetate in veterinary vaginal sponges. A single high-performance liquid chromatography/UV isocratic run was used for the analytical assay of the active ingredient medroxyprogesterone. The chromatographic system consisted of a reverse-phase C18 column as the stationary phase and a mixture of 60% acetonitrile and 40% potassium dihydrogen phosphate buffer as the mobile phase; the pH was adjusted to 5.6. The method was validated according to the International Council for Harmonisation (ICH guidelines. Forced degradation studies were also performed to evaluate the stability-indicating properties and specificity of the method. Medroxyprogesterone was eluted at 5.9 minutes. The linearity of the method was confirmed in the range of 0.0576 to 0.1134 mg/mL ( R 2 > 0.999. The limit of quantification was shown to be 3.9 µg/mL. Precision and accuracy ranges were found to be %RSD <0.2 and 98% to 102%, respectively. Medroxyprogesterone capacity factor value of 2.1, tailing factor value of 1.03, and resolution value of 3.9 were obtained in accordance with ICH guidelines. Based on the obtained results, a rapid, precise, accurate, sensitive, and cost-effective analysis procedure was proposed for quantitative determination of medroxyprogesterone in vaginal sponges. This analytical method is the only available method to analyse medroxyprogesterone in veterinary intravaginal dosage form.

Progesterone and estradiol-17β concentrations in blood plasma of buffaloes during different reproductive disorders

International Nuclear Information System (INIS)

Kaur, Harjit; Arora, S.P.; Sawhney, Ajay

1982-01-01

Six Murrah buffaloes in group I were fed as per NRC requirements and the same number in group II were kept at low level of nutrition. Blood samples were collected from all the buffaloes during estrus, anoestrus or even pregnancy, for estimation of progesterone and estradiol-17β. Progesterone levels were consistently low during anoestrus period (<1.0 ng/ml), but, peak occurred on day minus 10 of the next following estrus indicating that luteal activity preceded the first estrus after a prolonged anoestrum. The estradiol-17β levels did not show any distinct trend during anoestrus and subsequent estrous cycles. Underfed buffaloes required more services per conception. The mean progesterone concentrations during early pregnancy were 6.12 +- 0.21 and 5.31 +- 0.29 ng/ml in groups I and II, respectively, which were persistent. Plasma progesterone drop was recorded in buffaloes which aborted or showed foetal resorption, abrupt in the former case and at a slow rate in the latter case. (author)

Progesterone up-regulates vasodilator effects of calcitonin gene-related peptide in N(G)-nitro-L-arginine methyl ester-induced hypertension.

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Gangula, P R; Wimalawansa, S J; Yallampalli, C

1997-04-01

We recently reported that calcitonin gene-related peptide can reverse the hypertension produced by N(G)-nitro-L-arginine methyl ester in pregnant rats. In the current study we investigated whether these vasodilator effects of calcitonin gene-related peptide were progesterone dependent. Calcitonin gene-related peptide or N(G)-nitro-L-arginine methyl ester was infused through osmotic minipumps, either separately or in combination, to groups of five pregnant rats from day 17 of gestation until day 8 post partum or to nonpregnant ovariectomized rats for 8 days. Progesterone was injected during days 1 to 6 post partum and for 6 days after ovariectomy. Systolic blood pressure was measured daily. Animals receiving N(G)-nitro-L-arginine methyl ester exhibited significant elevations of blood pressure during pregnancy and post partum. Coadministration of calcitonin gene-related peptide to these rats reversed the hypertension during pregnancy but not during the postpartum period. At the dose used in this study calcitonin gene-related peptide administered alone was without significant effects on blood pressure. However, it reduced both the mortality and growth restriction of the fetus associated with N(G)-nitro-L-arginine methyl ester in these animals. Calcitonin gene-related peptide reversed the hypertension in N(G)-nitro-L-arginine methyl ester-infused postpartum rats during the periods of progesterone treatment only, and these effects were lost when progesterone treatment was stopped. Neither progesterone nor calcitonin gene-related peptide alone were effective. To further confirm these observations, progesterone effects were tested in ovariectomized adult rats. Similar to the findings in postpartum rats, calcitonin gene-related peptide completely reversed the elevation in blood pressure in N(G)-nitro-L-arginine methyl ester-treated rats receiving progesterone injections. The effects of calcitonin gene-related peptide were apparent only during the progesterone treatment

Efficiency of different hormonal treatments for estrus synchronization in tropical Santa Inês sheep.

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Texeira, Tarcísio Alves; da Fonseca, Jeferson Ferreira; de Souza-Fabjan, Joanna Maria Gonçalves; de Rezende Carvalheira, Luciano; de Moura Fernandes, Daniel Andrews; Brandão, Felipe Zandonadi

2016-03-01

The aim of this study was to evaluate the effect of (i) the duration of hormone treatment with progestogen sponges during the seasonal anestrus and (ii) the administration of two doses of prostaglandin at 7 days apart during the breeding season on reproductive parameters of Santa Inês ewes. In experiment 1, 32 ewes received intravaginal MAP sponges for 6 (G6 days), 9 (G9 days), or 12 (G12days) days and 75 μg D-cloprostenol i.m. and 300 IU eCG i.m. 1 day before sponge removal. In experiment 2, 23 ewes received two doses of 0.48-mg sodium cloprostenol i.m. 7 days apart. Ovarian follicular dynamic was assessed through transrectal ultrasonography. Blood samples were collected daily to determine progesterone concentrations. In experiment 1, estrus and ovulation rates did not differ (P > 0.05) among protocols and between cyclic and acyclic ewes at the beginning of the experiment. The G9 days treatment showed a lower dispersion of ovulations in relation to onset of estrus when compared to G6 days and G12 days. In experiment 2, all ewes exhibit estrus and ovulated after the second dose of prostaglandin, although ewes that were in diestrus at D0 showed subluteal concentrations of progesterone during the follicle development stage of the treatment. In conclusion, the use of progestogen device during 9 days promotes lower dispersion of ovulation when compared to its use for 6 or 12 days, and the protocol of two doses of prostaglandin 7 days apart synchronizes estrus efficiently but results in follicular development under low progesterone concentrations.

Delaying farrowing using intravaginal devices impregnated with progestagen does not affect the proportion of piglets born alive O atraso do parto utilizando dispositivos intravaginais impregnados com progestágeno não afeta a proporção de leitões nascidos vivos

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Gabriel Fernando Freling

2013-01-01

Full Text Available The objective of this study was to evaluate the efficiency of progestagen intravaginal devices (IVDs in preventing parturition in sows by determining the effect of delaying parturition on the alive/total born piglets ratio. Evaluations of IVDs containing 0.5, 1.0 or 1.5g progesterone (P4 showed they were not effective in delaying parturition at any dosage tested. In a second experiment, seventy-five sows at day 112 of pregnancy were equally distributed (n=15 per group in the following treatments: prostaglandin (PGF2α; 250µg sodium cloprostenol; control group or PGF2α and simultaneous insertion of an IVD containing medroxyprogesterone acetate (MPA for 48h. Control sows initiated labor 27.7±1.6h after PGF2α injection. The mean time (±SEM between PGF2α administration and parturition was 72.1±8.8h, 72.7±3.8h, 82.7±7.1h and 81.8±3.5h for MPA 100, 200, 400 and 800mg, respectively, differing from control group (P0.05. These findings confirm that IVDs impregnated with MPA can effectively prevent parturition in sows without affecting the alive/total born piglets ratio and therefore represent an alternative to avoid weekend farrowing in swine herds.O objetivo do presente estudo foi avaliar a eficiência de dispositivos intravaginais (DIVs contendo progestágeno na prevenção do parto e determinar o efeito do atraso do parto sobre a proporção de leitões vivos/nascidos totais. DIVs contendo 0,5, 1,0 ou 1,5g de progesterona (P4 não foram eficientes na prevenção do parto em nenhuma das doses. No experimento 2, setenta e cinco porcas aos 112 dias de gestação foram equilibradamente distribuídas (n=15 por grupo nos seguintes tratamentos: prostaglandina (PGF2α; 250µg cloprostenol sódico; grupo controle ou PGF2α e simultânea inserção de DIV contendo acetato de medroxiprogesterona (MAP por 48h. Fêmeas do grupo controle iniciaram o parto 27,7±1,6h após injeção de PGF2α. O tempo médio entre a administração de PGF2α e início do

Progesterone Receptor Scaffolding Function in Breast Cancer

Science.gov (United States)

2012-10-01

leiomyoma cells in response to RU486 revealed little overlap [101]. PR-A and PR-B are most often co-expressed in the same tissues, and cells that... leiomyoma cells. PLoS One 7 (2012) e29021. [102]P.A. Mote, S. Bartow, N. Tran, C.L. Clarke, Loss of co-ordinate expression of progesterone receptors

Taenia pisiformis cysticercosis induces decreased prolificacy and increased progesterone levels in rabbits.

Science.gov (United States)

Hallal-Calleros, Claudia; Morales-Montor, Jorge; Orihuela-Trujillo, Agustín; Togno-Peirce, Cristián; Murcia-Mejía, Clara; Bielli, Alejandro; Hoffman, Kurt L; Flores-Pérez, Fernando Iván

2016-10-15

Reproductive alterations in hosts infected by parasites have been recognized in several phyla, especially in arthropods and mollusks, but it has been less studied in higher vertebrates, particularly in mammals. In the present study, ten eight week-old female New Zealand rabbits (Oryctolagus cuniculus) were either infected with Taenia pisiformis eggs or uninfected, and 7 weeks later they were mated. We found that serum progesterone levels were increased during pregnancy in infected does. At birth, litter size of infected does was reduced by half as compared to the control group, and, at weaning, the number of kits and the weight of litters was lower. Since serum progesterone levels have a key role in the maintenance of pregnancy and implantation, we propose that the observed prolificacy alterations in does infected with T. pisiformis infection were due to changes in the levels of circulating progesterone during pregnancy. Copyright © 2016 Elsevier B.V. All rights reserved.

Relationship between time post-ovulation and progesterone on oocyte maturation and pregnancy in canine cloning.

Science.gov (United States)

Kim, Joung Joo; Park, Kang Bae; Choi, Eun Ji; Hyun, Sang Hwan; Kim, Nam-Hyung; Jeong, Yeon Woo; Hwang, Woo Suk

2017-10-01

Canine oocytes ovulated at prophase complete meiosis and continue to develop in presence of a high progesterone concentration in the oviduct. Considering that meiotic competence of canine oocyte is accomplished in the oviductal environment, we postulate that hormonal milieu resulting from the circulating progesterone concentration may affect oocyte maturation and early development of embryos. From 237 oocyte donors, 2620 oocytes were collected and their meiotic status and morphology were determined. To determine optimal characteristics of the mature oocytes subjected to nuclear transfer, a proportion of the meiotic status of the oocytes were classified in reference to time post-ovulation as well as progesterone (P4) level. A high proportion of matured oocytes were collected from >126h (55.5%) post-ovulation or 40-50ngmL -1 (46.4%) group compared to the other groups. Of the oocyte donors that provided mature oocytes in vivo, there was no correlation between serum progesterone of donors and time post ovulation, however, time post-ovulation were significantly shorter for cloned embryos were reconstructed and transferred into 77 surrogates. In order to determine the relationship between pregnancy performance and serum progesterone level, embryos were transferred into surrogates showing various P4 serum levels. The highest pregnancy (31.8%) and live birth cloning efficacy (2.2%) rates were observed when the embryos were transferred into surrogates with circulating P4 levels were from 40 to 50ngmL -1 . In conclusion, measurement of circulating progesterone of female dog could be a suitable an indicator of the optimal time to collect quality oocyte and to select surrogates for cloning. Copyright © 2017 Elsevier B.V. All rights reserved.

Behavioral effects of endogenous or exogenous estradiol and progesterone on cocaine sensitization in female rats

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M.F. Souza

2014-06-01

Full Text Available Cocaine sensitization is a marker for some facets of addiction, is greater in female rats, and may be influenced by their sex hormones. We compared the modulatory effects of endogenous or exogenous estradiol and progesterone on cocaine-induced behavioral sensitization in 106 female rats. Ovariectomized female rats received progesterone (0.5 mg/mL, estradiol (0.05 mg/mL, progesterone plus estradiol, or the oil vehicle. Sham-operated control females received oil. Control and acute subgroups received injections of saline, while the repeated group received cocaine (15 mg/kg, ip for 8 days. After 10 days, the acute and repeated groups received a challenge dose of cocaine, after which locomotion and stereotypy were monitored. The estrous cycle phase was evaluated and blood was collected to verify hormone levels. Repeated cocaine treatment induced overall behavioral sensitization in female rats, with increased locomotion and stereotypies. In detailed analysis, ovariectomized rats showed no locomotor sensitization; however, the sensitization of stereotypies was maintained. Only females with endogenous estradiol and progesterone demonstrated increased locomotor activity after cocaine challenge. Estradiol replacement enhanced stereotyped behaviors after repeated cocaine administration. Cocaine sensitization of stereotyped behaviors in female rats was reduced after progesterone replacement, either alone or concomitant with estradiol. The behavioral responses (locomotion and stereotypy to cocaine were affected differently, depending on whether the female hormones were of an endogenous or exogenous origin. Therefore, hormonal cycling appears to be an important factor in the sensitization of females. Although estradiol increases the risk of cocaine sensitization, progesterone warrants further study as a pharmacological treatment in the prevention of psychostimulant abuse.

Effects of environmental stress during pregnancy on maternal and fetal plasma corticosterone and progesterone in the rat

International Nuclear Information System (INIS)

Fleming, D.E.; Rhees, R.W.; Williams, S.R.; Kurth, S.M.

1986-01-01

Prenatal stress applied during a presumed critical period (third trimester) for sexual differentiation of the brain has been shown to alter development and influence sexual behavior. This experiment was designed to study the effects of environmental stress (restraint/illumination/heat) on maternal and fetal plasma corticosterone and progesterone titers. These hormones were studied since corticosterone has been shown to alter brain differentiation and progesterone has anti-androgen properties and since the secretion of both from the adrenal cortex is stimulated by ACTH. Plasma corticosterone and progesterone titers of both stressed and control gravid rats and their fetuses were measured on gestational days 18 and 20 by radioimmunoassay. Prenatal stress significantly reduced fetal body weight and fetal adrenal weight. Maternal pituitary weight was significantly increased. Prenatal stress caused a significant elevation in maternal corticosterone and progesterone titers and in fetal corticosterone titers. There was no difference between prenatal stressed and control fetal plasma progesterone levels. These data demonstrate that environmental stress significantly increases adrenal activity beyond that brought about naturally by pregnancy, and therefore may modify sequential hormonal events during fetal development

High exposure to progesterone between the end of menstruation and the day of triggering final oocyte maturation is associated with a decreased probability of pregnancy in patients treated by in vitro fertilization and intracytoplasmic sperm injection.

Science.gov (United States)

Kyrou, Dimitra; Kolibianakis, Efstratios M; Fatemi, Human M; Camus, Michel; Tournaye, Herman; Tarlatzis, Basil C; Devroey, Paul

2011-10-01

To investigate the association between the probability of pregnancy and hormone exposure between the end of menstruation and the day of triggering final oocyte maturation (menstruation-free interval). Prospective study. University. One hundred women (aged ≤ 39 years) stimulated with a fixed dose of recombinant follicle-stimulating hormone (200 IU). Daily gonadotropin-releasing hormone antagonist (GnRH, 0.25 mg) used from day 6 of stimulation onward, final oocyte maturation triggered by administration of 10,000 IU of human chorionic gonadotropin (hCG) as soon as ≥ 3 follicles ≥ 17 mm were present, and hormone assessment performed at initiation of stimulation, on the first day after menstruation had stopped, on the day of antagonist initiation, and on the day of hCG administration. The association between hormone exposure during the menstruation-free interval and the probability of ongoing pregnancy. The exposure to progesterone during the menstruation-free interval was statistically significantly higher in patients who did not become pregnant compared with those who did (4.20 ± 2.54 vs. 3.13 ± 1.14, respectively). Binary logistic regression confirmed the adverse effect of the increased exposure to progesterone for the achievement of pregnancy. In recombinant follicle-stimulating hormone/gonadotropin-releasing hormone antagonist in vitro fertilization/intracytoplasmic sperm injection cycles, a lower probability of pregnancy is associated with a higher exposure to progesterone during the menstruation-free interval. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Progesterone promotes maternal-fetal tolerance by reducing human maternal T-cell polyfunctionality and inducing a specific cytokine profile.

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Lissauer, David; Eldershaw, Suzy A; Inman, Charlotte F; Coomarasamy, Aravinthan; Moss, Paul A H; Kilby, Mark D

2015-10-01

Progesterone is a steroid hormone essential for the maintenance of human pregnancy, and its actions are thought to include promoting maternal immune tolerance of the semiallogenic fetus. We report that exposure of maternal T cells to progesterone at physiological doses induced a unique skewing of the cytokine production profile of CD4(+) and CD8(+) T cells, with reductions not only in potentially deleterious IFN-γ and TNF-α production but also in IL-10 and IL-5. Conversely, production of IL-4 was increased. Maternal T cells also became less polyfunctional, focussing cytokine production toward profiles including IL-4. This was accompanied by reduced T-cell proliferation. Using fetal and viral antigen-specific CD8(+) T-cell clones, we confirmed that this as a direct, nonantigen-specific effect. Yet human T cells lacked conventional nuclear progesterone receptors, implicating a membrane progesterone receptor. CD4(+) and CD8(+) T cells responded to progesterone in a dose-dependent manner, with subtle effects at concentrations comparable to those in maternal blood, but profound effects at concentrations similar to those at the maternal-fetal interface. This characterization of how progesterone modulates T-cell function is important in understanding the normal biology of pregnancy and informing the rational use of progesterone therapy in pregnancies at risk of fetal loss. © 2015 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Revisiting progesterone receptor (PR) actions in breast cancer: Insights into PR repressive functions.

Science.gov (United States)

Proietti, Cecilia J; Cenciarini, Mauro E; Elizalde, Patricia V

2018-05-01

Progesterone receptor (PR) is a master regulator in female reproductive tissues that controls developmental processes and proliferation and differentiation during the reproductive cycle and pregnancy. PR also plays a role in progression of endocrine-dependent breast cancer. As a member of the nuclear receptor family of ligand-dependent transcription factors, the main action of PR is to regulate networks of target gene expression in response to binding its cognate steroid hormone, progesterone. Liganded-PR transcriptional activation has been thoroughly studied and associated mechanisms have been described while progesterone-mediated repression has remained less explored. The present work summarizes recent advances in the understanding of how PR-mediated repression is accomplished in breast cancer cells and highlights the significance of fully understanding the determinants of context-dependent PR action. Copyright © 2018 Elsevier Inc. All rights reserved.

Autoimmune progesterone dermatitis: Case report with history of urticaria, petechiae and palpable pinpoint purpura triggered by medical abortion.

Science.gov (United States)

Mbonile, Lumuli

2016-03-17

Autoimmune progesterone dermatitis (APD) is a rare autoimmune response to raised endogenous progesterone levels that occur during the luteal phase of the menstrual cycle. Cutaneous, mucosal lesions and other systemic manifestations develop cyclically during the luteal phase of the menstrual cycle when progesterone levels are elevated. APD symptoms usually start 3 - 10 days before menstruation and resolve 1 - 2 days after menstruation ceases. A 30-year-old woman presented with urticaria, petechiae and palpable pinpoint purpura lesions of the legs, forearms, neck and buttocks 1 week prior to her menses starting and 2 months after a medical abortion. She was diagnosed with allergic contact dermatitis and topical steroids were prescribed. Her skin conditions did not improve and were associated with her menstrual cycle. We performed an intradermal test using progesterone, which was positive. She was treated with oral contraceptive pills and the symptoms were resolved. This is a typical case of APD triggered by increased sensitivity to endogenous progesterone induced a few months after medical abortion.

Effect of progesterone receptor status on maspin synthesis via nitric oxide production in neutrophils in human breast cancer.

Science.gov (United States)

Ganguly Bhattacharjee, Karabi; Bhattacharyya, Mau; Halder, Umesh Chandra; Jana, Pradipta; Sinha, Asru K

2014-09-01

Although progesterone receptor (PR) status, similarly to estrogen receptor status, is of prognostic importance in breast cancer, the involvement of the PR in breast cancer remains obscure. Studies were conducted to determine the function of the PR in neutrophils in the nitric oxide-induced synthesis of maspin, an anti-breast-cancer protein produced in nonmalignant mammary cells and in neutrophils in the circulation. PR status was determined by immunohistochemistry. Maspin synthesis was determined by in-vitro translation of messenger RNA and quantified by enzyme-linked immunosorbent assay. Nitric oxide was determined by the methemoglobin method. It was found that PR status in neutrophils was identical with that in malignant breast tissues. A Scatchard plot for progesterone binding to normal and PR-positive (PR+) neutrophils revealed that whereas normal neutrophils had 11.5 × 10(10) PR sites/cell with K d = 47.619 nM, PR+ neutrophils had 6.6 × 10(10) PR sites/cell with K d = 47.619 nM. The progesterone negative (PR-) neutrophils failed to bind to progesterone. Incubation of normal and PR+ neutrophils with 25 nM progesterone produced 1.317 μM NO and 2.329 nM maspin; the PR+ neutrophils produced 0.72 μM NO and 1.138 nM maspin. The PR- neutrophils failed to produce any NO or maspin in the presence of progesterone. Inhibition of progesterone-induced NO synthesis led to complete inhibition of maspin synthesis in all neutrophils. These results suggest that estrogen and progesterone complement each other in NO-induced maspin synthesis, and do not necessarily antagonize in the synthesis of the anti-breast-cancer protein.

Facilitating wider application of progesterone RIA for improving livestock production in developing countries

International Nuclear Information System (INIS)

Oswin Perera, B.M.B.

2000-01-01

Full text: Research and development programmes supported by the Joint FAO/IAEA Division on improving livestock production in developing countries have identified three major biological constraints: feeding, breeding management and diseases. Proper breeding management is important in order to achieve optimum economic benefits (through products such as milk, meat and offspring) from an animal during its lifespan. This requires early attainment of puberty, short intervals from calving to conception, high conception rates and low number of matings or artificial inseminations (Als) per conception. The use of radioimmunoassay (RIA) for measuring progesterone in milk of dairy animals or in blood of meat animals, together with recording of data on reproductive events and production parameters, is an indispensable tool that provides information both on problems in breeding management by farmers as well as deficiencies in the Al services provided to them by government, co-operative or private organizations. This allows appropriate strategies and interventions to be adopted to overcome these limitations. Progesterone RIA can also detect animals that have not conceived by Al within 21 days after mating (early non-pregnancy diagnosis or N-PD), and alert farmers to the need to have these animals closely observed for oestrus and re-inseminated at the appropriate time. In order to ensure the sustained use of RIA technology for progesterone measurement in developing Member States, the IAEA has been engaged in the development and transfer of simple, robust and cheap methods of RIA. The system currently being used is based on a direct (non-extraction) method, using a 125 I-progesterone tracer and a solid-phase separation method (antibody coated tubes). In order to ensure wider availability (and lower cost) of the two key reagents required for the assay, the IAEA has initiated a programme to assist Member States to develop the capability to produce these in selected regional or

Progesterone amplifies oxidative stress signal and promotes NO production via H2O2 in mouse kidney arterial endothelial cells.

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Yuan, Xiao-Hua; Fan, Yang-Yang; Yang, Chun-Rong; Gao, Xiao-Rui; Zhang, Li-Li; Hu, Ying; Wang, Ya-Qin; Jun, Hu

2016-01-01

The role of progesterone on the cardiovascular system is controversial. Our present research is to specify the effect of progesterone on arterial endothelial cells in response to oxidative stress. Our result showed that H2O2 (150 μM and 300 μM) induced cellular antioxidant response. Glutathione (GSH) production and the activity of Glutathione peroxidase (GPx) were increased in H2O2-treated group. The expression of glutamate cysteine ligase catalytic subunit (GCLC) and modifier subunit (GCLM) was induced in response to H2O2. However, progesterone absolutely abolished the antioxidant response through increasing ROS level, inhibiting the activity of Glutathione peroxidase (GPx), decreasing GSH level and reducing expression of GClC and GCLM. In our study, H2O2 induced nitrogen monoxide (NO) production and endothelial nitric oxide synthase (eNOS) expression, and progesterone promoted H2O2-induced NO production. Progesterone increased H2O2-induced expression of hypoxia inducible factor-α (HIFα) which in turn regulated eNOS expression and NO synthesis. Further study demonstrated that progesterone increased H2O2 concentration of culture medium which may contribute to NO synthesis. Exogenous GSH decreased the content of H2O2 of culture medium pretreated by progesterone combined with H2O2 or progesterone alone. GSH also inhibited expression of HIFα and eNOS, and abolished NO synthesis. Collectively, our study demonstrated for the first time that progesterone inhibited cellular antioxidant effect and increased oxidative stress, promoted NO production of arterial endothelial cells, which may be due to the increasing H2O2 concentration and amplified oxidative stress signal. Copyright © 2015. Published by Elsevier Ltd.

STOPPIT Baby Follow-up Study: the effect of prophylactic progesterone in twin pregnancy on childhood outcome.

Directory of Open Access Journals (Sweden)

Helen Christine McNamara

Full Text Available To determine the long-term effects of in utero progesterone exposure in twin children.This study evaluated the health and developmental outcomes of all surviving children born to mothers who participated in a double-blind, placebo-controlled trial of progesterone given for the prevention of preterm birth in twin pregnancies (STOPPIT, ISRCTN35782581. Follow-up was performed via record linkage and two parent-completed validated questionnaires, the Child Development Inventory and the Health Utilities Index.Record linkage was successfully performed on at least one record in 759/781 (97% children eligible for follow-up. There were no differences between progesterone-exposed and placebo-exposed twins with respect to incidence of death, congenital anomalies and hospitalisation, nor on routine national child health assessments. Questionnaire responses were received for 324/738 (44% children. The mean age at questionnaire follow-up was 55.5 months. Delay in at least one developmental domain on the Child Development Inventory was observed in 107/324 (33% children, with no evidence of difference between progesterone-exposed and placebo-exposed twins. There was no evidence of difference between the progesterone and placebo groups in global health status assessed using the Health Utilities Index: 89% of children were rated as having 'excellent' health and a further 8% as having 'very good' health.In this cohort of twin children there was no evidence of a detrimental or beneficial impact on health and developmental outcomes at three to six years of age due to in utero exposure to progesterone.

Cervical HSV-2 infection causes cervical remodeling and increases risk for ascending infection and preterm birth

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McGee, Devin; Poncil, Sharra; Patterson, Amanda

2017-01-01

Preterm birth (PTB), or birth before 37 weeks gestation, is the leading cause of neonatal mortality worldwide. Cervical viral infections have been established as risk factors for PTB in women, although the mechanism leading to increased risk is unknown. Using a mouse model of pregnancy, we determined that intra-vaginal HSV2 infection caused increased rates of preterm birth following an intra-vaginal bacterial infection. HSV2 infection resulted in histological changes in the cervix mimicking cervical ripening, including significant collagen remodeling and increased hyaluronic acid synthesis. Viral infection also caused aberrant expression of estrogen and progesterone receptor in the cervical epithelium. Further analysis using human ectocervical cells demonstrated a role for Src kinase in virus-mediated changes in estrogen receptor and hyaluronic acid expression. In conclusion, HSV2 affects proteins involved in tissue hormone responsiveness, causes significant changes reminiscent of premature cervical ripening, and increases risk of preterm birth. Studies such as this improve our chances of identifying clinical interventions in the future. PMID:29190738

Abnormal pathways in endometriosis in relation to progesterone resistance

DEFF Research Database (Denmark)

Lode, Lise; Sveen, Magnhild Often; Rudnicki, Martin

2017-01-01

Introduction: Endometriosis is an estrogen-dependent disorder, and recent studies suggest that progesterone resistance may contribute to the development and pathophysiology of the disorder. Based on this, identification of genetic and molecular perturbations in the endometrium of women...

Clinical Value of Basal Serum Progesterone Prior to Initiate Ovarian Hyper-Stimulation with GnRH Antagonists: A Retrospective Cohort Study.

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Faulisi, Sonia; Reschini, Marco; Borroni, Raffaella; Paffoni, Alessio; Busnelli, Andrea; Somigliana, Edgardo

2017-01-01

The routine assessment of day 3 serum progesterone prior to initiation of ovarian hyper-stimulation with the use of GnRH antagonists is under debate. In this study, we evaluated the clinical utility of this policy. Retrospective cohort study of women undergoing in vitro fertilization (IVF) with the use of GnRH antagonists aimed at determining the frequency of cases with progesterone levels exceeding the recommended threshold of 1,660 pg/ml and at evaluating whether this assessment may be predictive of pregnancy. Serum progesterone exceeded the recommended threshold in one case (0.3%, 95% CI 0.01-1.5). The median (interquartile range) basal progesterone in women who did (n = 95) and did not (n = 217) become pregnant were 351 (234-476) and 380 (237-531) pg/ml, respectively (p = 0.28). The 90th percentile of the basal progesterone distribution in women who became pregnant was 660 pg/ml. Cases with serum progesterone exceeding this threshold in successful and unsuccessful cycles were 10 (10%) and 30 (14%), respectively (p = 0.47). The capacity of basal progesterone to predict pregnancy was evaluated using receiver operating characteristic curve (area under the curve = 0.54, 95% CI 0.47-0.61, p = 0.28). No graphically evident threshold emerged. Routine day 3 serum progesterone assessment in IVF cycles with the use of GnRH antagonists is not justified. Further evidence is warranted prior to claiming its systematic use. © 2016 S. Karger AG, Basel.

Marginal activity of progesterone receptor B (PR-B) in dogs but high incidence of mammary cancer

NARCIS (Netherlands)

Gracanin, Ana; Voorwald, Fabiana A; van Wolferen, Monique; Timmermans-Sprang, Elpetra; Mol, Jan A

2014-01-01

Progesterone plays an important role in the normal development and carcinogenesis of the mammary gland. In vitro studies have shown that the canine progesterone receptor B (cPR-B), which is essential for mammary development in the mouse, does not transactivate reporter constructs containing

Prenatal Exposure to Progesterone Affects Sexual Orientation in Humans

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Reinisch, June M.; Mortensen, Erik Lykke; Sanders, Stephanie A.

2017-01-01

Prenatal sex hormone levels affect physical and behavioral sexual differentiation in animals and humans. Although prenatal hormones are theorized to influence sexual orientation in humans, evidence is sparse. Sexual orientation variables for 34 prenatally progesterone-exposed subjects (17 males...... and 17 females) were compared to matched controls (M age = 23.2 years). A case–control double-blind design was used drawing on existing data from the US/Denmark Prenatal Development Project. Index cases were exposed to lutocyclin (bioidentical progesterone = C21H30O2; MW: 314.46) and no other hormonal...... preparation. Controls were matched on 14 physical, medical, and socioeconomic variables. A structured interview conducted by a psychologist and self-administered questionnaires were used to collect data on sexual orientation, self-identification, attraction to the same and other sex, and history of sexual...

Malignant peritoneal cytology in stage I endometrial adenocarcinoma: the effect of progesterone therapy (a preliminary report).

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Piver, M S; Lele, S B; Gamarra, M

1988-01-01

From February 1982-June 1986, 25 consecutive patients with surgical stage I endometrial adenocarcinoma (no evidence of metastasis at surgery or occult cervical or adnexal involvement on histopathologic review) and malignant peritoneal cytologic washings were treated with progesterone therapy. Twenty-two patients have undergone a second look laparoscopy and repeat cytologic washings, one of those also underwent a third look laparoscopy. Two patients refused second look laparoscopy, and in a third patient laparoscopy was medically contraindicated; all three have no evidence of disease (NED) at 15, 46, and 64 months respectively and are off therapy. Of the 22 patients who underwent second look laparoscopy, 21 (95%) had no macroscopic evidence of recurrent endometrial carcinoma and repeat negative peritoneal cytology; 1 patient (5%) had persistent malignant peritoneal cytology but was NED at third look laparoscopy one year later. All 25 patients are off progesterone therapy and remain clinically NED from 12-64 months. Although progesterone therapy for malignant peritoneal cytology resulted in a 100% reversal of malignant peritoneal cytology to normal in the 22 patients who underwent second or third look laparoscopy and all 25 patients remain clinically NED, the true value of progesterone therapy can only be ascertained by a randomized trial of progesterone versus no therapy.

A blueprint for the prevention of preterm birth: vaginal progesterone in women with a short cervix

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Romero, Roberto; Yeo, Lami; Miranda, Jezid; Hassan, Sonia; Conde-Agudelo, Agustin; Chaiworapongsa, Tinnakorn

2014-01-01

Preterm birth is the leading cause of perinatal morbidity and mortality worldwide, and is the most important challenge to modern obstetrics. A major obstacle has been that preterm birth is treated (implicitly or explicitly) as a single condition. Two-thirds of preterm births occur after the spontaneous onset of labor, and the remaining one-third after “indicated” preterm birth; however, the causes of spontaneous preterm labor and “indicated” preterm birth are different. Spontaneous preterm birth is a syndrome caused by multiple etiologies, one of which is a decline in progesterone action, which induces cervical ripening. A sonographic short cervix (identified in the midtrimester) is a powerful predictor of spontaneous preterm delivery. Randomized clinical trials and individual patient meta-analyses have shown that vaginal progesterone reduces the rate of preterm delivery at cervix, and therefore, the compound of choice is natural progesterone (not the synthetic progestin). Routine assessment of the risk of preterm birth with cervical ultrasound coupled with vaginal progesterone for women with a short cervix is cost-effective, and implementation of such a policy is urgently needed. Vaginal progesterone is as effective as cervical cerclage in reducing the rate of preterm delivery in women with a singleton gestation, history of preterm birth, and a short cervix (<25mm). PMID:23314512

PROGESTERONE INCREASES BDNF EXPRESSION AND PROTECTS AGAINST GLUTAMATE TOXICITY IN A MAPK- AND PI3-K - DEPENDENT MANNER IN CEREBRAL CORTICAL EXPLANTS

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Kaur, Paramjit; Jodhka, Parmeet K.; Underwood, Wendy A.; Bowles, Courtney A.; de Fiebre, NancyEllen C.; de Fiebre, Christopher M.; Singh, Meharvan

2009-01-01

The higher prevalence and risk for Alzheimer’s disease in women relative to men has been partially attributed to the precipitous decline in gonadal hormone levels that occur in women following the menopause. While considerable attention has focused on the consequence of estrogen loss, and thus, estrogen’s neuroprotective potential, it is important to recognize that the menopause results in a precipitous decline in progesterone levels as well. In fact, progesterone is neuroprotective, although the precise mechanisms involved remain unclear. Based on our previous observation that progesterone elicits the phosphorylation of ERK and Akt, key effectors of the neuroprotective MAPK and PI3-K pathways, respectively, we determined if activation of either of these pathways was necessary for progesterone-induced protection. Using organotypic explants (slice culture) of the cerebral cortex, we found that progesterone protected against glutamate-induced toxicity. Further, these protective effects were inhibited by either the MEK1/2 inhibitor, UO126, or the PI-3K inhibitor, LY294002, supporting the requirement of both the MAPK and PI-3K pathways in progesterone-induced protection. In addition, at a concentration and duration of treatment consistent with our neuroprotection data, progesterone also increased the expression of Brain-Derived Neurotrophic Factor (BDNF), at the level of both protein and mRNA. This induction of BDNF may be relevant to the protective effects of progesterone since inhibition of Trk signaling, using K252a, inhibited the protective effects of progesterone. Collectively, these data suggest that progesterone is protective via multiple and potentially related mechanisms. PMID:17549730

Improving food and agricultural production. Thailand. Application on monoclonal antibodies for progesterone measurement

International Nuclear Information System (INIS)

Butcher, G.W.

1991-01-01

The duties of the mission were to provide instructions on the maintenance of hybridoma cell lines and their culture and the harvesting of monoclonal antibodies; to assist the counterparts in Thailand to develop work plans for the use of monoclonal antibodies in radioimmunoassay measurements of progesterone; and to assess the need for and feasibility of establishing a laboratory for producing monoclonal antibodies directed against progesterone. The report contains a summary of the activities performed in fulfillment of these duties

Safety and availability of dapivirine (TMC120) delivered from an intravaginal ring.

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Romano, J; Variano, B; Coplan, P; Van Roey, J; Douville, K; Rosenberg, Z; Temmerman, M; Verstraelen, H; Van Bortel, L; Weyers, S; Mitchnick, M

2009-05-01

Vaginal delivery of 200 mg or 25 mg dapivirine from intravaginal rings (IVRs) was evaluated over a 7-day period in two phase 1 safety trials (IPM001 and IPM008, respectively) in a total of 25 healthy women 19 to 46 years of age. The IVR was generally safe and well tolerated with similar adverse events observed in the placebo and dapivirine groups. Across both studies, dapivirine concentrations in vaginal fluids measured at the introitus, cervix, and ring area were within the mean range of 0.7-7.1 microg/ml. Mean dapivirine concentrations in vaginal and cervical tissues on day 7 were 0.3-0.7 microg/g in IPM001 and 1.5-3.5 microg/g in IPM008. Mean plasma concentrations of dapivirine were Dapivirine from both IVRs was successfully distributed throughout the lower genital tract at concentrations >1000x the EC(50) against wild-type HIV-1 (LAI) in MT4 cells suggesting that IVR delivery of microbicides is a viable option meriting further study.

Use of radioimmunoassay to measure progesterone levels during different reproductive stages in female Damascus goats

International Nuclear Information System (INIS)

Zarkawi, M.; Al-masri, M. R.

2002-01-01

Jugular serum progesterone concentrations were measured in female Damascus goats using radioimmunoassay (RIA) during prepubertal, puberty, pregnancy and parturition stages, to monitor the reproductive performance. Age at puberty ranged between 266 - 653 days with an average of 475 days, while average weight at puberty was 35.6 kg. Progesterone level rose from around zero ng/ml at prepubertal stage to 2.14 ng/ml at the onset of puberty ranging from 1.12 to 5.38 ng/ml. Average maximum progesterone concentration during pregnancy was 13.84 ng/ml, occurring on day 115 post-mating, and dropped sharply to 0.29 ng/ml soon after kidding. Average overall duration of pregnancy was 149 days. The accuracy of pregnancy diagnosis on day 21 post-mating using RIA was 100%. The results also indicate that the breeding season of the experimental Damascus goats started in September. It could be concluded that the assessment of progesterone levels in serum is considered to be a vital tool in monitoring the reproductive performance in the indigenous Damascus goat breed. (author)

Expression of glucocorticoid and progesterone nuclear receptor genes in archival breast cancer tissue

International Nuclear Information System (INIS)

Smith, Robert A; Lea, Rod A; Curran, Joanne E; Weinstein, Stephen R; Griffiths, Lyn R

2003-01-01

Previous studies in our laboratory have shown associations of specific nuclear receptor gene variants with sporadic breast cancer. In order to investigate these findings further, we conducted the present study to determine whether expression levels of the progesterone and glucocorticoid nuclear receptor genes vary in different breast cancer grades. RNA was extracted from paraffin-embedded archival breast tumour tissue and converted into cDNA. Sample cDNA underwent PCR using labelled primers to enable quantitation of mRNA expression. Expression data were normalized against the 18S ribosomal gene multiplex and analyzed using analysis of variance. Analysis of variance indicated a variable level of expression of both genes with regard to breast cancer grade (P = 0.00033 for glucocorticoid receptor and P = 0.023 for progesterone receptor). Statistical analysis indicated that expression of the progesterone nuclear receptor is elevated in late grade breast cancer tissue

Control of the estrous cycle to improve fertility for fixed-time artificial insemination in beef cattle: a review.

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Lamb, G C; Dahlen, C R; Larson, J E; Marquezini, G; Stevenson, J S

2010-04-01

Early estrus-synchronization protocols focused on regressing the corpus luteum (CL) with an injection of PGF(2alpha) followed by detection of estrus or involved the use of exogenous progestins that prevent estrus from occurring. Later, protocols combining the use of PGF(2alpha) and exogenous progestins were developed. Gonadotropin-releasing hormone was utilized to control follicular waves, synchronize ovulation, or to luteinize large dominant follicles. Our research aimed to develop reliable protocols that 1) relied solely on fixed-timed AI (TAI); 2) required a maximum of 3 animal handlings, and 3) were successful in estrous-cycling and noncycling females. In cows, insertion of an intravaginal progesterone insert during the 7-d interval between the initial GnRH and PGF(2alpha) injections enhanced pregnancy rates by 9 to 10%. In a multi-location study, a TAI protocol yielded pregnancy rates similar to a protocol involving detection of estrus plus a fixed-time clean-up AI for females not detected in estrus (54 vs. 58%, respectively, for cows and 53 vs. 57%, respectively, for heifers). Initiation of estrous cycles in noncycling cows is likely the primary manner in which beef producers may improve fertility in response to estrus synchronization and TAI protocols. Treatment of noncycling females with progesterone and GnRH increases the percentage of cycling females and improves fertility to a TAI, but inducing cyclicity with hCG failed to enhance fertility in TAI protocols. Supplementing progesterone after TAI failed to increase pregnancy rates in beef cattle. In contrast, administration of hCG 7 d after TAI induced an accessory CL, increased progesterone, and tended to enhance pregnancy rates. Development of TAI protocols that reduce the hassle factors associated with ovulation synchronization and AI provide cattle producers efficient and effective tools for capturing selective genetic traits of economic consequences. Location variables, however, which may include

Effects of vaginal progesterone on pain and uterine contractility in patients with threatened abortion before twelve weeks of pregnancy.

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Palagiano, A; Bulletti, C; Pace, M C; DE Ziegler, D; Cicinelli, E; Izzo, A

2004-12-01

Fifty women with previous diagnosis of inadequate luteal phase and threatened abortion underwent a prospective, randomized, double-blind study in one medical center carried out with a parallel trial. The primary objective was to establish the effects of vaginal progesterone (Crinone 8%) in reducing both pain and uterine contractions (UCs). The gel with or without (placebo) vaginal progesterone was administered once a day since the diagnosis of threatened abortion and for 5 days. The efficacy on pain symptom amelioration was evaluated by a 5-score intensity gradation, while the UCs were evaluated by ultrasound. The secondary objective of the study was to evaluate the outcome of the pregnancies. The use of progesterone was effective both on pain relief and on the frequency of the UCs that decreased after 5 days of vaginal progesterone administration (P pregnancy and spontaneous abortion in both study groups after 60 days showed that 4 patients of group A and 8 patients of group B miscarried (P threatened abortion benefit from vaginal progesterone by a reduction of UCs and pain. The use of vaginal progesterone improved the outcome of pregnancies complicated by threatened abortion and previous diagnosis of inadequate luteal phase.

Ex-vivo release of Pipeline Embolization Device polytetrafluoroethylene (PTFE) sleeves for improved distal landing zone accuracy in-vivo: A technical note.

Science.gov (United States)

Griessenauer, Christoph J; Gupta, Raghav; Moore, Justin; Thomas, Ajith J; Ogilvy, Christopher S

2016-12-01

Distal landing zone accuracy is critical in some intracranial aneurysms treated with the Pipeline Embolization Device (PED), and delayed opening of the distal end of the device can complicate the procedure. Here, we report a technical nuance that facilitates accurate placement of the distal end of the PED by ex-vivo, pre-implantation release of the PED Flex polytetrafluoroethylene (PTFE) sleeves. The PED Flex is partially pushed out of the introducer sheath ex-vivo, pre-implantation until the distal PED opens entirely and the PTFE sleeves are located distal to the device. Without inverting the PTFE sleeves, the PED is carefully pulled back into the introducer sheath placing the PTFE sleeves inside the device. The PED is loaded into the microcatheter and advanced toward the site of implantation. When the PED is initially deployed and pushed out of the microcatheter, it opens immediately and provides an anchor for the remainder of the deployment process. We present a video (supplementary material) that illustrates the technique along with an illustrative case. Ex-vivo, pre-implantation release of the PTFE sleeves is an option in aneurysm treatment where distal landing accuracy is critical. Even without the protection of the PTFE sleeves, our clinical observation shows that the PED can be advanced safely through the microcatheter in selected cases. © The Author(s) 2016.

Serum concentrations of progesterone and oestradiol during the ovarian cycle of Syrian Awassi ewes

International Nuclear Information System (INIS)

Zarkawi, M.

2005-01-01

It was possible, for the first time, to characterise hormonally and precisely the oestrous cycle of the Syrian Awassi ewes, and to determine normal progesterone and oestradiol concentrations during the different phases of oestrous cycle. It is concluded that progesterone and oestradiol concentrations showed a cyclic pattern during the oestrous cycle, in addition, a negative and significant correlation between the concentrations of the two hormones was found. (author)

Progesterone supplementation after ovulation: effects on corpus luteum function and on fertility of dairy cows subjected to AI or ET.

Science.gov (United States)

Monteiro, Pedro L J; Nascimento, Anibal B; Pontes, Guilherme C S; Fernandes, Gabriela O; Melo, Leonardo F; Wiltbank, Milo C; Sartori, Roberto

2015-10-15

Three experiments were done to evaluate the effects of progesterone (P4) supplementation starting during metestrus on formation of the CL and on fertility of lactating dairy cows subjected to fixed-time artificial insemination (FTAI) or embryo transfer (ET). In experiment 1, 42 Holstein cows were randomly allocated to untreated (Control) or to receive an intravaginal implant containing 1.9 g of P4 from Day 3 to 20 after FTAI (controlled internal drug release [CIDR]). Blood samples were collected on Days 3, 4, 7, 11, 14, 17, 20, and 21 after FTAI to evaluate the effect of CIDR supplementation on plasma concentration of P4 using radioimmunoassay. Ultrasound scans were performed at Days 4, 7, 11, 14, and 20 to evaluate CL volume. In experiment 2, the effect on CIDR supplementation on fertility was evaluated in 668 Holstein and crossbred dairy cows that were subjected to FTAI and allocated randomly to untreated (AI-Control) or to receive a CIDR from Day 3 to 17 (AI-CIDR) after FTAI. In experiment 3, 360 Holstein cows were treated with PGF and after heat detection (Day 0), they were allocated to untreated (ET-Control) or to receive a CIDR from Day 4 ± 1 to 8 ± 1 (ET-CIDR-4) or a CIDR from 4 ± 1 to 18 ± 1 (ET-CIDR-14). In vitro-produced embryos were transferred on Day 8 ± 1. Pregnancy diagnoses were performed by ultrasound. In experiment 1, there was interaction between treatment and day in relation to plasma P4 on Days 4 and 7 due to CIDR supplementation. Independent of treatment, pregnant cows had higher plasma P4 from Day 14 to 21 than nonpregnant cows (P ≤ 0.05). Supplementation with CIDR did not alter CL development. In experiment 2, there was no effect of supplementation of P4 on pregnancy per AI on Day 32 (32.0% vs. 31.8%, for AI-Control and AI-CIDR, respectively) or pregnancy loss (15.6% vs. 17.6%, for AI-Control and AI-CIDR, respectively). In experiment 3, P4 supplementation compromised pregnancy per ET (P/ET) on Day 32 in both supplemented groups (39

4-Aminopyridine Decreases Progesterone Production by Porcine Granulosa Cells

Directory of Open Access Journals (Sweden)

Mitchell Brianna M

2003-04-01

Full Text Available Abstract Background Ion channels occur as large families of related genes with cell-specific expression patterns. Granulosa cells have been shown to express voltage-gated potassium channels from more than one family. The purpose of this study was to determine the effects of 4-aminopyridine (4-AP, an antagonist of KCNA but not KCNQ channels. Methods Granulosa cells were isolated from pig follicles and cultured with 4-AP, alone or in combination with FSH, 8-CPT-cAMP, estradiol 17β, and DIDS. Complimentary experiments determined the effects of 4-AP on the spontaneously established pig granulosa cell line PGC-2. Granulosa cell or PGC-2 function was assessed by radio-immunoassay of media progesterone accumulation. Cell viability was assessed by trypan blue exclusion. Drug-induced changes in cell membrane potential and intracellular potassium concentration were documented by spectrophotometric determination of DiBAC4(3 and PBFI fluorescence, respectively. Expression of proliferating cell nuclear antigen (PCNA and steroidogenic acute regulatory protein (StAR was assessed by immunoblotting. Flow cytometry was also used to examine granulosa cell viability and size. Results 4-AP (2 mM decreased progesterone accumulation in the media of serum-supplemented and serum-free granulosa cultures, but inhibited cell proliferation only under serum-free conditions. 4-AP decreased the expression of StAR, the production of cAMP and the synthesis of estradiol by PGC-2. Addition of either 8-CPT-cAMP or estradiol 17β to serum-supplemented primary cultures reduced the inhibitory effects of 4-AP. 4-AP treatment was also associated with increased cell size, increased intracellular potassium concentration, and hyperpolarization of resting membrane potential. The drug-induced hyperpolarization of resting membrane potential was prevented either by decreasing extracellular chloride or by adding DIDS to the media. DIDS also prevented 4-AP inhibition of progesterone production

High dose progesterone effects the growth of early chick embryo

International Nuclear Information System (INIS)

Iqbal, I.; Qamar, K.

2014-01-01

Objective: To find out the effect of high dose progesterone on the development of early chick embryo. Study Design: Lab based randomized controlled trial. Place and Duration of study: This study was carried out in Army Medical College and Post Graduate Institute of Poultry Sciences, Rawalpindi from June 2010 - December 2010. Material and Methods: Forty five specific pathogen free, fertile, eggs of Fyoumi species of chick were selected at zero hour of incubation. They were incubated at 37.5oC and 75% relative humidity for 26 hrs until the embryos reached stage 8 of the development. Then on stage 8 the eggs were divided into three groups consisting of 15 eggs per group. The first group (GI) was incubated without any operation. The second (G2) and third groups (G3) were injected with two and twenty times more than physiologic does of progesterone respectively. After 48 hours of incvbation, all embryos were examined for their development under light microscopy. Results: All the embryos of G1 and G2 showed normal development according to their stage of development, while 4 out of 11 embryos of G3 were under developed and their survival rate was also less. Conclusion: Exogenous progesterone at levels twenty times above its physiologic range effects the development of chick embryos. Further studies are needed to explain the mechanisms of this effect. (author)

Validation of a serum immunoassay to measure progesterone and diagnose pregnancy in the West Indian manatee (Trichechus manatus)

Science.gov (United States)

Tripp, K.M.; Verstegen, J.P.; Deutsch, C.J.; Bonde, R.K.; Rodriguez, M.; Morales, B.; Schmitt, D.L.; Harr, K.E.

2008-01-01

The objective was to validate a high-sensitivity chemiluminescent assay of serum progesterone concentrations for pregnancy diagnosis in manatees. Assay analytical sensitivity was 0.1 ng/mL, with mean intra- and inter-assay coefficients of variation of 9.7 and 9.2%, respectively, and accuracy had a mean adjusted R2 of 0.98. Methods comparison (relative to Siemen's Coat-A-Count RIA) demonstrated r = 0.98, Deming regression slope of 0.95, and an intercept of 0.01. Based on ROC analysis, a progesterone concentration ???0.4 ng/mL was indicative of pregnancy. Assay results were not significantly altered by two freeze-thaw cycles of samples. Characteristic progesterone concentrations during pregnancy were Months 1-4 (1.7-4.7 ng/mL), 5-8 (???1.0 ng/mL), and 10 and 11 (0.3-0.5 ng/mL), whereas two late-pregnant females with impending abortion had progesterone concentrations of 0.1 ng/mL. Among pregnant females, maximum progesterone concentrations occurred in autumn (3.9 ?? 1.8 ng/mL), and were greater during all seasons than concentrations in non-pregnant females (0.1-0.2 ng/mL). Progesterone concentrations were also significantly higher in pregnant females than in non-pregnant females and males. This highly sensitive, specific, and diagnostic assay will be valuable for monitoring pregnancy and abortion in manatees. ?? 2008 Elsevier Inc.