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1.
Theriogenology ; 153: 112-121, 2020 Sep 01.
Article in English | MEDLINE | ID: mdl-32450469

ABSTRACT

This study assessed animal welfare in ewes subjected to transcervical (TC) or laparotomy (LP) embryo collection, and the efficiency of these two techniques. Santa Inês ewes (n = 57) received a protocol for estrus synchronization and superovulation. Cervical dilation protocol was initiated 12 h before embryo collection in all ewes. Depending on the success of cervical passage, the embryos were collected from ewes by either TC or LP. Records were made of physiological (rectal temperature (RT) and heart rate (HR)), endocrine (cortisol concentration), biochemical (glycaemia, total proteins, globulin and albumin concentrations), and behavioral variables. Data were recorded before fasting (BF) and sedation (BS), during (DC) and immediately after embryo collection (IAC), and 1 h (1hAC), 3 h (3hAC), 6 h (6hAC), 12 h (12hAC), 24 h (24hAC), and 48 h (48hAC) after embryo collection. The LP and TC procedures were applied to 22 and 35 ewes (with 100.0% and 94.3% of procedures being successful, respectively). The use of LP took longer than TC (P = 0.007) but was less effective in the recovery of uterine fluid and structures (P = 0.0002 and P = 0.0180, respectively), with no difference in the number of viable embryos recovered per animal. The TC procedure induced a greater RT at DC (P = 0.002) and IAC moments (P < 0.0001). The heart rate was greater in TC than LP in IAC (P = 0.036). On the other hand, HR was greater with LP at 12hAC (P = 0.033) and 24hAC (P = 0.002). There was no interaction between the procedures and time on total proteins, albumin, or globulin concentrations. The TC procedure induced greater glycaemia than LP in IAC (P < 0.0001). LP induced greater serum cortisol concentration than TC at DC, IAC, 1hAC (P = 0.0004; P = 0.0006; P = 0.036, respectively), even though it was greater in the TC than the LP procedure at 3hAC (P = 0.008). In conclusion, the TC embryo collection was more effective than the traditional LP procedure. Although both embryo collection procedures affected ewes' welfare, the TC procedure is probably less stressor than the LP.


Subject(s)
Animal Welfare , Embryo Transfer/veterinary , Laparotomy/veterinary , Sheep , Tissue and Organ Harvesting/veterinary , Abortifacient Agents, Nonsteroidal/pharmacology , Animals , Chorionic Gonadotropin/pharmacology , Cloprostenol/pharmacology , Dinoprost/pharmacology , Embryo, Mammalian , Female , Gonadotropin-Releasing Hormone/pharmacology , Luteolytic Agents/pharmacology , Medroxyprogesterone Acetate/pharmacology , Pregnancy , Reproductive Control Agents/pharmacology , Superovulation
2.
Biotech Histochem ; 94(8): 583-591, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31478750

ABSTRACT

We investigated the potential hepatoprotective effects of misoprostol (MP) on doxorubicin (DOX) induced liver injury in rats using histology and biochemistry. We used 21 male Sprague-Dawley rats divided randomly into three groups: group 1, control; group 2, DOX; group 3, DOX + MP. The control group was injected intraperitoneally (i.p.) with 0.5 ml 0.9% w/v NaCl and given 1 ml 0.9% NaCl orally for 6 days. DOX was administered i.p. as a single dose of 20 mg/kg. MP, 0.2 mg/kg, was given orally for 6 days. Treatment with MP increased high density lipoprotein cholesterol levels and decreased serum alanine aminotransferase, aspartate aminotransferase, low density lipoprotein cholesterol, triglycerides and total cholesterol levels significantly in serum. Increased malondialdehyde level and decreased catalase, glutathione and superoxide dismutase levels caused by DOX were suppressed significantly in liver tissue by MP. DOX + MP reduced loss of body weight. Oxidative stress was decreased, antioxidant activity was increased and histopathological changes were reduced in the DOX + MP group compared to the DOX group. Liver injury caused by DOX was attenuated by MP treatment owing to the antioxidative and anti-apoptotic effects of MP, which might be useful for reducing the severity of DOX induced liver injury.


Subject(s)
Chemical and Drug Induced Liver Injury/prevention & control , Doxorubicin/toxicity , Misoprostol/pharmacology , Abortifacient Agents, Nonsteroidal/pharmacology , Animals , Antibiotics, Antineoplastic/toxicity , Biomarkers/blood , Body Weight/drug effects , Catalase/blood , Glutathione/blood , Male , Oxidative Stress/drug effects , Random Allocation , Rats , Rats, Sprague-Dawley , Superoxide Dismutase/blood
3.
Arch Gynecol Obstet ; 300(5): 1287-1293, 2019 11.
Article in English | MEDLINE | ID: mdl-31422461

ABSTRACT

PURPOSE: We aimed to assess the role of repeat misoprostol administration in those with thickened endometrium in the management of early pregnancy failure (EPF). METHODS: A retrospective cohort study in two university hospitals among women receiving misoprostol treatment for EPF. Those with thickened endometrium at the first follow-up visit, who received a repeat 800 µg dose of vaginal misoprostol in institution B and no treatment in institution A, constituted the study group. The primary outcome was treatment success, defined as complete uterine evacuation without the need for any operative intervention RESULTS: Overall, 608 women with thickened endometrium as assessed by transvaginal ultrasonography 2 days following initial misoprostol administration for EPF were included. Of them, 427 did not receive repeat misoprostol dose, and 181 received repeat misoprostol dose. The rate of surgical intervention did not differ between those who received a repeat misoprostol dose (6.1%) and those who did not (4.3%) (P = 0.32). The median endometrial thickness was similar in those that did and did not require subsequent surgical intervention (P = 0.65), and was a poor predictor of treatment outcome. CONCLUSIONS: Repeat misoprostol administration among women with thickened endometrium following initial misoprostol administration for EPF was not associated with improved treatment success rates.


Subject(s)
Abortifacient Agents, Nonsteroidal/therapeutic use , Abortion, Induced/methods , Misoprostol/therapeutic use , Abortifacient Agents, Nonsteroidal/pharmacology , Administration, Intravaginal , Adult , Female , Humans , Misoprostol/pharmacology , Pregnancy , Retrospective Studies , Treatment Outcome
4.
Theriogenology ; 132: 45-52, 2019 Jul 01.
Article in English | MEDLINE | ID: mdl-30991168

ABSTRACT

An inhibitor of PGF2α biosynthesis (flunixin meglumine, FM) was used to study the role of endogenous PGF2α on the luteolytic effect of exogenous PGF2α in mares. A 2-h infusion of PGF2α at a constant rate (total dose, 0.1 mg) on Day 10 (ovulation = Day 0) was used to mimic the maximal concentrations of a spontaneous pulse of a PGF2α metabolite (PGFM). Treatment with FM (1.7 mg/kg) was done 1 h before and 5 h after the start of PGF2α infusion. In hourly blood samples beginning 1 h before the start of PGF2α infusion, progesterone decreased (P < 0.05) similarly by 5 h in each of the PGF2α and PGF2α+FM groups but not in the controls (n = 5). In a study of spontaneous luteolysis, the same FM dose was given every 6 h from Day 13 until Day 17 or earlier if CL regression was indicated by an 80% decrease in luteal blood-flow signals. Blood was sampled for progesterone assay each day and 8 h of hourly blood sampling was done each day to characterize PGFM concentrations and pulses. Progesterone (P4) was lower (P < 0.05) in controls than in an FM group (n = 7) by Day 15. Luteolysis (P4 < 1 ng/mL) ended on Days 14-19 in individual controls. In contrast, luteolysis did not end until after Day 20 in 4 of 7 FM-treated mares. In the three mares with completion of luteolysis before Day 20 in the FM group, the interval from beginning to end of luteolysis was longer (P < 0.02) (4.5 ± 0.6 days) than in the controls (3.0 ± 0.4 days). During 8-h sessions of hourly blood sampling on Day 14, concentration of PGFM was significantly lower in the FM group for the minimal, mean, and maximal per session. Pulses of PGFM were identified by a CV methodology on each day in 7 of 7 and 3 of 7 mares in the controls and FM group, respectively. The four FM-treated mares without a CV-identified pulse were the four mares in which luteolysis did not occur before Day 20. In mares with detected pulses, PGFM was lower at each nadir and at the peak (86% lower) in the FM group than in controls, but the interval between nadirs or base of a pulse was not different between groups. Hypothesis 1 that endogenous PGF plays a role in the luteolytic effect of exogenous PGF2α was not supported. Hypothesis 2 that an inhibitor of PGF2α biosynthesis prevented or minimized the prominence of PGFM pulses and increased the frequency of persistent CL was supported.


Subject(s)
Clonixin/analogs & derivatives , Dinoprost/pharmacology , Horses , Luteolysis/drug effects , Abortifacient Agents, Nonsteroidal/administration & dosage , Abortifacient Agents, Nonsteroidal/metabolism , Abortifacient Agents, Nonsteroidal/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Clonixin/administration & dosage , Clonixin/pharmacology , Corpus Luteum/metabolism , Dinoprost/administration & dosage , Dinoprost/metabolism , Female , Ovulation/drug effects
5.
J Obstet Gynaecol Res ; 44(5): 907-913, 2018 May.
Article in English | MEDLINE | ID: mdl-29484784

ABSTRACT

AIM: To evaluate the efficacy of conservative treatment with methotrexate against placenta increta by two different routes of administration through retrospective analysis. METHODS: A total of 54 women diagnosed with placenta increta after vaginal delivery were enrolled in this retrospective study. The participants accepted conservative management with methotrexate through either intravenous injection or local multi-point injection under ultrasound guidance. The treatment was considered effective if no hysterectomy was mandatory during the follow-up period. RESULTS: Out of the 54 cases, 21 patients were treated with methotrexate intravenously (group 1), and 33 patients received local multi-point injection to the placenta increta under ultrasound guidance (group 2). No maternal death occurred. In group 1, 10 patients expelled the placentas spontaneously, 7 patients underwent uterine curettage and 4 patients underwent hysterectomy for uncontrollable post-partum hemorrhage and infection. In group 2, 25 patients expelled placentas spontaneously and 8 patients underwent uterine curettage with no incidence of hysterectomy. The success rate in group 1 and group 2 was 17/21 and 33/33, respectively. The average time of the spontaneous placenta expulsion was 79.13 ± 29.87 days in group 1 and 42.42 ± 31.83 days in group 2. CONCLUSION: Local multi-point methotrexate injection under ultrasound guidance is a better alternative for patients with placenta increta, especially for preserving fertility.


Subject(s)
Abortifacient Agents, Nonsteroidal/pharmacology , Conservative Treatment/methods , Methotrexate/pharmacology , Placenta Accreta/drug therapy , Placenta Accreta/surgery , Ultrasonography, Interventional/methods , Abortifacient Agents, Nonsteroidal/administration & dosage , Adult , Female , Humans , Injections , Methotrexate/administration & dosage , Pregnancy , Retrospective Studies , Young Adult
6.
J Gynecol Obstet Hum Reprod ; 47(3): 113-117, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29122709

ABSTRACT

BACKGROUND: Abortion, spontaneous or induced, is a common complication of pregnancy and exploration of available and safe regimens for medical abortion in developing countries seems crucial. AIMS: The present study was aimed to assess the effect of letrozole in combination with misoprostol in women eligible for legal therapeutic abortion with gestational age ≤14weeks. MATERIALS AND METHODS: This clinical randomized trial was conducted on 78 women who were candidate of medical abortion and eligible for legal abortion with gestational age ≤14 weeks that were randomly divided into two groups of case and controls. Case group received daily oral dose of 10mg letrozole for three days followed by vaginal misoprostol. In control group the patients received only vaginal misoprostol. The rate of complete abortion, induction-of-abortion time, and side-effects were assessed. RESULTS: Complete abortion was observed in 30 patients (76.9%) in case group and 9 (23.1%) cases were failed. In control group there was 16 (41.03%) complete abortions and 23 (58.97%) cases were failed to abort. Patients with gestational age of between 6 and 10 weeks did not show significant difference in both groups (P=0.134). Regarding pregnancy remnants there were significant differences between two groups (P=0.034). The time form admission to discharge in case groups were significantly shorter than those in control group (P=0.001). The indication for curettage in case group was significantly less than control group (P=0.001). CONCLUSION: A 3-day course of letrozole (10mg/daily) followed by misoprostol was associated with a higher complete abortion and lower curettage rates and reduction in time from admission to discharge in women with gestational age ≤14 weeks compared to misoprostol alone.


Subject(s)
Abortifacient Agents, Nonsteroidal/pharmacology , Abortion, Therapeutic/methods , Aromatase Inhibitors/pharmacology , Misoprostol/pharmacology , Nitriles/pharmacology , Outcome Assessment, Health Care , Triazoles/pharmacology , Abortifacient Agents, Nonsteroidal/administration & dosage , Abortifacient Agents, Nonsteroidal/adverse effects , Adult , Aromatase Inhibitors/administration & dosage , Aromatase Inhibitors/adverse effects , Case-Control Studies , Drug Therapy, Combination , Female , Humans , Letrozole , Misoprostol/administration & dosage , Misoprostol/adverse effects , Nitriles/administration & dosage , Nitriles/adverse effects , Pregnancy , Triazoles/administration & dosage , Triazoles/adverse effects
7.
PLoS One ; 12(5): e0177878, 2017.
Article in English | MEDLINE | ID: mdl-28542188

ABSTRACT

Heat shock protein 90 (HSP90) that is ubiquitously expressed in various tissues, is recognized to be a major molecular chaperone. We have previously reported that prostaglandin F2α (PGF2α), a potent bone remodeling mediator, stimulates the synthesis of interleukin-6 (IL-6) through p44/p42 mitogen-activated protein (MAP) kinase and p38 MAP kinase in osteoblast-like MC3T3-E1 cells, and that Rho-kinase acts at a point upstream of p38 MAP kinase. In the present study, we investigated the involvement of HSP90 in the PGF2α-stimulated IL-6 synthesis and the underlying mechanism in MC3T3-E1 cells. Geldanamycin, an inhibitor of HSP90, significantly amplified both the PGF2α-stimulated IL-6 release and the mRNA expression levels. In addition, other HSP90 inhibitors, 17-allylamino-17demethoxy-geldanamycin (17-AAG) and 17-dimethylamino-ethylamino-17-demethoxy-geldanamycin (17-DMAG) and onalespib, enhanced the PGF2α-stimulated IL-6 release. Geldanamycin, 17-AAG and onalespib markedly strengthened the PGF2α-induced phosphorylation of p38 MAP kinase. Geldanamycin and 17-AAG did not affect the PGF2α-induced phosphorylation of p44/p42 MAP kinase and myosin phosphatase targeting subunit (MYPT-1), a substrate of Rho-kinase, and the protein levels of RhoA and Rho-kinase. In addition, HSP90-siRNA enhanced the PGF2α-induced phosphorylation of p38 MAP kinase. Furthermore, SB203580, an inhibitor of p38 MAP kinase, significantly suppressed the amplification by geldanamycin, 17-AAG or 17-DMAG of the PGF2α-stimulated IL-6 release. Our results strongly suggest that HSP90 negatively regulates the PGF2α-stimulated IL-6 synthesis in osteoblasts, and that the effect of HSP90 is exerted through regulating p38 MAP kinase activation.


Subject(s)
Benzoquinones/pharmacology , Dinoprost/pharmacology , HSP90 Heat-Shock Proteins/antagonists & inhibitors , Interleukin-6/biosynthesis , Lactams, Macrocyclic/pharmacology , Osteoblasts/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism , Abortifacient Agents, Nonsteroidal/pharmacology , Animals , Cells, Cultured , Gene Expression Regulation/drug effects , Interleukin-6/genetics , Mice , Osteoblasts/cytology , Osteoblasts/drug effects , Phosphorylation/drug effects , p38 Mitogen-Activated Protein Kinases/genetics , rho-Associated Kinases/metabolism
8.
Int J Gynaecol Obstet ; 136(2): 210-214, 2017 Feb.
Article in English | MEDLINE | ID: mdl-28099731

ABSTRACT

OBJECTIVE: To investigate the feasibility of providing harm-reduction services to reduce unsafe abortion in Tanzania. METHODS: A cross-sectional study was conducted among 110 women who received harm-reduction counseling at a public health center in Dar es Salaam between February 10 and October 10, 2014. Background and clinical information was collected for all women; a subgroup (n=50) undertook a semi-structured survey that measured the type of services women received, women's perception of the services, and pregnancy outcome. The main study outcomes were attendance at the follow-up visit, type and quality of information women received on both visits, and misoprostol use for pregnancy termination. RESULTS: Overall, 55 (50.0%) women attended follow-up services. Misoprostol was used for induced abortion among 54 (98.2%); 38 (70.4%) of these women had obtained contraception at the follow-up visit. Likelihood of attendance for follow-up was increased among women who were older than 34 years (odds ratio [OR] 2.2, 95% confidence interval [CI] 0.1-35.8), were married (OR 2.1, 95% CI 0.8-5.7), and had a post-primary education level (OR 2.0, 95% CI 0.8-5.3). On average, 44 (87.0%) women received all required information at the initial counseling session and none reported major complications that required hospitalization. CONCLUSION: Harm-reduction services for unsafe abortion are feasible and acceptable, and could provide an excellent opportunity to fight abortion-related morbidity and mortality in Tanzania.


Subject(s)
Abortifacient Agents, Nonsteroidal/pharmacology , Abortion, Induced/methods , Contraception/statistics & numerical data , Counseling/statistics & numerical data , Harm Reduction , Misoprostol/pharmacology , Adolescent , Adult , Cross-Sectional Studies , Female , Humans , Logistic Models , Maternal Mortality , Multivariate Analysis , Pregnancy , Pregnancy Outcome , Pregnancy, Unplanned , Socioeconomic Factors , Surveys and Questionnaires , Tanzania , Young Adult
9.
Eur J Contracept Reprod Health Care ; 21(6): 436-442, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27636701

ABSTRACT

OBJECTIVES: The aim of the study was to assess the extent to which misoprostol alters mucosal or systemic immune responses following either buccal or vaginal administration. METHODS: This was a prospective, crossover pilot study of 15 healthy, reproductive-age women. Women first received 800 µg misoprostol either via buccal or vaginal administration and were crossed over 1 month later to receive the drug via the other route. Cervicovaginal lavage samples, cervical Cytobrush samples, cervicovaginal swabs, urine and blood were obtained immediately prior to drug administration and the following day. Parameters assessed included urine and cervicovaginal misoprostol levels, whole blood cytokine responses (by ELISA) to immune stimulation with lipopolysaccharide, peripheral blood and cervical lymphocyte phenotyping by flow cytometry, cervicovaginal antimicrobial peptide measurement by ELISA and vaginal microbial ecology assessment by 16S rRNA sequencing. RESULTS: Neither buccal nor vaginal misoprostol significantly altered local or systemic immune and microbiological parameters. CONCLUSION: In this pilot study, we did not observe significant alteration of mucosal or systemic immunology or vaginal microbial ecology 1 day after drug administration following either the buccal or vaginal route.


Subject(s)
Abortifacient Agents, Nonsteroidal/pharmacology , Cervix Uteri , Misoprostol/pharmacology , Vagina , Abortifacient Agents, Nonsteroidal/administration & dosage , Administration, Buccal , Administration, Intravaginal , Cervix Uteri/drug effects , Cervix Uteri/immunology , Cervix Uteri/microbiology , Cross-Over Studies , Elafin/blood , Enzyme-Linked Immunosorbent Assay , Female , Humans , Immune System/drug effects , Lymphocytes/drug effects , Microbiota , Misoprostol/administration & dosage , Pilot Projects , United States , Vagina/drug effects , Vagina/immunology , Vagina/microbiology
10.
Eur J Obstet Gynecol Reprod Biol ; 205: 150-2, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27592417

ABSTRACT

OBJECTIVE: To investigate the effects of salpingectomy and methotrexate treatments on ovarian reserve in ectopic pregnancy. STUDY DESIGN: In this prospective study, a total of 131 patients with ectopic pregnancy were divided into 3 groups of methotrexate (MTX) only (Group-1, n: 55), salpingectomy only (Group-2, n: 61), and salpingectomy following MTX (Group-3, n: 15). Pretreatment and post-treatment anti-Müllerian hormone (AMH) levels were evaluated. RESULTS: Significant differences in AMH levels were detected between group 1 and group 2 (2.52±1.28 vs. 1.96±1.66, p=0.043), and group 1 and group 3 (2.52±1.28 vs. 1.77±0.76, p=0.035) at one month postoperative. However, these differences disappeared at the 3rd postoperative month. When AMH levels were compared within the same group, postoperative one month AMH levels were significantly lower than the preoperative AMH levels only in group 3 (p=0.03). However, this difference also disappeared at the 3rd postoperative month. CONCLUSION: Systemic single-dose methotrexate treatment, unilateral salpingectomy, and salpingectomy following methotrexate administration in ectopic pregnancy were reassuring based on pretreatment and post-treatment AMH levels. Current medical and surgical treatment approaches do not have an obvious negative effect on ovarian reserve.


Subject(s)
Abortifacient Agents, Nonsteroidal/therapeutic use , Methotrexate/therapeutic use , Ovarian Reserve/drug effects , Pregnancy, Ectopic/therapy , Salpingectomy , Abortifacient Agents, Nonsteroidal/pharmacology , Adult , Female , Humans , Methotrexate/pharmacology , Ovary/drug effects , Pregnancy , Pregnancy, Ectopic/drug therapy , Pregnancy, Ectopic/surgery , Prospective Studies , Treatment Outcome , Young Adult
11.
J Gynecol Obstet Biol Reprod (Paris) ; 45(7): 673-8, 2016 Sep.
Article in French | MEDLINE | ID: mdl-26993077

ABSTRACT

INTRODUCTION: Interstitial pregnancy accounts for 3 to 11% of ectopic pregnancy; these pregnancies are the more frequently non-tubal ectopic pregnancy. Medical treatment can be used in case of unruptured interstitial pregnancy and is used more and more frequently to avoid hemorrhagic risk and risk of conversion to radical surgery when a surgical management is decided. However, a larger use of methotrexate in interstitial pregnancy and conditions of use are not clearly defined. The aim of this study is to report a series of unruptured interstitial pregnancy managed by in situ injection of methotrexate. WOMEN AND METHODS: This retrospective observational study included women treated for an interstitial pregnancy between 2010 and 2013 in a teaching hospital. Medical management used was an in situ injection of methotrexate (1mg/kg) guided by vaginal sonography plus an intramuscular injection of methotrexate (1mg/kg) in the 48hours following in situ injection and 600mg of mifepristone when progesterone blood rate was more than 9ng/mL. A great decrease of serum hCG without surgery was considered a success. RESULTS: Fourteen women had an interstitial pregnancy during the study period. Six were managed surgically in 5 cases for suspicion of uterine rupture and one for pregnancy of unknown location. Eight women had a medical management and the success rate was 100%. Mean time for decrease of serum hCG until 2 UI/L was 54.4 days [34.0-74.8]. No uterine rupture or immediate complication was reported. Five women out of 8 had a spontaneous pregnancy after management of interstitial pregnancy. CONCLUSION: Medical management by in situ injection of methotrexate under sonographic guidance with an intramuscular injection within the 48hours following the in situ injection and mifepristone when ectopic pregnancy was active can be proposed in first-line therapy in case of unruptured interstitial pregnancy. This treatment has a great efficiency and low rate of complications.


Subject(s)
Abortifacient Agents, Nonsteroidal/administration & dosage , Abortifacient Agents, Nonsteroidal/pharmacology , Methotrexate/administration & dosage , Methotrexate/pharmacology , Pregnancy, Cornual/drug therapy , Abortifacient Agents, Steroidal/therapeutic use , Adult , Drug Therapy, Combination , Female , Humans , Mifepristone/therapeutic use , Pregnancy , Pregnancy, Cornual/diagnostic imaging , Retrospective Studies , Treatment Outcome
12.
Reproduction ; 151(5): 517-26, 2016 May.
Article in English | MEDLINE | ID: mdl-26908917

ABSTRACT

In mares, prostaglandin F2α (PGF2α) secreted from the endometrium is a major luteolysin. Some domestic animals have an auto-amplification system in which PGF2α can stimulate its own production. Here, we investigated whether this is also the case in mares. In an in vivo study, mares at the mid-luteal phase (days 6-8 of estrous cycle) were injected i.m. with cloprostenol (250 µg) and blood samples were collected at fixed intervals until 72 h after treatment. Progesterone (P4) concentrations started decreasing 45 min after the injection and continued to decrease up to 24 h (P < 0.05). In turn, 13,14-dihydro-15-keto-PGF2α (PGFM) metabolite started to increase 4h after an injection and continued to increase up to 72 h (P < 0.05). PGF receptor (PTGFR) mRNA expression in the endometrium was significantly higher in the late luteal phase than in the early and regressed luteal phases (P < 0.05). In vitro, PGF2α significantly stimulated (P < 0.05) PGF2α production by endometrial tissues and endometrial epithelial and stromal cells and significantly increased (P < 0.05) the mRNA expression of prostaglandin-endoperoxide synthase-2 (PTGS2), an enzyme involved in PGF2α synthesis in endometrial cell. These findings strongly suggest the existence of an endometrial PGF2α auto-amplification system in mares.


Subject(s)
Corpus Luteum/metabolism , Dinoprost/pharmacology , Endometrium/metabolism , Estrous Cycle/metabolism , Stromal Cells/metabolism , Abortifacient Agents, Nonsteroidal/pharmacology , Animals , Blotting, Western , Cells, Cultured , Corpus Luteum/drug effects , Dinoprost/analogs & derivatives , Dinoprost/blood , Endometrium/drug effects , Estrous Cycle/drug effects , Female , Horses , Progesterone/blood , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Stromal Cells/drug effects
13.
Reproduction ; 151(5): 539-52, 2016 May.
Article in English | MEDLINE | ID: mdl-26908918

ABSTRACT

Implantation in humans and other mammals is a critical period during which high embryonic mortality rates occur. Prostaglandins (PGs) are key mediators regulating interactions between the reproductive tract and the conceptus (embryo with extraembryonic membranes). Although the significance of PGF2α as a regulator of corpus luteum regression is well established, the role of its high amounts in the uterine lumen in most mammals, regardless of placentation type, during the implantation period remains unresolved. We hypothesized that PGF2α acting as an embryonic signal mediator contributes to pregnancy establishment. Using a porcine model, we demonstrated that the conceptus and its signal (estradiol-17ß) elevated endometrial expression of PGF2α receptor (PTGFR) in vivo and in vitro PTGFR protein was expressed mainly in luminal epithelial (LE) and glandular epithelial cells and blood vessels in the endometrium. PGF2α stimulated the MAPK1/3 pathway in endometrial LE cells that coincided with elevated gene expression and secretion of endometrial vascular endothelial growth factor A (VEGFA) protein. PGF2α-PTGFR and adenylyl cyclase signaling were involved in this process. PGF2α-induced VEGFA acting through its receptors stimulated proliferation of endometrial endothelial cells. Moreover, PGF2α elevated gene expression of biglycan, matrix metalloproteinase 9, transforming growth factor ß3, and interleukin 1α in the endometrium. In summary, our study indicates that PGF2α participates in pregnancy establishment by promoting angiogenesis and expression of genes involved in tissue remodeling and conceptus-maternal interactions in porcine endometrium during early pregnancy.


Subject(s)
Abortifacient Agents, Nonsteroidal/pharmacology , Dinoprost/pharmacology , Embryo Implantation/drug effects , Embryo, Mammalian/blood supply , Endometrium/blood supply , Neovascularization, Physiologic/drug effects , Receptors, Prostaglandin/metabolism , Animals , Blotting, Western , Cells, Cultured , Embryo, Mammalian/drug effects , Embryo, Mammalian/metabolism , Embryonic Development/drug effects , Endometrium/drug effects , Endometrium/metabolism , Female , Immunoenzyme Techniques , Pregnancy , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction , Receptors, Prostaglandin/genetics , Reverse Transcriptase Polymerase Chain Reaction , Swine
14.
J Vet Med Sci ; 78(2): 213-20, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26369365

ABSTRACT

Pregnant rats were treated with 30 mg/kg of methotrexate (MTX) on gestation day (GD) 16, and fetal brains were examined time-dependently. On GD 20, the appearance of the telencephalon in the MTX group was different from that in the control group, and the major axis of the telencephalon of the MTX group was shortened, compared to that of the control group. In the sagittal section of the telencephalon in the MTX group on GD 20, histopathological findings of deformation and narrowing of the cerebral ventricle, the disturbance of the arrangement of the marginal cell layer of subventricular zone (SVZ) and thickening of telencephalic wall, cortical plate and ventricular zone (VZ)/SVZ were possibly attributable to neuronal migration disorders by MTX. Through all the experimental period, few pyknotic cells or TUNEL-positive cells were observed in the VZ/SVZ of the telencephalic wall and striatum in the control group. On the other hand, in the VZ/SVZ of the telencephalic wall and striatum in the MTX group, pyknotic cells or TUNEL-positive cells were observed on GD 17, and they increased significantly on GD18 and then decreased to the control levels from GD 19 onward. The phospho-Histone H3-positive rate decreased remarkedly in the VZ/SVZ of the telencephalic wall and striatum of the MTX group on GDs 17 and 18, compared to the control group, but they recovered on and after GD 19. These results suggested that there was a high possibility that development of the telencephalon in this period required strong folic acid.


Subject(s)
Abortifacient Agents, Nonsteroidal/pharmacology , Methotrexate/pharmacology , Telencephalon/drug effects , Telencephalon/embryology , Animals , Embryonic Development/drug effects , Female , Folic Acid Deficiency , Gestational Age , Pregnancy , Rats , Rats, Wistar
15.
J Obstet Gynaecol Res ; 42(3): 246-51, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26663590

ABSTRACT

AIM: The aim of this study was to compare vaginal misoprostol versus intravenous (i.v.) oxytocin in the management of pregnancies with second-trimester intrauterine fetal death (IUFD). METHODS: This randomized clinical trial was conducted on 85 pregnant women with IUFD and unripe cervix who were admitted for labor induction. Forty were randomly allocated to receive 200 mcg vaginal misoprostol every 12 h, and 45 were randomly assigned to receive high-dose i.v. oxytocin (starting from 6 mU/min to reach the maximum dose of 40 mU/min). This study is registered at www.irct.ir (IRCT201307159568N5). RESULTS: The induction-to-delivery interval in the misoprostol group (10.5 ± 5.3 [range 4-27] h) was significantly lower than that in the oxytocin group (14 ± 6.8 [range 4-30] h) (P = 0.009). The total hospital stay in the misoprostol group (22.6 ± 9.5 [range 12-48] h) was significantly lower than that in the oxytocin group (35.3 ± 16.4 [range 12-72] h) (P = 0.000). Although the successful induction rate was higher in the misoprostol group, this was not significant (95% vs 86.7%, P = 0.1). Placenta retention occurred more in the oxytocin group (20% vs 5%, P = 0.03). CONCLUSION: Both vaginal misoprostol and high-dose i.v. oxytocin are highly effective in labor induction in second-trimester pregnancies with IUFD and an unripe cervix. However, vaginal misoprostol seems to be superior to i.v. oxytocin.


Subject(s)
Abortifacient Agents, Nonsteroidal/pharmacology , Abortion, Induced/methods , Misoprostol/pharmacology , Outcome Assessment, Health Care , Oxytocics/pharmacology , Oxytocin/pharmacology , Abortifacient Agents, Nonsteroidal/administration & dosage , Administration, Intravaginal , Adult , Female , Fetal Death , Humans , Infusions, Intravenous , Misoprostol/administration & dosage , Oxytocics/administration & dosage , Oxytocin/administration & dosage , Pregnancy , Pregnancy Trimester, Second , Young Adult
16.
J Obstet Gynaecol Res ; 42(3): 286-90, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26694788

ABSTRACT

AIM: Ectopic pregnancy is a medical emergency. The classic treatment for this condition is surgery but early diagnosis allows for non-surgical treatment. In recent years, intramuscular methotrexate has been considered, due to easy administration, its less invasive nature and low complications, but there are arguments about its effects. The aim of this study was to evaluate tubal patency after treatment of ectopic pregnancy with methotrexate and related factors. METHODS: This cross-sectional study was conducted on 80 women with ectopic pregnancy who were admitted to Sanandaj Be'sat Hospital in 2014. Patients who had successful treatment for ectopic pregnancy with single or multiple doses of methotrexate 50 mL/m(2) were enrolled. Three to 6 months after treatment, the patients were evaluated for tubal patency by hysterosalpingography. Data were analyzed using spss, t-tests, χ(2) -test and logistic regression. RESULTS: The tubal patency rate after treatment of ectopic pregnancy with methotrexate was 75% in hysterosalpingography. The average size of the ectopic pregnancy mass of women with open fallopian tubes was 22.5 ± 7.0 mm and for women with closed fallopian tubes it was 34.7 ± 10.0 mm (P = 0.0001). ß-human chorionic gonadotropin levels were 642.1 ± 850.5 in women with open fallopian tubes and 3816.3 ± 4487.3 for women with closed fallopian tubes (P = 0.0001). There was no significant correlation statistically between tubal patency with a history of stillbirth and number of pregnancies (P > 0.5). There was a statistically significant relation between tubal patency and the number of births and also methotrexate dose (P < 0.05). CONCLUSION: Treatment of ectopic pregnancy with methotrexate is effective for saving tubal patency. Levels of human chorionic gonadotrophin-ß < 1745, the treatment regimen of methotrexate (single or multiple doses) and ectopic pregnancy mass size smaller than 33.5 mm are significant predictors of tubal patency.


Subject(s)
Abortifacient Agents, Nonsteroidal/pharmacology , Fallopian Tubes/diagnostic imaging , Methotrexate/pharmacology , Outcome Assessment, Health Care , Pregnancy, Ectopic/drug therapy , Abortifacient Agents, Nonsteroidal/administration & dosage , Adult , Cross-Sectional Studies , Female , Humans , Hysterosalpingography , Methotrexate/administration & dosage , Middle Aged , Pregnancy , Young Adult
17.
J Gynecol Obstet Biol Reprod (Paris) ; 44(3): 203-11, 2015 Mar.
Article in French | MEDLINE | ID: mdl-25661493

ABSTRACT

Methotrexate is a folic acid analog, which is a thymidylate synthetase and dihydrofolate reductase inhibitor. It is used in oncology, dermatology and rheumatology and off labelling in the treatment of ectopic pregnancies. This paper is a review of methotrexate pharmacology with focus on data concerning ectopic pregnancies.


Subject(s)
Abortifacient Agents, Nonsteroidal/pharmacology , Methotrexate/pharmacology , Pregnancy, Ectopic/drug therapy , Female , Humans , Pregnancy
18.
Reprod Health Matters ; 22(44 Suppl 1): 75-82, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25702071

ABSTRACT

Extensive evidence exists regarding the efficacy and acceptability of medical abortion through 63 days since last menstrual period (LMP). In Mexico City's Secretariat of Health (SSDF) outpatient facilities, mifepristone-misoprostol medical abortion is the first-line approach for abortion care in this pregnancy range. Recent research demonstrates continued high rates of complete abortion through 70 days LMP. To expand access to legal abortion services in Mexico City (where abortion is legal through 12 weeks LMP), this study sought to assess the efficacy and acceptability of the standard outpatient approach through 70 days in two SSDF points of service. One thousand and one women seeking pregnancy termination were enrolled and given 200 mg mifepristone followed by 800 µg misoprostol 24-48 hours later. Women were asked to return to the clinic one week later for evaluation. The great majority of women (93.3%; 95% CI: 91.6-94.8) had complete abortions. Women with pregnancies ≤ 8 weeks LMP had significantly higher success rates than women in the 9th or 10th weeks (94.9% vs. 90.5%; p = 0.01). The difference in success rates between the 9th and 10th weeks was not significant (90.0% vs. 91.2%; p = 0.71). The majority of women found the side effects (82.9%) and the use of misoprostol (84.4%) to be very acceptable or acceptable. This study provides additional evidence supporting an extended outpatient medical abortion regimen through 10 weeks LMP.


Subject(s)
Abortifacient Agents, Nonsteroidal/pharmacology , Abortifacient Agents, Steroidal/pharmacology , Abortion, Induced/methods , Mifepristone/pharmacology , Misoprostol/pharmacology , Abortion, Induced/psychology , Adolescent , Adult , Drug Combinations , Female , Humans , Mexico , Middle Aged , Outpatients , Patient Acceptance of Health Care , Patient Satisfaction , Pregnancy , Pregnancy Trimester, First , Public Sector , Treatment Outcome , Young Adult
19.
Theriogenology ; 81(7): 947-51, 2014 Apr 15.
Article in English | MEDLINE | ID: mdl-24576713

ABSTRACT

The aim of the present study was to compare the clinical and endocrinological effects of different applications of misoprostol (MIS) and aglepristone (AGL) for the induction of abortion in bitches. For this purpose, 28 healthy pregnant bitches from different breeds, ages, body weights (Body weigt, BWs, 10-40 kg), and between Days 25 to 35 of gestation were used. Bitches were randomly assigned to four groups. In group 1 (GI, n = 7), AGL (10 mg/kg BW, s.c. on 2 consecutive days); in group 2 (GII, n = 7), AGL (as in GI), intravaginal MIS (IVag, 200 µg for bitches with ≤20 kg BW, 400 µg for bitches with >20 kg BW, daily intravaginally until completion of abortion); in group 3 (GIII, n = 7), AGL (as in GI), ICVag (as in GII), per os MIS (400 µg for bitches with ≤20 kg BW, 800 µg for bitches with >20 kg BW, daily orally, until completion of abortion); in group 4 (GIV, n = 7), AGL (as in GI), per os MIS (as GIII) were used. Clinical, vaginal, and ultrasonographic examinations were performed daily until abortion was completed. For measurement of serum progesterone, blood samples were collected in all groups immediately after the first AGL administration and every other day until completion of abortion. No statistical differences were found between groups concerning the duration until completion of abortion after treatment (nonsignificant); however, in GII, one bitch completed abortion 2 days after the start of treatment.


Subject(s)
Abortifacient Agents, Nonsteroidal/pharmacology , Abortion, Veterinary/chemically induced , Dogs , Estrenes/pharmacology , Misoprostol/pharmacology , Abortifacient Agents, Nonsteroidal/administration & dosage , Animals , Estrenes/administration & dosage , Female , Misoprostol/administration & dosage , Pregnancy
20.
Minerva Ginecol ; 65(4): 445-51, 2013 Aug.
Article in English | MEDLINE | ID: mdl-24051944

ABSTRACT

AIM: The aim of this paper was to evaluate the effectiveness of sublingual use of misoprostol in women undergoing first trimester surgical abortion. Special consideration was given in a sub-group analysis according to parity. METHODS: A retrospective study was conducted, enrolling patients during 2006-2009. Pregnancies less than 12 weeks of gestation were exclusively included. Our sample was divided in: group 1, in which we included women who had received 400 mcg of misoprostol sublingually two hours before surgical abortion and group 2, with no use of misoprostol. Cervical dilatation and estimated blood loss (EBL) were compared between the two groups. Moreover, a sub-group analysis of the former parameters was made separately in nulliparous and multiparous women. RESULTS: Out of 79 patients included, 48 (60.75%) received misoprostol, while 31 (39.25%) did not. Cervical dilatation was significantly higher in group 1 (6.4±2.1 mm vs. 4.7±1.7 mm in group 2, P=0.001), while EBL was significantly lower in the same group (105.0±22.1 mL vs. 120.3±24.2 mL for group 2, P=0.005). Concerning the sub-analysis, cervical dilatation was significantly increased and EBL was significantly lower in multiparous receiving misoprostol comparing with those who did not (P=0.001 and P=0.002, respectively). However, the same parameters did not differ significantly between the two sub-groups of nulliparous women. CONCLUSION: Sublingual administration of 400mcg misoprostol is effective concerning cervical ripening and EBL in women undergoing first trimester surgical abortion. According to the results of the present clinical trial prostaglandin E1 is more effective in multiparous group of women.


Subject(s)
Abortifacient Agents, Nonsteroidal/pharmacology , Abortion, Induced/methods , Cervical Ripening/drug effects , Misoprostol/pharmacology , Premedication , Abortifacient Agents, Nonsteroidal/administration & dosage , Administration, Sublingual , Adult , Dilatation and Curettage , Drug Evaluation , Female , Humans , Misoprostol/administration & dosage , Parity , Pregnancy , Pregnancy Trimester, First , Retrospective Studies , Young Adult
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