dinoprost and sulprostone

Preparing the cervix prior to surgical abortion is intended to make the procedure both easier and safer. Options for cervical preparation include osmotic dilators and pharmacologic agents. Many formulations and regimens are available, and recommendations from professional organizations vary for the use of preparatory techniques in women of different ages, parity or gestational age of the pregnancy.. To determine whether cervical preparation is necessary in the first trimester, and if so, which preparatory agent is preferred.. We searched Cochrane, Popline, Embase, Medline and Lilacs databases for randomised controlled trials investigating the use of cervical preparatory techniques prior to first trimester surgical abortion. In addition, we hand-searched key references and contacted authors to locate unpublished studies or studies not identified in the database searches.. Randomised controlled trials investigating any pharmacologic or mechanical method of cervical preparation, with the exception of nitric oxide donors (the subject of another Cochrane review), administered prior to first trimester surgical abortion were included. Outcome measures must have included the amount of cervical dilation achieved, the procedure duration or difficulty, side-effects, patient satisfaction or adverse events to be included in this review.. Trials under consideration were evaluated by considering whether inclusion criteria were met as well as methodologic quality. Fifty-one studies were included, resulting in 24 different cervical preparation comparisons. Results are reported as odds ratios (OR) for dichotomous outcomes and weighted mean differences for continuous data.. When compared to placebo, misoprostol (400-600 microg given vaginally or sublingually), gemeprost, mifepristone (200 or 600 mg), prostaglandin E and F(2alpha) (2.5 mg administered intracervically) demonstrated larger cervical preparation effects. When misoprostol was compared to gemeprost, misoprostol was more effective in preparing the cervix and was associated with fewer gastrointestinal side-effects. For vaginal administration, administration 2 hours prior was less effective than administration 3 hours prior to the abortion. Compared to oral misoprostol administration, the vaginal route was associated with significantly greater initial cervical dilation and lower rates of side-effects; however, sublingual administration 2-3 hours prior to the procedure demonstrated cervical effects superior to vaginal administration.When misoprostol (600 microg oral or 800 microg vaginal) was compared to mifepristone (200 mg administered 24 hours prior to procedure), misoprostol had inferior cervical preparatory effects. Compared to day-prior laminaria tents, 200 or 400 microg vaginal misoprostol showed no differences in the need for further mechanical dilation or length of the procedure; similarly, the osmotic dilators Lamicel and Dilapan showed no differences in cervical ripening when compared to gemeprost, although gemeprost had cervical effects which were superior to laminaria tents. Older prostaglandin regimens (sulprostone, prostaglandin E(2) andF(2alpha)) were associated with high rates of gastrointestinal side-effects and unplanned pregnancy expulsions. Few studies reported women's satisfaction with cervical preparatory techniques.. Modern methods of cervical ripening are generally safe, although efficacy and side-effects between methods vary. Reports of adverse events such as cervical laceration or uterine perforation are uncommon overall in this body of evidence and no published study has investigated whether cervical preparation impacts these rare outcomes. Cervical preparation decreases the length of the abortion procedure; this may become increasingly important with increasing gestational age, as mechanical dilation at later gestational ages takes longer and becomes more difficult. These data do not suggest a gestational age where the benefits of cervical dilation outweigh the side-effects, including pain, that women experience with cervical ripening procedures or the prolongation of the time interval before procedure completion. Mifepristone 200 mg, osmotic dilators and misoprostol, 400microg administered either vaginally or sublingually, are the most effective methods of cervical preparation.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Alprostadil; Cervical Ripening; Dinoprost; Dinoprostone; Female; Humans; Mifepristone; Misoprostol; Pregnancy; Pregnancy Trimester, First

Topics: Dinoprost; Dinoprostone; Female; Humans; Menstruation-Inducing Agents; Pregnancy; Puerperal Disorders; Uterine Inertia

This article outlines the current modalities of pregnancy termination, as well as their risks and complications, in 3 phases of pregnancy: 1) up to 49 days past the last menstrual period, 2) 8-15 weeks, and 3) 16-24 weeks. Before 8 weeks of pregnancy, suction dilatation and curettage (D and C) is the preferred method. However, a medical approach, possibly self-administered, is viewed as more satisfactory and requires only an improvement in side effects. From 8-15 weeks' gestation, suction D and C and dilatation and evacuation (D and E) are the methods of choice. The use of laminaria tents improves both the facility and safety of these procedures in nulliparous patients and perhaps in multiparous patients. Priming of the cervix with prostaglandin could further decrease the difficulty and risks of these procedures. The use of a hydrogel compound is especially worthy of consideration. There is controversy about the preferred method between 16-20 weeks' gestation. D and E appears to have fewer complications and to be more cost-effective than hypertonic saline injection. Urea-prostaglandin has fewer and less severe complications than saline injection, and seems to be more cost-effective than saline injection in terms of duration of hospitalization. The high frequency of failure and side effects, combined with the possibility of expulsion of a live fetus, make prostaglandin-only injection less desirable. After 20 weeks' gestation, urea-prostaglandin injection is probably the safer method. Given the rapid increase in complications with passing weeks, any delay in providing late abortion services should be avoided. 2nd trimester pregnancy terminations, especially those after 18 weeks' gestation, are associated with increased mortality and morbidity and should be performed at specialized centers where providers are better equipped to manage complications.

Topics: 16,16-Dimethylprostaglandin E2; Abortifacient Agents; Abortion, Induced; Alprostadil; Amnion; Anesthesia; Animals; Arbaprostil; Bacterial Infections; Carboprost; Cervix Uteri; Dilatation and Curettage; Dinoprost; Dinoprostone; Female; Humans; Hypertonic Solutions; Oxytocin; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Progestins; Prostaglandins E; Prostaglandins E, Synthetic; Prostaglandins F; Pulmonary Embolism; Risk; Saline Solution, Hypertonic; Time Factors; Urea; Uterine Hemorrhage; Uterine Perforation

In this prospective multi-centre-study, the new treatment of tubal pregnancies by means of local prostaglandin (PG) F2 alpha and systemic PG E2 application was compared to the usual surgical technique of eliminating the conceptus. In 71 patients treated with PG, the method proved to be successful in 81%; 21 patients (19%) required surgical intervention later. With an initial beta-hCG level of 2500 mIE/ml, the success rate increased to 88%. The duration of hospitalisation was significantly reduced in the PG group compared to the patients treated by primary operation (3 +/- 1 versus 6 +/- 2 days). In the PG-group, only 2 of 24 hysterosalpingograms showed tubal occlusions after treatment, whereas occlusion was present in 3 of 8 patients of the surgically treated group. Four subsequent intrauterine pregnancies in the PG-group occurred compared to none in the surgical group. PG treatment of tubal pregnancy in patients with a low initial beta-hCG value (less than 2500 mIE/ml) revealed promising results with regard to reduced postoperative morbidity and future fertility.. In this prospective, multicenter study, the new treatment of tubal pregnancies by means of local prostaglandin (PG) F2alpha and systemic PGE2 application was compared to the usual surgical technique of eliminating the conceptus. In 71 patients treated with PGs, the method proved to be successful in 81%; 21 patients (195) required surgical intervention at a later date. With an initial beta-hCG level of 2500 mIE/ml, the success rate increased to 88%. The duration of hospitalization was significantly reduced in the PG group compared to the patients treated by primary operation ()3 +or- 1 vs 6+or- 2 days). In the PG group, only 2 of 24 hysterosalpingograms showed tubal occlusions after treatment, whereas occlusion was present in 3 of 8 patients of the surgically treated group. 4 subsequent intrauterine pregnancies in the PG group occurred compared to none in the surgical group. PG treatment of tubal pregnancy in patients with a low initial beta-hCG value (2500 mIE/ml) revealed promising results with regard to reduced postoperative morbidity and future fertility. (author's)

Topics: Abortifacient Agents; Abortifacient Agents, Nonsteroidal; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Clinical Trials as Topic; Dinoprost; Dinoprostone; Drug Therapy, Combination; Female; Humans; Injections, Intralesional; Injections, Intramuscular; Laparoscopy; Peptide Fragments; Pregnancy; Pregnancy, Tubal; Prospective Studies

In 64 patients for therapeutic abortion between the 17th to 26th week of pregnancy abortion was induced with a standardized two-step procedure. After priming of the cervix with intracervical application of prostaglandin gel, labour was induced with extraamniotic PG-administration under epidural anaesthesia. The priming effect was demonstrated objectively in 10 patients with a mechanical tonometer. Prostaglandin F2 alpha, PGE2 and sulprostone were used in the study. There were no significant differences in the total length of therapy (cervix priming time plus induction of labour to abortion interval) between the three groups of patients. Except for 4 patients who required an instrumental extraction of the fetus, abortion occurred in all the patients within a total time of 30 hours (93.8%). The mean induction of labour to abortion interval was 8.3 hours (range: 1.0 to 17.3 hours) in all patients and there was, again, no significant difference between the three groups. Epidural anaesthesia gave a painless induction of abortion in 60 out of 62 patients, while 2 patients required additional analgesics. In 2 patients epidural anaesthesia was contraindicated. In contrast to the systemic administration of PG the incidence of gastrointestinal side effects was low (10.9%). In one case a cervical lesion was observed due to a tenaculum laceration. Although there was no general antibiotic prophylaxis endometritis occurred in only 3 cases (4.7%). The combination of intracervical PG gel for cervical priming, extraamniotic PG gel for labour induction and epidural anaesthesia presents a gentle and efficient method for the termination of pregnancy in the middle to late second trimester.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Eugenic; Abortion, Therapeutic; Adolescent; Adult; Cervix Uteri; Dinoprost; Dinoprostone; Female; Humans; Labor, Induced; Middle Aged; Pregnancy; Prostaglandins E; Prostaglandins E, Synthetic; Prostaglandins F; Prostaglandins, Synthetic

Prostaglandins (PG) are currently the drugs of choice to terminate pathological 2nd trimester pregnancies. 6 different dose schedules of were are tested in 100 women with missed abortion, hydatidiform mole, and fetal malformations: extraamniotic PGF2 alpha, intravenous PGE2, intravenous sulprostone (2 schedules), and intramuscular sulprostone (2 schedules). All tested regimens were effective. Induction-to-abortion times and incidence of side effects were different. Extraamniotic PGF2 alpha and intramuscular sulprostone appear to be the most practicable regimens.

Topics: Abortion, Missed; Congenital Abnormalities; Dinoprost; Dinoprostone; Female; Humans; Hydatidiform Mole; Infant, Newborn; Injections, Intramuscular; Injections, Intravenous; Labor, Induced; Pregnancy; Pregnancy Trimester, Second; Prostaglandins; Prostaglandins E; Prostaglandins E, Synthetic; Prostaglandins F

The aim of this study was to determine whether the magnitude of the intraocular-pressure (IOP)-lowering response in monkeys to the nonselective prostaglandin (PG)F(2a)-isopropyl ester (ie) can be reproduced by combining other PG-subtype-selective compounds. IOP was lowered by approximately 25% after 4-5 days of topical administration with latanoprost (FP agonist, 1.5 microg, q.d.), bimatoprost (prostamide, whose metabolites have been shown to be FP agonists; 9 microg, q.d.), or travoprost (FP agonist, 1.2 microg, q.d) or the EP2 agonist, butaprost (25 microg, b.i.d.). The EP1 agonist, 17-phenyl trinor (PhT) PGE2 (b.i.d.), and EP3 agonist, sulprostone (b.i.d.), had no IOP-lowering effects. The addition of butaprost, sulprostone (10 microg), or 17PhTPGE2 (25 microg) to latanoprost did not lower IOP more than latanoprost alone. However, treatment with the combination of latanoprost, 17PhTPGE2, butaprost, and sulprostone produced a similar 50-55% reduction in IOP, as did PGF(2)alpha-ie (b.i.d.). In conclusion, latanoprost, travoprost, and bimatoprost produce similar IOP-lowering responses in normotensive monkeys and are most efficacious when administered q.d. pm, compared to b.i.d. The combination of the FP, EP1, EP2, and EP3 agonists used in this study was sufficient to lower IOP by the same magnitude as PGF(2)alpha-ie, suggesting that combining PG-subtype agonists may be a potent antiglaucoma strategy.

Topics: Administration, Topical; Alprostadil; Amides; Animals; Antihypertensive Agents; Bimatoprost; Cloprostenol; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Drug Therapy, Combination; Humans; Intraocular Pressure; Latanoprost; Macaca fascicularis; Male; Ophthalmic Solutions; Prostaglandins F, Synthetic; Receptors, Prostaglandin; Receptors, Prostaglandin E; Tonometry, Ocular; Travoprost

The inflammatory cytokine interleukin-1 (IL-1) decreases mineralisation by immortalized mouse-derived cementoblastic cells (OC-CM cells), whilst various prostanoids, including fluprostenol (flup) increase it. Subtraction hybridisation conducted on flup minus IL-1-treated OC-CM cells revealed that one of the primary response genes preferentially induced by flup is the transcription factor Nur77. The objective of this study was to examine the signal transduction cascades regulating prostanoid induction of Nur77 gene expression in OC-CM cells.. Confluent OC-CM cells were treated with prostaglandin E(2) (PGE(2)), prostaglandin F(2alpha) (PGF(2alpha)), specific activators of the various EP prostanoid receptors and of the FP prostanoid receptor, and direct activators/inhibitors of the cyclic AMP-protein kinase A (PKA), protein kinase C (PKC) and intracellular calcium pathways. Nur77 gene expression was examined by mRNA extraction and Northern blot analysis.. PGE(2) and PGF(2alpha) treatment of OC-CM cells significantly increased Nur77 mRNA expression in a time- and dose-dependent fashion. Both the EP1 prostanoid receptor-specific activator 16,16-dimethyl-PGE(2) and the FP prostanoid receptor-specific activator flup significantly increased Nur77 gene expression by OC-CM cells as compared to vehicle-treated controls. Increase in Nur77 gene expression was also observed when direct activators of the PKA, PKC and intracellular calcium pathways were used to treat OC-CM cells. Direct inhibition of the PKA, PKC and intracellular calcium pathways abrogated Nur77 gene expression induced by OC-CM cell treatment with PGE(2) and PGF(2alpha).. Nur77 is a primary gene expressed by OC-CM cells and its induction appears to be mediated by the PKA, PKC and intracellular calcium pathways. Nur77 may affect expression of downstream target genes in OC-CM cells and partially regulate cementoblast cell function.

Topics: Alprostadil; Animals; Calcium Signaling; Cells, Cultured; Colforsin; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Dental Cementum; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; Gene Expression Regulation; Mice; Misoprostol; Nuclear Receptor Subfamily 4, Group A, Member 1; Prostaglandins; Prostaglandins F, Synthetic; Protein Kinase C; Receptors, Prostaglandin; Receptors, Prostaglandin E; Signal Transduction; Time Factors

The cyclooxygenase-prostanoid pathway regulates myometrial contractility through activation of prostanoid receptors on uterine smooth muscles. However, the possible expression of prostanoid receptors on autonomic nerves cannot be excluded completely. The aim of the present study was to clarify the presence of neural prostanoid receptors on adrenergic nerves in the porcine uterine longitudinal muscle. In [(3)H]-noradrenaline-loaded longitudinal muscle strips of porcine uterus, electrical field stimulation (EFS) evoked [(3)H]-noradrenaline release in a stimulation frequency-dependent manner. The EFS-evoked release was completely abolished in Ca(2+)-free (EGTA, 1mM) incubation medium and by tetrodotoxin or omega-conotoxin GVIA, suggesting that [(3)H]-noradrenaline was released from neural components. The EFS-evoked [(3)H]-noradrenaline release was significantly enhanced by treatment with indomethacin. In the presence of indomethacin, PGE(2) and PGF(2alpha), but not PGD(2), inhibited the EFS-evoked [(3)H]-noradrenaline release. Of synthetic prostanoid receptor agonists examined, both U46619 (TP) and sulprostone (EP(1)/EP(3)) decreased the EFS-evoked [(3)H]-noradrenaline release in a concentration-dependent manner, while fluprostenol (FP), BW245C (DP) and butaprost (EP(2)) were almost ineffective. SQ29548 (TP receptor antagonist) blocked the effect of U46619, but SC19220 (EP(1) receptor antagonist) did not change the inhibition by sulprostone or PGE(2). Double immunofluorescence staining using protein gene product 9.5, tyrosine hydroxylase, EP(3) receptor and TP receptor antibodies suggested the localization of EP(3) or TP receptors on adrenergic nerves in the porcine uterus. These results indicated that neural EP(3) and TP receptors are present on adrenergic nerves of the porcine uterine longitudinal muscle. Endogenous prostanoid produced by cyclooxygenase can regulate noradrenaline release in an inhibitory manner through activation of these neural prostanoid receptors.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Alprostadil; Animals; Dinoprost; Dinoprostone; Electric Stimulation; Female; In Vitro Techniques; Microscopy, Confocal; Microscopy, Fluorescence; Myometrium; Neurons; Norepinephrine; Prostaglandin D2; Prostaglandins; Prostaglandins F, Synthetic; Receptors, Androgen; Receptors, Prostaglandin; Swine

Topics: Adult; Contraindications; Dinoprost; Dinoprostone; Female; France; Guidelines as Topic; Humans; Oxytocics; Postpartum Hemorrhage; Pregnancy; Uterus

The role of prostaglandins in mechanical scratching-induced cutaneous barrier disruption in mice was investigated. Skin prostaglandins contents were measured after cutaneous barrier function was disrupted by scratching using a stainless-steal wire brush (mechanical scratching), then effects of prostanoids on recovery of cutaneous barrier functions were examined. This mechanical scratching increased transepidermal water loss and skin prostaglandins (prostaglandin D2, prostaglandin E2, 6-keto-prostaglandin F1alpha and prostaglandin F2alpha) contents, count-dependently. Topical application of indomethacin immediately after cutaneous barrier disruption delayed the recovery period of cutaneous barrier disruption. We examined effects of several prostanoids (prostaglandin D2, prostaglandin E2, prostaglandin F2alpha, prostaglandin I2 and U46619) on delay of the recovery process of mechanical scratching-induced cutaneous barrier disruption with treatment of indomethacin. Topically applied prostaglandin D2 and prostaglandin E2 accelerated the recovery of cutaneous barrier disruption and topical application of prostaglandin J2, limaprost, sulprostone and ONO-4819, but not 13,14-dihydro-15-keto-prostaglandin D2, 15-deoxy-Delta(12,14)-prostaglandin J2, 17-phenyl-trinor-prostaglandin E2 or butaprost had effects on recovery of the cutaneous barrier. These results suggest that prostaglandin D2 and prostaglandin E2 accelerate the recovery process of cutaneous barrier disruption caused by mechanical scratching, via specific prostanoid DP1, EP3 and EP4 receptors.

Topics: 6-Ketoprostaglandin F1 alpha; Alprostadil; Animals; Anti-Inflammatory Agents, Non-Steroidal; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; Heptanoates; Indomethacin; Male; Mice; Mice, Inbred BALB C; Prostaglandin D2; Pruritus; Receptors, Prostaglandin E; Receptors, Prostaglandin E, EP4 Subtype; Skin; Stress, Mechanical; Time Factors; Water Loss, Insensible

We have investigated the actions of various prostanoid receptor agonists on an isolated preparation of the ferret cervical vagus using a grease-gap extracellular recording technique. The potency ranking for depolarization was BW245C (5-(6-carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl) hydantoin; DP-selective, EC50=0.14 microM)>prostaglandin E2 (nonselective EP agonist)>U-46619 (11alpha, 9alpha-epoxymethano-15S-hydroxyprosta-5Z,13E-dienoic acid; TP agonist)>prostaglandin F2alpha (FP receptor agonist). Sulprostone (EP1/EP3-selective), fluprostenol (FP-selective) and cicaprost and iloprost (both IP-selective) had minimal effects. It is likely that DP, EP2/EP4 and TP receptors are present on the vagal fibres of the ferret.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Biguanides; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; Electrophysiology; Epoprostenol; Ferrets; Hydantoins; Iloprost; In Vitro Techniques; Male; Prostaglandins; Prostaglandins F, Synthetic; Serotonin; Vagus Nerve

This study characterized the subtype of prostanoid receptors on the cholinergic neurones and smooth muscle cells in circularly oriented muscle strips of the pig gastric fundus. Tissues were electrically stimulated (40 V, 4 Hz, 0.25 ms, 2 min) to induce tritium outflow after incubation with [3H]-choline. Indomethacin increased the electrically induced tritium outflow, suggesting an inhibitory effect of endogenous prostanoids. In the presence of indomethacin, PGE2 > PGF2alpha >PGI2 inhibited tritium release while the TP-receptor agonist U-46619 and PGD2 had no effect. The EP2-receptor agonist butaprost had no effect while the EP1- and EP3-receptor agonist sulprostone mimicked the effect of PGE2. The effect of sulprostone was not affected by AH 6809, that antagonizes EP1- and EP2-receptors, suggesting the presence of presynaptic EP3-receptors on the cholinergic nerve endings. All prostanoid receptor agonists, except butaprost, contracted the tissues concentration-dependently; the rank order of potency (U-46619 > sulprostone > PGE2 > PGF2alpha > PGD2 = PGI2) suggests the presence of TP- and EP1- and EP3-receptors on the circular smooth muscle cells.

Topics: Animals; Choline; Cyclooxygenase Inhibitors; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; Drug Interactions; Electric Stimulation; Epoprostenol; Gastric Fundus; In Vitro Techniques; Indomethacin; Menstruation-Inducing Agents; Muscle Contraction; Myocytes, Smooth Muscle; Neurons; Potassium Chloride; Prostaglandins; Receptors, Prostaglandin E; Receptors, Prostaglandin E, EP2 Subtype; Receptors, Prostaglandin E, EP3 Subtype; Swine; Tritium

1. A variety of prostanoids were examined for their ability to alter the periarterial nerve stimulation-induced release of noradrenaline (NA) and neuropeptide Y immunoreactive compounds (NPY-ir) from the perfused mesenteric arterial bed of the rat. 2. Periarterial nerve stimulation (16 Hz) increased the overflow of NA, NPY-ir and perfusion pressure. 3. The prostacyclin (PGI2) analogues, carbaPGI2 and cicaprost both produced a concentration-dependent attenuation of the nerve stimulation-induced increase in NA, NPY-ir overflow and perfusion pressure. 4. The prostaglandin (PG) analogue PGE2 attenuated the evoked increase in NPY-ir overflow as well as a modest decrease in NA. 5. PGE1, sulprostone and iloprost attenuated the nerve stimulation-induced increase in NA overflow but not NPY-ir. 6. Neither PGF2alpha nor the thromboxane A2 analogue U46619 altered the evoked increase in NA or NPY-ir overflow. 7. The results support the view that sympathetic co-transmitter release can be differentially modulated by paracrine/autocrine mediators at sympathetic neuroeffector junctions.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Alprostadil; Animals; Dinoprost; Dinoprostone; Electric Stimulation; Epoprostenol; Iloprost; Male; Mesenteric Arteries; Neuropeptide Y; Norepinephrine; Perfusion; Prostaglandins; Radioimmunoassay; Rats; Rats, Sprague-Dawley

We report the case of a 31-year-old woman who delivered twins by Caesarean section in whom atonic uterine haemorrhage developed 6 h postoperatively. During conservative treatment with the high-dose prostaglandin analogs sulprostone (PGE(2)) and dinoprost (PGF(2alpha)), acute pulmonary oedema and cardiac decompensation developed and, subsequently, the patient suffered cardiopulmonary arrest. After a 2h-period of cardiopulmonary resuscitation (CPR), it was possible to restore and stabilize circulation under the highest dose of catecholamines. Despite 2h of CPR, the patient was discharged from hospital 3 months later without any major physical or neurocognitive deficit.

Topics: Adult; Cardiopulmonary Resuscitation; Cesarean Section; Dinoprost; Dinoprostone; Female; Heart Arrest; Heart Failure; Heart Massage; Humans; Oxytocics; Postoperative Hemorrhage; Pregnancy; Pulmonary Edema; Uterine Contraction; Uterine Hemorrhage

Prostaglandins (PG) E1, E2 and F2alpha induce bone resorption in isolated neonatal parietal bone cultures, and an associated increase in interleukin-6 (IL-6) production. Indomethacin had little effect on the response to PGE2, or the relatively non-selective EP receptor agonists 11-deoxy PGE1 and misoprostol, but blocked the effects of PGF2alpha and the F receptor agonist fluprostenol, indicating an indirect action via release of other prostaglandins. It is more likely that there is positive autoregulation of prostaglandins production in this preparation mediated via stimulation of F receptors. The effects of selective EP receptor agonists sulprostone (EP1,3) and 17-phenyl trinor PGE2(EP1), indicated the involvement of EP2 and/or EP4 receptors, which signal via cAMP. The relatively weak increase in IL-6 production by misoprostol (with respect to resorption) suggests that these responses are controlled by different combination of EP2 and EP4 receptors. The PKA activator, forskolin, induced small increases in bone resorption at lower concentrations (50-500 ng/ml) but a reversal of this effect, and inhibition of resorption induced by other stimuli (PTH, PGE2), at higher concentrations (0.5-5 microg/ml). IL-6 production was markedly increased only at the higher concentrations. The inhibitory effect of forskolin may be a calcitonin-mimetic effect. PMA induced both resorption and IL-6 production which were both blocked by indomethacin, indicating a role for PKC in the control of prostaglandin production.

Topics: Alprostadil; Animals; Animals, Newborn; Bone Resorption; Colforsin; Culture Techniques; Cyclic AMP-Dependent Protein Kinases; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; Indomethacin; Mice; Misoprostol; Prostaglandins; Prostaglandins F, Synthetic; Skull

Prostaglandins (PGs) have been implicated in the regulation of vasopressin (VP) and oxytocin (OT) release in response to various stimuli. To examine the site and mechanism of actions of PGs, we studied effects of PGE2 and PG-receptor agonists on supraoptic nucleus (SON) neurones of rat hypothalamic slice preparations using extracellular recording and whole-cell patch-clamp techniques. PGE2 modulated the electrical activity of more than 80% of the neurones studied. The effects of PGE2 on both phasic and non-phasic neurones were mostly excitatory, and dose-dependent. The effects of PGE2 were mimicked by PGF2alpha or the FP agonist, fluprostenol, whereas PGD2 or the selective EP, IP or TP agonist was less effective or had no effect. The effects of PGE2 were unaffected by the EP1 antagonist, SC-51322, but reduced to 80% of control by the EP1/FP/TP antagonist, ONO-NT-012, which reduced the effects of fluprostenol to 32% of control. Moreover, some neurones responsive to PGE2 did not respond to fluprostenol. Patch-clamp analysis in SON slice preparations revealed that PGE2 at 10(-6) M depolarized the membrane potential by 3.9+/-0.3 mV from the resting membrane potential of -58.4+/-2.2 mV in the current-clamp mode. In the voltage-clamp mode, PGE2 induced inward currents at a holding potential of -70 or -80 mV, while it did not affect spontaneous excitatory postsynaptic currents. PGE2 induced currents also in dissociated SON neurones and the reversal potential of the currents was -35.5+/-0.9 mV, which was similar to that of currents induced by fluprostenol. These results suggest that SON neurones possess at least two types of PG receptors, FP receptors and EP receptors of a subclass different from EP1, EP2, or EP3, and that activation of these receptors leads to the opening of nonselective cation channels, membrane depolarization and increase of the action potential discharge.

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Animals; Bridged Bicyclo Compounds; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; Excitatory Postsynaptic Potentials; In Vitro Techniques; Male; Neurons; Oxazepines; Patch-Clamp Techniques; Prostaglandin D2; Prostaglandins, Synthetic; Rats; Rats, Wistar; Receptors, Prostaglandin; Styrenes; Supraoptic Nucleus

Porcine iris sphincter muscle strips contracted in response to carbachol. The tissue contraction was inhibited by prostaglandin (PG) E2 but not by PGF2 alpha. In order to investigate the effect of PGs on the iris cells, the porcine sphincter muscle cells were grown in culture to a confluence and characterized. Using the secondary culture of cells, the effect of PGs on carbachol-induced cell contraction was investigated. Both PGE2 and PGF2 alpha at 100 microM blocked cell contraction completely. The concentration required to inhibit 50% of the maximum contraction in 15 minutes was 10(-6) M for PGE2 and 10(-6)-10(-7) M for PGF2 alpha. Using PGE2 receptor subtype agonists (EP2 agonist, 11-deoxy-16, 16 dimethyl PGE2 and EP3 agonist, sulprostone), PGE2 receptor involved in the inhibition of carbachol-induced contraction was identified to be of the EP2 subtype. In support of this characterization, the addition of PGE2 to cultured porcine sphincter muscle cells increased intracellular cAMP level. The discrepancy in PGF2 alpha effect on carbachol-induced sphincter muscle contraction between iris tissue strips and cultured cells suggests that nonmuscular cells may be involved in the modulation of the PGF2 alpha effect on sphincter muscle cells in vivo.

Topics: Animals; Carbachol; Cells, Cultured; Cyclic AMP; Dinoprost; Dinoprostone; Iris; Muscarinic Agonists; Muscle Contraction; Muscle, Smooth; Receptors, Prostaglandin E; Swine

1. We studied the effects of intracerebroventricular (i.c.v.) administration of prostaglandin E2 (PGE2) and its receptor subtype ligands on plasma levels of catecholamines in urethane-anaesthetized rats. 2. Administration of PGE2 (0.15, 0.3 and 1.5 nmol per animal, i.c.v.) dose-dependently elevated plasma levels of noradrenaline (NA), while the levels of adrenaline were not affected. 3. Administration of sulprostone (EP3/EP1 agonist) and misoprostol (EP3/EP2 agonist) effectively elevated plasma NA levels in a dose-dependent manner (0.1, 0.3, and 1.0 nmol per animal). Butaprost (EP2 agonist) (0.3, 1.0 and 3.0 nmol per animal) was without effect. 17-Phenyl-omega-trinor PGE2 (EP1/EP3 agonist) effectively elevated plasma NA levels only at its highest dose (1.0 nmol per animal), but this elevation was not attenuated by pretreatment with SC-19220 (selective EP1 antagonist) (20 nmol per animal, i.c.v.). 4. The potency of these test agents in elevating plasma levels of NA was as follows; misoprostol > sulprostone > PGE2 > > 17-phenyl-omega-trinor PGE2 > > > butaprost. These results suggest that activation of central prostanoid EP3-receptors induces central sympathetic outflow in rats.

Topics: Abortifacient Agents, Nonsteroidal; Alprostadil; Anesthetics, Intravenous; Animals; Brain; Dibenz(b,f)(1,4)oxazepine-10(11H)-carboxylic acid, 8-chloro-, 2-acetylhydrazide; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; Injections, Intraventricular; Male; Misoprostol; Norepinephrine; Prostaglandin Antagonists; Rats; Rats, Wistar; Receptors, Prostaglandin E; Urethane

We wished to determine whether any evidence indicates that the ductus arteriosus has prostanoid receptors coupled to contractile pathways and whether the sensitivity of the ductus to the dilator effect of prostaglandin E2 (PGE2) was inhibited by other prostanoids. Rings of ductus arteriosus were isolated from fetal New Zealand White rabbits (28 days of gestation) and mounted in vitro. In the presence of 1 microM indomethacin, the vessel was relaxed with either 300 nM forskolin or 10 nM PGE2, and cumulative concentration-contraction response curves to several synthetic prostanoids were obtained with or without a receptor antagonist when available. The vessel was also precontracted with 1 microM indomethacin and 25 mM K+ in 13-14.5 kPa O2, and cumulative concentration-relaxation response curves to PGE2 were obtained with and without addition of prostanoids. In 300 nM forskolin, both U46619 and sulprostone caused concentration-dependent contractions of the ductus in the nanomolar range (EC50 values, i.e., the interpolated molar concentration of the drug causing 50% of its own eventual maximum response of 33 and 42 nM, respectively). Responses to GR63799X and PGF2 alpha were complicated by the fact that these agonists caused relaxation at high concentrations (> or = 30 nM). The response to U46619 was shifted to the right by the thromboxane receptor antagonist EP 092. In 10 nM PGE2, U46619, sulprostone, and GR63799X elicited similar contractile responses, whereas PGF2 alpha had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; Analysis of Variance; Animals; Colforsin; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; Ductus Arteriosus; Female; In Vitro Techniques; Indomethacin; Muscle Contraction; Muscle Relaxation; Muscle, Smooth, Vascular; Pregnancy; Prostaglandin Endoperoxides, Synthetic; Prostaglandins E, Synthetic; Rabbits; Receptors, Prostaglandin; Thromboxane A2; Thromboxanes; Vasoconstrictor Agents

1. We have shown that intracisternal (i.c.) administration of interleukin-1 beta (IL-1 beta) attenuates naloxone-precipitated withdrawal jumps in morphine-dependent mice, and the effect was partly mediated by the corticotropin-releasing factor. To elucidate further other possible mechanisms involved in the inhibitory effect of IL-1 beta on morphine withdrawal jumping behaviour, in this study, we examined the involvement of the prostaglandin-synthesis pathway, because prostaglandins have been shown to mediate the several central effects of IL-1. Furthermore, we examined the effects of subtype-selective prostaglandin receptor agonists on morphine withdrawal jumping behaviour. 2. Mice were rendered morphine-dependent by subcutaneous implantation of a pellet containing 11.5 +/- 0.3 mg morphine hydrochloride for 48 h. Morphine withdrawal syndromes were precipitated by intraperitoneal (i.p.) injection of naloxone (10 mg kg-1). The degree of physical dependence on morphine was estimated by counting the number of jumps, one of the typical withdrawal signs in mice, for 40 min. 3. The inhibitory effect of IL-1 beta (1 ng/mouse) administered intracisternally 30 min before naloxone (10 mg kg-1, i.p.) was significantly blocked by pretreatment with sodium salicylate (a cyclo-oxygenase inhibitor, 10 ng or 30 ng/mouse) administered intracisternally 15 min before IL-1 beta, while i.c. administration of sodium salicylate alone (3 ng, 10 ng or 30 ng/mouse) followed by i.c. administration of vehicle instead of IL-1 beta did not significantly change the number of jumps precipitated by naloxone. 4. Intracisternal administration of M&B28,767 (an EP3-receptor agonist, 1 fg-30 ng/mouse) and sulprostone (an EP1/EP3-receptor agonist, 10 fg-100 ng/mouse) 30 min before naloxone (10 mg kg,-1 i.p.) attenuated withdrawal jumps with a U-shaped dose-response, reaching a peak at 10 pg/mouse and 100 pg/mouse, respectively. On the other hand, i.c. administration of iloprost (an EP1/IP-receptor agonist, 10 fg-100 ng/mouse), butaprost (an EP2-receptor agonist, 10 fg-100 ng/mouse) or prostaglandin F2 alpha (a FP-receptor agonist, 10 fg-100 ng/mouse) 30 min before naloxone (10 mg kg-1, i.p.) did not significantly change the number of jumps precipitated by naloxone. 5. These results indicate that the prostaglandin-synthesis pathway is, at least in part, involved in the inhibitory effect of IL-1 beta on naloxone-precipitated withdrawal jumps in morphine-dependent mice, and that the prostaglandin s

Topics: Alprostadil; Analgesics, Opioid; Animals; Behavior, Animal; Dinoprost; Dinoprostone; Interleukin-1; Male; Mice; Mice, Inbred Strains; Morphine; Naloxone; Prostaglandins; Receptors, Prostaglandin E; Sodium Salicylate; Stimulation, Chemical; Substance Withdrawal Syndrome; Substance-Related Disorders

1. In segments of the rat vena cava preincubated with [3H]-noradrenaline and superfused with physiological salt solution (containing desipramine and corticosterone), we studied the effects of prostaglandins of the D, E and F series, of a prostacyclin analogue and a thromboxane-mimetic and of subtype-selective prostaglandin E-receptor (EP-receptor) ligands on the electrically (0.66 Hz)-evoked tritium overflow. 2. The electrically-evoked tritium overflow was inhibited by prostaglandin E2 (maximum inhibition by about 80%; pIC40 7.49). The effect of prostaglandin E2 was not affected by rauwolscine, which, by itself, increased the evoked overflow; the alpha 2-adrenoceptor antagonist was added to the superfusion medium in all subsequent experiments. Indomethacin failed to affect either the evoked tritium overflow or its inhibition by prostaglandin E2. 3. The inhibitory effect of prostaglandin E2 on the electrically-evoked tritium overflow was not altered by the EP1-receptor antagonist. AH 6809 (6-isopropoxy-9-oxoxanthene-2-carboxylic acid) at a concentration at least 30 fold higher than its pA2 value at EP1-receptors. The following compounds mimicked the effect of prostaglandin E2 showing the following rank order of potencies: misoprostol (EP2-/EP3-receptor agonist) congruent to sulprostone (EP1-/EP3-receptor agonist) congruent to prostaglandin E1 = prostaglandin E2 >> iloprost (EP1-/IP-receptor agonist) = prostaglandin F2 alpha. The evoked overflow was not affected by high concentrations of prostaglandin D2 or the thromboxane-mimetic U46619 (9,11-dideoxy-11 alpha, 9 alpha-epoxy-methano-prostaglandin F2 alpha). 4. The present results suggest that the postganglionic sympathetic nerve fibres innervating the rat vena cava are endowed with presynaptic EP3-receptors.They are not tonically activated by endogenously formed products of cyclo-oxygenase and do not interact with the presynaptic M2-adrenoceptors.

Topics: Alprostadil; Animals; Dinoprost; Dinoprostone; Electric Stimulation; Indomethacin; Misoprostol; Norepinephrine; Prostaglandin Antagonists; Prostaglandin D2; Prostaglandins; Rats; Receptors, Prostaglandin; Receptors, Prostaglandin E; Vena Cava, Inferior; Xanthenes; Xanthones; Yohimbine

Topics: Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Fallopian Tubes; Female; Humans; Injections; Injections, Intramuscular; Peptide Fragments; Pregnancy; Pregnancy, Tubal

Over the past years laparoscopic surgery has become widely accepted in the treatment of tubal pregnancy and instillation of prostaglandin is well established. However, the failure rate is around 20%. This report describes a case of tubal pregnancy treated according to this procedure where the therapy initially seemed to be successful. Instillation of prostaglandin F2 alpha was followed by decreasing beta-HCG values, which continued to decrease after discharge. Thus, rupture of the operated tube on day 17 after surgery was completely unexpected.

Topics: Adult; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Dinoprost; Dinoprostone; Fallopian Tube Diseases; Female; Humans; Injections, Intralesional; Injections, Intramuscular; Laparoscopy; Peptide Fragments; Postoperative Complications; Pregnancy; Pregnancy, Tubal; Rupture, Spontaneous

The injection of different substances into early, unruptured tubal pregnancies is increasingly advocated. In this study, fertility was evaluated after treatment of tubal pregnancy by means of prostaglandins. The overall tubal patency rate was 86.4% and 14 of 20 patients (70%) could subsequently achieve pregnancy.

Topics: Abortifacient Agents, Nonsteroidal; Adolescent; Adult; Dinoprost; Dinoprostone; Drug Therapy, Combination; Fallopian Tubes; Female; Follow-Up Studies; Humans; Hysterosalpingography; Infant, Newborn; Injections, Intramuscular; Laparoscopy; Pregnancy; Pregnancy, Tubal

Topics: Blood Platelets; Calcium; Cyclic AMP; Dinoprost; Dinoprostone; Humans; Iloprost; Platelet Activation; Receptors, Epoprostenol; Receptors, Prostaglandin; Receptors, Prostaglandin E; Tetradecanoylphorbol Acetate

Topics: Animals; Dexamethasone; Dinoprost; Dinoprostone; Epoprostenol; Female; Graft Survival; Granulocytes; Humans; Iloprost; Mice; Mice, Inbred C57BL; Prostaglandins; Skin Transplantation; Thromboxane B2; Thromboxanes

In a study, the clinical use of prostaglandin F2 alpha in local and systemic application in women with ectopic pregnancies were studied (1, 9). Two different treatment schedules were defined and applied. In group A, patients with a diagnosed ectopic and beta-HCG level lower than 850 mIU/ml were treated with prostaglandin F2 alpha i.m. injected only. In group B, prostaglandin F2 alpha were injected in the chorionic cavity of the ectopic by laparoscopy after localisation with a thin needle. In spite of prostaglandin F2 alpha treatment, 6 of 30 patients (20.0%) had to be operated by microsurgery because of increasing serum beta-HCG levels. A control of tubal patency 6 month later showed one closed tube only (4.5%). Up to now, 8 spontaneous intrauterine pregnancies occurred in our study groups after successful prostaglandin F2 alpha treatment; one pregnancy was seen in a women with a single fallopian tube. The conserving treatment of one ectopic pregnancy using prostaglandin F2 alpha yields positive results, if serum beta-HCG levels are below 2000 mIU/ml.

Topics: Abortifacient Agents, Nonsteroidal; Adult; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Dinoprost; Dinoprostone; Drug Therapy, Combination; Fallopian Tube Patency Tests; Fallopian Tubes; Female; Follow-Up Studies; Humans; Injections; Injections, Intramuscular; Peptide Fragments; Pregnancy; Pregnancy, Tubal

Fifteen patients with laparoscopically diagnosed tubal pregnancy and constant or rising plasma beta-hCG levels were treated with prostaglandin F2 alpha and prostaglandin E2. Prostaglandin F2 alpha (5 mgms diluted in 10 cc of isotonic sodium solution) was injected transabdominally with a 22 gauge spinal needle during laparoscopy into the Fallopian tube. Prostaglandin E2 (500 micrograms ms) was given intramuscularly during three consecutive postoperative days. The treatment was defined as successful if plasma beta-hCG levels declined below the lower limit of detection and no further intervention other than prostaglandin application was required. The treatment was successful in eight patients. Six patients underwent laparotomy and salpingotomy because of rising beta-hCG levels. None of the treated patients displayed any adverse reactions following prostaglandin F2 alpha application. One patient underwent explorative laparotomy during the second postoperative day because of lower abdominal pain. During operation, no pathological change could be found. This patient was excluded from the study. In the group treated successfully (n = 8) seven out of eight patients had beta-hCG levels below 2500 mlU/ml preoperatively. In the unsuccessfully treated group (n = 6), four out of six patients had beta-hCG levels above 2500 mlU/ml preoperatively. Mean duration of beta-hCG decline to 10 percent of the maximum preoperative value was 15.8 +/- 8.64 days (mean +/- S.D.). Postoperatively, hysterosalpingography was performed in six out of eight successfully treated patients after three menstrual cycles (one patient had an intrauterine pregnancy, one patient refused written consent). The Fallopian tubes were patent bilaterally in all six patients.

Topics: Abortifacient Agents; Abortifacient Agents, Nonsteroidal; Chorionic Gonadotropin; Chorionic Gonadotropin, beta Subunit, Human; Dinoprost; Dinoprostone; Female; Humans; Hysterosalpingography; Laparoscopy; Oximetry; Peptide Fragments; Pregnancy; Pregnancy, Tubal; Prospective Studies

Topics: Corpus Luteum; Dinoprost; Dinoprostone; Drug Therapy, Combination; Estrogens, Conjugated (USP); Fallopian Tubes; Female; Humans; Injections, Intramuscular; Laparoscopy; Pregnancy; Pregnancy, Tubal

Due to improved diagnosis most tubal pregnancies are detected today before tubal rupture. Therefore various conservative treatment modalities have been described lately. In the present study 73 cases of unruptured tubal pregnancies are described that where treated with local and systemic PG application. With an initial beta-hCG level of below 2,500 mIU/ml serum, 45 of 53 cases could be treated successfully without classical operation. With an initial beta-hCG above 2,500 mIU/ml serum the results were less satisfactory. Hysterosalpingography controls showed that almost all pertinent tubes are patent after such treatment.

Topics: Abortifacient Agents, Nonsteroidal; Corpus Luteum; Dinoprost; Dinoprostone; Drug Therapy, Combination; Estrogens, Conjugated (USP); Female; Humans; Injections, Intramuscular; Injections, Intraperitoneal; Laparoscopy; Pilot Projects; Pregnancy; Pregnancy, Tubal

The authors, using immunofluorescence, studied the effect of different prostaglandins (F2 alpha, E1, dimethyl PGE1) on cervical connective tissue. They analysed 80 biopsies which were carried out before and after the prostaglandins had been applied locally, both in pregnant and in non-pregnant women. The method showed that there were changes in the collagen fibres but not in fibronectin. On the other hand, there does not seem to be any difference in the collagen effect with the methods used: 1) between pregnant and non-pregnant women, and 2) between the different types of prostaglandin that were studied.

Topics: Adolescent; Adult; Aged; Alprostadil; Biopsy; Cervix Uteri; Dinoprost; Dinoprostone; Female; Fluorescent Antibody Technique; Humans; In Vitro Techniques; Middle Aged; Pregnancy; Prostaglandins; Prostaglandins E, Synthetic

A variety of conservative surgical techniques is available for the termination of ectopic pregnancy with preservation of the tube. We report on a new treatment by means of intratubal prostaglandin F2 alpha application followed by intramuscular administration of a prostaglandin E2 derivative (sulprostone) for 3 days. Only 5 of the 30 patients enrolled had to undergo laparotomy later. The results were compared with those obtained by different surgical procedures during the 2 preceding years. Hysterosalpingography was performed in 12 patients of the prostaglandin treated group and 14 of the surgically treated group. Tubal patency was demonstrated in 11 patients of the PG group but only in two patients of the surgically treated group.. Injection of PGF2alpha intratubally, with other conservative management, was compared in 30 consecutive women with proven ectopic pregnancy, to 100 prior women treated surgically. The patient group were all 45 admitted after November 1987 to University of Vienna Hospital with suspected ectopic pregnancy, later proven in 30 by history, positive hCG, ultrasound and laparoscopy; the controls were 74 confirmed cases out of 101 suspected ectopic pregnancies admitted from January 1986- October 1987. They were treated with 5 or 10 mg PGF2alpha (Miniprostin F2alpha, Upjohn, Vienna), injected transabdominally with a 17-gauge needle, during laparoscopic visualization. In 6 patients, 2-3 mg Pgf2alpha was injected into the corpus luteum, but this practice was discontinued when 3 developed tachycardia, hypertension and extrasystole. 25 mg estrogen was injected into the ovary as a luteolytic subsequently. Most women also received PGE2 (Sulprostone, Schering, Berlin) twice daily im, although 4 could not tolerate side effects of nausea and vomiting. All women had hCG levels daily. 5 were treated by laparotomy because of rising hCG or clinical indications. In the control group 74 (73.3%) had laparotomy, and of these, 39 had total or partial salpingectomy, and 21 salpingotomy. Hysterosalpingography demonstrated tubal patency in 11 of 12 PG treated women tested to date; in contract, of 14 of the controls tested, none had patent tubes. 4 of the PG group have since conceived and delivered term infants. The benefits of this conservative method of treating ectopic pregnancy are apparent in the reduced morbidity, shorter hospital stay, simpler treatment technique, lower costs, and especially the higher rate of subsequent tubal patency and fertility.

Topics: Abortifacient Agents; Abortifacient Agents, Nonsteroidal; Dinoprost; Dinoprostone; Fallopian Tubes; Female; Humans; Hysterosalpingography; Pregnancy; Pregnancy, Tubal

Three antiprogestogens of the RU 38.486, ZK 98.734, and ZK 98.299, were studied at different stages of pregnancy in the guinea pig. Treatment starting on postconception day 4 completely prevented nidation; all three compounds had comparable inhibitory potency. Treatment after nidation, starting on postconception day 8, induced decidual collapse and bleeding, but embryonic tissue was retained in nidation sites. In contrast to results in animals in nonfertile cycles, luteolysis was not induced, indicating that antiprogestogens lack the ability to induce uterine prostaglandin synthesis/liberation. On postconception day 43, RU 38.486 showed marginal abortifacient activity. The other compounds induced expulsion more rapidly and at a higher rate. The comparatively pronounced antiglucocorticoid activity of RU 38.486 may account for this difference. With RU 38.486, a high level of uterine prostaglandin sensitivity and a cervical ripening were induced consistently and fast; spontaneous labor, on the other hand, occurred after several days, if at all. Complete uterine evacuation was induced within hours by otherwise inactive doses of sulprostone in various combinations with ZK 98.299 RU 38.486 but surprisingly not with ZK 98.734. A single dose of ZK 98.299 induced an approximately thirtyfold increase in uterine prostaglandin sensitivity within 24 hours, exceeding that present before term, but did not induce spontaneous labor. This is evidence that endogenous prostaglandins were not activated, analogous to perinidation stages. Observation of antiluteolytic activity of antiprogestogens in nonpregnant animals is considered of major theoretical importance in this context. It seems that inhibition of progesterone leads to suppressed uterine prostaglandin liberation. The same effect in pregnancy could explain the inability of the uterus to expel a seriously compromised conceptus. In conclusion, we suggest that progesterone is a stimulator rather than a depressor of uterine prostaglandins in the late luteal phase and pregnancy. The ability of the conceptus to neutralize this stimulatory action of progesterone is considered to be essential for the rescue of the corpus luteum and uterine motor quiescence in the guinea pig. The clinical significance of these findings is that the high frequency of incomplete abortions and protracted, sometimes heavy bleeding in pregnant women treated with RU 38.486 may reflect decidual compromise and simultaneous uterine prostaglandin deficie

Topics: Abortion, Induced; Animals; Dinoprost; Dinoprostone; Dose-Response Relationship, Drug; Embryo Implantation; Endometrium; Estrenes; Female; Gonanes; Guinea Pigs; Mifepristone; Myometrium; Pregnancy; Pregnancy, Animal; Progesterone; Prostaglandins E, Synthetic; Prostaglandins F; Uterine Contraction

Therapeutic abortion in the first trimester of pregnancy have been done in ten primigravidae using PGF2 alpha, 15-methyl-PGF2 alpha, or Sulprostone. Bleeding and recalcification time, platelet count, fibrin, platelet adhesiveness, partial thromboplastin time and thromboplastin time were examined before, during and after treatment. We found a decrease of platelet count and a prolongation of bleeding and recalcification time. There was no intensive-influence on coagulation system by the prostaglandin used. Therefore prostaglandins may be used for therapeutic abortion.. 30 healthy primigravidae aged 16-19 were treated (10 each) with PGF2 alpha, 15-Methyl-PGF2 alpha or Sulproston. Bleeding time, recalcification time, platelet count, fibrin, platelet adhesiveness, partial thromboplastin time and thromboplastin time were examined before, during, and after treatment. A decrease in platelet count and a prolongation of bleeding and recalcification time were observed. In all, none of the coagulation parameters showed any harmful change. PGF2 alpha and 15-Methyl-PGF2 alpha showed a greater tendency toward prolongation of bleeding and recalcification time than did Sulproston. The authors conclude that Sulproston is especially suitable for induction of abortion in the 1st trimester of pregnancy in young primigravidae.

Topics: Abortifacient Agents; Abortifacient Agents, Nonsteroidal; Abortion, Induced; Adolescent; Adult; Blood Coagulation Factors; Blood Coagulation Tests; Carboprost; Dinoprost; Dinoprostone; Female; Humans; Platelet Count; Pregnancy; Prostaglandins E, Synthetic; Prostaglandins F; Prostaglandins F, Synthetic

Laminaria japonica was used as pre-dilator of the pregnant uterine cervix prior to termination of pregnancy in the first and second trimester. In the first trimester (6-11 weeks, n=26) no other method was used, while in the second trimester pharmacological stimulation--prostaglandin F2 alpha or the prostaglandin analogue Sulprostone was used after or simultaneously with the laminaria insertion (12-18 weeks n=34 and 40, respectively). The dilatatory effect of laminaria was an obvious help in termination of both first and second trimester pregnancies.. Premature labor is a serious problem in Hungary where it often comes about after the cervix has been injured by a previous 1st or 2nd trimester induced abortion. The incidence of such abortions in high because with girls in the 15- to 19-year age group the 1st pregnancy is often not wanted. In the past the usual methods of dilating the cervix were either a rapid surgical dilatation or intraamniotic injection of prostaglandins to cause violent uterine contractions. Both of these methods caused lacerations of the cervix often resulting in permanent cervical incompetence. What was needed was a method of inducing smooth, slow, gentle dilatation of the uterine cervix. Such a method is the use of laminaria tents made from the seaweed Laminaria japonica, which, when dried, has the capability of absorbing water and slowly expanding. For a 1st trimester abortion 1 medium-sized laminaria is inserted in the morning into the cervical canal to 2-3 mm beyond the internal os. The procedure is repeated 3 hours later. For a 2nd trimester abortion 1 to 3 medium-sized laminarias are inserted and left for 12 hours. Or the laminarias may be inserted and an intraamniotic injection of prostaglandin F given at the same time. The cervical dilation achieved by the laminaria is always greater than the size of the swelled, wet laminaria. Complications of the method, such as displacement of the laminaria into the vagina or into the uterus, impactment of laminaria in the cervix, or infection, are rare if the laminaria are carefully placed parallel to each other and are properly sterilized if reused.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Dilatation; Dinoprost; Dinoprostone; Female; Humans; Laminaria; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Second; Prostaglandins E, Synthetic; Prostaglandins F; Seaweed

Antifertile effects of PGF2 alpha, PGE2, PGE1, sulprostone and other PGs were evaluated in different pregnancy models in rats, guinea pigs and rhesus monkeys and the underlying mechanisms of action were investigated. Quantitative and qualitative species differences and pregnancy stage dependency were recorded. Basic regulatory differences of the pregnant uterus seem to exist in these species. In early pregnant rats, abortifacient effects were based on luteolytic effects, independent of the PG used. The myometrium was found to be refractory to the injected PG as long as serum progesterone levels were kept high. By contrast, in guinea pigs after the luteoplacental shift of progesterone secretion (tested after day 40 p.c.) and in rhesus monkeys even before this shift (tested day 20 p.c.) abortifacient effects were found to be exerted by direct stimulation of the myometrium. Uterine stimulation was possible in the presence of any level of serum progesterone. The induction of uterine PG synthesis was probably of importance supporting the expulsion. The role of obvious tissue damage within the conceptus remained uncertain. In contrast to rats there seems to be a pre-existing PG-sensitivity of the pregnant myometrium in guinea pigs and primates. In guinea pigs sensitivity slightly increased for E- but not for F-type PG toward term. Oxytocin sensitivity was found to increase by a factor of more than 100 between days 23-63 of pregnancy. Time dependent changes in uterine receptivity to PG and oxytocin may be considered as a regulatory principle which might permit parturition to occur in the presence of progesterone as an evolutionary adaptation to a placental progesterone secretion which cannot be abolished. It was concluded that in the presence of already established gradual uterine responsiveness to PG (and Oxytocin) during gestation efficient blocking mechanisms for uterine PG-formation must exist in order to explain uterine quiescence. Almost complete resistance of pregnancy to oestrogen which exists in humans, monkeys and guinea pigs was considered as to be pharmacological evidence of such a mechanism. The principles of endocrine control of the myometrium and its pharmacology seem similar in guinea pig and primate pregnancy. The guinea pig might therefore provide a relevant model to study potential drug effects on the regulatory balance of the pregnant uterus and also to achieve a better understanding of human uterine physiology.

Topics: Abortifacient Agents; Abortifacient Agents, Nonsteroidal; Alprostadil; Animals; Castration; Dinoprost; Dinoprostone; Female; Guinea Pigs; Macaca mulatta; Oxytocin; Pregnancy; Pregnancy, Animal; Progesterone; Prostaglandins; Prostaglandins E; Prostaglandins E, Synthetic; Prostaglandins F; Rats; Species Specificity; Structure-Activity Relationship

Since 1977 the number of therapeutic abortions has been decreasing in Norway, a trend which is probably due to improved contraceptive practice. The results with PGs used for cervical dilatation in late first trimester and induction of abortion in the second trimester are reported. Pretreatment overnight or for 3-4 hours simplified the surgical procedure and Sulprostone (Schering AG) caused fewer side effects than 15(S) 15 Me F2 alpha. In the second trimester 15(S) 15 Me F2 alpha was administered by different routes and in different doses. 16,16 diMe trans delta 2E2 was given only as vaginal suppositories. Side effects were fewer by the intraamniotic route than by the other routes. The need for and benefits of PGs for therapeutic abortions are discussed.

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Therapeutic; Age Factors; Carboprost; Dinoprost; Dinoprostone; Female; Gestational Age; Humans; Norway; Pelvic Inflammatory Disease; Pregnancy; Prostaglandins; Prostaglandins E, Synthetic; Prostaglandins F

Topics: Abortifacient Agents, Nonsteroidal; Abortion, Induced; Amnion; Carboprost; Cardiovascular Diseases; Cervix Uteri; Dinoprost; Dinoprostone; Female; Humans; Injections; Injections, Intramuscular; Oxytocin; Pregnancy; Pregnancy Trimester, Second; Prostaglandins; Prostaglandins E, Synthetic; Prostaglandins F; Suppositories; Uterus; Vagina

13 ,14 -Dihydro-15-keto-PGF2 alpha (PGFM) serum levels were determined by radioimmunoassay in 101 postpartum women who were treated with 200 micrograms methergin, 5 I.U. oxytocin and 500 micrograms sulprostone, respectively, 30 min after expulsion of placenta. All patients had normal deliveries. The present radioimmunoassay system did not show cross-reactivity with sulprostone. In addition, radioimmunoassayable sulprostone serum levels were monitored. Covariance analysis of area under PGFM serum levels between time zero and 180 min after application of oxytocics was performed. A higher but statistically not significantly PGFM serum level was maintained in subjects treated with sulprostone. Sulprostone serum levels are rapidly attained after application. Decrease of radioimmunoassayable sulprostone indicates a half-life of 75 min. These data corroborate clinical findings of an accompanying paper and combine to suggest that sulprostone may be a useful alternative therapy in high-risk patients with severe postpartum atony and hemorrhage in whom prior preventive measures have failed.

Topics: Dinoprost; Dinoprostone; Female; Half-Life; Humans; Methylergonovine; Oxytocin; Postpartum Period; Pregnancy; Prostaglandins E, Synthetic; Prostaglandins F; Radioimmunoassay

Prostaglandins are mainly used in clinical medicine for midterm abortion and to terminate pregnancy. Systemic adverse reactions include nausea and vomiting, which occur in approximately half of the patients and, to a lesser extent, diarrhea. Although bronchospasm occurs infrequently, PGF2 should be avoided in asthmatics. Cardiorespiratory failure culminating in prolonged coma and death has been reported. Moreover, convulsions and EEG changes have been observed in a comparatively small number of cases.

Topics: Abortifacient Agents; Abortion, Induced; Bronchial Spasm; Diarrhea; Dinoprost; Dinoprostone; Female; Heart Arrest; Humans; Pregnancy; Prostaglandins; Prostaglandins E; Prostaglandins E, Synthetic; Prostaglandins F; Seizures; Vomiting