Hormone levels during prostaglandin F 2 infusions for therapeutic abortion.

PIP: This study determines the effect of prostaglandins (PGs) on fetal-placental hormone production or luteal steroidogenesis early in pregnancy by measuring plasma levels of unconjugated estrone, 17-beta estradiol, estriol, progesterone, 17-hydroxyprogesterone, human chorionic gonadotropin (HCG), and human chorionic somatomammotropin (HCS) in 7 healthy women aged 15-30 years receiving PGF2alpha for therapeutic abortion. The patients were 7-20 weeks pregnant and were all from the Clinical Research Unit of the Yale-New Haven Hospital. 5 patients participated in a dose-response tolerance study in which the drug was given over a 12-hour period at predetermined dose levels from 25-200 mcg/minute. The remaining 2 patients received 50 mcg for 12 consecutive hours, and 2 6-hour periods respectively. Heparinized blood samples were collected prior to the beginning of the infusion, at least hourly during the infusion, and also 24 hours after the beginning of the study. Transabdominal and transcervical catheters were used to monitor intrauterine pressures. A definite decline in estradiol levels (from 50-70% of initial levels) was observed during the PGF2alpha infusions. Plasma levels of unconjugated estriol were found to decline earlier and more markedly than the estradiol levels. 17-hydroxyprogesterone was undetectable in all but 1 patient who was 7 weeks pregnant. There were no significant changes in HCG levels in 4 patients until abortion and or curettage was performed. HCS levels gradually declined in 3 patients during the infusion process. This study shows that PGF2alpha does not exert a luteolytic effect in terminating pregnancy from 7-20 weeks gestation, confirming the study of Wiqvist et.al. Further study of the 1st few weeks of gestation should be done before ruling out the possibility of luteolysis in humans.^ieng

Separation, identification, and estimation of prostaglandins.

PIP: The procedures which may be and are being used to provide a basis for the analysis of submicrogram quantitities of prostaglandins are surveyed. Discussion is focused on the following: 1) sources of standards; 2) properties (effect of different pH values, effect of blood, metabolism, solubility); 3) extraction; 4) detection; 5) estimation (ultraviolet, optical rotatory dispersion, densitometry, radioimmunoassay, enzymatic assay, isotopic methods, bioassay); 6) separation of prostaglandins (separation of PGE, PGF, and PGA with PGB compounds, separation of PGA and PGB compounds, and separation of individual prostaglandins); and 6) structural identification. Methods of prostaglandin analysis, with the required sensitivity for application to individual tissue and fluid specimens, are still in the developmental state. Although prostaglandins may be ubiquitous throughout the animal kingdom, no systematic study of their distribution has been made to date. Recent work has shown that PGE1 has a potent effect on the formation of 3',5' cyclic adenosine monophosphate (cyclic AMP) which is widely believed to be an intracellular intermediate in hormone action.^ieng

Plasma concentrations of vasopressin and a prostaglandin F2 alpha metabolite in women with primary dysmenorrhoea before and during treatment with a combined oral contraceptive.

Oral contraceptives reduce menstrual pain but the interaction with vasopressin and prostaglandin F2 alpha, two uterine stimulants related to the condition, is unknown. Ten women with a history of moderate to severe dysmenorrhoea were studied. Repeated blood samples were taken during a first menstrual cycle without treatment, during the first 21 days of a second cycle when they received an oral contraceptive (150 micrograms levonorgestrel and 30 micrograms ethynyloestradiol) and on the first or second day of the bleeding following hormonal withdrawal. Measurements were made of plasma concentrations of arginine vasopressin, 15-keto-13,14-dihydroprostaglandin F2 alpha, oestradiol-17 beta, progesterone, ethynyloestradiol, levonorgestrel, FSH, LH and prolactin, and serum osmolality was measured. Seven of the women rated their discomfort as moderate to severe on the first two menstruations, but as none or light at the withdrawal bleeding; with the rating scale for degree of pain that was used, this decrease in pain was significant (P less than 0.001). The plasma concentration of vasopressin in these seven women showed significant variation, with the highest concentrations being obtained at the beginning of the two painful menstruations (3.76 +/- 0.76 and 1.75 +/- 0.30 (S.E.M.) pmol/l) and at ovulation in the control cycle (1.91 +/- 0.58 pmol/l). During treatment the concentrations were consistently low, except on the first day of withdrawal bleeding (2.33 +/- 0.35 pmol/l). The concentrations of the prostaglandin F2 alpha metabolite showed less variation, but again the values at withdrawal bleeding (271 +/- 39 pmol/l) were not different from those obtained over the painful menstruations (255 +/- 24 and 217 +/- 25 pmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: To learn more about the beneficial effect of combined oral contraceptives (OCs) on symptoms in primary dysmenorrhea, plasma levels of vasopressin and a prostaglandin F2-alpha metabolite in dysmenorrheic women were investigated before and during treatment with a gestagen-dominated OC. The 10 subjects were administered an OC containing 150 mcg of levonorgestrel and 30 mcg of ethinyl estradiol for 21 days. The 7 women with dysmenorrheic symptoms at the time of blood sampling during the 1st menstruation graded their pain as averaging 2.1 (moderate to severe) + or - 0.3; during the 2nd menstruation, the average value was 2.9 (severe) + or - 0.1, indicating a significant increase in pain at the start of the withdrawal bleeding. Vasopressin concentrations in samples obtained on days 1-3 of the control cycle were significantly higher than those on days 6-8, 20-22, and 24-26 of the control cycle and days 1-2 of the next menstruation. Thus, the highest concentrations were obtained at the beginning of the 2 painful menstruations and at ovulation in the control cycle. During treatment, vasopressin concentrations were consistently low, except on the 1st day of withdrawal bleeding. The concentrations of the prostaglandin F2-alpha metabolite showed less variation, again, values at withdrawal bleeding were not different from those obtained during painful menstruation. Plasma concentrations of ovarian and adenohypophysial hormones, as well as osmolality, were normal throughout. Thus, the present study provided no evidence that there is a reduced release of vasopressin and/or prostaglandin F2-alpha capable of accounting for the beneficial effect of OCs on dysmenorrhea. It is possible, however, that a difference in ovarian hormone concentrations is more pronounced in uterine tissue than in plasma.

Prostaglandins: current therapeutic status in obstetrics.

PIP: Recent research suggests that the action of prostaglandins on the pregnant uterus is more complex than that of oxytocin. Despite the fact that prostaglandins, like oxytocin, may fall short of the ideal, preliminary work makes it apparent that prostaglandins have attributes for induction of labor that will ultimately rank them as far superior to oxytocin. A 1st sign that prostaglandins might be more than just oxytocic agents came from the discovery of the effectiveness of prostaglandin F2alpha (PGF2alpha) and prostaglandin E2 (PGE2) in inducing mid-trimester abortion. For a long time it has been known that oxytocin seldom causes abortion of a normal pregnancy. Prostaglandins cause rapid dilatation of the cervix and expulsion of the conceptus despite a lesser degree of measurable uterine activity than that induced by oxytocin. Prostaglandins do something more, either to the quality of uterine contractions or to the cervix. A major problem associated with the pharmacological use of prostaglandins has been a high incidence of unpleasant side-effects when given by routes that are associated with substantial systemic uptake. In general, doses of prostaglandins that are oxytocic result in nausea, vomiting and diarrhea when administered by the intravenous, oral or intravaginal routes. The intra-amniotic and extra-ovular routes of administration for induction of mid-trimester abortion, as described by Doctors Karim and Hillier, are examples of the successful application of the principle that prostaglandins can be effective without side-effects when they are delivered close to the site of action. Prostaglandins appear particularly well suited to induction of labor in women with prolonged fetal death, anencephaly or hydatidiform mole.^ieng

Prostaglandins: pharmacology and clinical application.

PIP: Prostaglandin research has been 1 of the most stimulating features of biomedical investigation in the past decade. Interest developed at a time of expanding knowledge of hormonal and neurohormonal behavior and research work received a tremendous impetus in the early 1960s with the elucidation in Sweden of the chemical structures of prostaglandins, followed by the discovery of their biosynthetic pathways. The original findings of large amounts of prostaglandin in the male accessory genital glands and their secretions, and subsequent discovery in the menstrual and amniotic fluids linked these substances with human production. As a result of further investigation, clinical applications of prostaglandins for the induction of labor and termination of early unwanted pregnancies have been developed. Apart from the functions of the prostaglandins in the reproductive area, they have been shown to have a widespread distribution in the body and produce many different pharmacological effects. Prostaglandins are thought to be involved in the regulation of blood pressure and through their vascular effects have therapeutic potential in the treatment of hypertension and peripheral vascular disease. Through their bronchodilator effect, some prostaglandins may become useful in the treatment of asthma.^ieng

Discussion of session on prostaglandins in female reproductive physiology.

PIP: The effects of prostaglandins (PGs) on the ovary are contradictory; in vivo studies with PGF2alpha have shown evident luteolytic effects, while in vitro studies have shown that PGs are usually steroidogenic. It is difficult to reconcile these differences, and a clearer understanding of the mechanism of action of PGs is needed. How PGs work in the induction of labor or for abortion is not very clear. The most simple explanation would indicate a direct muscle stimulating effect. While there is evidence that plasma progestin and estrogen levels are unchanged during PG infusion during delivery at term, there is some suggestion that the mechanism in early pregnancy may be related to an effect on the corpus luteum. Initial studies indicate that plasma progestin level during PG infusion for the induction of abortion does not change until after passage of the placenta; on the other hand it has been found that plasma estrogen levels consistently drop during infusion, especially with high doses of PGs. Also, it is doubtful whether PGs induce oxytocin secretion or enhance the effect of endogenous or administered oxytocin. PGs will induce labor, but it is still not known whether there are any advantages over oxytocic preparations in terms of efficiency. There are 3 major areas of investigation on PGs which require a concentrated effort: 1) the development of a sensitive and specific assay which would allow the measurement of endogenous levels of PGs, 2) clearer ideas about doses and systems of delivery, and 3) the safety level of the drug.^ieng

Cyclic 3',5'-adenosine monophosphate in human blood platelets. IV. Regulatory role of cyclic amp in platelet function.

PIP: Evidence which bears on the hypothesis that agents that increase platelet cyclic adenosine 3',5' monophosphate (cAMP) tend to inhibit platelet aggregation, whereas agents whose action is to induce or augment platelet aggregation are associated with a decrease in platelet content of this cyclic nucleotide is reviewed. Using radiolabeled cAMP in incubation with various agents, it was found that caffeine, colagen, thrombin, prostaglandins E1 and E2, and phosphodiesterase inhibitors are all agents that increase platelet cAMP and inhibit platelet aggregation.^ieng

Prostaglandin content of human endometrium.

Prostaglandin levels in 46 human endometrium specimens were determined and expressed as both total uterine content and on a dry weight basis. Concentrations of PGF2alpha and PGE did not differ significantly between specimens obtained during the proliferative or secretory phases of the menstrual cycle. There was, however, a fourfold higher total uterine content of prostaglandins during the secretory phase. There was also a more than fourfold higher level of PGF2alpha than of PGE during the secretory phase. The two types of prostaglandins were present in nearly equal amounts during the proliferative phase. Atrophic endometrium was characterized by a high concentration of prostaglandins, but a low total amount consisting of nearly equal amounts of PGF2alpha and PGE.

PIP: The study objective was to establish the endogenous levels of prostaglandins in endometrium by specific radioimmunoassays and to express the determined values in terms of dry weight of tissue examined. Endometrial specimens were obtained from 46 patients (age range 23-59 years) at Magee-Womens Hospital in Pittsburgh who were undergoing medically warranted abdominal or vaginal hysterectomy. Each uterus was bisected vertically within 5 minutes of the final clamping of the uterine blood supply. The endometrium was sharply dissected from the more normal-appearing half uterus and homogenized at high speed for 5 minutes in methanol. The remaining half of the uterus was examined histologically and categorized as being obtained during either the proliferative or the secretory phase of the menstrual cycle or as atrophic. Radioimmunoassays were performed with regents obtained from Clinical Assays, Inc. (Cambridge). All 46 specimens were analyzed for prostaglandin F2alpha (PGF2alpha). 3 were excluded because their antigenic behavior did not parallel that of known PGF2alpha. Of 28 specimens analyzed for prostaglandin E (PGE), 2 were excluded because of nonparallelism. Concentrations of PGF2alpha and PGE did not differ significantly between specimens obtained during the proliferative or secretory phases of the menstrual cycle. There was a 4-fold higher total uterine content of prostaglandins during the secretory phase, and there was a more than 4-fold higher level of PGF2alpha than of PGE during the secretory phase. The 2 types of prostaglandins were present in nearly equal amounts during the proliferative phase. Atrophic endometrium was characterized by a high concentration of prostaglandins but a low total amount consisting of nearly equal amounts of PGF2alpha and PGE.

The contractile response of the human uterus, fallopian tubes, and ovary to prostaglandins in vivo.

PIP: In vivo studies were carried out in 8 women to ascertain the effects of prostaglandins (PGs) E2 and F2alpha on the human fallopian tubes and ovaries. Recording devices were surgically implanted into the tubal lumen through catheters. 100 mcg. of either PGE2 or PGF2alpha or a mixture of equal amounts of the 2 totaling 100 mcg. were administered intravenously and the effects recorded. Graphs of the effects are presented. The 2 pure substances and the mixture all had a stimulatory effect on the uterus at all phases of the menstrual cycle. There were, however, qualitative and potency differences between PGE2 and PGF2alpha. On a weight basis, PGE2 had more powerful effects on the myometrium. The 2 PGs had opposing effects on the fallopian tubes, with PGF2alpha stimulating while PGE2 inhibited tubal motility. A contractile response of the ovary following intravenous administration of PGF2alpha was noted; no change in intraovarian pressure was recorded following injection of up to 100 mcg. PGE2. The compound was mildly stimulatory. The ability of PGE2 to induce relaxation of the tubes while stimulating uterine activity provides a clue as to why it is more effective in inducing abortion than PGF2alpha. It is suggested that relaxation of the tubal isthmus induced by seminal PGE2 facilitates sperm penetration into the tube.^ieng

Hypolipidemic agents.

PIP: Despite the fact that the role of lipids and cholesterol in atherosclerosis has not been totally clarified to the clinician's satisfaction, medicinal chemistry has been very successful in this last decade in showing that a diverse group of compounds is capable of reducing blood lipid levels in many animal species and in humans. The pharmacological basis for the evaluation of many hypolipidemic agents is summarized. The prostaglandins are vasodepressor agents. They inhibit uterine contraction, yet, on the other hand, they increase cardiac output and induce contraction of intestinal smooth muscle. Prostaglandins exhibit marked antilipolytic activity. It has been shown that 0.2 mug/kg/min, of intravenous infusion of prostaglandin E1 produced an increase in serum-free fatty acide levels in the dog. At a 4 times higher rate of infusion, the plasma-free fatty acid concentration was lowered. The pharmacological activities of individual prostaglandins embrace a great variety of biological phenomena. In certain systems their effects are antagonistic. The rationale for the use of estrogens as hypolipidemics is the observation of the low incidence of atherosclerotic heart disease in Caucasian women of childbearing age.^ieng

Pharmacological modulation of cervical compliance in the first and second trimesters of pregnancy.

PIP: Health practitioners use many methods and agents to bring on cervical ripening in early pregnancy, such as intracervical tents and pharmacological techniques, to induce a therapeutic abortion. Prostaglandins alter myometrial and cervical tissue and are the most often used pharmacological technique. Reduced collagen concentration, an increase in water volume, an increase in prostaglandins (PGE2, PGI2, and PGF2 alpha), and a change in the glycosaminoglycan (GAG) content coincide with cervical ripening, yet the mechanism responsible for these changes is obscure. Prostaglandins appear to cause the breakdown of collagen or change the GAG/proteoglycan content. Research shows that prostaglandins can initiate cervical ripening at any stage of pregnancy. Estradiol stimulates prostaglandin production thereby al so inducing cervical dilation. Relaxin also demonstrates an ability to ripen the cervix. In addition, mifepristone (RU-486) is gaining acceptance as a cervical ripening agent. In fact, RU-486 and gemeprost have at least 95% success rate compared to 92% for gemeprost alone or 85% with RU-486 alone. The only effective and acceptable prostaglandins to use at gestation of 0-8 weeks are sulprostone, gemeprost, and 9-methylene-PGE2. At t his gestational age, pharmacological modulation is all that is needed. Even though they are effective (abortion rate 90%), side effects are expected to occur (pain, nausea, and vomiting). Similarly, prostaglandin analogues are preferable for cervical ripening in women at 8-12 weeks gestation. Suction curettage or other surgical techniques then are used to remove the conceptus. At 12-16 weeks gestation, many physicians prefer the same protocol as that of 8-12 weeks gestation. Other choose to infuse PGE2 and saline into the amniotic fluid to stimulate uterine contractions. Another procedure at 12-16 weeks involves 1mg vaginal pessaries of gemeprost every 3 hours to ripen the cervix and stimulate contractions. After 16 weeks, the methods for 12-16 weeks still apply.^ieng

Prostaglandins.

PIP: Prostaglandins are analogs of the parent 20 carbon prostanoic acid. They are divided into 4 series: PGE; PGF; PGA; PGB, according to the presence of functionalities in the cyclopentane structure. Biosynthesis of prostaglandins were first independently reported by Bergstrom et.al. and van Dorp et.al. who showed that certain w-6-unsaturated fatty acids were biological precursors of prostaglandins. Later, various investigators reported the biosynthesis of prostaglandins of the different series. The 2 most widely used routes of prostaglandins synthesis are 1) the Corey cyclopentyl-lactone route, and 2) the bicyclohexane route. The synthesis is divided into 1) naturally occuring primary prostaglandins and 2) the prostaglandin analogs and derived prostaglandins. Because of the general instability of natural prostaglandins in the basic and acidic milieu, various preparations of prostaglandins and chemically stable dosage forms have been developed. Various methods used in analyzing prostaglandins include: 1) TLC; 2) GLC; 3) spectral methods; 4) radioimmunoassay; and 5) enzymatic assay. In vitro and in vivo studies on the metabolism and catabolism of various prostaglandins showed that they are rapidly metabolized in various animal systems and humans. The major routes for this metabolic transformation are: 1) oxidation of the secondary C15 hydroxy group; 2) reduction of the C13 double bond; 3) B-oxidation; 4) w-hydroxylation; and 5) w-oxidation. Prostaglandins produce a wide range of biological effects on animal and human systems (the reproductive; gastrointestinal; respiratory; and cardiovascular systems). The biological actions of prostaglandins on animal and human reproductive tissue vary depending on the particular prostaglandin studied and hormonal state of the tissue. Certain prostaglandins can decrease the tonus, frequency, and amplitude of spontaneous contractions of human uterine strips while other prostaglandins can cause contraction of isolated myometrial strips. Prostaglandins are widely used in labor induction; induction of therapeutic abortion; and fertility control. Prostaglandins have also been found to either increase or decrease cyclic AMP; inhibit ADP-induced platelet aggregation; lower blood pressure in animals; affect lipid and carbohydrate metabolism, and prevent adjuvant arthritis.^ieng

Prostaglandins in conception control.

PIP: A clinical team in the Dept. of Obstetrics and Gynecology of the Albert Einstein College of Medicine investigated the effects of several prostaglandin compounds of human pregnancy. Women between 8 to 20 weeks gestational age had pregnancy termination through: 1) intraamniotic PGF2alpha (prostaglandin F2a) administration (n=20, 15.9 + or - 0.6 weeks pregnant, 1.4 + or - 0.4 parity); 2) extraovular PGF2a administration (n=20, 13 + or - 0.3 weeks gestation); 3) intramuscular 15-methyl PGF2a administration; 4) vaginal suppositories of PGE2 (n=110 women, 1.45 + or - 0.17 parity, 15.4 + or - 0.3 gestational weeks); and 5) induction of term labor through PGF2a and PGE2 administered orally, intravenously, vaginally, and extraovularly. In the 1st group, the 20 women aborted in 16.5 + or 2.1 hours with an average total dose of 24.3 + or - 1.1 mg. In the 2nd group, the 20 women aborted in 17.9 + or - 2.9 hours with 11 + or - 1.8 mg PGF2a. The 24-hour cumulative abortion rate was 83%. In both intraamniotic and extraovular groups, prostaglandin side effects were noted in 25% to 70% of the women. Incidence of retained placentas was also high. In the 3rd group, abortion did not follow a predictable pattern and side effects occurred in virtually all women, making this approach unacceptable as a therapeutic method. The vaginal suppositories resulted in a mean abortion interval of 14.12 + or 0.7 hours with an average total dose of 78.3 + or - 0.12 mg. Induction of term labor using PGF2a and PGE produced results which are not superior to those of intravenous oxytocin in term pregnancies, possibly because of the biophysical properties of the term uterus. Prostaglandins appear to be effective abortifacient agents with minimal material risk, and are most effective when administered intraamniotically, extraovularly, and paracervically. The chemistry and pharmacology of prostaglandins are briefly described.^ieng

Ultrastructural changes of the human corpus luteum of pregnancy induced by prostaglandin E2 in vitro.

PIP: A study was carried out to assess the effects of prostaglandin(PG)E2 on the fine structure of human luteal tissue in vitro. The laboratory procedures are explained and microscopic photographs of the results are included. Biopsies of corpora lutea from 4 normal women at 10-16 weeks gestation were incubated in a buffer medium containing acetate-C and 20-40 mcg/ml of PGE2 for 3 hours. Preincubation and incubation controls and the PGE2-treated samples from each of the 4 biopsies were studied by electron microscopy. In all cases, the controls were well preserved and the luteal cells had the fine structural characteristics previously described in early pregnancy. The morphologic changes which occurred in the human luteal cells incubated in PGE2 solution varied from cell to cell in each sample. The changes were remarkable, indicating cell damage. Main changes were: collapse and disarrangement of the smooth endoplasmic reticulum, ballooning or condensation of mitochondria, disappearance of the rough endoplasmic reticulum, dilatation and/or disappearance of the Golgi system, accumulation of lipid droplets, and increased lysosomes. The results also indicate that not only the synthesis of progesterone is impeded, but more significantly, the de novo synthesis of cholesterol from incorporation of acetate may be severely impaired. Findings in this study contradict the results of several earlier studies. This study shows a direct luteolytic effect of PGE2 in vitro.^ieng

Prostaglandins: perspective in obstetrics and gynecology.

PIP: Prostaglandins (PGs) are metabolic regulators produced at the cellular level to exert a local action, usually of a modulating type. Their biological function is analogous to cycle adenosine 3",5' monophosphate (cAMP) (i.e., acting as messengers) rather than to a steroid function, although PGs interact with both cAMP and steroids. Clinicians need to know the endogenous biosynthesis of PGs, their metabolism, and their detection to use PGs therapeutically with competence. Apparently, endogenous biosynthesis of PGs is catalyzed by a microsomal enzyme system composed of many different enzyme types. The required precursors are essential fatty acids, arachidonic acid, and bis-homo-y-linolieic acid in the unesterified form. Molecular oxygen and other cofactors are also required. This biosynthesis was worked out in sheep seminal vesicles, but it is now recognized that virtually all tissue types in mammals synthesize PGs. The metabolic degradation and inactivation of PGEs and PGFs, both derived from the same intermediate, are extremely rapid (Samuelsson et al., 1971, 1972). The most important first step is oxidation of the 15-hydroxyl group to a carbonyl, which modifies the activities of PGs and allows further degradation and elimination via urine; this series of steps protects the body from these potent agents. Detection and analysis are best achieved by deuterium-labeled intermediates which are determined by mass spectrometry. It is important to remember that various tissues have widely varying responses to PGs; for example, PGs have luteolytic action in sheep but do not induce uterine contractions, whereas the opposite seems true in humans.^ieng

The use of prostaglandins in obstetrics.

PIP: The prostaglandins (PGs), a group of pharmacologically active and modified fatty acids, were first discovered in association with male sex organs and their secretions, and have subsequently been shown to be widely distributed in mammalian tissues and fluids. The chemical structures of 14 naturally occurring PGs are shown in figure form; 6 are considered as "primary PGs" and the remaining 8 are derived metabolically from these. The only established clinical applications of PGs are in the field of obstetrics. These include induction of labor at or near term, therapeutic termination of early pregnancy, and the treatment of missed abortion, missed labor, and hydatidiform mole. Successful induction of labor in 6 women in which PGF2alpha had failed indicated a possible superiority of PGE2 for the induction of labor. The high rate of successful inductions with PGE2 could be because of a relaxant effect on the human cervix over and above its stimulant effect on the upper uterine segment. Intravenous infusion of 50 mcg/min of PGF2alpha was found to stimulate the pregnant uterus "in vivo" in the 1st and 2nd trimesters of pregnancy. In 1 study of 15 consecutive cases, abortion was successful in 14 and complete in 13. PGE2 infused at the rate of 5 mcg/min has been used as an abortifacient in 150 women. Pregnancy was successfully terminated in 145 of these women. Medical induction in cases of missed abortion and missed labor with PGE2 has been carried out in 45 cases and has been successful in 43. PGE2 has been used in 3 cases of hydatidiform mole. In all these cases the mole was delivered within 12 hours of starting the infusion.^ieng

Comparative study of labour induced by oral prostaglandin E2 and intravenous syntocinon.

PIP: The use of prostaglandin E2 for the induction of labor with intact membranes is described and its effectiveness is compared to intravenous syntocinon. 40 primigravida and 60 multigravid patients with previous medical and obstetrical histories were studied. The patients were numbered as they entered the trial, with the odd numbers in each group being given oral prostaglandin and the even numbers intravenous syntocinon. In no case was the pregnancy less than 38 weeks maturity. No patient was in labor prior to being given either drug. Prostaglandin E2 (PGE2) was supplied in ampoules containing 5 milligrams in 0.5 milliliter of ethanol. This was added to 49.5 milliliters of sterile water to produce a concentration of the drug of 0.1 milligrams per ml. The syntocinon infusion was prepared by putting 20 units of syntocinon into 1 liter of 5% dextrose in water to produce a solution concentration of 20 mu/ml. The accepted criteria for diagnosing established labor for both groups of patients was the presence of uterine contractions occurring once every 3 minutes, associated with progressive dilatation of the cervix. For both groups of patients it was decided that cervical dilatation should be at least 6 cm within 18 hours of the infusion starting. Using this criterion there was only 1 failure, occurring in the 1st primigravid patient given PGE2, the labor in this instance being completed with intravenous syntocinon. A further 8 patients failed to complete the trial as they had to be delivered by cesarian section. Syntocin was considerably more efficient than PGE2 in inducing labor in the remaining 91 patients particularly in primigravida. This was the case whether judged by the length of labor or by the induction delivery interval. Toco-dynamometric studies showed that the contractions produced by prostaglandin more closely resembled those of normal labor and were less painful.^ieng

[F2 alpha prostaglandins and oxytocin in multipara: a comparative study]. / Prostaglandin F2 alpha y oxitocina en la induccion del parto de multiparas: estudio comparativo.

PIP: Differences existing between F2 alpha prostaglandin and oxytocin, as labor inductors, are studied on 2 groups of multipara by means of intravenous administration. The percent of success was somewhat higher with oxytocin. Labor's duration was prolonged with the use of prostaglandin. The interval between the start of drug's administration and the first contractions onset was shorter in cases in which oxytocin was used. No side effects were observed. (Author's modified)^ieng

An improved method for the extraction of prostaglandins.

PIP: Present methods of extracting prostagalndins (PGs) give poor recoveries from synovial fluid, probably because the PGs bind to protein and are lost in the precipitation stage of extraction. Addition of the nonpolar detergent sodium lauryl sulphate prior to extraction improves recovery of PGs. It is suggested that sodium lauryl sulphate competes with PGs for the binding sites.^ieng

Prostaglandin release from the human umbilical artery in vitro.

PIP: Release of prostaglandins from human umbilical artery preparations into the surrounding bathing fluid was studied by radioimmunoassay using PGF2a antibodies. A significant release of prostaglandins was found under conditions where a spontaneous tone of the artery could be maintained. Indometacin reduced the prostaglandin release and the spontaneous tone of the artery. Intramural synthesis of prostaglandins in the human umbilical arteries is postulated.^ieng