Dose Of PG Research Articles

Central sites mediating reproductive responses to melatonin in juvenile male Siberian hamsters

Juvenile male Siberian hamsters received infusions of varying doses of melatonin (MEL), or saline vehicle, via microdialysis probes implanted in brain regions which have previously been shown to contain MEL receptors. Daily infusions were 10 h in length and occurred during exposure to constant light on days 22–34 of age. All animals were sacrificed on day 35 and paired testis weights recorded prior to preparation of the brain tissue for histological evaluation of the infusion site. Some animals were also blood-sampled prior to sacrifice for determination of circulating levels of prolactin (PRL). Saline infusions did not have a significant effect upon gonadal maturation, regardless of the infusion site, when compared with unoperated control animals reared under similar photoperiod conditions. In contrast, animals which received infusions of 75 pg MEL into the suprachiasmatic nucleus (SCN), paraventricular nucleus of the thalamus, or nucleus reuniens regions, showed a marked inhibition of gonadal growth. Infusions of this dose of MEL into various other neural regions (e.g. lateral hypothalamus, ventromedial nucleus of the hypothalamus, paraventricular nucleus of the hypothalamus) did not result in decreased testis weights at the time of sacrifice. Daily administration of 20 pg MEL inhibited gonadal maturation and resulted in decreased circulating PRL levels only when infused into the SCN region. For animals receiving the 7.5 pg dose, infusions into the midline thalamic nuclei were not successful in inhibiting testis growth, and infusions in the SCN region had only a marginal effect. These results indicate that endogenous MEL may influence at least one seasonal response in this species, i.e. reproductive responses to photoperiod, by acting at some or all of these central MEL binding sites.

Action of cyclosporine on fever induced in rats by intrahypothalamic injection of macrophage inflammatory protein-1 (MIP-1)

In order to examine the central mechanism of pyrexic action of macrophage inflammatory protein-1 (MIP-1), guide cannulae for injections were implanted stereotaxically just above the anterior hypothalamic, pre-optic area of the rat. Following post-operative recovery, the body temperature ( t b) of each rat was monitored by a colonic thermistor probe over a test interval of 4hr. Injected in a 0.5 μ1 volume into the anterior hypothalamic pre-optic area, MIP-1, in a dose of 5.6 or 28 pg, evoked an intense fever with a latency of 15–30 min. Pretreatment of the anterior hypothalamic pre-optic area with 1.0 μg cyclosporine A (CsA), delivered in a volume of 0.5 μ1, delayed the onset of the fever induced by 5.6 pg MIP-1, injected at the same site. Similar injections of CsA also attenuated significantly the magnitude of the fever, following either the 5.6 or 28 pg dose of MIP-1. As a systemic control, 15 mg/kg CsA was administered intraperitoneally, 2.0 hr before the injection of MIP-1 in the anterior hypothalamic pre-optic area. By this route, CsA also delayed the rise in temperature but the fever induced by 5.6 pg MIP-1 reached the same magnitude as that after MIP-1 alone. Conversely, intraperitoneal administration of CsA did not antagonize the pyrexic response evoked by 28 pg MIP-1, injected into the anterior hypothalamic pre-optic area, but rather enhanced the fever. These results demonstrate that CsA was effective in suppressing the fever induced by MIP-1 when it was applied directly to the thermosensitive-pyrogen-reactive neurons of the anterior hypothalamic pre-optic area, prior to the cytokine. However, the nature of the systemic action of the immunosuppressant agent was dependent on the concentration of the cytokine present in the anterior hypothalamic pre-optic area and, by this route, did not inhibit the fever of MIP-1. In terms of the mechanism of action of MIP-1, these findings with CsA suggest that the febrile response to the cytokine depends in part on the activity in the diencephalon of an interleukin, thought to underlie the acute phase of the response of fever. It is envisaged that the initial thermogenic action on neurons of the anterior hypothalamic pre-optic area of MIP-1, in a trace amount, is brought about by the local synthesis or release of another cytokine, which appears to be an obligatory mediator for the fever evoked by MIP-1.

Unsatisfactory results with the transfer of embryos from gilts superovulated with PMSG and hCG

Prepuberal gilts received an intramuscular injection of either a single dose of PG 600 (400 IU pregnant mare serum and 200 IU human chorionic gonadotropin) (n = 21), twice (n = 18) or three times (n = 24) that amount. This was followed by 500 IU hCG 56 h later. Most of the gilts were inseminated 36 h following treatment. Of the 63 donors, 58 responded to treatment with, on average, 20.8, 36.7 and 55.8 ovulations, and embryo/ova recovery rates of 80, 76.3 and 53.8% for the three respective dosages. Within 2 to 4 h after collection, synchronized gilts received 16 to 18 morphologically normal embryos transferred into the oviduct. The recipients were slaughtered at 28 to 32 d after embryo transfer, and 10 of 11, 6 of 11 and 9 of 13 gilts in the three treatment groups were found to be pregnant; the average number of viable conceptuses was 6.6, 6.1 and 6.6. There was a lower embryo recovery and pregnancy rate associated with the administration of increasing dosages of PMSG and hCG; thus this regimen is not recommended.

Two signals are required for accessory cells to induce B cell unresponsiveness. Tolerogenic Ig and prostaglandin.

We previously demonstrated that a lymphoid dendritic cell-like tumor line (P388AD.2) presented a normally tolerogenic signal, fluoresceinated sheep gamma-globulin (FL-SGG), as an immunogenic one. In contrast, macrophages derived from the peritoneal cavity potentiated the ability of FL-SGG to induce B cell unresponsiveness. In this paper we examined whether two different Ia+ splenic accessory cells differentially presented tolerogen to spleen cells or fluorescein (FL)-binding B cells. Interestingly, lymphoid dendritic cells presented FL-SGG to spleen cells and elicited augmented anti-FL antibody responses, whereas splenic macrophages presented this same moiety and elicited hapten-specific B cell unresponsiveness. The mechanism of splenic macrophage-elicited B cell negative signaling was investigated, and it was found that B cell unresponsiveness was abrogated in the presence of the cyclooxygenase inhibitor indomethacin. This observation suggested a crucial role for PG in B cell negative signaling. The addition of 10 nM PGE2 restored unresponsiveness in cultures treated with indomethacin and tolerogen-pulsed macrophages, even though this dose of PG had no effect on the ability of B cells to be triggered by an immunogenic signal. A role for T cells was excluded, inasmuch as purified hapten-specific B cells were specifically tolerized by FL-SGG-pulsed macrophages. Lymphoid dendritic cells pulsed with FL-SGG did not deliver a tolerogenic or immunogenic signal to FL-specific B cells. However, when PGE2 was supplied, B cell unresponsiveness was induced. Finally, we tested whether "non-tolerogenic" doses of FL-SGG could render hapten-specific B cells unresponsive in the presence of PGE2, but in the absence of accessory cells. Interestingly, the combination of non-tolerogenic amounts (10 to 1000 pg/ml) of FL-SGG in conjunction with PGE2 induced unresponsiveness, whereas neither moiety alone was effective. These results suggest that splenic macrophages and lymphoid dendritic cells exert opposing effects on the immune system as evidenced by the induction of negative or positive B cell signaling. Our observations suggest that one of the key factors in controlling whether an accessory cell delivers a tolerogenic signal is the ability to secrete PG.

EFFECT OF DILUENT VOLUME ON ANALGESIA PRODUCED BY EPIDURAL FENTANYL

Injection of opioids into the epidural space produces postoperative analgesia by acting on receptors in lamina 11, IV, and V of the substantia gelatinosa (1). Morphine, due to its low lipid solubility produces numerous side effects when injected into the epidural space; most notably delayed respiratory depression (2). Fentanyl, a highly lipid soluble narcotic agonist, has a more rapid onset of action and a significantly lower incidence of side effects than those of morphine. In a dose-response study in patients after cesarean delivery, 50 pg of epidural fentanyl was found to provide maximal analgesia with minimal incidence of side effects (3). The effect of varying the volume of injectate on the onset, duration, and incidence of side effects produced by 50 pg of fentanyl has not been reported. This standard dose of fentanyl diluted in larger volumes could increase the surface area of drug exposure and thus augment the number of opioid receptors affected. Conversely, diluting the opioid in greater volume may reduce the concentration gradient between the central nervous system and epidural space and thereby decrease both the rapidity of onset and duration of analgesia. Fentanyl is being given epidurally in several different dilutions. To determine the most effective diluent volume, a double-blind, randomized study was undertaken with varying volumes of normal saIine solution to dilute a single 50 pg dose of epidural fentanyl.

Effect of acetylation on arthropathic activity of group A streptococcal peptidoglycan-polysaccharide fragments.

Purified group A streptococcal peptidoglycan-polysaccharide (PG-PS) fragments were either de-O-acylated, or acetylated and then de-O-acylated to yield N-acetylated PG-PS. Native PG-PS was poorly degraded, N-acetylated PG-PS was extensively degraded, and de-O-acylated PG-PS was only slightly degraded by hen egg white lysozyme. N-acetylated PG-PS was also extensively degraded by human lysozyme and partially degraded by rat serum or rat liver extract. After a single intraperitoneal injection of rats with a sterile, aqueous suspension, all PG-PS preparations induced acute arthritis. The acute arthritis induced by N-acetylated PG-PS was significantly more severe than that induced by native PG-PS; that induced by de-O-acylated PG-PS was of intermediate severity. After the acute reaction, rats injected with native PG-PS developed chronic relapsing erosive synovitis which remained severe for the duration of the experiment (83 days). In contrast, joint inflammation induced by N-acetylated PG-PS resolved within 6 weeks with little evidence of recurrent disease. Chronic arthritis induced by de-O-acylated PG-PS was of intermediate severity. In another assay of arthropathic activity, the arthritis in all rat ankle joints, which had been injected directly with native PG-PS, could be reactivated 3 weeks later by the intravenous injection of a small dose of PG. In contrast, only 50% of the joints initially injected with de-O-acylated PG-PS and none of the joints injected with N-acetylated PG-PS could be reactivated. These studies support the concepts that the resistance of PG-PS to muralytic digestion is crucial for chronic arthropathic activity and that the nature and degree of PG acetylation are important molecular determinants of the phlogistic activities of PG-PS polymers.

Effect of Progesterone on Cell Proliferation in the MXT Mouse Hormone-Sensitive Mammary Neoplasm<xref ref-type="fn" rid="FN1">2</xref>

The transplantable MXT mouse mammary tumor is an experimental model for which the growth is modulated by ovarian hormones; because of scant knowledge about the effects of progesterone (Pg) alone on cancer cells, the present investigation was made. By measuring the percentage of cells with labeled nuclei after tritiated thymidine ([3H]dThd) injection 1 hour prior to sacrifice [dThd labeling index (TLI)], a study was made of the effect (in vivo) of a near physiologic dose of Pg (125 micrograms ip) on cell proliferation in uteri (as the control Pg target organ) and on tumors of spayed (C57BL female X DBA/2F male)F1 mice. Pg induced a significant and transient rise in TLI, which increased from the 12th to the 24th hour after its injection. This mitogenic effect on tumors was comparable to that elicited by 0.25 microgram 17 beta-estradiol injected under similar conditions. In vivo brief exposure of castrated mice to Pg induced a significant mitogenic effect on MXT tumors. These observations might have important consequences for a better understanding of the endocrine mechanisms involved in human hormone-dependent breast cancer.

Central administration of prostaglandin E 2 facilitates while F 2α attenuates acute dependence upon morphine rats

The effects of prostaglandin D 2 (PGD 2), E 2 (PGE 2), and F 2α (PGF 2α) on acute dependence on morphine were investigated. Five mature, male Long-Evans rats were trained to lever press for food reinforcement on a fixed-ratio 30 schedule (FR 30 behavior) and implanted with permanent guide cannulas with the tips of the cannulas in their right lateral brain ventricles. The experimental protocol began with a 45 minute behavioral session and brain infusion (1 μl/minute of a solution containing 2.3 mM CaCl 2 in 0.9% saline, ICV). Fifteen minutes into the session the rats were injected with 7.5 mg morphine/kg (IP). Beginning 2.25 hours later the brain infusion was reinitiated during a second 45 minute behavioral session which was interrupted after 15 minutes to inject 1.0 mg naloxone/kg (IP). In several experiments a dose of PG, which did not in-and-of-itself affect behavior, was added to the infusion medium. Prior to the naloxone injection it was ascertained that the behavioral effects of morphine has dissipated. The injection of naloxone or saline did not alter behavior of the rats while they were being infused with a PG or PG vehicle. Injection of naloxone, 3 hours after the injection of morphine, resulted in a significant suppression of FR 30 behavior (withdrawal). A dose of PGE 2, which did not alter the initial suppressant action of morphine, potentiated the naloxone effect. A dose of PGF 2α, which likewise did not alter the initial action of morphine, antagonized the naloxone effect. However, a higher dose of PGF 2α which enhanced the initial morphine effect, caused an enhanced naloxone effect as well. PGD 2 did not alter the actions of morphine or naloxone. It is concluded that infusion of various PGs into the brains of rats differentially alters their responsiveness to morphine and dependence upon the opiate. It is further concluded that the dose and initial interactive effect of PGs and morphine are important determinants of the direction and degree of the expression of withdrawal.

Topical 16,16-dimethyl-prostaglandin E2

Using a canine chambered stomach preparation, the effects of topical 16,16-dimethylprostaglandin E2 (dmPGE2) on gastric mucosal morphology, H+ loss and HCO3-secretion were assessed. Compared to control studies in which acid alone (100 mM HCl) bathed the epithelium, dmPGE2 (1 or 4 micrograms/ml), when applied to gastric mucosa in acid medium, significantly (P less than 0.01) enhanced H+ loss from the bathing solution in a dose-related fashion. These effects, however, were independent of any injury to the epithelium as confirmed by both light and electron microscopy. In other studies in which dmPGE2 was applied to gastric mucosa in neutral solution (150 mM NaCl, pH 7.0) using identical doses, a dose-related increase (P less than 0.01) in HCO3-secretion was observed. When the net HCO3-output (microEq/15 min) for each dose of dmPGE2 employed was compared with the net H+ loss (microEq/15 min) for each dose of PG used, no differences were noted. The correlation between H+ loss and HCO3-secretion was highly significant (r = 0.87; P less than 0.01). We conclude that with the doses studied, dmPGE2 is not damaging to gastric mucosa and that the apparent increase in H+ loss elicited by dmPGE2 in acid medium is due to acid neutralization secondary to HCO3-secretion.

Selective attenuation of passive avoidance behaviour by microinjection of β-LPH 62–77 and β-LPH 66–77 into the nucleus accumbens in rats

Various fragments of β-lipotropin were micro-injected into the nucleus accumbens of freemoving rats and the effects on one-trial passive avoidance behaviour were studied. The following peptides were used: β-endorphin (β-LPH 61–91, met-enkephalin(β-LPH 61–65) des-tyrosine-γ-endorphin (DTγE, β-LPH 62–77), des-enkephalin-γ-endorphin (DEγE, β-LPH 66–77), des-tyrosine-α-endorphin (DTαE, β-LPH 62–76) and β-LPH 47–53(ACTH 4–10). The γ-type endorphins (DTγE and DEγE) were the only peptides which significantly attenuated passive avoidance behaviour when given in a 20 pg dose 1 hr before the 24-hr retention test. All the other peptides were ineffective. Microinjection of DTγE into the dentate gyrus of the dorsal hippocampus, on the other hand, was without effect on passive avoidance. The accumbens nucleus, therefore, is a preferential highly sensitive brain site for γ-type endorphins. The attenuation of passive avoidance behaviour following systemic administration of these peptides might be the result of an interaction with this mesolimbic structure.

Central and Peripheral Effects of Desogestrel 15–60 μg Daily for 21 Days in Healthy Female Volunteers

Abstract. Desogestrel (Org 2969, 17α‐ethinyl‐18‐methyl‐11‐methylene‐4‐estrene‐17β‐01) was given for 21 days to 6 female volunteers in daily doses of 15, 30 or 60 μg until ovulation inhibition was achieved. Control cycles were studied before and after each treatment cycle. Blood samples for determinations of serum FSH, LH, unconjugated 17β‐estradiol, progesterone, prolactin, ceruloplasmin, and orosomucoid were taken at intervals of 1–2 days. The karyopyknotic index and the amount of cervical mucus, ferning, Spinnbarkeit and sperm penetration were also assessed at 2‐day intervals. An endometrial biopsy was taken on day 22 from 5 volunteers receiving the 30 μg dose.The results of FSH, LH, 17β‐estradiol and progesterone determinations indicate that 2 of the 4 volunteers ovulated whilst taking the 15 pg dose; however, one of the 2 displayed corpus luteum dysfunction. On the 30 μg dose, 5 out of 6 volunteers had anovulatory cycles; the sixth volunteer was then given 60 μg desogestrel, which resulted in inhibition of ovulation.In all volunteers treated with desogestrel (even those who ovulated during treatment), the cervical mucus was under progestational influence, resulting in a low Spinnbarkeit and impaired sperm penetration. The microscopic appearance of the endometrium varied but was clearly under progestational influence in all volunteers treated with desogestrel. Ovulation occurred in all post‐treatment cycles. No side effects were seen, except for ‘spottings’ during half of the treatment cycles. No changes attributable to the treatment were seen in serum concentrations of prolactin, ceruloplasmin or orosomucoid.

Effect of Orally Administered 15(R)-15-Methyl Prostaglandin E2and/or an Anticholinergic Drug on Meal-induced Gastric Acid Secretion and Serum Gastrin Level in Patients with Duodenal Ulcers

The purpose of the present series of tests was to measure and compare the effects of ingestion of gelatin capsules containing 15(R)-15-methyl PGE2 (PG) and/or an anticholinergic drug (methscopolamine bromide, Pamine) on meal-induced gastric acid secretion and serum gastrin level. Eleven duodenal ulcer patients were stimulated by a 5% peptone meal. Acid secretion was determined by the intragastric titration technique, and serum gastrin was measured by radioimmunoassay. The tests were randomized and double-blind. PG alone given 30 min before a test meal at a dose of 50 micrograms or 100 micrograms produced no side effects and inhibited meal-stimulated acid secretion by about 43% and 55%, respectively. Gastric acid inhibition after a single dose of PG was most pronounced in the first hour of a test meal and was accompanied by almost complete suppression of the meal-induced serum gastrin level. Pamine alone in a dose of 2.5 mg reduced gastric acid response to a meal by about 29% but caused a further rise of postprandial serum gastrin level over control values. The combination of PG, 50 micrograms, and Pamine, 2.5 mg, did not result in significantly greater acid inhibition (about 48%) than when either compound was given alone. When the higher dose of PG (100 micrograms) was given together with Pamine (2.5 mg), the degree of inhibition produced by PG alone was not changed. It is concluded that PG given orally in capsules is a potent inhibitor of gastric acid and serum gastrin response to a meal and that this effect may be of potential value in the treatment of peptic ulcer disease.

INDUCTION OF LABOUR WITH PROSTAGLANDIN E2 GEL IN CASES OF INTRAUTERINE FETAL DEATH

In established intrauterine fetal death, 20 patients were treated with prostaglandin E2 gel administered extraamniotically. The results were compared with those of another group of 20 patients who had received combined treatment. In this group, one or more of the following agents had been administered :- i.v. oxytocin, 20% NaCl solution or Premarin instilled intraamniotically, introduction of a balloon catheter or Rivanol administered extraamniotically. Average induction-abortion interval for the PG group was about 12 hours while for the second group it was about 30 hours. The side effects observed were slight in both groups. The results show that administration of PG-gel can be used with advantage in fetal demise because of the relatively short induction-abortion intervals obtained, the insignificant side effects and the low dose of PG required.

Prostaglandins and pacemaker activity in isolated guinea pig SA node

Prostaglandins PGE 2, PGE 1, PGF 2α, and PGA 1 substantially increase automaticity in SA-nodal, right atrial preparations excised from guinea pigs. This natural pacemaker tissue is sensitive to nanomolar doses of PG with, for example, 10 −8 M PGE 2, increasing SA rate by about 20%. If these preparations are pretreated with 2 μM indomethacin, a blocker of endogenous prostaglandin synthesis, then spontaneous rate drops and subsequent rate increases due to PGE 2 administration can be more easily demonstrated. Guinea pig pacemaker tissue differs from similar rabbit tissue not only in that it is directly responsive to PGE 2, but also in that PGE 2 does not depress the absolute response to transmural stimulation (adrenergically mediated rate increase). The positive chronotropic responses to PGE 2 also occur when the guinea pig tissue is pretreated in 0.6 μM propranolol, which causes blockade of beta-adrenergic receptors. The pacemaker myocardium in the guinea pigs thus appears to be directly stimulated by exogenous PGE 2 at very low doses. The observation that 2 μM indomethacin reduces SA-nodal rate suggests the presence of a very sensitive, functionally important, PGE-like system which modulates heart rate in this mammalian species.

Induction of labour with prostaglandin E 2 gel in cases of intrauterine fetal death

In established intrauterine fetal death, 20 patients were treated with prostaglandin E 2 gel administered extraamniotically. The results were compared with those of another group of 20 patients who had received combined treatment. In this group, one or more of the following agents had been administered: - i.v. oxytocin, 20% NaCl solution or Premarin instilled intraamniotically, introduction of a balloon catheter or Rivanol administered extraamniotically. Average induction-abortion interval for the PG group was about 12 hours while for the second group it was about 30 hours. The side effects observed were slight in both groups. The results show that administration of PG-gel can be used with advantage in fetal demise because of the relatively short induction-abortion intervals obtained, the insignificant side effects and the low dose of PG required.

Work in progress menstrual induction with PGF2α and PGE 2

The "prostaglandin impact" (PGI), a massive intrauterine dose of PG, converts the refractory pregnant uterus into a reactive organ by provoking a regulatory imbalance. This regulatory conversion releases the endogenous mechanism of menstruation or abortion. During initial studies, PGI successfully provoked menstrual induction (MI) in 22 and subsequently in 65 volunteers. These results were confirmed and complemented by 2 independent trials in 14 and 36 gravidas respectively. The best clinical outcome was obtained in 20 volunteers, when a "PG-Pellet" (a mini-suppositorium) was inserted in utero, containing only 2.5 mg PGF2alpha. These 157 trials in sedated volunteers had the common features of over 90% efficiency, transient and medically acceptable side effects and infrequent complications. The present study of 542 volunteers focused upon the collection of clinical data regarding efficacy, side effects and complications of MI. All patients had committee approval for legal abortion, during the 2nd week of their missed menstrual period. They volunteered to participate because of their preference for pharmacological rather than surgical pregnancy termination. The clinical outcome of the 542 MI with 5 mg PGF2alpha (428 cases) and 1.5 mg PGE2 (114 cases) was identical. On the average, 95% of the gravidas had complete evacuation of the uterus with the clinical symptoms of delayed menstruation rather than abortion; they experienced spontaneous menstruation in 34 days after having received a single dose of PG.

Pregnancy termination in the rat “model” by a synthetic prostaglandin analogue ICI 81008

The abortifacient efficacy of the PGF2α analogue ICI 81008 had been examined in 378 Spraque-Dawley rats. Of the 3 systemic routes of administration studied: intramuscular (i.m.), subcutaneous (s.c.) and per vaginam (p.v.), the p.v. treatment had been the most effective. Complete abortions were provoked invariably by a single p.v. dose of 20 μg ICI 81008 in the broad gestational range of 6 to 10 days of pregnancy and the “abortion rate” (AbR) remained 86% at day 12. The reduction of the p.v. dose to 10 μg only decreased efficacy slightly and its increase to 40 μg improved it. The analogue ICI 81008 was highly more effective than the natural PGs: F2α and E 2, in spite of their comparable oxytocic actions on the excised uterus. This high efficacy of ICI 81008 in p.v. formulation, without apparent side effects, is a therapeutic promise which demands early clinical investigation. At day 3 the AbR decreased to 0% and at day 14 to 30%. Plotting AbR, as a function of the gestational timing of treatment, yielded a reversed U shape curve, which reflected upon the mechanism of ICI 81008 action. The pituitary, the corpus luteum and the blastocyst are equally indispensable and accessible to drugs at days 3 and 6 of gestation. Yet the efficacy of ICI 81008 increased from 0% to 100% during this 3 days period, suggesting that the primary target of ICI 81008 is the uterine environment of the implanted conceptus. Thus the earlier premise had been substantiated that in inducing abortion PGs provoke: reduction of uterine microcirculation, sustained contracture, suppression of feto-placental endocrine function (including luteotrophic support), luteolysis, progesterone (P)-withdrawal and the evolution of uterine activity. However, progesterone treatment prevented the effect of ICI 81008, completely or partly, depending on the dose of PG administered. Furthermore, extensive studies of the ICI research team showed that ICI 81008 can provoke luteolysis without pregnancy, suggesting that under certain conditions the ovary is the primary target of this drug. If this effect on the ovary also involves a microcirculatory disturbance, then the mechanism of action of ICI 81008 is retained, in a variety of species and reproductive conditions, and only the threshold of the organ serving as primary target changes. From the Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri This work was supported by the Agency for International Development Contract AID/csd 3160 and the National Institute of Health Career Award, HD 20169-11.

The abortifacient action of the extraovular “Prostaglandin impact” during the first half of human pregnancy

In 30 volunteers, 7 to 22 weeks pregnant, legal abortion had been induced successfully with the extraovular “Prostaglandin Impact” (PGI) (1). The patients were 24.8±1.1 years old (Means ± S.E.), para 1.6±0.3. At the 14.8±0.7 weeks of pregnancy and under sedation an initial dose of 10.0±0.0 mg PG F2α had been delivered transcervically into their extraovular (E.O.) space. This dose had been increased if accidental rupture of their fetal membranes resulted in intraamniotic (I.A.) treatment. The initial PGI of 16.0±2.0 mg was supplemented by additional PG doses, up to 27.0±2.9 mg, if clinical progress was slow. The patients responded to the initial PGI with sustained uterine contracture; rapid and continued progesterone (P) withdrawal, from 59.9±3.0 ng/ml to 30.7±2.1 ng/ml (49%); and with the progress of time high level cyclic intrauterine pressure (IUP). The 26% P-withdrawal, measured 3 hours after PGI was already significant (P < 0.001). Abortion was complete in 25 and incomplete in 4 patients, while 1 gravida had been curetted at 2 cm cervical dilatation. The instillation-abortion time (IAT) was short, only 13.0±1.1 hours. No side effects were observed in 17 patients, while 8 gravidas vomited (usually once) and 5 had transient increase in blood pressure. Extensive laboratory tests revealed no significant deviations from normality, during and after PG treatment. Blood transfusion was given to 2 patients (partly detached placentae and hemorrhage), antibiotics resolved 2 cases of endometritis and curettage removed (2 weeks after abortion) a small placental residue. The fetal membranes were accidentally ruptured in 11 patients and in these women the slow contracture response of the uterus signaled I.A. (rather than E.O.) PGI. The initial PG dose was increased, therefore, from 10.0±0.0 mg to 25.9±3.9 mg (P < 0.001) and the total dose from 20.0±2.0 to 42.3±4.8 mg (P < 0.001), to compensate for the lesser efficacious I.A. administration. In spite of this massive increase in the initial and total doses of PG, the rate and degree of P-withdrawal, the IAT, the incidence of side effects and the “Abortion Score” (AbS) of these 11 patients were similar to those of the 19 gravidas who received E.O. PGI. This finding, the good clinical outcome of the earlier (1) and the present study suggests that the transcervical E.O. PGI (regardless of accidental I.A. treatment) is a recommendable procedure for the non-surgical termination of pregnancy during the 1st half of gestation.

PROSTAGLANDIN INDUCTION OF MIDTRIMESTER ABORTIONS: THREE YEARS' EXPERIENCE OF 626 CASES

In the first part of the survey 424 midtrimester abortion inductions with 11 different regimes of treatment were analyzed according to PG dose, PG type (PGF2alpha or PGE2), the route of administration (intravenous, extra-amniotic, and intra-amniotic), and the dose of concomitant intravenous oxytocin. Intraamniotic PG was given as a single injection, and the dose was repeated after 24 hours, if the abortion was not imminent. The highest efficacy, a 90% success rate within 24 hours and a 100% rate in 48 hours, as well as the shortest induction-abortion interval were achieved with the intra-amniotic administration of 50 mg of PGF2alpha either alone or with supplementary oxytocin, or with the intra-amniotic 10 mg PGE2 plus oxytocin.

Induced Spawning of &lt;i&gt;Puntius gonionotus&lt;/i&gt; (Bleeker)

An experiment was conducted to study the induced spawning of Rajputi Puntius gonionotus (Bleeker) in the months of April, May, June and July 2005. Five different doses of PG were used in the experiment. In Puntius gonionotus all the different doses (doses D1-3.00 mg/kg, D2-6.00 mg/kg, D3-9.00 mg/kg, D4- 12.00 mg/kg and D5-15.00 mg/kg) were affected equally (100%) in egg release. In the experiment both the males and females were given the 1st dose but the 2nd injection was given only to the females after 6 hours. The highest fertilization rates were 70.10±2.25% in April (dose D4), 75.00±2.10% in May (dose D3), 80.00±2.14% in June and 79.20±2.65% in July (dose D3). The highest hatching and survivability rates were 61.50±3.10 and 55.00±2.13 in April (dose D4), 68.00±3.5 and 63.00±2.20 in May (dose D3), 71.80±2.00 and 68.50±2.60 in June (dose D2), and 70.25±3.50 and 65.70±2.16 in July (dose D3) respectively. The month of June and the dose D2 (2mg in first injection and 4 mg in second injection) were found to be most effective for induced spawning of P. gonionotus. &#x0D; &#x0D; Key words: Induced spawning, hatchling, PG dose. &#x0D; &#x0D; J. bio-sci. 14: 121-125, 2006