Use Of Prostaglandin Analogues Research Articles

Editorial

Nonsalicylate, nonsteroidal anti-inflammatory drug (NSAID)-induced injury to the gastroduodenal mucosa may be responsible for significant ulceration and bleeding. The pathophysiology of gastroduodenal injury is reviewed and risk factors predisposing to NSAID injury are discussed. Finally, data are presented on the concurrent use of prostaglandin analogues and sucralfate in preventing mucosal injury.

FACTORS INFLUENCING SEXUAL MATURATION, PUBERTY AND REPRODUCTIVE EFFICIENCY IN THE GILT

Sexual development of the gilt involves the three distinct phases of sexual maturation, attainment of puberty, and pregnancy. Our knowledge of sexual maturation is at the stage of understanding the process, while puberty and pregnancy are at the stage of manipulation to improve efficiency. The developmental changes associated with sexual maturation are indicative of an orderly sequence of hormonal and anatomical changes that lead to puberty. This process is completed at an average age of 140 d (range > 80 d) and is followed by a "resting" period to the time of puberty. The reasons for variability in the rate of development are unknown and there is no easy method of determining when a gilt is sexually mature. In contrast, puberty is easily defined and occurs an average of 60 d after "completion" of prepubertal development (age range > 100 d). While it is not possible to substantially reduce age at puberty except by selection, puberty can be delayed by dietary intake restriction and by confinement housing (no movement or exposure to mature boars). When gilts are moved and exposed to mature boars, they will be in estrus in a short period of time provided that they have attained sexual maturity. Attempts to induce puberty with hormone injections at a younger age have not been effective because of the variability in age at sexual maturity. Research on the many facets of pregnancy has resulted in development of nutritional and mating management procedures to maximize ovulation rate, pregnancy rate and conception rate. However, there has been little change in litter size at birth, suggesting that the size of the uterus may ultimately limit litter size. Survival of the piglets born can be substantially improved by assisting the gilt during parturition and careiully managing the gilt and litter during lactation. The efficiency of management has been greatly increased by the use of prostaglandin analogues to control the time of parturition. Key words: Gilts, sexual maturation, puberty, litter size

2 - The Use of Prostaglandins and their Analogues for Abortion

In general, termination of second trimester pregnancy is associated with three to five times higher morbidity and mortality risks than termination during the first trimester. The procedures mainly used are extra- or intra-amniotic administration of solutions such as hypertonic saline, ethacridine lactate, PGF2α and PGE2. In comparison with these procedures, the use of prostaglandin analogues may offer important advantages, the most important one being the possibility of using non-invasive routes of administration. The continuous development of new analogues has now resulted in compounds that are highly effective in stimulating uterine contractility and are associated with a low frequency of side-effects; these compounds are suitable for both vaginal and intramuscular administration and are applicable for termination of pregnancy during both the early and late parts of the second trimester. The most widely used method for termination of first trimester pregnancy is vacuum aspiration. It is a highly effective procedure and the overall complication rate is low. One problem with vacuum aspiration is the mechanical dilatation of the cervical canal which is necessary from at least the 8th week and onwards. Pretreatment with laminaria tents or with prostaglandin analogues eliminates or reduces the need for mechanical dilatation and significantly facilitates the procedure. Pretreatment with prostaglandin analogues also reduces the risk of both operative and postoperative complications. The prostaglandins also offer a possibility as a non-surgical procedure for termination of very early pregnancy. Both vaginal and intramuscular administration of the latest generation of PG analogues have been shown in several studies to be equally as effective as vacuum aspiration if the treatment is restricted to the first three weeks following the first missed menstrual period. Gastrointestinal side-effects are still a problem although of significantly less importance than if natural prostaglandins are used. Preliminary studies in which one of these PGE analogues was administered by the vaginal route indicate that self-administration at home starts to be a reality in selected patients.

Multiple dose extraamniotic prostaglandin gel for second trimester termination of pregnancy.

Multiple doses of PGF2 alpha gel were administered into the extraamniotic space in 30 patients to induce mid-trimester termination of pregnancy. In 18 of these patients, repeat doses of gel were given only in the absence of uterine contractions and in 12 patients the gel was administered every 4 hours, irrespective of uterine activity. The mean time to abortion in all patients was 13.9 hours; no benefit seemed to accrue from using routine 4-hourly doses and it is recommended that repeat doses are given only when contractions are absent. The latter technique compares favourably with the use of other natural prostaglandins and prostaglandin analogues.

Further studies on the use of synthetic prostaglandin analogues for inducing luteolysis in mares.

SUMMARYICI‐81008, a synthetic prostaglandin analogue structurally related to Prostaglandin F2α, was shown to be a safe and effective luteolytic agent in mares. It consistently induced luteolysis in Welsh Pony mares at a dose of 125 μg and only produced detectable adverse side effects when given at more than six times this dose. Of 63 Thoroughbred mares in prolonged dioestrus which were treated with ICI‐81008, 55 returned to oestrus and ovulated; 40 per cent of the mares covered during the induced oestrus conceived. A total of 144 Thoroughbred mares in prolonged dioestrus were treated with another prostaglandin analogue, ICI‐79939; 134 returned to oestrus and ovulated and 46 per cent of those covered during the induced oestrus conceived. However, ICI‐79939 produced marked adverse side effects in mares when given at only three to four times the normal therapeutic dose.This study supported previous findings that the majority of non‐pregnant mares which are not showing regular oestrous cycles during the breeding season are in prolonged dioestrus rather than anoestrus.RÉSUMÉOn a démontré l'innocuité et l'efficacité du produit, ICI 81,008, un analogue synthétique de la prostaglandine et qui est structurellement apprenté avec la prostaglandine F2α, comme agent luteolytique chez les juments. En administration dans une dose de 125 mcg (microgrammes) la substance induit une répons luteolytic constante chez les juments de la race poney gallois. Des effets collaterau néfastes sont decelables seulement après l'administration des doses 6 fois plus grandes.De 63 juments pur sang en dioestrus prolongé, qui ont reçu ce traitment avec l'ICI 81,008, 55 sont revenues en oestrus avec ovulation ulterieure. 40% des juments couvertes pendant cet oestrus induit ont conçu. Un total de 144 juments pur sang en dioestrus prolongé ont reçu un traitement avec un autre analogue de prostaglandine (le composé denommé ICI 79,939); 134 sont revenu en oestrus, avec ovulation; 46% des juments couvertes pendant cet oestrus induit sont devenues gravides. Pourtant le composé ICI 79,939 produisit des effets collateraux indésirables marqués chez les juments même dans les doses qui ne depassent le niveau therapeutic normal que par un facteur de 3 à 4. Cette investigation confirme les observations anterieures; elle montre que la plupart des juments non‐gravides qui ne presentente pas des cycles d'oestrus regulaires pendant la monte se trouvent en effet en dioestrus prolongé, plutôt que dans un état d'anoestrus.ZUSAMMENFASSUNGEs wurde gezeigt, dass ICI‐81008, ein synthetisches Prostaglandin, strukturanalog zum Prostaglandin F2α ein sicheres und wirksames luteolytisches Agens für Stuten darstellt. Eine Dosis von 125 μg löste bei Welsh‐Pony‐Stuten durchweg Luteolyse aus und verursachte nachweisbare nachteilige Nebenwirkungen erst nach einer sechsfachen Dosierung. Von 63 Vollblut‐Stuten mit verlängertem Diöstrus, die mit ICI‐81008 behandelt wurden, kamen 55 in Brunst und ovulierten: 40% der Stuten, die während dieser induzierten Brunst belegt wurden, konzepierten. Weitere 144 Vollblut‐Stuten mit verlängertem Diöstrus wurden mit einem anderen Prostaglandin‐Analog (ICI‐79939) behandelt; von diesen zeigten 134 Tiere eine ovulatorische Brunst und 46% der während dieser so ausgelösten Brunst belegten Tiere konzepierten. Jedoch verursachte ICI‐79939 deutliche nachteilige Nebenwirkungen bei Stuten schon nach der Applikation einer drei‐ bis vierfachen Menge der therapeutischen Dosis.Diese Untersuchungen erhärten vorangegangene Ergebnisse, nämlich dass die Mehrzahl aller nicht‐tragender Stuten, die keinen regelmässigen Zyklus während der Paarungssaison zeigen, sich eher in einem verlängerten Diöstrus befinden als in einem Anöstrus‐Stadium.