The luteolytic properties of prostaglandin F2\g=a\(PGF2\g=a\) were studied in experiments on sheep with ovarian autotransplants. PGF2\g=a\ was infused at the rate of 40, 10 and 2 \g=m\g/h for 4\m=.\0, 7\m=.\0and 9\m=.\5-18\m=.\0h respectively. At rates of 40 and 10 \g=m\g/h,progesterone secretion decreased to 50% of the control levels in 2\m=.\6\ m=+-\1\m=.\4h and fell to 8-30 \g=m\g/h within 36-52 h from the start of infusion. The onset of oestrus occurred 42-66 h after the infusions had started and a typical pre-ovulatory surge of luteinizing hormone (LH) was observed 52-66 h after infusing PGF2\g=a\. On occasions, this surge was accompanied by a brief peak of oestradiol-17\g=b\ secretion and shortly thereafter ovarian steroidogenesis decreased to very low levels.In four sheep infused at a rate of 2 \g=m\g/h,peripheral progesterone values decreased gradually and only one animal returned to oestrus. It would seem that 2 \g=m\g/h is close to the minimum intra-arterial dose to cause luteolysis in the sheep.
A synthetic decapeptide (Gn-RH) structurally identical to ‘ovine LH-releasing hormone’ was given by intra-carotid infusions (0, 0.5 and 1.5 µg/h for 3 h) to two groups of ewes late in the anoestrous season. One group received pretreatment with intra-venous progesterone (500 µg/h for 24 h) and the other no such treatment. Gn-RH was found to be a highly potent LH releasing agent capable of inducing ovulation. Physiological amounts of pro gesterone were incapable of preventing Gn-RH-induced pituitary LH release. It is con cluded that the blockade of LH release during the luteal phase or after progesterone administration may be due to steroid action at the level of the hypothalamus rather than at the pituitary.
Ml for non-therapeutic reasons is recognized to be of increasing importance among younger people in Britain (Connell, 1964;Bewley, 1965). Dependence on an extensive range of other drugs is also becoming more common (Wilson, 1965 ;Madden and Wilson, 1966). This alarming increase in non-therapeutically-induced dependence must not be allowed to withdraw attention from the possibility of causing dependence in patients as a result of unwise or ignorant prescription of dependence-producing drugs for therapeutic reasons.
SummaryTwo cases showing the features of dependence on dextromoramide are described. Dependence had been produced in both patients after dextromoramide administration for relatively slight and temporary pain. On admission to hospital they were taking dextromoramide in doses of 15 mg. six-hourly and 20 mg. at one-hourly intervals. The diagnosis was confirmed in both cases by production of the abstinence syndrome by substitution of dummy tablets for dextromoramide under double-blind conditions, and in one case by the administration of nalorphine. The abstinence syndrome was more severe, but occurred later, after the administration of the dummy tablets. The possibility that the features of the abstinence syndrome can lead to misdiagnosis is discussed and the importance of recognizing therapeutically induced drug dependence in hospital is stressed.We should like to express our thanks to Dr. J. S. Madden, consultant psychiatrist in charge of the addiction unit at Moston Hospital, for his interest, and to the nursing staff in the unit for their assistance and co-operation in those investigations. We also wish to thank M.C.P. Pure Drugs Limited for supplying the dummy tablets of dcxtrormoranlide which wcre used in thc investigation.
Antisera to 14-day-old sheep embryos were raised in rabbits and used to detect antigens specific to pregnancy by immunofluorescent staining and haemagglutination. Non-specific antibodies were removed by repeated absorptions of the antisera with homogenates of liver and kidney from non-pregnant ewes. The pregnancy-specific antigens were detected using immunofluorescence in the embryo, myometrium, maternal blood and CL as early as Day 8. No fluorescence was detected in pituitary, hypothalamus, liver, kidney, skeletal muscle or endometrium of pregnant ewes, or in any tissues of non-pregnant ewes. Haemagglutination occurred when a 1:8 dilution of rabbit anti-sheep embryo sera was added to blood obtained from ewes between Days 6 and 50 of pregnancy, but not when added to blood from non-pregnant ewes, rams and wethers or from pregnant mares, sows and cows. The immunological activity was removed from the anti-sheep embryo sera by absorption with homogenates of 14-day-old sheep embryo or pregnant uterus, or erythrocytes from Day 14 pregnant ewes, confirming that the antigens were specific to pregnancy. The presence of these antigens provides a basis for a haemagglutination test for pregnancy from Day 6 after mating and may be involved in the maternal recognition of pregnancy in the ewe.
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