Clinical Evaluation of the Use of Aglepristone Associated with Oxytocin to Induce Parturition in Bitch

To evaluate the efficacy and safety of aglepristone 15 mg kg⁻¹ for induction of parturition in bitches, 22 pregnant beagle bitches were injected subcutaneously on day 60 post-estimated LH surge, and again 24 h later with aglepristone and subsequently were given 0.15 IU kg⁻¹ oxytocin at hourly intervals until delivery of the last puppy. Six pregnant beagle bitches were used as a non-treated control group. In the control group, parturition occurred at 63.2 ± 0.5 days, 29 pups were born and the average expulsion time per puppy was 1.0 ± 0.6 h. In the treated group, parturition was obtained on average 29.7 ± 5.6 h after aglepristone administration, 121 pups were born and average expulsion time per pup was 1.1 ± 0.4 h. The percentage of live puppies, 7 weeks after birth, was 86.1% (25/29) and 86.8% (105/121) for the control and treated groups, respectively. No significant difference was observed between the control and treated groups for the average expulsion time per live puppy and for the percentage of live puppies at birth, 48 h, 7 days or 7 weeks after birth (p > 0.05). This study confirms previous results and demonstrates that the combination of aglépristone and oxytocin can be safely and reliably used to induce parturition in beagle bitches, at 60 days post-estimated LH surge.     

An Experimental Model to Study Resistance Index and Systolic/Diastolic Ratio of Uterine Arteries in Adverse Canine Pregnancy Outcome

The aim of this study was to describe the changes in the resistance index (RI) and systolic/diastolic ratio ( S / D ) of the uterine arteries during mid-pregnancy abortion induction in the dog. Sixteen 30–35 day pregnant bitches were randomly assigned to either a pharmacological protocol to interrupt gestation (n = 8) or were used as untreated control group (n = 8). Doppler assessments of uterine arteries blood flow were carried out before the initiation of the protocol and then every other day up to abortion (treated group) or parturition (control group). All treated bitches aborted 6 ± 1.2 days after initiation of the treatment (while none of the non-treated bitches aborted). Pre-treatment RI and S / D did not differ between groups (p > 0.2) while average post-treatment indexes were (mean ± SD): 0.62 ± 0.1 vs 0.53 ± 0.1 (p < 0.01) and 2.96 ± 0.9 vs 2.23 ± 0.3 (p = 0.01), for the treated and non-treated group respectively. Correlations between days to abortion and RI or S / D were 0.75 (p < 0.01) and 0.79 (p < 0.01) and, −0.78 (p < 0.01) and −0.73 (p < 0.01) for the treated and non-treated groups respectively. In the treated group, correlations between serum progesterone (P₄) concentrations and RI and S / D were −0.76 (p < 0.01) and −0.59 (p < 0.01) respectively. It is concluded that, during induction of abortion, RI and S / D of uterine arteries progressively increased while P₄ decreased.     

Role of Eicosanoids in the Regulation of the Periparturient Period in Cattle

Contents: In this review, the role of eicosanoids in regulation of parturition and the postpartum period was described with special emphasis on the bovine species. The metabolism of arachidonic acid and the production of eicosanoids during the peripartum period was discussed. Prostaglandin E₂ and F_2α (PGE₂, PGF_2α) play an important role in mechanisms controlling parturition. They are involved in luteolysis, uterine contractions and dilation of the cervix. Eicosanoids also seem to influence the loosening processes of the fetal membranes. However, in the literature, conflicting results were found. Many investigations suggested that retained placental membranes could be related to low PGF_2α production and/ or an imbalance of arachidonic acid metabolism in the uterus. The possible role of the lipoxygenase pathway metabolite 15-hydroxy-eicosatetraenoic acid (15-HETE) in expulsion of the fetal membranes was also discussed. As far as the postpartum period is concerned, a relationship between postpartum PGF_2α release and the involution of the uterus was found. Cows with undisturbed uterine involution had higher PGF_2α production than cows with delayed involution. In contrast to the positive effect of PGF_2α on uterine involution, PGE₂ seems to delay the involution processes. Further experiments are necessary in order to study the function of eicosanoids in mechanisms regulating parturition, release of the fetal placental membranes and involution of the uterus.     

Influence of Progesterone Withdrawal on Pregnancy-Related Parameters During Post-Implantation Early Pregnancy Loss

Pharmacologically-induced luteolysis or treatment with an antiprogestin in early post-implantation pregnancy in dogs results in asynchronous death and resorption of conceptuses, indicating variable rates of response of individual conceptuses towards progesterone deficiency. This variability also seems to occur in bitches showing pregnancy failure in response to spontaneous luteal deficiency. In a total of 10 beagle pregnancies (two consecutive pregnancies of five bitches), abortifacient treatments beginning on day 24 after ovulation (ov) involved either administration of a progestin antagonist (total of six pregnancies, in three bitches) or a luteolytic regimen of prostaglandin F_2α-analogue together with a dopamine agonist (total of four pregnancies, in two bitches). The outcomes were evaluated in relation to four control pregnancies in two bitches by assay of serum progesterone, prolactin and relaxin at selected time points or within selected time periods, by ultrasound of conceptuses including measurement of uterine blood flow, and parameters of the blood fibrinolytic system including plasma fibrinogen and plasminogen. The process of embryonic death and conceptus resorption was variable in onset and duration both in bitches that received the progesterone antagonist aglepristone (AGLE) and in those under the luteolytic treatment (cloprostenol combined with cabergoline). Pregnancy termination (death of all embryos or foetuses, respectively) occurred as early as day 29 and as late as day 41 after ov in AGLE-treated bitches, and not earlier than day 37 after ov in luteolytic-treatment bitches. Impending embryonic death was not predicted by changes in relaxin concentration, parameters of the fibrinolytic system, or in the perfusion of small uteroplacental vessels.     

The Role of Uterine and Ovarian Hormones in Luteolysis: A Comparison among Species

Luteolytic mechanisms have evolved in mammals to improve reproductive efficiency. The hormonal interactions that control the onset and progress of luteolysis are complex. They involve endocrine and paracrine signals that link the corpus luteum, uterus and posterior pituitary gland. Current concepts concerning these interactions will be examined in the five major domestic ungulate species commonly raised in Europe and North America (cattle, sheep, goats, pigs and horses). Some of these interactions are similar across species. All five depend on prostaglandin F_2α secreted from the uterus, to induce luteolysis. Three hormones, progesterone, estradiol and oxytocin interact to regulate uterine secretion of PGF_2α. Oxytocin is an acute stimulus for uterine PGF_2α secretion. Progesterone and estradiol interact to regulate uterine secretary responsiveness to oxytocin. Precisely how these hormones interact varies across species.     

Effect of GnRH Dose on Occurrence of Short Oestrous Cycles and LH Response in Cyclic Dairy Heifers

Prostaglandin F_2α (PGF_2α) and GnRH treatments given 24 h apart have been shown to result in short oestrous cycles (8–12 days) in some cows and heifers. The differences in responses may depend on the dose of GnRH. Therefore, the effect of the dose of GnRH on occurrence of short cycles and LH response was studied here. Oestrus was induced with dexcloprostenol (0.15 mg) in two groups of Ayrshire heifers. A second luteolysis was induced similarly on day 7 after ovulation; 24 h after PGF_2α treatment, the heifers were administered either a high (0.5 mg, n = 15, group T500) or low (0.1 mg, n = 10, group T100) dose of gonadorelin. Blood samples for progesterone analyses were collected daily from the second PGF_2α administration to the second ovulation after the PGF_2α injection. Beginning 24 h after the GnRH treatment, ovaries were examined by transrectal ultrasonography every 6 h until ovulation, and daily between day 4 and the next ovulation. Five heifers from both groups were sampled for LH analyses via a jugular catheter every 30 min from 1 h before to 6 h after the GnRH administration. Short oestrous cycles were detected in 7 of 10 cases in group T100 and in 12 of 15 cases in group T500. No significant differences in LH responses were detected between the groups. In group T500, the rise in LH concentration tended to be somewhat slower than in group T100. The dose of GnRH (0.1 vs 0.5 mg) did not affect the occurrence of short oestrous cycles and LH response.     

Expression Pattern of Markers in the Canine Ovarian Cycle

Although hormonal changes during different phases of the oestrous cycle of bitches are well-described, knowledge about the luteal phase and anoestrus is incomplete. Furthermore, which paracrine and autocrine critical factors that differentiate between follicles destined for atresia and those that continue to develop are unknown. In this study, ovarian tissue was collected from 39 healthy bitches that were subject to ovariectomy or ovariohysterectomy for surgical neutering or medical purposes such as unwanted pregnancy. Bitches were allocated to different groups depending on the stage of the oestrous cycle. Serum progesterone, LH, FSH and 17β-estradiol (E₂) -levels were determined and immunhistochemistry was performed for a variety of receptor antigens; Ki-67, vimentin, pan cytokeratin antibody, p53 and oestrogen receptor (ER) α antigens. Marked differences were found in progesterone concentration between pregnant and non-pregnant animals. Oestrogen concentration was significantly lower in pro-oestrus and ovulation than during the luteal phase. Although progesterone could be detected in cytoplasm of ovarian cells at each stage, its presence was restricted to follicular cells during anoestrus. A strong presence of AE1/AE3, vimentin and p53 was found in each oestrous stage, in contrast with Ki67. The localization of ERα appeared to vary during the oestrous cycle, a phenomenon that suggests a switch between target cells of oestrogen; while as a proliferation marker, the mild reaction of p53 during parturition suggests an apoptotic process at this stage of the cycle.     

Comparison of Two Doses of the GnRH Antagonist, Acyline, for Pregnancy Termination in Bitches

Gonadotropin-releasing hormone (GnRH) antagonists are particularly useful when a rapid inhibitory effect on the gonadal axis is required. The aim of this study was to test the efficacy and clinical safety of a low and high dose of the third generation GnRH antagonist, acyline, on pregnancy termination in female dogs. The effect of the antagonist on the progesterone (P₄) serum concentration was also described. Twenty-one mid-pregnant bitches were randomly assigned to a single subcutaneous (SC) dose of a placebo (PLACE; n = 7), a low (ACY-L; 110 μg/kg; n = 6) or high (ACY-H; 330 μg/kg; n = 8) dose of acyline. The animals were followed up for 15 days. All ACY treated but no placebo-treated animals terminated their pregnancy by abortion (p < 0.01). The ACY-L and ACY-H groups interrupted their pregnancy 7 ± 1.9 and 6.4 ± 1.3   days after treatment, respectively (p = 0.7). A significant interaction between treatment and day was found (p < 0.01) for P₄ serum concentrations when PLACE was compared with both ACY groups. No difference was found for this hormone between both ACY groups (p > 0.05) where P₄ diminished throughout the study. The decreasing rate varied among animals and was closely related to the time of abortion when P₄ reached basal concentrations. In PLACE animals, gestation progressed normally and P₄ did not change throughout the study (p > 0.05). None of the bitches presented side effects. It was concluded that acyline safely terminated mid-pregnancy by permanently decreasing P₄ serum concentrations.     

Affinity of detomidine, medetomidine and xylazine for alpha-2 adrenergic receptor subtypes

α₂-Adrenergic receptor agonists are widely used in veterinary medicine as sedative/hypnotic agents. Four pharmacological subtypes of the α₂-adrenergic receptor (A, B, C and D) have been identified based primarily on differences in affinity for several drugs. The purpose of this study was to examine the affinities of the sedative agents, xylazine, detomidine and medetomidine at the four α₂-adrenergic receptor subtypes. Saturation and inhibition binding curves were performed in membranes of tissues containing only one subtype of a₂-adrenergic receptor. The K_D for the α₂-adrenergic receptor radioligand, [³H]-MK-912, in HT29 cells (α_2A-), neonatal rat lung (α_2B-), OK cells (α_2C-) and PC12 cells transfected with RG20 (α_2D-) were 0.38 ± 0.08 n m , 0.70 ± 0.5 n m , 0.07 ± 0.02 n m and 0.87 ± 0.03 n m , respectively. Detomidine and medetomidine had approximately a 100 fold higher affinity for all the α₂-adrenergic receptors compared to xylazine but neither agonist displayed selectivity for the α₂-adrenergic receptor subtypes. These data suggest that available sedative/hypnotic α₂-adrenergic receptor agonists can not discriminate between the four known α₂-adrenergic receptor subtypes.     

SCINTIGRAPHIC EVALUATION OF FOUR DOGS WITH PROTEIN-LOSING ENTEROPATHY USING 111INDIUM-INDIUM-LABELED TRANSFERRIN

The purpose of this sutdy was to determine the clinical utility of ¹¹¹ In-labeled transferrin ( 111 In-TF) scintigraphy for evaluating dogs suspected of having protein-losing enteropathies. Four dogs were injected intravenoulsy with autologous ¹¹¹In-TF after 30 min incubation (at 37°C) of 18.5 MBq (0.5mCi) ¹¹¹In CI₃ with one ml of autologous plasma, Serial right lateral, left lateral and dorsal images were obtained 2, 4, and 24 hours post ¹¹¹ In-TF administration, Images were subjectively evaluated for the presence or absence of ¹¹¹ within the gastrointestinal tract. The results of total protein, albumin and globulin legels and results form gastrointestinal tract. the results of total protein, albumin and globulin levels and results from gastrointestinal biopsies were recorded. In one dog, a follow-up scientigraphic study was done six months after initial evaluation and initiation of treatment for plasmocytic-lymphocytic enteritis. Gastrointestinal activity was noted by two hours in two dogs, while all four dogs had gastrointestinal activity on the 24 hour images. The mean (±std dev) plasma protein, albumin and globulin levels were 3.5 (±0.9), 1.7 (±1) and 1.8 (±0.3) respectively at the time of initial presentation. In the one dog that was evaluated after therapy, faint visualization of radioactivity within the colon was noted on the 24 hour image. Based on this study, ¹¹¹In-TF appears to be a viable scientigraphic method for evaluating dogs with suspected dogs withfd suspected protein-losing enteropathies, Potential limitations of tjis radiopharmaceutical include cost and prolonged isolation of the animal prior to release to the client due to the long physical half-life (T_½= 2.82 days).     

GASTRIC EMPTYING OF SOLID RADIOPAQUE MARKERS IN HEALTHY DOGS

The gastric emptying of 1.5 mm diameter (small) and 5.0 mm diameter (large) radiopaque markers (BIPS) was assessed in 20 dogs. The markers were fed to the dogs in a test meal and abdominal radiographs were made hourly thereafter. Studies were repeated three times in each dog. The variation between two veterinarians interpreting the radiographs was low. The sex, age and day of the study did not have a significant effect on the lag phase or the time taken to empty 25%, 50% and 75% of the markers (T₂₅, T₅₀ and T₇₅ respectively). There was a weak but significant positive correlation between the body weight and T₅₀. There was no significant difference in gastric emptying parameters between the large and small markers.
The mean gastric emptying versus time curve of the small markers on day one was chosen to represent the reference curve for healthy dogs. The lag phase of the small markers on day one was 2.45 ± 2.04 hours, the T₂₅ was 4.85 ± 2.15 hours, the T₅₀ was 6.05 ± 2.99 hours and the T₇₅ was 8.32 ± 2.72 hours (mean ± SD).     

Proteins Associated With the Early Intrauterine Equine Conceptus

A critical period of early gestation in the mare involves the immobilization (fixation) of the encapsulated conceptus at around days 16–17. We compared the major proteins in the normal equine embryonic capsule and endometrial secretions around the period of fixation with those from pregnancies in the process of termination induced by administration of an analogue of prostaglandin F_2α (PGF_2α). Uterocalin and β₂-microglobulin (β₂M) associated with the embryonic capsule were proteolytically converted to smaller forms during the fixation period. These conversions were similar in conceptuses from control and treated mares. A 17 kDa cationic protein identified as a secretory phospholipase A2 (sPLA2) type IIA was detected bound to normal capsules but increased substantially in response to PGF_2α. Two forms of uteroglobin were distinguished by partial amino acid sequences of ∼6 kDa bands in flush fluids from normal pregnant uteri. After administration of PGF_2α one immunoreactive form of uteroglobin was preferentially increased. These studies demonstrate that failure of pregnancy in this model is associated with an increase in secretory phospholipase in the capsule and a change in the forms of uteroglobin in the uterine secretions.     

The effects of pentoxifylline infusion on plasma 6-keto-prostaglandin F1α and ex vivo endotoxin-induced tumour necrosis factor activity in horses

Pentoxifylline (7.5 mg/kg) was bolused intravenously to eight healthy horses and was immediately followed by infusion (1.5 mg/kg/h) for 3 h. Clinical parameters were recorded and blood samples were collected for 24 h. Plasma was separated and concentrations of pentoxifylline, its reduced metabolite I, and 6-keto-prostaglandin F_1α were determined. Heparinized whole blood was also incubated ex vivo with 1 ng Escherichi coli endotoxin/mL blood for 6 h before determination of plasma tumour necrosis factor activity. The peak plasma concentrations of pentoxifylline and metabolite I occurred at 15 min after bolus injection and were 9.2± 1.4 and 7.8± 4.3 μg/mL, respectively. The half-life of elimination ( t _½β) of pentoxifylline was 1.44 h and volume of distribution ( V d_area) was 0.94 L/kg. The mean plasma concentration of 6-keto-prostaglandin F_1α increased over time, with a significant increase occurring 30 min after the bolus administration. Ex vivo plasma endotoxin-induced tumour necrosis factor activity was significantly decreased at 1.5 and 3 h of infusion. These results indicate that infusion of pentoxifylline will increase 6-keto-prostaglandin F_1α and significantly suppress endotoxin-induced tumour necrosis factor activity in horses during the period of infusion.     

Functional characterization of post-junctional adrenergic receptor subtypes in bovine intra-mammary arteries

We examined the functional role of adrenergic receptor subtypes (ARs) in bovine intra-mammary arteries (IMAs), 1.5–2.5 mm internal diameter. Norepinephrine (NE) and phenylephrine (PE) produced concentration-dependent increases in tone in segments maintained at a previously determined optimal basal tension in vitro . The sensitivity of the tissue to NE and PE, based on -log molar ED_50s was 6.87 ± 0.17 and 7.05 ± 0.35, respectively. In addition a Schild analysis yielded antagonist affinities for the receptor mediating contractile responses to NE (pA2 value) of 10.46 ± 0.85 for prazosin and 6.29 ± 0.18 for yohimbine. These data indicate a dominance of functional alpha 1 (α₁) over alpha 2 (α₂)-ARs in this tissue. Based on the inhibitory effects of chloroethylclonidine (CEC) on PE responses and the further reduction in sensitivity when nifedipine was added to the CEC, also in the presence of PE, we conclude that there is more than one α₁-AR subtype, with a predominant role for α_1B-ARs in phenylephrine responses. Stimulation of beta (β)-ARs, resulted in relatively small reductions in tone (the highest magnitude of response was 25.94 ± 6.46% of the papaverine maximum at 3×10⁻⁶ M isoproterenol); in addition, propranolol did not significantly alter tissue sensitivity to NE. Additional characterization of functional autonomic receptor populations in this circulatory bed will form a basis for future studies on circulatory dynamics in the mammary gland.     

Pharmacokinetics and tissue residues of norfloxacin and its N-desethyl- and oxo-metabolites in healthy pigs

The pharmacokinetic properties of norfloxacin were determined in healthy pigs after single intramuscular (i.m.) and intravenous (i.v.) dosage of 8 mg/kg body weight After i.m. and i.v. administration, the plasma concentration-time graph was characteristic of a two-compartment open model. After single i.m. administration, norfloxacin was absorbed rapidly, with a t _max of 1.46 ± 0.06 h. The elimination half-life ( t _1/2β) and the mean residence time of norfloxacin in plasma were 4.99 ± 0.28 and 6.05 ± 0.22 h, respectively, after i.m. administration and 3.65 ± 0.16 and 3.34 ± 0.16 h, respectively, after i.v. administration. Intramuscular bioavailability was found to be 53.7 ± 4.4%. Plasma concentrations greater than 0.2 μg/mL were achieved at 20 min and persisted up to 8 h post-administration. Maximal plasma concentration was 1.11 ± 0.03 μg/mL. Statistically significant differences between the two routes of administration were found for the half-lives of both distribution and elimination phases ( t _1/2α, t _1/2β) and apparent volume of distribution (V_d(area)). In pigs, norfloxacin was mainly converted to desethylenenorfloxacln and oxonorfloxacin. Considerable tissue concentrations of norfloxacin, desethylenenorfloxacin, and oxonorfloxacin were found when norfloxacin was administered intramuscularly (8 mg/kg on 4 consecutive days). The concentration of the parent fluoroquinolone in liver and kidney ranged between 0.015 and 0.017 μg/g on day 12 after the end of dosing.     

TERMINATION OF EARLY PREGNANCY IN EWES BY USE OF A PROSTAGLANDIN ANALOGUE AND SUBSEQUENT FERTILITY

SUMMARY Of 87 Dorset ewes injected at 20 to 60 days of pregnancy with either 125 μg or 250 μg of the prostaglandin F^2α analogue, cloprostenol, 72 (83%) were detected in oestrus by teaser rams within 7 days. A total of 60 ewes mated with fertile rams 14 to 28 days after treatment and 36 of these (60%) subsequently lambed. Thirty-eight ewes mated with fertile rams 29 to 56 days after treatment and 30 of these (79%) subsequently lambed. The difference in fertility between the 2 periods was not significant.
Six additional ewes which did not respond to the cloprostenol lambed normally within 6 weeks. They were more than 100 days pregnant when treated.
In ewes which first exhibited oestrus by 7 days of treatment, plasma progesterone concentrations fell from near 4 ng/ml to 0.6 ng/ml within 48 h of treatment. In ewes not detected in oestrus progesterone concentrations did not decrease to similar low levels (1.4 ng/ml; t-test p < 0.005). Concentrations in the 6 ewes treated near 100 days of pregnancy dropped from 7.4 to 4.4 ng/ml over 48 h. Overall, the progesterone concentrations indicated that 92% of ewes treated at 20 to 60 days of pregnancy experienced rapid luteolysis in response to the cloprostenol.
There were no differences between the 2 doses of cloprostenol in the responses or subsequent fertility of the ewes.     

Investigation of pharmacokinetic parameters of tiamulin after intramuscular and subcutaneous administration in normal dogs

Laber, G. Investigation of pharmacokinetic parameters of tiamulin after intramuscular and subcutaneous administration in normal dogs. J. vet. Pharmacol. Therap. 11 , 45–49.
Kinetic variables for tiamulin in the normal dog have been determined. Serum concentrations of tiamulin were compared after intramuscular (i.m.) and subcutaneous (s.c.) administration of a single dose of tiamulin. Following a single i.m. dose of 10 mg/kg body weight, the compound was calculated to have a C_max= 0.61 ± 0.15 μg/ml, a T _max= 6 h and a t _½= 4.7 ± 1.4 h. Tiamulin showed dose-dependent pharmacokinetics when given as a single s.c. dose of either 10 mg or 25 mg/kg body weight. For the lower dose, the values C_max= 1.55 ± 0.11 μg/ml, T _max= 8 h and 1 _max= 4.28 ± 0.18 h were obtained. For the higher dose C _max= 3.14 ± 0.04 μg/ml, T _max= 8 h and t _½= 12.4 ± 3.4 h were calculated. When tiamulin was administered subcutaneously at a dose rate of 10 mg/kg body weight, higher and better maintained serum levels were achieved than those following i.m. administration. After repeated s.c. doses no significant accumulation of tiamulin occurred. Assuming that a continuous effective serum concentration is necessary throughout the course of therapy, these data would indicate that tiamulin should be given every 24 h.     

Characterization of bradykinin-induced endothelium-independent contraction in equine basilar artery

We investigated the effect of bradykinin (BK) on isolated equine basilar arterial rings with and without endothelium. BK induced concentration-dependent contraction of resting arterial rings and no relaxation when the rings were precontracted by prostaglandin F_2α. The maximal response and pD₂ value were 161.2 ± 28.1% (to 60 m m KCl-induced contraction) and 8.24 ± 0.25 respectively. The cumulative concentration–response curve for BK was not shifted to the right by des-Arg⁹-[Leu⁸]-BK (a B₁-receptor antagonist), HOE140 (a B₂-receptor antagonist) or NPC567 (another B₂-receptor antagonist). In four of six basilar arteries, NPC567 induced concentration-dependent contraction. Indomethacin (a cyclooxygenase inhibitor), nordihydroguaiaretic acid (a lipoxygenase inhibitor), quinacrine (a phospholipase A₂ inhibitor), tetrodotoxin (a selective blocker of Na⁺ channels), guanethidine (a nor-adrenergic neuron blocking drug), phentolamine (an α-adrenoceptor antagonist), Nω-nitro- l -arginine ( l -NNA, a nitric oxide (NO) synthase inhibitor) and endothelial denudation did not affect the BK-induced contraction. l -NNA and indomethacin induced contraction and relaxation under resting vascular tone respectively. These results suggest that endothelial cells are not involved in BK-induced contraction and that the contraction is not mediated via activation of known B₁ and B₂ receptors. Arachidonic acid metabolites and neurotransmitters like norepinephrine and NO might not play a role in BK-induced contraction in equine basilar artery.     

Specific binding of dl-cloprostenol and d-cloprostenol to PG F2α receptors in bovine corpus luteum and myometrial cell membranes

Prostaglandin F_2α receptors (PGF_2α Rs) were measured in bovine corpus luteum and myometrial cell membranes using a radiometric method. The inhibition of labelled PGF_2α binding exerted by d-cloprostenol, dl-cloprostenol, PGF_2α and PGE₁ (l0–¹¹ M to 10^–4 M) was evaluated in vitro. Results strongly suggest that cloprostenol binding to PGF_2αRs is stereospecific. d-Cloprostenol and PGF_2α were equipotent, about 150 times more potent than d-cloprostenol (P < 0.05) and approximately 280 times more potent than PGE, (P < 0.05) in inhibiting [3H]PGF_2α binding to corpus luteum cell membranes. Such differences were less evident in myometrial cell membranes, where d-cloprostenol and PGF_2α were about 10 times more potent than d-cloprostenol (P < 0.05) and approximately 95 times more potent than PGE_l (P < 0.05).     

Termination of mid-term pregnancy in the dog with oral RU 486

A total of four pregnancies were terminated in three bitches (two beagles and one flatcoated retriever) with a single dose of 20 mg/kg (one case), two doses of 8-3 mg/kg (one case) or 20 mg/kg plus 40 mg/kg (two cases) RU 486 by mouth (Mifepristone; Roussel-Uclaf, France) from day 26 to day 36 after the first day of mating of the bitch. Abortions occurred within two, four, 11 and 11 days after the initial treatment, respectively. The clinical status of the bitches was similar to that observed during a normal parturition, ie, lowering of the body temperature, shivering, panting and nesting behaviour. No side effects were seen. The beagle bitch that aborted twice, was mated at the first oestrus after the first abortion, conceived and aborted the same number of puppies the second time. The peripheral plasma progesterone concentration at the time of treatment in all bitches was < 75 nmol/litre. It had decreased to between 24-2 and 13-1 nmol/litre at the time of abortion and to between 4-0 to 0–5 nmol/litre at four to 15 days after the initial treatment. Peripheral plasma levels of prolactin increased three- to fourfold within 24 to 48 hours after treatment, concomitant with the drop in progesterone and had returned to basal levels within two to three days. Prolactin concentrations also increased around the time of intrauterine fetal death. Prostaglandin F_2aα-metabolite concentrations increased slowly after treatment, and around the time of abortion the levels increased five- to 10-fold. RU 486 seems to be a safe and effective abortifacient for use during mid-term pregnancy in the dog.