Pharmacokinetics of ceftiofur sodium in equine pregnancy.

Eleven pregnant pony mares (D270-326) were administered ceftiofur sodium intramuscularly at 2.2 mg/kg (n = 6) or 4.4 mg/kg (n = 5), once daily. Plasma was obtained prior to ceftiofur administration and at 0.5, 1, 2, 4, 8, 12, and 24 hr after administration. Eight pony mares were re-enrolled in the study at least 3 days from expected foaling to ensure steady-state concentrations of drug at the time of foaling. Mares were administered ceftiofur sodium (4.4 mg/kg, IM) daily until foaling. Parturition was induced using oxytocin 1 hr after ceftiofur sodium administration. Allantoic and amniotic fluid, plasma, and colostrum samples were collected at time of foaling. Serial foal plasma samples were obtained. Placental tissues were collected. Desfuroylceftiofur acetamide (DCA) concentrations were measured in samples by high-performance liquid chromatography (HPLC). Mean (±SD) peak serum concentrations of DCA were 3.97 ± 0.50 µg/ml (low dose) and 7.45 ± 1.05 µg/ml (high dose). Terminal half-life was significantly (p = .014) shorter after administration of the low dose (2.91 ± 0.59 hr) than after administration of the high dose (4.10 ± 0.72 hr). The mean serum concentration of DCA from mares at time of foaling was 7.96 ± 1.39 µg/ml. The mean DCA concentration in colostrum was 1.39 ± 0.70 µg/ml. DCA concentrations in allantoic fluid, amniotic fluid, placental tissues, and foal plasma were below the limit of quantification (<0.1 µg/ml) and below the minimum inhibitory concentration of ceftiofur against relevant pathogens. These results infer incomplete passage of DCA across fetal membranes after administration of ceftiofur sodium to normal pony mares.

Effects of topical application of misoprostol on cervical relaxation in mares.

Mares who have not delivered a foal early in life may experience limitations in cervical relaxation, primarily during oestrus. A closed cervix prevents intrauterine deposition of semen during natural breeding, may delay uterine clearance after insemination leading to intrauterine fluid accumulation in, and subsequent infertility. Therefore, a reliable pharmacological method of dilating the equine cervix would have practical application in veterinary medicine. The goal of this study was to investigate the effectiveness of topically applied, synthetic prostaglandin E1 analogue (PGE1 ) for stimulating dilation of the equine cervix. Ten mares in dioestrus were randomly assigned to one of two treatments in a single-blind crossover study: (treatment) PGE1 gel (1000 mcg compounded misoprostol cream) applied topically to the external cervical os (n = 5), and (control) a vehicle cream applied topically to the external cervical os (n = 5). Transrectal palpation and ultrasonographic measurements of the cervix were performed prior to, six and 24 h post-treatment. Digital measurements were taken, per vagina, at six and 24 h post-treatment. Mares were monitored through the subsequent oestrous cycle for ovulation. Mares were assigned to the opposite treatment group such that each mare served as her own control (crossover). Data were analysed using parametric (split-plot anova), as well as nonparametric (Kruskal-Wallis anova, Wilcoxon's rank-sum test) methods. At six and 24 h there were no significant differences for tone, length, height, degree of relaxation or echotexture between control and PGE1 treated groups at the measured time points (p > 0.05). Topical cervical application of PGE1 did not induce a measurable degree of cervical relaxation under the conditions of this experiment.

Acute and chronic effects of a contraceptive compound RTI-4587-073(l) on testicular histology and endocrine function in miniature horse stallions.

The objective of this study was to evaluate acute endocrine effects as well as histological changes in testicular parenchyma induced by the contraceptive compound RTI-4587-073(l). Six miniature stallions were used in this experiment. The treatment group (n = 3) received one oral dose of 12.5 mg/kg of RTI-4587-073(l), and the control group (n = 3) received placebo only. The stallions' baseline parameters (semen, testicular dimensions, endocrine values) were collected and recorded for 5 weeks before treatment and for 6 weeks after treatment. Multiple blood samples were collected for endocrine analysis. Testicular biopsies were obtained before treatment, 1 day after treatment and every other week after treatment. Ultrasound exams were performed to monitor the dimensions of the stallions' testes. All stallions were castrated 6 weeks after treatment. Sperm numbers, motility and percentage of morphologically normal sperm decreased (p < 0.05), while the number of immature germ cells increased in ejaculates from treated animals (p < 0.05). Serum concentrations of inhibin and follicle-stimulating hormone did not change. Testosterone concentrations initially transiently decreased (p < 0.05) after administration of RTI-4587-073(l), and increased several days later (p < 0.05). Testicular content of testosterone and estradiol 17-ß was lower in treated stallions than in control stallions on Day 1 after treatment (p < 0.05). Severe disorganization of the seminiferous tubules, significant loss of immature germ cells and complete depletion of elongated spermatids were observed in testicular biopsies obtained from treated stallions 1 day, 2 and 4 weeks after treatment. These changes were still present in the testicular samples taken from treated stallions after castration. The results of this study confirmed that RTI-4587-073(l) has antispermatogenic effects in stallions. Furthermore, we concluded that this compound causes acute sloughing of immature germ cells from the seminiferous tubules. RTI-4587-073(l) has significant but transient effects on Leydig cell function in stallions.

Semen characteristics in a sub-fertile Arabian stallion with idiopathic teratospermia.

A 5-year-old Arabian stallion was managed for breeding with fresh/extended semen during a period of 8 months with a resulting per cycle pregnancy rate of 26.3%. The stallion was in good health and no abnormalities of the reproductive tract were observed. Evaluation of several ejaculates revealed that sperm production and semen quality were mostly unchanged during the period of evaluation, that sperm production was normal and that semen quality was extremely poor. The most prevalent sperm defects were abnormal heads and mid-pieces. Most abnormal heads were microcephalic and/or tapered and considerable variation in sperm head dimensions within and among ejaculates was observed. A unique defect characterized by swollen/roughened mid-piece caused by accumulation of cytoplasmic-like material and abnormal mitochondrial sheath was observed. Nuclear vacuoles, acrosome defects, and teratoids were also prevalent and most sperm presented multiple abnormalities. The absence of any clear cause or any signs of testicular degeneration, combined with normal sperm production, and constant abnormal sperm production suggest an inherent, congenital disturbance of spermatogenesis as the cause of teratospermia in this case.

Maintaining fetal normoglycemia prevents the increase in myometrial activity and uterine 13,14-dihydro-15-keto-prostaglandin F2 alpha production during food withdrawal in late pregnancy in the ewe.

Food deprivation during pregnancy leads to an increase in maternal and fetal prostaglandin (PG) production and increased uterine contractility. We investigated the effect of maintaining fetal normoglycemia during food withdrawal-induced maternal hypoglycemia on uterine 13,14-dihydro-15-keto-prostaglandin F2 alpha (PGFM) production and myometrial activity in late pregnant sheep. Pregnant sheep were surgically instrumented with fetal and maternal catheters and electromyogram leads under halothane anesthesia. Maternal and fetal blood plasma samples were obtained once a day at 0900 h, 24 h before (baseline sample) and after 48 h of food withdrawal. Food, but not water, was withdrawn from ewes in group I (n = 5). During food withdrawal in group II (n = 5), glucose was infused into a fetal vein to maintain fetal normoglycemia. All data were normalized to the concentration in the baseline sample in each animal as 100%. After 48 h of food withdrawal, maternal whole blood glucose fell by 42.2 +/- 4.4% (mean +/- SEM: group I) and 31.4 +/- 6.2% (group II). These values were not significantly different. Fetal blood glucose fell by 40.4 +/- 5.7% (group I). In group II, fetal blood glucose was maintained in the normal range (99.6 +/- 1.6% of baseline). Maternal uterine electromyogram activity, uterine venous estrone sulfate, and uterine veno-arterial difference in PGFM rose significantly during food withdrawal in group I ewes, but not in group II ewes. Maternal and fetal arterial plasma ACTH and cortisol did not change in group II animals. We conclude that maintenance of fetal normoglycemia during 48 h of food withdrawal in sheep prevents the increase in myometrial activity, maternal plasma estrogens, and uterine PGFM production during food withdrawal in late pregnancy.

The effect of interval from day of administration of bovine somatotropin (bST) to synchronization of ovulation and timed-insemination on conception rate of dairy cows with and without ovarian cysts.

The objective of this study is to evaluate the effect of the interval from the day of administration of bovine somatotropin (bST) to the day of initiation of synchronization of ovulation (Day 0 and 7) and timed-insemination (TAI) on conception rate (CR) of dairy cows with and without ovarian cysts, respectively. Lactating dairy cows (n = 359) were divided into two groups. Cows in Group 1 (n = 238, without ovarian cysts) were treated with 100 microg, i.m. GnRH on Day 0; 25 mg, i.m. PGF2a on Day 8. 100 mirog. i.m. GnRH on Day 10; and inseminated 16 h later without detection of estrus. Cows in Group 2 (n = 121, with ovarian cysts) were treated with 100 microg, i.m. GnRH on Day 0; 100 microg, i.m. GnRH on Day 7; 25 mg, i.m. PGF2alpha on Day 14, 100 ug, i.m. GnRH on Day 16; and inseminated 16 h later without detection of estrus. Between 60 and 63 days postpartum, all cows in the herd were given bST every 14 days for the duration of the study. Logistic regression was used to assess the risk of nonpregnancy associated with interval from bST treatment to Day 0 for cows without ovarian cysts. and both Day 0 and 7 for cows with ovarian cysts adjusting for parity and days in milk. The CR for cows in Group 1 was significantly higher when the interval from last treatment with bST to Day 0 was between 1 and 3 days (28%) compared to 4-6 days (14%). In addition, the risk of nonpregnancy was 2.19 times greater in cows 4-6 days after bST treatment compared to 1-3 days after adjusting for parity and days in milk. The CR for cows in Group 2 was not significantly different when the interval from last treatment with bST to both Day 0 and 7 was between 1 and 3, 4 and 6, and 7 and 14 days. In conclusion, the results of this study suggested bST treatment closer to Day 0 had a positive effect on CR of cows without ovarian cysts, but bST treatment closer to both Day 0 and 7 had no effect on CR of cows with ovarian cysts. This was interpreted to mean that bST had a beneficial effect on either, or both, the preovulatory follicle and the oocyte in dairy cows without ovarian cysts, but not in dairy cows with ovarian cysts.

Prostaglandin production in the umbilical and uterine circulations in pregnant sheep at 129-136 days gestation.

Prostaglandins circulating in the maternal and foetal blood have been implicated in important physiological systems. These functions include foetal adrenal function, maintenance of patency of the ductus arteriosus, regulation of uterine and umbilical circulations, and labor and delivery type myometrial contractions. The placenta is a major site of prostaglandin production in pregnancy. Limited data are available which combine measurements of veno-arterial differences across the uterine and umbilical circulations with blood flow in these circulations to enable calculation of umbilical-placental and utero-placental production rates for the prostaglandins. In chronically instrumented pregnant ewes, between 129 and 136 days of gestation, prostaglandin F2 alpha(PGF2 alpha), 13, 14 dihydro-15-keto prostaglandin F2 alpha (PGFM), prostaglandin E2 (PGE2) were measured in the maternal carotid artery and uterine vein. Foetal PGE2, and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) (the major metabolite of prostacyclin) were measured in umbilical venous and foetal descending aorta arterial plasma. Umbilical and uterine blood flow were measured using the diffusion-equilibrium technique. Uterine blood flow was 1693 +/- 137 ml.min-1 (mean +/- SEM); uterine production rates were 480 +/- 88 ng.min-1 for PGF2 alpha, 517 +/- 144 ng.min-1 for PGFM, and 165 +/- 27 ng.min-1 for PGE2. Umbilical blood flow was 147 +/- 17 ml.min-1.kg-1 foetal body weight. Umbilical production rates into the foetal circulation were 11 +/- 2 ng.min-1.kg-1 for PGE2 and 6 +/- 2 ng. ng.min-1.kg-1 foetal body weight for PGI2.

Insulin induced fetal hypoglycaemia and fetal and maternal plasma prostaglandin concentrations in sheep in late gestation.

Fetal hypoglycaemia consequent on food withdrawal for 48 h in sheep in late pregnancy is accompanied by an increase in fetal PGE2 plasma concentrations and myometrial contractility. To assess the contribution of fetal hypoglycaemia and related cellular glucopenia in the increased production of fetal PGE2 we studied the effect of 48 h insulin infusion to the fetus. Fetal whole blood glucose was lowered from 19 +/- 2 to 9 +/- 1 mg.dl-1. This experimental regimen maintains glucose availability to those fetal cells in which insulin increases glucose uptake. Fetal umbilical venous and femoral arterial PGE2 concentrations and umbilical veno-arterial PGE2 difference were unchanged, but maternal uterine veno-arterial difference for PGFM increased during the insulin induced fetal hypoglycaemia. Myometrial activity was also unchanged. We conclude that the increased fetal PGE concentration previously reported during food withdrawal is due to a deficiency of glucose to specific insulin dependent cells within vascular beds served by the fetal cardiovascular system. In addition, the findings suggest a need for a supply of glucose of fetal origin for cells that are responsible for increased PGFM concentrations in the maternal uteroplacental circulation.