Betamethasone alcohol suspensions for the induction of parturition in dairy cows: a comparison with dexamethasone trimethyl acetate

A field trial was conducted to compare the efficacy suspensions of betamethasone alcohol with dexamethasone trimethyl acetate on the induction of parturition before term in dairy cows. Initial treatment consisted of a subcutaneous injection of either 20 mg of betamethasone as a 10 mg/ml suspension (Group A), 30 mg of a 15 mg/ml suspension (Group B), or 20 mg of dexamethasone TMA (Group C). Those cows not calving within 10 days received a further 25 mg of betamethasone alcohol as a 2 mg/ml suspension. Data were collected from 619 cows on 41 farms. A marked difference between groups was noted in the proportion of animals calving to the initial injection (55.0, 61.4 and 26.4% calved to first injection in Groups A, B and C respectively); the differences between the groups receiving the betamethasone suspensions and the group receiving dexamethasone trimethyl acetate were highly significant (P<0.001). Of the animals treated 6.9, 3.6 and 10.2% failed to calve within 17 days of the initial treatment in Groups A, B and C respectively (Group B significantly different from Group C (0.02 > P> 0.01). Nevertheless, the response-time (mean of 7.5 days for all those calving to the first injection, and of 12.4 days for all those calving to the second injection) was not significantly different between the three treatment groups. Calf mortality over all treatments was 15.2% at birth and 26.6% by 4 days old. The incidence of metabolic disease was 5.9%, and 203% of cows had retained foetal membranes 24 hours after calving. No differences were observed between groups in the incidence of dystocia and cow mortality. Four cases of mastitis were recorded in Group A and 12 cases in Group C. No cases were recorded in Group B.     

A comparison of the pharmacological activity in cows of two suspensions of betamethasone alcohol

The activity of two betamethasone (BM) suspensions, which differed only in their solids:vehicle ratio, was examined in cattle. Two groups of 10 cows received by subcutaneous injection either 20ml of a 2mg/ml aqueous suspension of BM alcohol or 2ml of a 20mg/ml aqueous suspension. A further 10 cows served as a saline-treated control group.

The mean peak plasma BM concentration was significantly higher in cows treated with 2mg/ml suspension. However, plasma BM levels tended to be maintained for longer by the 20mg/ml suspension. A depression of early morning cortisol levels, similar to that seen with other synthetic glucocorticoids, was recorded with both BM preparations; the depression outlasted the presence of BM. Plasma glucose levels and circulating neutrophil numbers were elevated by BM treatment, and the magnitude and duration of these changes was related to the solids:vehicle ratio of the injected suspensions. The more concentrated suspension was absorbed more slowly and thus produced effects of greater duration.     

A comparison of the pharmacological activity in cows of two suspensions of betamethasone alcohol

The activity of two betamethasone (BM) suspensions, which differed only in their solids:vehicle ratio, was examined in cattle. Two groups of 10 cows received by subcutaneous injection either 20 ml of a 2 mg/ml aqueous suspension of BM alcohol or 2 ml of a 20 mg/ml aqueous suspension. A further 10 cows served as a saline-treated control group. The mean peak plasma BM concentration was significantly higher in cows treated with 2 mg/ml suspension. However, plasma BM levels tended to be maintained for longer by the 20 mg/ml suspension. A depression of early morning cortisol levels, similar to that seen with other synthetic glucocorticoids, was recorded with both BM preparations; the depression outlasted the presence of BM. Plasma glucose levels and circulating neutrophil numbers were elevated by BM treatment, and the magnitude and duration of these changes was related to the solids:vehicle ratio of the injected suspensions. The more concentrated suspension was absorbed more slowly and thus produced effects of greater duration.     

Plasma estradiol-17ß concentrations in the cow during induced estrus and after injection of estradiol-17ß benzoate and estradiol-17ß cypionate -a preliminary study

Plasma estradiol-17 beta concentrations were investigated in cows during induced estrus and after an intramuscular injection of 10 mg of estradiol-17 beta benzoate and estradiol-17 beta cypionate to determine a withdrawal period for both preparations. After the estradiol-17 beta benzoate injection, the plasma estradiol-17 beta concentration was higher than the physiological maximum of 24 pg/ml obtained during induced estrus for a period of 114 +/- 10 h (mean +/- SEM). For estradiol-17 beta cypionate the corresponding value was 170 +/- 17 h (mean +/- SEM). A withdrawal period of 7 days for the benzoate ester and of 10 days for estradiol-17 beta cypionate is therefore proposed. These results were confirmed by biopsies taken at the injection site 8 and 15 days after the injection of estradiol-17 beta benzoate and estradiol-17 beta cypionate, respectively. In these biopsies no residues of estradiol-17 beta nor of its esters could be detected.     

Effects of pre-natal glucocorticoids on testicular development in sheep

We tested the hypothesis that acute pre-natal exposure to high levels of synthetic glucocorticoid (betamethasone) would alter fetal testicular development through actions on gonadal glucocorticoid receptors (GRs). Pregnant Merino ewes bearing singleton male fetuses (n = 24) were allocated randomly among four equal groups to be injected intramuscularly with saline or betamethasone (0.5 mg/kg) either on day 109 of gestation or on both day 109 and day 116 of gestation. Fetal testes were collected at post-mortem, 5 days after each treatment. The volume of interstitial tissue and the volume, length and diameter of the sex cords were measured, and Sertoli cells and gonocytes were counted. For cord volume and interstitial tissue volume, control testes demonstrated maturational changes as fetal age advanced from 109 to 116 days of gestation. For that period, the single injection of betamethasone significantly reduced Leydig cell proliferation (P < 0.05), but had no effect on Sertoli cell numbers. Immunohistochemistry was used to localize GR and proliferating cell nuclear antigen in testicular cells. GR immunoexpression in Leydig cells was higher in fetuses exposed to betamethasone at 109 days of gestation than in control fetuses. Sertoli cells showed low levels of GR. It was concluded that, during mid-gestation, a brief period of glucocorticoid treatment could affect testicular development in male sheep fetuses. The mechanism probably involves direct effects on Leydig cells, as these cells express extra-GR in response to the treatment. Sertoli cells seem to produce less GR than Leydig cells, perhaps explaining their lack of response to betamethasone. These outcomes may have important implications for future fertility in male offspring.     

Induction of estrus in greyhound bitches with prolonged idiopathic anestrus or with suppression of estrus after testosterone administration

Twelve anestrous adult Greyhound bitches were used to study a regimen for induction of estrus. Once daily, 7 bitches were given diethylstilbestrol (DES; 5 mg, PO) until sanguineous vaginal discharge and vulvar edema were observed (designated as day 1 of proestrus) and for 2 days thereafter. If no response was elicited after 7 days, a doubled DES dose was given for up to an additional 7 days. Luteinizing hormone (5 mg, IM) was given on day 5 of proestrus, and follicle-stimulating hormone (10 mg, IM) was given on days 9 and 11 of proestrus. Bitches were bred once on day 13. Five bitches were used as a control group; they were given candy tablets for 7 days (first day on tablets, treatment day 1) and 0.9% NaCl (1.0 ml, IM) on treatment days 12, 16, and 18. The 7 bitches treated with DES had a mean proestrus period of 7.7 days and a mean estrus period of 5.7 days up to the day of mating. After mating, they had a mean gestation interval of 64 days and delivered a mean of 4 pups/litter. In 5 bitches, initial treatment with 5 mg of DES/day induced proestrus within 7 days; however, in 2 bitches, additional treatment with 10 mg of DES/day was needed for 5 and 6 days, respectively. Serum estradiol-17 beta and progesterone concentrations remained at base line during the period of DES treatment. Concentrations of both hormones increased after injection with luteinizing hormone and remained high for the next 4 days.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of growth hormone-releasing factor on growth hormone response, growth and feed conversion efficiency in buffalo heifers (Bubalus bubalis)

The aim of this study was to determine the benefits of growth hormone-releasing factor (GRF) on growth and feed conversion efficiency (FCE) in buffaloes. Twelve Murrah buffalo heifers (Bubalus bubalis) of mean age 24.8 months and mean body weight 302.4kg were divided into two groups (treatment and control) with six animals in each group. The buffaloes were given intravenous injections of bovine GRF (bGRF) at a dose rate of 10microg/100kg body weight or an equal volume of saline at 15-day intervals for a period of 9 months. Plasma growth hormone (GH) responses to bGRF challenge were measured in blood samples collected at 90-day intervals on days 1, 90, 180 and 270 and samples were taken at -60, -30, 0, +10, +20, +30, +60, +120 and +180min relative to bGRF injection. Blood samples were also collected weekly by jugular venepuncture for the quantification of plasma GH. The average growth rate (AGR) and FCE of all animals were recorded at 15-day intervals. Plasma GH concentrations increased (P=0.001) steadily following bGRF challenge, peaking 10-20min after challenge and declining to baseline by 180min. In the treatment group, there were no significant differences (P>0.05) in either the peak heights of the GH response or the area under the curve (AUC) of the GH response after bGRF challenge on any of the four occasions of intensive bleeding. There were overall increases in plasma GH concentrations (P<0.01), AGR (P<0.01) and FCE (P=0.05) in the treatment group compared with the control animals. The study showed that GH responsiveness to administration of bGRF at 15-day intervals over 9 months of treatment remained unchanged in buffalo heifers. Exogenous bGRF treatment for a long period can therefore enhance GH release leading to higher growth rates and better feed conversion efficiency in buffalo heifers.     

Evaluation of progesterone deficiency as a cause of fetal death in mares with experimentally induced endotoxemia

The role of decreased luteal activity in embryonic loss after induced endotoxemia was studied in mares 21 to 35 days pregnant. Fourteen pregnant mares were treated daily with 44 mg of altrenogest to compensate for the loss of endogenous progesterone secretion caused by prostaglandin F2 alpha (PGF2 alpha) synthesis and release following intravenous administration of Salmonella typhimurium endotoxin. Altrenogest was administered daily from the day of endotoxin injection until day 40 of gestation (group 1; n = 7), until day 70 (group 2; n = 5), or until day 50 (group 3; n = 2). In all mares, secretion of PGF2 alpha, as determined by the plasma 15-keto-13,14-dihydro-PGF2 alpha concentrations, followed a biphasic pattern, with an initial peak at 30 minutes followed by a second, larger peak at 105 minutes after endotoxin injection. Plasma progesterone concentrations decreased in all mares to values less than 1 ng/ml within 24 hours after endotoxin injection. In group 1, progesterone concentrations for all mares were less than 1 ng/ml until the final day of altrenogest treatment. In 6 of 7 mares in group 1, the fetuses died within 4 days after the end of treatment, with progesterone concentrations less than 1 ng/ml at that time. In the mare that remained pregnant after the end of treatment, plasma progesterone concentration was 1.6 ng/ml on day 41 and increased to 4.4 ng/ml on day 44. In group 2, all mares remained pregnant, even though plasma progesterone concentrations were less than 1 ng/ml in 4 of 5 mares from the day after endotoxin injection until after the end of altrenogest treatment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clearance of penicillin G in the newborn calf

Sodium penicillin G was administered intravenously (4545 IU/kg) to calves on the day of birth (12-24 h old) and at 5, 10, and 15 days of age. Serum was collected at varying intervals for 120 min after injection and analysed for penicillin G. The mean total body clearance (ClB) of penicillin G on the day of birth was 2.98 ml/min/kg compared to 4.83 ml/min/kg at 5 days, 3.11 ml/min/kg at 10 days and 4.65 ml/min/kg at 15 days of age. Clearances at 5 and 15 days were significantly (P less than or equal to 0.05) higher than on the day of birth. The half-life (t1/2 beta), however, did not change significantly over the 15-day period of the study. These results indicate that the newborn calf has an appreciable ability to excrete penicillin G before it is 24 h old, and that total body clearance of the antibiotic increases rapidly in the immediate postnatal period.     

Pharmacokinetics of tulathromycin following subcutaneous administration in meat goats

Tulathromycin is a triamilide antibiotic that maintains therapeutic concentrations for an extended period of time. The drug is approved for the treatment of respiratory disease in cattle and swine and is occasionally used in goats. To investigate the pharmacokinetics of tulathromycin in meat goats, 10 healthy Boer goats were administered a single 2.5 mg/kg subcutaneous dose of tulathromycin. Plasma concentrations were measured by ultra-high pressure liquid chromatography tandem mass spectrometry (UPLC–MS/MS) detection. Plasma maximal drug concentration (C_max) was 633 ± 300 ng/ml (0.40 ± 0.26 h post-subcutaneous injection). The half-life of tulathromycin in goats was 110 ± 19.9 h. Tulathromycin was rapidly absorbed and distributed widely after subcutaneous injection 33 ± 6 L/kg. The mean AUC of the group was 12,500 ± 2020 h ng/mL for plasma. In this study, it was determined that the pharmacokinetics of tulathromycin after a single 2.5 mg/kg SC injection in goats were very similar to what has been previously reported in cattle.     

Effect of intra-articular gentamicin sulfate on normal equine synovial membrane

Gentamicin sulfate (3 ml; 50 mg/ml) was administered intra-articularly into 30 normal equine radiocarpal joints after arthrocentesis. Arthrocentesis alone was performed on 10 normal radiocarpal joints. Synovial fluid evaluations and gross and microscopic examinations were performed on synovial fluid and synovial membrane of designated joints at selected daily intervals over a period of 10 days. Synovial fluid from gentamicin-injected joints had greater turbidity, higher RBC and WBC counts, and higher refractive indices than did joints not injected with gentamicin. The largest increases developed on days 1 or 2 after gentamicin injection, with mean total WBC, large mononuclear cell, small mononuclear cell, and polymorphonuclear cell counts of 23,860, 11,853, 857, and 11,150 cells/microliter, respectively. Arthrocentesis alone resulted in smaller increases in these counts. Microscopic changes seen in the synovial membrane of gentamicin-injected joints included edema, leukocytic infiltration, and loss of synovial lining cells. These inflammatory changes resolved within 7 days after gentamicin injection.     

Ampicillin trihydrate in foals: serum concentrations and clearance after a single oral dose

Five foals from two to three days old were given a single oral dose of ampicillin trihydrate (20 mg/kg bodyweight [bwt]). Serum ampicillin concentrations were measured serially over a 24 h period. The study was repeated in the same foals at 16 to 21 days old. The mean peak serum ampicillin concentration at two to three days old was 5.0 micrograms/ml at 1 h after treatment; the mean peak serum concentration at 16 to 21 days old was 2.7 micrograms/ml at 2 h. The concentrations steadily declined and ampicillin was not detected in the serum from any of the foals by 24 h. Serum clearance averaged 17.7 ml/min/kg at two to three days and 35.8 ml/min/kg at 16 to 21 days.     

Carprofen in veterinary medicine. II. Inhibitory effect on the release of PGF2 alpha in the early postpartum cow

Carprofen, a non-steroidal anti-inflammatory drug (NSAID) known to inhibit prostaglandin synthesis, was given intravenously in five cows at a daily dose of 0.7 mg/kg for five days beginning on day 1 postpartum. Blood samples were collected at various times over a period of six days following the first injection. At this dose, carprofen reached highest plasma values of about 45 micrograms/ml after the fifth injection and was well tolerated by all the cows. During the whole experimental period, mean plasma levels of 15-keto-13, 14-dihydro-prostaglandin F2 alpha, the primary metabolite of PGF2 alpha, were significantly (p less than 0.05) lower in treated than in control animals (28-47% vs 64-101% of pretreatment concentrations). The suppressive effect of carprofen on PGF2 alpha-production occurred immediately after its application and was maximal 3-6 h post injection on the first and on the fifth experimental day (60-80% and 40-85%, respectively). We conclude from our results that carprofen in a single dose of 0.7 mg/kg b.w. effectively suppresses PGF2 alpha-release in the postpartum cow. Whether this effect is beneficial in the treatment of uterine inflammatory processes remains to be determined.     

Plasma chloramphenicol concentrations in cats after parenteral administration of chloramphenicol sodium succinate

Five cats were dosed on five occasions with 20 mg chloramphenicol/kg body weight. The drug was given three times as chloramphenicol sodium succinate (by intravenous, intramuscular and subcutaneous injections) and twice as crystalline chloramphenicol in capsules. Plasma chloramphenicol concentrations were determined at fixed intervals after administration. Parenteral injection of the ester usually produced highest plasma levels at the initial sampling, 0.5 h after dosing. When capsules were given, there was greater variation between cats: highest plasma levels were recorded usually at 0.5-2 h after dosage but delayed absorption was evident in some cases. There were no statistically significant differences between the different routes with regard to mean plasma antibiotic levels at each sampling or mean area under the curve of plasma level versus time, except that mean plasma levels at 0.5 h were higher with intravenous or intramuscular injection than with oral administration.     

Plasma luteinizing hormone response to increasing doses of synthetic gonadotrophin-releasing hormone in heifers

The dosenresponse relationship for a synthetic gonadotrophin-releasing hormone (GnRH) was studied in normally cycling heifers using the area under the luteinizing hormone (LH) curve as a response parameter. Oestrus was synchronized by an injection of 0.5 mg cloprostenol before the experiment started and after the 3rd treatment with GnRH. Treatment with GnRH as assigned in a Latin square included 5 dose levels (0, 10, 50, 100, 250 μg) and 5 treatment days over a period of 22 days. GnRH was capable of inducing an increase of plasma LH within 30 min after injection. Plasma LH response increased with increasing doses of GnRH, the largest increase being observed when the dose was raised from 50 μg to 100 μg. One heifer did not respond to any of the doses applied. The existence of an individual treshold dose of GnRH is suggested.     

Steroid concentrations in cows with corticotropin-induced cystic ovarian follicles and the effect of prostaglandin F2alpha and indomethacin given by intrauterine injection.

In 7 instances, cystic ovarian follicles resulted when adrenocorticotropin (ACTH) was administered daily during the follicular phase of the estrous cycle in cows. Two cows given daily injections of hydrocortisone (cortisol) during the follicular phase of the estrous cycle did not develop cystic ovaries. Plasma concentrations of estradiol in cows with induced cystic ovarian follicles were similar to the peak values observed at estrus and were between 6 and 12 pg/ml. Progesterone concentrations in plasma of cows with cystic ovaries were low, between 1 and 2 ng/ml. Ovulation occurred when 2 cows were given human chorionic gonadotropin (HCG) during the period of ovarian cyst development with ACTH administration. Several days of administration of ACTH was required to cause cyst development. Ovulation occurred at the expected time in 1 cow when injections began on day 19, that is, late in the follicular period. In another cow, when treatment was stopped on day 3, after the expected time of estrus a delayed ovulation occurred. In 2 cows with induced cystic ovarian follicles, cyst atresia occurred spontaneously about day 13 to 17 of the cycle. In these cows, new follicular growth and ovulation followed (although delayed in 1 cow). The time of atresia of cystic follicles was not influenced by the intrauterine injection of 10 ml of sterile saline solution on days 8, 9, and 10 in 1 cow. When 5 mg of prostaglandin F2alpha in 10 ml of sterile saline solution was given (uterine injection) in 2 cows on days 8, 9, and 10, cyst atresia occurred earlier than the time of spontaneous atresia. Intrauterine administration of 100 mg of indomethacin in 10 ml of sterile saline solution daily for 13 or 14 days to 2 cows, starting on day 12 or 13 of the cycle, resulted in persistence of the induced cystic ovarian follicles. After cessation of indomethacin treatment, atresia of cysts followed and new follicular growth and ovulation occurred.     

Concentration of ivermectin in bovine serum and its effect on the fecundity of psoroptic mange mites

The concentration-time profile of ivermectin in serum was determined for 3 Hereford heifers. The mean maximum serum concentration, 29 ng of ivermectin/ml, was obtained 48 hours after single subcutaneous injection of 200 micrograms/kg of body weight. The fecundity of mites placed on 9 treated animals at 5, 9, 12, 15, 18, and 21 days after injection was reduced by 96% to 99%. At 24 days after treatment, when serum concentration had decreased to about 2 ng/ml, the capability of mites to produce eggs increased to 50% of mites from nontreated calves. At 27 and 30 days after the drug was injected, egg production by mites on treated calves was equivalent to that of mites on nontreated calves. The reduced fecundity resulted from an almost complete cessation of oviposition by females after only a 1-day exposure to ivermectin-treated calves.     

Pharmacokinetic disposition of a long-acting oxytetracycline formulation after single-dose intravenous and intramuscular administrations in the American alligator (Alligator mississippiensis).

The pharmacokinetics of a long-acting oxytetracycline preparation administered i.v. and i.m. to American alligators (Alligator mississippiensis) at 10 mg/kg was determined. Plasma levels of oxytetracycline were measured using high-performance liquid chromatography, and the resulting concentration versus time curve was analyzed using compartmental modeling and noncompartmental modeling techniques for i.v. and i.m. samples, respectively. A two-compartment model best represented the i.v. data. Intravenous administration of oxytetracycline resulted in an extrapolated mean plasma concentration at time zero of 60.63 +/- 28.26 microg/ml, with average plasma drug levels of 2.82 +/- 0.71 microg/ml at the end of the 192-hr sampling period. Plasma volume of distribution for i.v. oxytetracycline was 0.20 +/- 0.09 L/kg, with a harmonic mean elimination half-life of 15.15 hr and mean total body clearance rate of 0.007 +/- 0.002 L/hr/kg. Intramuscular administration of oxytetracycline achieved a mean peak plasma concentration of 6.85 +/- 1.96 microg/ml at 1 hr after administration, with average plasma drug levels of 4.96 +/- 1.97 microg/ml at the end of the 192-hr sampling period. The harmonic mean terminal elimination half-life for i.m. oxytetracycline was 131.23 hr. Based on the results of this study, long-acting preparations of oxytetracycline administered parenterally to American alligators at 10 mg/kg q 5 days is expected to maintain plasma concentrations above the minimum inhibitory concentration of 4.0 microg/ml for susceptible organisms.     

Pharmacokinetics and synovial fluid concentrations of cephapirin in calves with suppurative arthritis

Six calves with suppurative arthritis were given a single IM injection of sodium cephapirin at a dosage of 10 mg/kg of body weight. Cephapirin concentrations were serially measured in serum and in normal and suppurative synovial fluid over a 24-hour period. Mean peak serum concentration was 6.33 microliters/ml at 20 minutes after injection. The highest cephapirin concentrations in normal and suppurative synovial fluid were 1.68 and 1.96 micrograms/ml, respectively, 30 minutes after injection. Overall mean cephapirin concentration in normal synovial fluid for the first 4 hours (1.04 +/- 0.612 micrograms/ml) was not significantly different from that in suppurative synovial fluid (0.88 +/- 0.495 micrograms/ml; P greater than 0.05). Elimination half-life was 0.60 hours and clearance was 1,593 ml/h/kg.     

Effects of anti-inflammatory steroid drugs on pain coping behaviours in a model of articular pain in the domestic fowl

The optimum dose rates of betamethasone, dexamethasone (sodium phosphate) and methylprednisolone (acetate salt) were determined for the treatment of inflammatory pain in domestic fowl using the microcrystalline sodium urate model of articular pain. The response criteria were the changes in behavioural profiles and pain-related activity over 60 minutes commencing 1 hour after an intra-articular injection of sodium urate and a course of intramuscular injections of a range of doses of each drug on the previous 2 days. The optimum dose rates for betamethasone, dexamethasone and methylprednisolone respectively were 0.04, 0.06 and 2 mg kg(-1)and are in the range of the recommended doses for these drugs in mammals.