Patrick J. Burns

Induction of mucosal and systemic antibody specific for SeMF3 of Streptococcus equi by intranasal vaccination using a sucrose acetate isobutyrate based delivery system

Streptococcus equi causes equine strangles, a highly contagious disease of the upper respiratory tract. The antiphagocytic surface protein SeM is strongly immunogenic and evokes mucosal and systemic antibodies during convalescence. The present study investigated the potential of sucrose acetate isobutyrate (SAIB); a high viscosity excipient that provides controlled release of biologically active substances, to enhance antibody responses following intranasal immunization of horses with a 108 a.a. peptide of SeM (SeMF3). SeMF3-SAIB was administered intranasally to each of the 11 adult horses on days 0 and 28. A second group of seven horses was vaccinated with SeMF3 alone. SAIB enhanced the mucosal and systemic immunogenicity of SeMF3, whereas SeMF3 by itself stimulated only a shortlived mucosal IgA and no systemic response. Moreover, nasal mucosal responses of horses immunized with SeMF3-SAIB were qualitatively and quantitatively similar to those observed in convalescent horses and involved similar linear epitopes of SeM. Epitope analysis also suggested that the nasal response was different from that observed in serum. A booster response was obtained after the second vaccination. These results suggest that SAIB has potential as a vehicle for intranasal immunization of horses with antigenic peptides.

Luteinizing hormone response to controlled-release deslorelin in estradiol benzoate primed ovariectomized gilts.

Development of a controlled release formulation of gonadotropin releasing hormone that would stimulate a LH surge capable of reducing the time span of ovulations would greatly benefit reproductive management because a single timed insemination could be used. A dose-response study was conducted to determine if Deslorelin, a potent gonadotropin releasing hormone analogue, delivered via the SABER system, a biodegradable controlled release system, would stimulate an ovulatory-like LH surge in the pig. Twenty ovariectomized gilts, approximately 200 d old and 100 kg body weight (BW), received estradiol benzoate (15 microg/kg BW im) and 48 h later, the gilts were given deslorelin at 0, 12.5, 25.0, 50.0 or 100.0 microg im (n = 4 each treatment group). Compared to controls, mean blood deslorelin concentrations were still elevated at 30 h after deslorelin. Mean deslorelin magnitude, area under the curve and duration were sequentially greater (P<0.05) in a dose-dependent sequence. Compared to controls, serum LH concentrations were elevated (P<0.05) for 6 to 12 h after deslorelin. A dose-response relationship was absent for all parameters of LH secretion. Magnitude of the serum LH response was greatest (P<0.05) in the 12.5 microg and 50.0 microg groups, whereas area under the curve was lower (P<0.05) after 25.0 microg of deslorelin than after 12.5, 50.0 and 100.0 microg, which were not different from each other. Thus, no more than 12.5 microg of deslorelin is necessary to obtain maximum LH release in the model studied and doses less than 12.5 microg may also be effective.

Evaluation of steroid microspheres for control of estrus in cows and induction of puberty in heifers

Two trials were designed to test whether a single treatment with a microsphere formulation of progesterone (P) could simulate the luteal phase of the estrous cycle and lead to estrus and subsequent luteal development. The first experiment was to characterize the pattern of serum P concentrations and estrus in cows treated with a microsphere formulation (P + E) that contained 625 mg P and 50 mg estradiol (E). Four cows with palpable corpora lutea were treated with 25 mg prostaglandin F2 m. Each cow was given P + E (i.m.) 12 h later. Tail vein blood samples were taken on Days 1 and 2 following P + E treatment and then three times weekly for 24 days. Serum P increased from 0.8 +/- 0.1 ng/ml at P + E treatment to 4.7 +/- 0.6 ng/ml on Day 1, declined gradually to 4.1 +/- 0.3 ng/ml on Day 7 and then declined more rapidly to 0.6 +/- 0.1 ng/ml on Day 13. Treated cows showed estrus 16.25 +/- 0.7 days after P + E treatment. Thereafter, serum P increased beginning on Day 20 after P + E treatment, as expected following estrus. In Experiment 2, Angus and Simmental heifers (10.5-11.5 months of age) were administered i.m. either the vehicle (controls), E (50 mg), P (625 mg) or P + E (n = 13 per group). While treatment with E resulted in behavioral estrus (1-2 days after treatment) in each treated heifer, it did not (P > 0.5) initiate estrous cycles as indicated by subsequent increased serum P. In contrast, the P and P + E treatments increased (P < 0.05) the proportion (11/13) of heifers that showed estrus by 21 days after treatment followed by elevated serum P. We conclude that the microsphere formulation of P simulated the pattern of serum P concentrations during the luteal phase of the estrous cycle and initiated estrous cycles in peripubertal heifers with or without E.

Controlled release drug delivery systems for estrous control of domesticated livestock

Publisher Summary The need for controlled release drug delivery systems in the field of estrous control of domesticated livestock arises due to the physicochemical and pharmacokinetic characteristics of the drugs. The first use of controlled release drug delivery systems to control the estrous cycle of sheep and cattle dates back to the mid 1960s and mid 1970s, respectively. In spite of the long history associated with this area of drug delivery, the opportunity to develop and commercialize controlled release drug delivery systems to control the estrous cycle of domesticated species has never been greater. This is because of the rise in on-farm use of procedures such as embryo transfer and new assisted reproductive technologies. This chapter describes the controlled release drug delivery systems which are currently available or in development for the control of the estrous cycle in sheep, cattle, pigs, and horses. It describes some of the formulation considerations for such products and highlights recent advances in the field of estrous control in horses and pigs.

Strategies for Increasing Reproductive Efficiency in a Commercial Embryo Transfer Program With High Performance Donor Mares Under Training

Abstract Exercise stress has a negative impact on embryo transfer efficiency (ET). For example, a 34% embryo recovery rate, 43% incidence of poor quality embryos, and a 29% pregnancy rate after transfer have been reported. Administration of nonsteroidal anti‐inflammatory drugs (NSAIDs) may reduce the inflammatory response produced after nonsurgical embryo transfer. In addition, progesterone supplementation is commonly administered to some recipient mares to improve uterine conditions before the transfer and to ensure adequate progestational support compatible with pregnancy. The aim of the study was to evaluate embryo recovery rates using BioRelease deslorelin versus hCG and to increase posttransfer pregnancy rates by jointly administering BioRelease progesterone and a NSAID (flunixin or meloxicam) to recipient mares. Seventeen upper‐level showjumping mares stabled and in daily training were used as embryo donors. To induce ovulation, 1‐mg IM BioRelease deslorelin (BioRelease Technologies, Lexington, KY) was injected in treated cycles (n = 66), or 2500‐IU hCG IV (Ovusyn, Syntex, Buenos Aires, Argentina) was given in control cycles (n = 79) when a ≥35 mm follicle was present. Artificial insemination with extended fresh semen (at least 500 × 106 progressively motile sperm) was carried out in both groups immediately after injecting the ovulation induction agent. Day 8 embryos were recovered and nonsurgically transferred using a speculum and a cervical traction forceps. Recipient mares (n = 73) were randomly assigned to one of three groups: Group A received a single injection of 1.5‐g IM BioRelease progesterone (Progesterone LA 300, BioRelease Technologies) and 3 IV injections of 0.5 g of flunixin meglumine (Flunix Deltavet, Argentina), one injection administered the day of the transfer and one on each of the next two successive days. Group B received 1.5‐g IM BioRelease progesterone and a single dose of 1.5‐g IM BioRelease meloxicam (Meloxicam LA, BioRelease Technologies) at the moment of embryo transfer. Group C did not receive any treatment. Pregnancy diagnosis was carried out 7 days after transfer. Results were analyzed using comparisons of proportions. More embryos were recovered per cycle (13% increase) when donor mares in training were induced to ovulate with BioRelease deslorelin (60.6%; 40/66) than with hCG (46.8%; 37 of 79; P < .05). Although both recipient groups given NSAIDs in combination with BioRelease progesterone numerically had higher pregnancy rates (A: 70.8%; 17/24 and B: 75%; 15/20) compared with nontreated control recipients (47.1%; 33/70), pregnancy rates were significantly higher only in recipients given LA meloxicam treatment at the time of transfer (P < .05). The LA meloxicam is released over a 72‐hour period making it more practical to use as it requires a single IM injection versus the 3 IV flunixin meglumine injections. Thus, to minimize the effects of exercise stress on ET efficiency, a combination of BioRelease deslorelin to induce ovulation in donors and BioRelease progesterone and LA meloxicam in recipients at the time of transfer may offer an interesting alternative for improving results in commercial ET programs. HighlightsNegative impact of exercise stress on embryo transfer efficiency.Use of BioRelease deslorelin to induce ovulation in donors.LA Meloxicam more practical to use in recipients.Use of BioRelease progesterone and LA Meloxicam in recipients.Combined treatments in donors and recipients improves results.