Macrocyclic lactone toxicity due to abamectin in farm dogs without the ABCB1 gene mutation

Abstract

CASE HISTORY: A 5-year-old entire female Huntaway from a sheep and beef farm was one of four dogs that developed clinical signs including hypersalivation, depression, blindness and ataxia after the death of another dog. A 4-year-old female Huntaway farm dog from a second farm was observed to be sitting down more often than usual on the day after being fed part of a calf carcass that had been treated with an abamectin pour-on.

CLINICAL FINDINGS: The first dog was ataxic and depressed but did respond to sound. The second dog presented with an acute onset of blindness, mydriasis, absence of a menace response, hypersalivation, gait abnormalities (e.g. high stepping gait and ataxia), and depression. Other presenting signs included muscle tremors, dehydration and difficulty eating. No abnormalities were detected from routine haematology and biochemistry. Analysis of samples of plasma from both dogs revealed concentrations of abamectin of 0.149 mg/L and 0.260 mg/L for the first and second dogs, respectively. Buccal swabs taken from the first dog for DNA testing for the ABCB1 gene mutation, gave a negative result.

DIAGNOSIS: In addition to the presenting signs which suggested a toxicosis, both dogs had measurable concentrations of abamectin in plasma confirming exposure.

CLINICAL RELEVANCE: Farm dogs exposed to concentrated pour-on products containing abamectin have been poisoned and recover or die. The product labels do not carry any warnings as to the risk of poisoning to dogs. This paper discusses two incidents affecting six farm dogs, but the authors are aware of more toxicoses in farm dogs exposed to abamectin.     

Using a GnRH agonist to obtain an index of testosterone secretory capacity in the cockatiel (Nymphicus hollandicus) and sulphur-crested cockatoo (Cacatua galerita)

Objective   Validation of a stimulation test for determining the steroidogenic capacity of the parrot testis. The major aim was to characterise testosterone secretion after injection of a gonadotropin-releasing hormone agonist (GnRHa), then use the test to investigate seasonal reproduction in the male cockatiel.
Procedure   A synthetic GnRHa (buserelin; 8.0 µg of peptide/kg bodyweight) was injected IM into male cockatiels (n = 7) and sulphur-crested cockatoos (n = 3) and serial blood samples collected at 0, 30, 60, 90 and 120 min after administration. Once validated, the technique was subsequently used to examine seasonal changes (23 months) in the testosterone profile of a captive cockatiel population.
Results   Injection of buserelin resulted in a significant increase in the testosterone concentration of cockatiel plasma, with maximal concentrations occurring at approximately 60 (1.33 ± 0.08 ng/mL) to 90 min (1.22 ± 0.08 ng/mL) after injection. Although no clear pattern of seasonal variation in testosterone secretion was detected in cockatiel plasma, samples taken 60 and 90 min after administration showed a significant increase in all seasons. Injection of buserelin in the sulphur-crested cockatoo also resulted in increased testosterone secretion, with maximal concentrations obtained after 90 min.
Conclusion   Buserelin can be used to obtain a reliable index of the prevailing testosterone capacity of the cockatiel and cockatoo testis. With further studies, this test may be incorporated into clinical assessment of reproductive status.     

Influence of dietary cobalt source and concentration on performance, vitamin B12 status, and ruminal and plasma metabolites in growing and finishing steers

Sixty Angus steers, averaging 274 kg, were used to evaluate the effects of Co source and concentration on performance, vitamin B12 status, and metabolic characteristics of steers. Treatments consisted of 0 (control, analyzed 0.04 mg Co/kg), 0.05, 0.10, and 1.0 mg of supplemental Co/kg of DM from CoCO3 or 0.05 and 0.10 mg of supplemental Co/kg of DM from Co propionate. Steers were individually fed a growing diet for 56 d followed by a high-concentrate finishing diet. Performance was not affected by Co supplementation during the growing phase. During the finishing phase, ADFI (DM basis) and ADG were higher (P < 0.05) for the entire finishing phase, and gain:feed was higher (P < 0.10) over the first 56 d for Co-supplemented steers. Steers supplemented with 0.10 mg Co/kg as Co propionate had higher (P < 0.05) ruminal propionate and lower (P < 0.05) acetate molar proportions than steers receiving 0.10 Co/kg as CoCO3 during the growing phase. Supplemental Co increased (P < 0.10) molar proportion of propionate during the finishing phase. Plasma vitamin B12 was higher (P < 0.05) in Co-supplemented steers by d 56 of the growing phase and remained higher (P < 0.10) throughout the study. Control steers had higher (P < 0.05) plasma methylmalonic acid on d 56 of the growing phase and on d 28, 56, and 112 of the finishing phase than steers receiving supplemental Co. Steers supplemented with Co had higher plasma glucose at d 56 (P < 0.01), 84 (P < 0.10), and 112 (P < 0.01) of the finishing phase. Steers supplemented with 0.10 mg Co/kg as Co propionate had higher plasma glucose than those receiving 0.10 mg Co/kg as CoCO3 at d 28 of the growing phase (P < 0.05) and d 28 of the finishing phase (P < 0.10). Final body weight and hot carcass weight were lower (P < 0.10) in steers receiving the control diet, whereas other carcass characteristics were not affected by dietary Co. Average daily gain and feed efficiency for the entire finishing phase did not differ among Co-supplemented steers. However, increasing supplemental Co above 0.05 mg/kg DM (total diet Co = 0.09 mg/kg) resulted in increased (P < 0.01) plasma (linear) and liver (quadratic) vitamin B12 concentrations and decreased (quadratic, P < 0.10) plasma methylmalonic acid concentrations toward the end of the finishing phase. These results suggest that finishing steers require approximately 0.15 mg Co/kg of DM. Vitamin B12 status was not affected by Co source; however, the two Co sources seemed to affect certain metabolites differently.     

The effect of fertility control on the transmission of bovine tuberculosis in wild brushtail possums

AIM: To determine the effect of fertility control on the rate of transmission of bovine tuberculosis (Tb), caused by Mycobacterium bovis, in brushtail possums (Trichosurus vulpecula).

METHODS: At two study sites with a history of Tb infection in the resident possum population, a sample of adult male and female possums (n=50), determined by palpation to be Tb-free, was surgically sterilised by gonadectomy. A sample of untreated Tb-free male and female possums (n=54) served as controls. Each study site was trapped every 2 months over a 3-year period, and the Tb status of the individuals in the trial assessed. At the conclusion of the trial, all remaining experimental individuals were killed, necropsied and examined for characteristic lesions typical of Tb. The rate of transmission of Tb infection was estimated using the incidence of tuberculous cases in the experimental animals and comparing it between sites, sex and sterilisation treatment.

RESULTS: Sterilisation by gonadectomy resulted in a reduction in the rate of transmission of Tb in male possums by 53%, but a corresponding increase in sterilised females for reasons that are still unclear. However, this interaction was statistically weak (p=0.10). When the sexes were combined, there was no overall effect of sterilisation on the rate of transmission of Tb (p=0.43). Sterility treatment notwithstanding, there was a highly significant difference in the rate of transmission between the sexes (p=0.01), being almost one order of magnitude higher in untreated males compared with untreated females.

CONCLUSIONS: Although lacking strong statistical support, these results suggest that fertility control that targets endocrine control of fertility may provide some additional benefits for disease control over that achieved by reductions in population density, by reducing the rate of transmission of M. bovis in male possums. However, additional studies are needed to confirm the validity of these results. The large difference in the rate of transmission of M. bovis in untreated males compared with untreated females suggests that transmission of Tb among males may be an important driver of the dynamics of Tb infection in possums.     

The effects of bimatoprost and unoprostone isopropyl on the intraocular pressure of normal cats

OBJECTIVE: To evaluate the effects on intraocular pressure (IOP), pupillary diameter (PD), blepharospasm score, conjunctival injection score, and aqueous humor flare score when either 0.03% bimatoprost solution is applied once daily or 0.15% unoprostone isopropyl solution is applied twice daily topically to the eyes of normal cats. MATERIALS AND METHODS: The aforementioned parameters were evaluated daily in each of 12 cats throughout the entirety of the study. During an initial 10-day treatment phase a single eye of six of the cats was treated with 0.03% bimatoprost solution while a single eye of the remaining six cats was treated with buffered saline solution (BSS) once daily. During a second 10-day treatment phase a single eye of six of the cats was treated with 0.15% unoprostone isopropyl solution while a single eye of the remaining six cats was treated with BSS twice daily. Contralateral eyes of all cats remained untreated at all time points. RESULTS: Blepharospasm score, conjunctival injection score, and aqueous humor flare score never rose from a value of 0, for any eye of any cat during the study. The mean +/- SD of IOP for eyes treated with 0.03% bimatoprost solution and BSS were 16.55 +/- 3.06 mmHg and 18.02 +/- 3.52 mmHg, respectively. The mean +/- of PD for eyes treated with 0.03% bimatoprost solution and BSS were 5.7 +/- 1.57 mm and 6.39 +/- 1.78 mm, respectively. The mean +/- SD of IOP for eyes treated with 0.15% unoprostone isopropyl solution and BSS were 15.7 +/- 2.91 mmHg and 17.2 +/- 2.9 mmHg, respectively. The mean +/- SD of PD for eyes treated with 0.15% unoprostone isopropyl solution and BSS were 5.8 +/- 1.43 mm and 6.9 +/- 1.37 mm, respectively. There was no significant difference (P > or = 0.05) in IOP or PD between eyes treated with 0.03% bimatoprost solution vs. eyes treated with BSS. Similarly, there was no significant difference (P > or = 0.05) in IOP or PD between eyes treated with 0.15% unoprostone isopropyl solution vs. eyes treated with BSS. CONCLUSION: Neither once daily topical administration of 0.03% bimatoprost solution nor twice daily topical administration of 0.15% unoprostone isopropyl solution significantly affect the IOP of normal cats. Both 0.03% bimatoprost solution and 0.15% unoprostone isopropyl solution induced no significant ocular side effects in normal cats when dosed over a 10-day treatment period.     

Exogenous paraoxonase‐1 during oocyte maturation improves bovine embryo development in vitro

Paraoxonase‐1 (PON1) is an enzyme found in serum and follicular fluid that protects cell membrane and circulating lipids against oxidative damage. The aims of this study were to measure the direct effects of recombinant PON1 (rPON1) on bovine oocyte maturation at the molecular level (gene expression) and to measure the carry‐over effects of PON1 on pre‐implantation embryo development in vitro. COCs were submitted to IVM with the addition of 0.0, 0.02, 0.04 and 0.08 mg ml^?1 of rPON1, corresponding to an average PON1 arylesterase enzyme activity of 2.2 ± 0.4, 15.5 ± 1.5, 30.2 ± 3.0 and 57.9 ± 5.0 U ml^?1, respectively. The results indicated that addition of rPON1 during IVM improved embryo development in a dose‐dependent manner as D7 embryo development was 22.2%, 29.4%, 32.2% and 37.0% for the treatment groups, respectively (p = 0.02). In conclusion, addition of PON1 enzyme during IVM exerted dose‐related positive effects on embryo development rates to blastocysts.     

First Established Pregnancies in Mediterranean Italian Buffaloes (Bubalus bubalis) Following Deposition of Sexed Spermatozoa near the Utero Tubal Junction

At the time of AI following Ovsynch protocol, a total of 51 buffaloes were randomly divided in a first group (n = 30) subjected to conventional AI into the uterine body with 20 million non-sex sorted frozen-thawed spermatozoa, while a second group (n = 21) was inseminated near the utero-tubal junction (UTJ) ipsilateral to the ovary carrying the preovulatory follicle with 2.5 million live (4 million total) sex-sorted frozen-thawed spermatozoa. The semen used for flowcytometric sorting was collected and processed on a farm in Italy, and then shipped to a laboratory in Germany. Eleven buffaloes were inseminated with X-chromosome bearing spermatozoa and 10 with Y-chromosome bearing spermatozoa. Conception rates after conventional and UTJ inseminations were 43.3% (n = 13) and 42.8% (n = 9) respectively (p = 0.97). Eight of the nine foetuses obtained after insemination with sexed spermatozoa corresponded to the sex as predicted by the cell sorting procedure (five male and four female foetuses by ultrasound vs six male and three female foetuses by cell sorting). In conclusion, for the first time buffalo semen has been successfully subjected to procedures for flowcytometric sperm sorting and freezing. Low doses of sexed spermatozoa have been deposited near the UTJ giving conception rates similar to those of conventional AI with full dose.     

Impact of foot-and-mouth disease on mastitis and culling on a large-scale dairy farm in Kenya

Foot and mouth disease (FMD) is a highly transmissible viral infection of cloven hooved animals associated with severe economic losses when introduced into FMD-free countries. Information on the impact of the disease in FMDV-endemic countries is poorly characterised yet essential for the prioritisation of scarce resources for disease control programmes. A FMD (virus serotype SAT2) outbreak on a large-scale dairy farm in Nakuru County, Kenya provided an opportunity to evaluate the impact of FMD on clinical mastitis and culling rate. A cohort approach followed animals over a 12-month period after the commencement of the outbreak. For culling, all animals were included; for mastitis, those over 18 months of age. FMD was recorded in 400/644 cattle over a 29-day period. During the follow-up period 76 animals were culled or died whilst in the over 18 month old cohort 63 developed clinical mastitis. Hazard ratios (HR) were generated using Cox regression accounting for non-proportional hazards by inclusion of time-varying effects. Univariable analysis showed FMD cases were culled sooner but there was no effect on clinical mastitis. After adjusting for possible confounders and inclusion of time-varying effects there was weak evidence to support an effect of FMD on culling (HR = 1.7, 95% confidence intervals [CI] 0.88-3.1, P = 0.12). For mastitis, there was stronger evidence of an increased rate in the first month after the onset of the outbreak (HR = 2.9, 95%CI 0.97-8.9, P = 0.057).

Electronic supplementary material

The online version of this article (doi:10.1186/s13567-015-0173-4) contains supplementary material, which is available to authorized users.