Pharmacokinetic comparison of six anthelmintics in sheep,goats, and cattle

This study was initiated to determine whether a comparative pharmacokinetic (PK) approach could be used to expand the pool of approved anthelmintics for minor ruminant species. Accordingly, the PK profiles of six anthelmintics (levamisole, albendazole, fenbendazole, moxidectin, doramectin, and ivermectin) in sheep, goats, and cattle were determined. The PK values determined for each anthelmintic included T_max, T_last, C_max, AUC, AUC/dose, and C_max/dose. The results of this study demonstrate that a comparative PK approach does not show commonality in the way these six anthelmintics are individually processed by these three ruminants. While some drugs demonstrated identical PK profiles between sheep and goats, none of these drugs demonstrated PK profiles in sheep and goats comparable to the PK profiles found in cattle. The results from this study suggest drug approval across these three ruminants is not a viable concept. However, the resulting PK profiles for each combination of drug and ruminant species represents a new dataset that can be used to support the US FDA Center for Veterinary Medicine's Minor Use/Minor Species indexing process for drug approvals in minor species such as sheep and goats.     

Bovine leukocyte adhesion deficiency: in vitro assessment of neutrophil function and leukocyte integrin expression.

Bovine leukocyte adhesion deficiency (BLAD) was identified in a two-month-old Holstein heifer calf using DNA-polymerase chain reaction analysis of the affected calf and other clinical parameters. Neutrophil integrin expression (CD18, CD11a, CD11c), aggregation, and transendothelial migration were studied in vitro. Neutrophils were isolated from the affected calf and from normal, healthy, age-matched control Holstein calves. Neutrophils isolated from the affected BLAD calf had decreased expression of leukocyte integrins on their cell surface, decreased ability to aggregate in response to chemotactic stimuli, and decreased ability to migrate across bovine endothelial cell monolayers in vitro. Transendothelial migration of neutrophils from normal calves was reduced to levels comparable to the BLAD neutrophils by treatment with an anti-CD18 monoclonal antibody (MAb 60.3). Peripheral-blood lymphocytes from the BLAD calf also expressed negligible levels of leukocyte integrins, similar to their neutrophil counterparts. Our experimental findings in vitro correlate well with the clinical observations of decreased leukocyte trafficking and diminished host defense in leukocyte adhesion-deficient animals. The syndrome of BLAD may be a suitable model for one of the human leukocyte adhesion deficiency disorders.     

Chemiluminescence of canine peripheral blood lymphocytes stimulated by mitogens

Luminol-dependent chemiluminescence of peripheral blood lymphocytes from dogs stimulated with concanavalin A (Con A) or phytohemagglutinin P (PHA) was measured with a Pico-Lite luminometer. 10 microliter of luminol gave optimal quantum yield from 1 X 10(6) lymphocytes sensitized with either 80 micrograms Con A or 160 micrograms PHA. Addition of superoxide dismutase did not influence the course of chemiluminescence. Whereas catalase produced 41% increase in quantum yield, mannitol caused a 51% inhibition of chemiluminescence. Lymphocytes exposed to varying doses of short term x-irradiation or lymphocytes isolated from dogs kept under continuous exposure through a gamma irradiation source showed dose-related depression of chemiluminescence. Membrane factors may be involved in lymphocyte stimulation to chemiluminescence as pulse experiments with Con A and PHA revealed. It is proposed that chemiluminescence measurements may be useful in monitoring early events in lymphocyte stimulation by antigens and mitogens.     

Canine toxocariasis and the associated environmental contamination of urban areas in eastern Nigeria

The prevalence of canine toxocariasis in pet dogs in two urban towns in eastern Nigeria and the associated environmental contamination were studied through examination of 262 faecal and 400 soil samples. Infection rates in dogs varied from 6.67% to 42.35%, the prevalence rate being inversely related to the age of dogs. Sex and breed of dogs had no significant influence (P greater than 0.05) on the prevalence of infection. There was no evidence of widespread contamination of public places, as Toxocara ova were recovered only from some private premises, namely, those of a dog owner and the kennel of a veterinary hospital.     

The use of atropine to control heart rate responses during detomidine sedation in horses

Detomidine is a sedative-analgesic which has a pharmacological profile similar to xylazine. There is evidence that the sedative effects are mediated through alpha-2 adrenoceptors.Cardiopulmonary responses were determined using detomidine as the principal agent and as a preanesthetic prior to the induction of general anesthesia. Compatibility with guaifenesin, sodium thia-mylal and halothane were determined.As in the case of xylazine, detomidine produces a slowing of heart rates. This was found to be either sinus bradycardia or heart block. There may be a corresponding increase in systolic blood pressures. The respiratory pattern is altered through the arterial blood gases and pH data supported evidence of adequate ventilation. The heart rate response to detomidine without anticholinergic treatment was transient and related to he duration of drug action.Atropine sulfate, 0.02 mg/kg i.v. was effective in preventing or treating bradycardia or heart block from detomidine. Heart rates also increased during the administration of guaifenesin and sodium thia-mylal when given 50 min poisit-detomidine.     

Asynchronous growth of the canine radius and ulna: effects of retardation of longitudinal growth of the radius.

After 2,000 rads of x-radiation to the right distal radial physis of eight 70-day-old dogs, the longitudinal growth of the right radius was retarded 42.1% when compared with the growth of the nonirradiated left radius. Asynchronous growth of the right radius and ulna resulted. The gross and radiographic changes that occurred over the subsequent 75 days were described. Subluxation of the humeroradial and humeroulnar joints occurred and was first observed 31 days after irradiation. By 75 days after irradiation, the radius was puller 7.8 mm distally by the radioulnar ligament. However, subluxation of the humeroradial joint was minimized by accelerated growth from the proximal radial physis and articular cartilage. Acceleration of growth also occurred at the distal radial articular cartilage. Growth from the distal ulnar physis and styloid process was retarded. It was thus apparent that after retardation of growth from the distal radial physis, considerable adjustment occurred in the relationship between the radius and the ulna and also in growth from their other physes, which reduced the deleterious effects of the growth retardation.     

Acute viral hepatitis in California sea lions

Acute viral hepatitis was diagnosed in five California sea lions (Zalophus californianus) stranded along the Los Angeles coast. Light microscopy revealed large nuclear inclusion bodies in hepatocytes. Electron microscopy provided evidence that these inclusion bodies were composed of adenovirus-like virions. Attempts to grow the virus in cell culture systems were unsuccessful.