Pharmacokinetics of cefquinome in healthy and Pasteurella multocida-infected rabbits.

The pharmacokinetics of cefquinome were studied in healthy and Pasteurella multocida-infected rabbits after a single intramuscular (IM) injection at 2 mg/kg of its sulfate salt. Twelve female New Zealand white rabbits (2.0-2.5 kg) were used; six of them served as controls, and the other six had been infected with P. multocida; the experiments were conducted 1-2 days after nasal inoculation of P. multocida when rabbits showed the signs of respiratory infection. Plasma concentrations of cefquinome were determined using high-performance liquid chromatography. The values of elimination half-life, area under the curve, area under the first moment curve, and mean residence time were significantly lower in infected rabbits (0.48 hr, 4.54 hr*µg/ml, 3.63 hr* hr*µg/ml and 0.8 hr, respectively) than healthy rabbits (0.72 hr, 9.11 hr*µg/ml, 9.85 hr* hr*µg/ml and 1.1 hr, respectively), whereas total body clearance was significantly higher in infected than healthy rabbits. Therefore, P. multocida infection caused significant changes in some of the pharmacokinetic parameters of cefquinome in rabbits. These pharmacokinetic changes may affect dose regimen when used in P. multocida-infected rabbits.

Myocardial toxicity in a group of greyhounds administered ractopamine.

Ractopamine, a synthetic ß(2)-adrenoceptor agonist, is widely used as a feed additive in the United States to promote a reduction in body fat and enhance muscle growth in cattle, pigs, and turkeys. It has the potential for illegal use in show and racing animals because it may affect performance via its ß-adrenergic agonist properties or anabolic activities. Nine greyhounds were orally administered 1 mg/kg of ractopamine to investigate the ability to detect the drug in urine. Postdosing, 7 of 9 dogs developed cardiac arrhythmias and had elevated troponin levels indicating myocardial damage. One dog necropsied 4 days postdosing had massive myocardial necrosis, mild to focally moderate skeletal muscle necrosis, and widespread segmental arterial mediolysis. A second dog necropsied 17 days postdosing had mild myocardial necrosis and fibrosis. Scattered arteries exhibited segmental medial and perimedial fibromuscular dysplasia. This is the first reported case of arterial, cardiac, and skeletal muscle damage associated with ractopamine.

Vitamin E and selenium levels are within normal range in pigs diagnosed with mulberry heart disease and evidence for viral involvement in the syndrome is lacking.

Mulberry heart disease (MHD) in pigs is characterized by lesions of acute haemorrhagic myocarditis and myocardial necrosis. The objectives of this study were to determine the levels of vitamin E and selenium and 13 other trace minerals in heart and liver tissues and to determine the prevalence of certain viral infections in heart tissues from MHD-affected and MHD-unaffected pigs and the vitamin E and selenium concentration in feed samples from selected farms with MHD. Based on the pathological examination, 114 pigs were separated into MHD lesion-negative (L-NEG) (n = 57) and MHD lesion-positive (L-POS) (n = 57) groups. Seventy-three samples (40 L-NEG and 33 L-POS) were subjected to chemical analysis, and 66 (32 L-NEG and 34 L-POS) were subjected to PCR detection for viral pathogens. Lower (P < 0.05) levels of myocardial copper, lower (P < 0.05) levels of hepatic magnesium and higher (P < 0.05) levels of myocardial and hepatic sodium were detected in the L-POS cases. Although lower (P < 0.05) levels of hepatic selenium were detected in L-POS group, all were within the normal range. Analysis of feed samples (n = 22) revealed that selenium levels in all the samples were above the legal limit (0.3 ppm) for pigs. Vitamin E levels in all feed samples were above 20 IU/kg. Among the 66 pigs subjected to PCR detection, there were 19, 4, 13, 8, 2 and 1 animals positive for porcine circovirus type 2, porcine reproductive and respiratory syndrome virus, pan-herpes virus, porcine enterovirus, pan-pestivirus and porcine parvovirus, respectively. Clear evidence of viral association with L-POS was lacking.

Renal effects of Dirofilaria immitis in experimentally and naturally infected cats.

Canine heartworm infection has been associated with glomerular disease and proteinuria. We hypothesized that proteinuria, likely due to glomerular damage, would also be found in cats experimentally and naturally infected with Dirofilaria immitis. Two populations of cats were evaluated, including 80 that were each experimentally infected with 60 infective heartworm larvae as part of a drug safety study, and 31 that were naturally infected with D. immitis. Each had a control population with which to be compared. In the experimentally infected group, we evaluated urine from 64 cats. Ten of these cats were shown to have microalbuminuria 8 months post infection. No cat refractory to infection with larvae and no cats from the control group demonstrated microalbuminuria. All 10 microalbuminuric cats were shown to have significant proteinuria, as measured by the urine protein:creatinine ratio. There was a subtle, but significant, association between worm burden and proteinuria, and although the presence of adult heartworms was required for the development of proteinuria, both microfilaremic and amicrofilaremic cats were affected. Neither the presence of circulating heartworm antibodies and antigen nor the presence of antigenuria predicted the development of proteinuria. Both heavily infected cats (5-25 adult heartworms) and cats with worm burdens compatible with natural infections (1-4 adult heartworms) developed proteinuria, and the relative numbers of cats so affected were similar between heavily and more lightly infected cats. Naturally infected cats, for which only dipstick protein determinations were available, were shown to have a significantly greater incidence of proteinuria (90% vs 35%) than did those in an age- and gender-matched control population. Additionally, the proteinuria in heartworm-infected cats was 3- to 5-fold greater in severity. We conclude that cats infected with mature adult heartworms are at risk for developing proteinuria and that this is recognized relatively soon after infection. While heavier infections may predispose cats to developing proteinuria, this complication is seen in naturally infected cats and experimental cats with worm burdens similar to those seen in natural infections (i.e., "clinically appropriate" worm burdens). The clinical relevance of heartworm-associated proteinuria is yet to be determined.

Evaluation of XPC and prototypes on aflatoxin-challenged broilers.

Various products and prototypes were added to poultry diets during an aflatoxin challenge on growth and histological parameters. Male broiler chicks were randomly assigned to 8 treatment groups with 8 replicates/treatment and 3 birds/replicate. Treatments were as follows: 1) negative control containing no aflatoxin (NC); 2) positive control containing aflatoxin (PC); 3) 0.1% glucomannan mycotoxin standard industry ameliorator (STD); 4) 0.1% prototype A, a proprietary mixture of a Saccharomyces cerevisiae product and diatomaceous clay; 5) 0.2% prototype A; 6) 0.15% prototype B, a proprietary mixture of a S. cerevisiae product and diatomaceous clay (PB); 7) 0.0625% XPC (S. cerevisiae fermentation product); and 8) 0.125% XPC (XPC2). All treatments except NC contained 2,280 +/- 102 ng/g of aflatoxin and were fed for 28 d. Body weight and feed intake were measured weekly. Livers were collected on d 28, weighed, and used for histopathological evaluation. Beginning weights were similar across treatments, but BW were lower (P /= 0.05) different among the treatment groups. Liver weights relative to BW were higher (P /= 0.05) compared with NC. Overall, BW gain in treatment groups PB and XPC2 was not different from NC and that corresponded to protective effects against liver lesions. Benefits observed during an aflatoxin challenge when broilers were supplemented with XPC, a fermentation product that does not contain any adsorbents, may be attributed to something other than adsorption as a primary mechanism.

Echocardiographic quantification of Dirofilaria immitis in experimentally infected cats.

The safety of heartworm preventives in heartworm-positive cats has traditionally been evaluated using adult Dirofilaria immitis removed from infected dogs and surgically implanted into the cats. An alternate study model uses infective larvae to establish adult infections in cats. Unfortunately, the number of adult worms resulting from the latter method varies widely from none to more than 30, both unacceptable for studies of natural heartworm infection and for studies evaluating product safety in heartworm-infected cats. We sought to determine infection severity in experimental infections via echocardiography to reduce the chances of enrolling uninfected and heavily infected cats into a study. Eighty adult cats were each inoculated with 60 infective D. immitis larvae and maintained for 8 months to allow for the development of adult worms. Antigen and antibody testing, as well as echocardiographic imaging, were performed to confirm and estimate adult worm burdens. Approximately 8 and 12 months post-infection, echocardiographic examination was performed to confirm and enumerate adult D. immitis populations in the cardiovascular system. Worm burdens were stratified as 0, 1-3, 4-11, and > 11 adults, with 0 being considered uninfected and more than 11 considered too heavily infected to be relevant for anthelmintic studies. Cats with clinically relevant infections (1-10 adults) subsequently received multiple treatments with the investigational drug, and worm burdens were confirmed by necropsy 30 days following the final treatment. Worm burden estimated with echocardiography correlated well, but not precisely, with post-mortem counts (p < 0.001, r2 = 0.67). Echocardiography under-, over-, and exactly estimated heartworm burden 53%, 27%, and 22% of the time, respectively. Although the correct category (0-4) was determined by echocardiography in only 54% of cats, positive cats were distinguished from negative cats 88% of the time and the heaviest infections (> 11) were correctly categorized 95% of the time. Both false negative and false positive results were observed. We conclude that echocardiography is useful for detecting mature experimental heartworm infections, identifying cats that have rejected mature infection, and detecting very heavy heartworm burdens, but it is only moderately accurate in classifying lesser burdens. While echocardiography cannot be relied upon to consistently determine the exact heartworm burden in experimentally infected cats, it is useful in stratifying worm burdens for anthelmintic safety studies.

Safety of imidacloprid plus moxidectin topical solution applied to cats heavily infected with adult heartworms (Dirofilaria immitis).

A topically applied formulation containing 10% imidacloprid+1% moxidectin (Advocate/Advantage multi) has been developed for monthly application to cats for the prevention of feline heartworm (HW) disease caused by Dirofilaria immitis; and for the treatment and control of flea infestations, ear mite infestations, and intestinal nematode infections. A study model was designed to evaluate the safety of this product in cats harboring adult D. immitis infections. Eighty adult cats (40 males/40 females) were each inoculated with 60 third-stage D. immitis larvae on test day (TD) 1. On TD 243-245 echocardiographic imaging was performed on each cat to confirm and estimate the number of adult D. immitis residing in the cardiovascular system. A total of 35 cats were subsequently eligible for safety evaluation based on inclusion criteria. Four treatment groups were established and randomly selected for treatment: imidacloprid+moxidectin solution at the label dose (n=9) (group 1), imidacloprid+moxidectin solution at 5x the Iabel dose (n=9) (group 2), 6% selamectin topical solution (Revolution) at the label dose (positive control, n=8) (group 3), and topical treatment with placebo (negative control, n=9) (group 4). All cats were treated on TD 250. Treatments for groups 1, 3, and 4 were repeated on TDs 278 and 306. Group 2 cats were euthanized and examined for adult D. immitis on TD 288. All other cats were euthanized and examined for adult D. immitis on TD 334. No adverse events attributable to treatment with the test articles were observed during the study. The geometric mean numbers of adult D. immitis recovered at necropsy from treatment groups 1-4 were 2.9, 3.2., 4.0, and 2.7, respectively. There were no statistically significant differences in the comparison of adult D. immitis recovered at necropsy (ANOVA overall group effect P-value of 0.5356). The results of this study demonstrate that imidacloprid+moxidectin topical solution can be used safely in cats heavily infected with adult D. immitis.