Diminazene aceturate is one of a limited number of drugs currently being used in animals to treat the tsetse fly-transmitted protozoal disease, African trypanosomiasis. Efficacy of the drug at the recommended single IM administered doses of 3.5 and 7.0 mg/kg of body weight is widely acknowledged. However, resistance to the drug at these dosages has been reported. Although the mechanisms of resistance to diminazene are poorly understood, field and experimental data indicate that it may develop naturally through administration of subcurative doses, or as a result of cross-resistance. Evidence from other experimental studies indicates that there are additional mechanisms by which trypanosomes may develop resistance to diminazene aceturate. For instance, some populations ot Trypanosoma brucei and T. vivax are refractory to treatment because of their ability to invade the CNS, a site that is believed to be poorly accessible to diminazene. Furthermore, in recent studies carried out in goats, it has been documented that the ability of T. Congolense IL 3274 to survive treatment with diminazene depends on the stage of infection when treatment is administered; populations of the parasite reappeared in animals that were treated on day 19 after tsetse fly challenge, whereas all goats were cured when treated on day 1 of infection. Because trypanosomes are confined to the skin on day 1 after infection, but thereafter invade the blood circulation, it is possible that the efficacy of the treatment on day 1 is attributable to exposure of the small number of parasites, relative to later stages of infection, to higher concentrations of drug than those attained in blood. The objective of the study reported here was to determine whether diminazene's pharmacokinetics differ between plasma and lymph draining the skin of goats and therefore account for the variation in therapeutic activity of the drug at different stages of a tsetse fly-transmitted infection. Peripheral lymph was used for this work because it appears to be identical in composition to tissue interstitial fluid, into which trypanosomes are inoculated by infected tsetse flies when feeding.

The efficacy of 4-methylpyrazole (4-MP) and ethanol as treatment for ethylene glycol (EG) intoxication in cats was compared. Twenty-two cats were assigned at random to 6 experimental groups. Cats of 1 experimental group were given only 4-MP; those of another experimental group were given only EG. Cats of 3 experimental groups were intoxicated with EG and given 4-MP at 0 hour or 2 or 3 hours after EG ingestion, and those of 1 experimental group were given EG and treated with ethanol 3 hours after EG ingestion. Physical, biochemical, hematologic, blood gas, serum and urine EG concentrations, and urinalysis findings were evaluated at 0, 1, 3, 6, 9, 12, 24, 48, and 72 hours, 1 week, and 2 weeks after EG ingestion, or 4-MP treatment in cats of the 4-MP only group. The half-life of EG and percentage of ingested EG excreted unchanged were determined for each group. 4-Methylpyrazole treatment at 0 hour was most effective at preventing metabolism of EG. 4-Methylpyrazole was not effective in preventing development of renal failure when given 2 or 3 hours after EG ingestion. Ethanol given 3 hours after EG ingestion was successful in preventing development of renal dysfunction in 2 of the 6 cats treated 3 hours after EG ingestion. Of the remaining 4 cats treated with ethanol, 2 developed transient renal dysfunction and 2 developed acute oliguric renal failure and were euthanatized. 4-Methylpyrazol given 2 or 3 hours after EG ingestion was less effective in preventing EG metabolism than was ethanol given 3 hours after EG ingestion. Therefore 4-MP, at the dose found to be effective in dogs, cannot be recommended as an alternative to ethanol for treatment of EG intoxication in cats.

Doxorubicin was encapsulated in canine erythrocytes, treated with 0.32% glutaraldehyde, and administered at a dosage equivalent to 30 mg of free doxorubicin/m(2) of body surface area to dogs with diagnosis of lymphosarcoma. Compared with administration of free doxorubicin, this method of drug delivery substantially reduced peak plasma concentration and prolonged higher plasma concentration of doxorubicin. As such, this method was comparable to continuous IV infusion. Previous studies have indicated this method's potential for reduction in toxic side effects, particularly cardiotoxicosis, while allowing higher total doses of doxorubicin to be administered. In this study, doxorubicin encapsulated in glutaraldehyde-treated erythrocytes induced a triphasic exponential decay of doxorubicin from plasma, the highest relative contribution to the total area of the curve being the terminal phase. The treatment was effective in inducing complete and partial remissions of lymphosarcoma, with minimal acute toxicosis and no evidence of cardiotoxicosis. However, substantial, unanticipated, chronic, nonregenerative myelosuppression developed, and was most strikingly expressed as profound thrombocytopenia. Efforts to ameliorate or circumvent this toxic effect will be required prior to further consideration of this doxorubicin delivery system for treatment of systemic neoplasia.

Studies were undertaken to determine the efficacy of milbemycin oxime against the enteric adult stages of Trichinella spiralis and of albendazole against the muscle stage larvae in experimentally infected dogs and cats. Specific-pathogen-free Beagle pups (n = 6) and domestic shorthair kittens (n = 6) were inoculated with 7,500 first-stage larvae of Trichinella spiralis. Physical examination (including collection of blood and fecal samples) was performed weekly. During the first week after inoculation, all animals had mild gastrointestinal tract disturbances, but stages of T. spiralis were not observed in the feces. Beginning on postinoculation day (PID) 10, 3 pups and 3 kittens were treated with milbemycin oxime (1.25 mg/kg of body weight, PO, q 12 h) for 10 days. Muscle biopsy specimens were taken from dogs and cats on PID 26 and 29, respectively. Mean numbers of larvae per gram of muscle were 30.3 in the control and 37.7 in the treated dogs. Mean numbers of larvae per gram of muscle in the control and treated cats were 318.7 and 89.3, respectively. Two dogs and 2 cats were removed from the study at that time. The remaining animals, 2 each of the control and milbemycin oxime-treated animals, were given albendazole (50 mg/kg, PO, q 12 h) for 7 days starting at PID 31 and 34 in dogs and cats, respectively. Muscle biopsy specimens were again taken at PID 46 and 49, for dogs and cats, respectively; mean numbers of larvae recovered from muscle were 0.6 for dogs and 13.5 for cats.

A rapid, simple chemosensitivity assay, assessing tumor cell nuclear uptake of doxorubicin hydrochloride, was evaluated in 16 dogs with appendicular osteosarcoma. Doxorubicin was administered to dogs in 5 biweekly treatments, and surgical resection was performed after the second or third treatment, The chemosensitivity assay was performed on biopsy specimens from all dogs before chemotherapy. It was repeated on tissue from resected tumors, and tumors were evaluated histologically to determine the degree of necrosis resulting from chemotherapy. Disease-free and total survival time correlated significantly (P < 0.05 in both cases) with the degree of postchemotherapy necrosis of the primary tumors. Significant correlation was not apparent between the percentage of tumor cells with nuclear uptake of doxorubicin (in either biopsy or resection samples) and disease-free or total survival time. The percentage of cells with nuclear uptake of doxorubicin in surgically resected tumors correlated significantly (P < 0.05) with percentage of necrosis,.

Eight of 10 pony foals reared under helminth-free conditions were inoculated PO with 50 Strongylus vulgaris infective larvae/week for 4 weeks, at which time 1 foal died of acute verminous arteritis. Inoculation of 7 remaining foals continued at 2-week intervals for 20 weeks. Of the 7 foals, 3 were treated with ivermectin (0.2 mg/kg of body weight) in an oral paste formulation at experiment weeks 8, 16, 24; 4 foals were not treated. Two foals were not inoculated or treated and served as controls. After the first ivermectin treatment, ivermectin-treated foals had fewer days (12 +/- 2.9) with rectal temperatures > 38.6 C than did nontreated foals (23.3 +/- 3.8). Mean baseline rectal temperatures were 38 +/- 0.2 C. Adverse clinical reactions to ivermectin treatment were not observed in foals. Foals were euthanatized and necropsied 3 weeks after the last ivermectin treatment (week 24). Ivermectin was effective in reducing S vulgaris arterial larval and intestinal adult parasite numbers by 100% in 3 treated foals. Strongylus vulgaris arterial larvae and/or adults were recovered from all 4 nontreated inoculated foals. One nontreated inoculated foal lacked arterial larvae or active arterial lesions, indicating that protective resistance had developed in this individual. Marked gross and histopathologic lesions typical of chronic S vulgaris infection were observed in the 3 nontreated inoculated foals with arterial larvae. Repeated killing of intra-arterial S vulgaris fourth-stage larvae in ivermectin-treated foals did not exacerbate lesions associated with verminous arteritis or induce unique lesions associated with repeated destruction of arterial larvae. Arterial lesions in treated inoculated foals were markedly reduced and had resolved, compared with those in nontreated inoculated foals.

Ceftiofur hydrochloride was tested for effectiveness against induced colibacillosis in neonatal swine. In this model, pigs < 12 hours old were inoculated via stomach tube with a virulent, K99+, nalidixic acid-resistant strain of Escherichia coli. Six hours after challenge exposure, 1 dose of ceftiofur was administered either IM or orally in experiment 1 and orally only in experiment 2. Mortality, shedding of bacteria, fecal consistency scores, and body weight changes were monitored for 10 days. In experiment 1 (n = 383 pigs), all treatments at dosage that ranged between 0.5 and 64.0 mg of ceftiofur/kg of body weight significantly (P < 0.001) reduced mortality, bacterial shedding, and diarrhea and increased weight gain, compared with findings in untreated controls. There were no detectable differences between oral and IM routes, except that there was greater reduction in bacteria shedding associated with the oral route of administration. In experiment 2 (n = 505 pigs), ceftiofur was administered orally either once at 6 hours after challenge exposure or twice at 6 and at 48 hours after the first dose. Dosage of ceftiofur was 0, 5, 10, 20, 30, or 60 mg/kg administered once, or half the same dose was administered at each of 2 times. At the optimal dosage (10 mg/kg), a single dose was as effective as 2 doses. The single administration at all dosages reduced mortality, bacterial shedding, and diarrhea scores and increased body weight gain, compared with findings in untreated pigs (P < 0.01). In this induced infection model, the optimal treatment dosage was determined to be 10 mg/kg administered once.

The macrolytic lactone F28249-alpha was titrated in experimentally infected sheep and found to be highly effective against most of the common gastrointestinal nematodes as a single oral dose, given at a rate of 0.025, 0.05, or 0.1 mg/kg. Specifically, maximal activity was evident at even the lowest dosage against adult Haemonchus contortus, Ostertagia circumcinta, Trichostrongylus axei, and T colubriformis and L4 O circumcinta. Activity against Oesophagostomum columbianum was also high at all dosages, with a calculated ED95 of 0.029 mg/kg. Cooperia curticei was eliminated at 0.1 mg/kg, but control was erratic at the lower dosages. The greatest weakness of this compound was its activity against C oncophora. The activity against this parasite was weak (<less than or equal to 85%) at all dosages, and the dosage-response curve was flat, suggesting dosages substantially higher than those given would be necessary for high-order control of this species.

Twenty-four rams inoculated with Brucella ovis by conjunctival and preputial routes were treated with a long-acting oxytetracycline alone or in combination with dihydrostreptomycin sulfate. The combined treatment eliminated Brucella ovis from 11 of 12 (91.6%) treated rams. Only 4 of 12 (33.3%) rams treated with oxytetracycline alone were bacteriologically negative. Neither treatment resolved clinical epididymitis in 2 rams affected before treatment. Many rams had pathologic lesions in the epididymis and ampullae, which limited the efficacy of antibiotic treatment.