Efficacy of thiabendazole, mebendazole, levamisole and ivermectin against gullet worm, Gongylonema pulchrum: in vitro and in vivo studies

In vitro and in vivo studies were conducted to evaluate the effects of thiabendazole, mebendazole, levamisole and ivermectin against Gongylonema pulchrum. For in vitro assays, third-stage larvae (L3) incubated with the drugs were administered orally to mice and the ability of larvae to invade the gastric mucosa of the animals was examined. After incubation, only those larvae treated with high concentrations of levamisole (1 and 10 microg/ml) were tightly coiled with intestines exhibiting morphological abnormalities. Good dose-response data for the drugs tested was observed at the time of worm recovery from mice, with no worms recovered at the two highest concentrations of levamisole. In vivo efficacy of the drugs against adult worms was evaluated in six groups of three rabbits, each of which was infected with 30 L3 of G. pulchrum and treated with thiabendazole at 100 mg/kg for 3 days, mebendazole at 70 mg/kg for 3 days, levamisole as a single dose of 8 mg/kg, and subcutaneously injected ivermectin as a single dose of 0.2 mg/kg or vehicles of the drugs (control) at 4 months post-infection. Necropsy 14 days after treatment revealed that levamisole, mebendazole and ivermectin reduced worm burdens by 63.2%, 22.8% and 25.8%, respectively, with no reductions in worms observed with thiabendazole. The surviving worms were principally found in the esophagus with the remainder distributed among the buccal mucosa, the tongue, and/or pharyngeal mucosa in all groups. A number of morphologically abnormal eggs were observed within the uterus and ovijector in female worms recovered from the thiabendazole-treated group. These findings suggest that levamisole exhibits in vivo efficacy against G. pulchrum infection and that the larval invasion tests using mice could be used to screen for anthelmintic susceptibility of nematodes.     

In vitro evaluation of the growth inhibitory activities of 15 drugs against Babesia gibsoni (Aomori strain)

The in vitro growth inhibitory activities of 15 drugs against Babesia gibsoni were evaluated following establishment of a continuous culture isolate (Aomori isolate). The culture was successfully continued in an RPMI-1640 medium supplemented with 20% normal canine serum or fetal bovine serum in a humidified atmosphere containing 5% CO(2) and 5% O(2) at 37 degrees C. We used this isolate to evaluate the growth inhibitory effect of naphthoquinone (atovaquone), aromatic diamidine (diminazene and pentamidine), artemisinin compounds (artesunate and dihydroartemisinin), an iron chelator (deferoxamine), quinoline-containing compounds (quinine and chloroquine), macrolide antibiotics (azithromycin), lyncomycin antibiotics (clindamycin), tetracycline antibiotics (doxycycline and minocycline), imidazole antifungals (clotrimazole and ketoconazole), and a nitroimidazole antiprotozoal (metronidazole). Atovaquone and aromatic diamidine showed the highest activity; they were followed by artesunate compounds with nanomole levels of IC(50). Metronidazole did not exhibit activity against the parasite. Other drugs exhibited intermediate in vitro activities with micromole levels of IC(50). This is the first report to screen drug activities against B. gibsoni in vitro. The results of our study may support further in vitro drug evaluation for the establishment of therapeutic strategies against canine B. gibsoni infections.     

Retrospective diagnosis of feline GM2 gangliosidosis variant 0 (Sandhoff-like disease) in Japan: possible spread of the mutant allele in the Japanese domestic cat population

GM2 gangliosidosis variant 0 (human Sandhoff disease) is a lysosomal storage disease caused by simultaneous deficiencies of acid beta-hexosaminidase (Hex) A and Hex B due to an abnormality of beta-subunit, a common component in these enzyme molecules, which is coded by the HEXB gene. In the present study, a retrospective diagnosis was performed in 2 previous suspected cases of feline Sandhoff-like disease using a DNA test to detect the causative mutation identified previously in 4 cats in 2 other families of Japanese domestic cats. Enzymic analysis was also performed using stored leukocytes and plasma collected from the subject families in order to investigate the usefulness of enzymic diagnosis and genotyping of carriers. The DNA test suggested that the 2 cases were homozygous recessive for the mutation. Consequently, 6 cats homozygous for the same mutation have been found in 4 separate locations of Japan, suggesting that this mutant allele may be spread widely in the Japanese domestic cat populations. In enzymic analysis, Hex A and Hex B activities in leukocytes and plasma measured using 4-methylumbelliferyl N-acetyl-beta-D-glucosaminide as a substrate were negligible in affected cats, compared with those in normal and carrier cats. However, there was a wide overlap in enzyme activity between normal and carrier cats. Therefore, it was concluded that enzymic analysis is useful for diagnosis of affected cats, but is not acceptable for genotyping of carriers.     

Intranasal hemangiosarcoma in a dog

Magnetic resonance (MR) was conducted for an 8-year-old, intact male Spitz with sneezing, serous discharge and epistaxis from the left nasal cavity. MR imaging showed a nasal cavity-occupied mass of iso-intensity on T1WI , high-intensity on T2WI and markedly enhanced on contrast-enhanced T1WI at parts of rostal to medial ocular angle in the left cavity. After Surgery and intraoperative radiation, the mass was diagnosed intranasal hemangiosarcoma by histopathology. Although the dog showed the finding, which suggested recurrence after the treatment ending, about 30 months later, it maintained good conditions without evidence of metastasis.     

Downregulation of male-specific cytochrome P450 by profenofos

The health hazards of individual organophosphorus insecticides have been characterized by their acute toxicity, mainly by investigating their cholinesterase inhibition. However, the chronic effects of most of these toxicants on the drug-metabolizing enzymes have not been investigated. Profenofos (O-4-bromo-2-chlorophenyl O-ethyl S-propyl phosphorothioate) is an organophosphorus pesticide widely used in cotton cultivation. In the present study, we investigated the effect of profenofos on male-specific cytochrome P450 (CYP) enzymes in adult Wistar rats. We orally administered 17.8 mg/kg body weight, twice weekly for 65 days. Profenofos downregulated levels of hepatic and testicular CYP2C11 and CYP3A2 mRNA and protein expression. Testicular aromatase (CYP19A) mRNA was decreased in the profenofos-treated rats compared to controls. Overall, the present study suggests that profenofos acts as an endocrine disruptor of male-specific CYP enzymes and affects testosterone concentration, which implicates its deleterious effects on animal or human males chronically exposed to organophosphorus pesticide.     

Pharmacokinetics and toxicity of zonisamide in cats

With the eventual goal of making zonisamide (ZNS), a relatively new antiepileptic drug, available for the treatment of epilepsy in cats, the pharmacokinetics after a single oral administration at 10mg/kg and the toxicity after 9-week daily administration of 20mg/kg/day of ZNS were studied in healthy cats. Pharmacokinetic parameters obtained with a single administration of ZNS at 10mg/day were as follows: Cmax=13.1microg/ml; Tmax=4.0h; T(1/2)=33.0h; areas under the curves (AUCs)=720.3microg/mlh (values represent the medians). The study with daily administrations revealed that the toxicity of ZNS was comparatively low in cats, suggesting that it may be an available drug for cats. However, half of the cats that were administered 20mg/kg/day daily showed adverse reactions such as anorexia, diarrhoea, vomiting, somnolence and locomotor ataxia.     

Insecticidal and neuroexciting actions of DDT analogs

The neuroexciting activity of DDT and its analogs to produce repetitive responses on the nerve cord of Periplaneta americana was determined using the extracellular electrode method. The convulsive activity on P. americana and the insecticidal effect on Callosobruchus chinensis were also examined. It was found that the convulsive and insecticidal activities increase almost proportionally with increase in the neuroexciting activity within a set of p,p′-substituted DDT analogs. The intimate connections among these biological effects suggest that symptoms such as convulsion and death caused by DDT analogs are closely related with their neuroexcitory effect and there is a common mode of action in spite of differences in insect species.     

Effect of culling age of does on milk and meat production in Japanese-Saanen goats

A functional herd dynamics model was developed to estimate the effect of culling age on milk and meat production for Japanese-Saanen goats in relation to changes in prices of milk and meat. The model simulates life cycle production of bucks and does and their kids. Every production trait is first modelled as an individual trait and thereafter as a trait in the herd using a herd dynamics model. At the individual level, the survival curve function, the litter size function and the production traits function are combined. Data on growth and lactation were used to fit growth and lactation curves to estimated parameters using non-linear least squares regression technique and used in the production traits function. Using herd dynamics, the individual level functions are combined with the total number of animals function to estimate the total herd output and income efficiency at the herd level. Here, variables of culling days including the effect of difference in meat price value among goat categories (bucks, does, male kids and female kids) are used. Analysis of interrelations among the culling days of does, the price ratio and the income efficiency indicated that optimal culling days of does was shortened with an increase in the price ratio of meat to milk. However, when meat price value was different among goat categories according to actual situation of Japanese goat production, the optimal culling days of does could be fixed regardless of the change in price ratio and was calculated as 1730 days. This functional herd dynamics model can aid in decision-making regarding culling under several situations especially when there is a wide fluctuation in prices at local markets.