The fungicide carbendazim induces meiotic micronuclei in the spermatids of the rat testis.

Whether the fungicide carbendazim affects the meiotic spermatocytes and consequently induces chromosome aberrations in the spermatids was determined in the adult rat testis using the micronucleus test. Round spermatids containing micronuclei (MN) were significantly increased in number at stages I and V on days 1 and 4.5 after treatment with carbendazim (100 mg/kg), respectively (p<0.05). Immunocytochemistry indicated that approximately 68% of the carbendazim-induced MN contained kinetochores. These results suggest that carbendazim induces chromosome aberrations in spermatids with a high incidence of aneuploidy.     

Cutaneous plasmacytoma in three golden hamsters (Mesocrietus auratus)

Spontaneously occurring cutaneous tumours in three golden hamsters were characterized using histological, immunohistochemical and ultrastructural methods. Histologically, the tumours were composed of sheets of round to oval plasmacytoid cells with eccentrically placed nuclei. Tissue sections were weakly positive for anti-B lymphocyte antigen (BLA) staining. Ultrastructurally, large amounts of rough endoplasmic reticulum in the cytoplasm were observed. BLA positivity and characteristics of ultrastructure showed the plasma cell origin.     

Biological properties of the novel fungicide cyazofamid against Phytophthora infestans on tomato and Pseudoperonospora cubensis on cucumber

Cyazofamid (ISO proposed common name), 4-chloro-2-cyano-N,N-dimethyl-5-p-tolylimidazole-1-sulfonamide is a novel fungicide exhibiting specific activity against diseases caused by Oomycetes. In tests, cyazofamid at 0.4-1.6 mg litre-1 exhibited excellent preventative activity against Phytophthora infestans on tomato and Pseudoperonospora cubensis on cucumber. Minimum inhibitory concentrations of cyazofamid against both diseases were over 63 times lower than those of mancozeb and at least 16 times lower than those of metalaxyl. Cyazofamid at 1.6-25 mg litre-1 exhibited not only preventative activity, but also stable residual activity and rainfastness. Cyazofamid at 6.3 mg litre-1 reduced zoosporangia formation of P infestans and P cubensis on host plants by 100 and 94% respectively. Cyazofamid also exhibited translaminar and curative activity. Cyazofamid has a new mode of action for fungicides and exhibits no cross-resistance with other currently registered and commonly used fungicides. These properties lead to a high level control by cyazofamid in field.     

Structure—activity relationships of pyridylcarbamates active against both benzimidazole-sensitive and -resistant isolates of Botrytis cinerea

A series of pyridylcarbamates showed high potency against cucumber gray mould (Botrytis cinerea Pers.). The most potent compound, propargyl-N-(6-ethyl-5-iodo-2-pyridyl)carbamate was effective against an isolate sensitive to benzimidazole and dicarboximide fungicides as well as against an isolate resistant to both types of compound. QSAR analyses and molecular modelling studies were carried out to investigate the structural requirements for highly active compounds and the structural feature of the binding site of each strain. Significantly different QSAR equations were obtained only for substituents at the 6-position of the pyridine ring. An ethyl-sized pocket or an ethyl terminal recognition was suggested in the case of the sensitive or resistant isolate respectively. These results could explain the phenomenon of negatively correlated cross-resistance between benzimidazoles and N-phenylcarbamate fungicides. Substituent effects at the 5- or 2-position were governed by steric factors. Substituent effects at the 3-position were explained by steric hindrance or by conformational effects. The propargyl-substituted compound above was the most desirable one from the viewpoint of QSAR.     

The discovery of pyridalyl: a novel insecticidal agent for controlling lepidopterous pests

Synthesis of analogues of two compounds with known insecticidal activity, both of which contain a 3,3-dichloro-2-propenyloxy group, produced 2-(trifluoromethyl)-4-phenoxyphenyl 3,3-dichloro-2-propenyl ether, which had weak activity against lepidopterous larvae. Structural modifications around this lead compound led to the development of pyridalyl [Pleo, S-1812; 2,6-dichloro-4-(3,3-dichloroallyloxy)phenyl 3-[5-(trifluoromethyl)-2-pyridyloxy]propyl ether], which belongs to a new class of insecticides. Pyridalyl gives very good control of various lepidopterous and thysanopterous pests on cotton and vegetables, without phytotoxicity. It controls populations of Heliothis virescens F and Plutella xylostella (L) which are resistant to various currently used insecticides. It also produces unique insecticidal symptoms, so it may have a different mode of action from other existing insecticides. Pyridalyl is also less harmful than existing insecticides to various beneficial arthropods, so it should provide an important tool in IPM and insecticidal management programmes for the control of lepidopterous and thysanopterous pests. The first market introduction is expected in Japan and some Asian countries in the years between 2004 and 2005.     

Prevalence of Cryptosporidium parvum infection and pattern of oocyst shedding in calves in Japan

Cryptosporidium parvum infection and the pattern of oocyst shedding were observed in calves. A total of 480 fecal samples were collected from 30 calves (age, < or =30 days) over a period of 10 months from June 1998 to March 1999. A sucrose centrifugal flotation technique revealed 28/30 (93%) calves were passing Cryptosporidium oocysts. Oocyst shedding was first detected on the sixth day after birth, with 8% of the calves testing positive. This rate increased day by day and reached approximately 80% by day 15. Oocyst shedding varied from 1 to 13 days, with a mean of 7 days. Calves infected with C. parvum had a significantly higher rate of diarrhea (33%) than non-infected calves (8%) (P<0.05), suggesting C. parvum infection as the likely cause. The mean number of oocysts excreted by calves < or =30 days old was approximately 6x10(7) per gram of feces. These results indicated that one calf would excrete some 6x10(11) oocysts in the first month after birth, taking both the quantity of feces in a day and the period of excretion into consideration. Accordingly, it is clear that calves are important in the spread of cryptosporidiosis to calves and humans.     

Malignant fibrous histiocytoma in a Djungarian hamster

A subcutaneous malignant fibrous histiocytoma (MFH) was observed in the region between the right posterior trunk and right hind limb of a 2-year-old male Djungarian hamster weighing 45 g. Histologically, the tumor consisted of bizarre multinucleated giant cells, histiocytic cells, and fibroblastic cells with a storiform pattern, and was considered to be of the storiform-pleomorphic type of MFH. Severe nuclear atypia with prominent nucleoli and many mitotic figures was also observed. Electron microscopy demonstrated fibroblastic cells and histiocytic cells. The fibroblastic cells were spindle-shaped, and sometimes had an invaginated nucleus. The histiocytic cells were polygonal with an oval or kidney-shaped nucleus. The cytoplasm of both cells contained numerous free ribosomes, small amounts of rough endoplasmic reticulum, and round mitochondria. Tumor cells were immunohistochemically positive for vimentin, and were thought to be of undifferentiated mesenchymal cell origin. This is the first report of spontaneous MFH in a hamster.     

Roles of oxygen radical production and lipid peroxidation in the cytotoxicity of cephaloridine on cultured renal epithelial cells (LLC-PK1)

To clarify the mechanism of cephalosporin nephrotoxicity, the cytotoxic effects of cephaloridine (CER), a nephrotoxic cephalosporin antibiotic, on the pig kidney proximal tubular epithelial cell line (LLC-PK1) were studied in culture. CER increased the content of hydrogen peroxide and decreased the activity of catalase in the treated cells, followed by an increase in the content of lipid peroxide and decreases in both glutathione peroxidase activity and in the non-protein sulfhydryl content. The levels of NADPH-dependent hydrogen peroxide and superoxide anion production by microsomes prepared from LLC-PK1 cells, and by NADPH-cytochrome P-450 reductase purified from the rat renal cortex were significantly increased by paraquat. The production of these molecules was antagonized by p-chloromer-curibenzoate, an inhibitor of NADPH-cytochrome P-450 reductase. On the other hand, CER did not significantly affect the production of hydrogen peroxide or superoxide anions. These results suggested that the cytotoxic effect of CER on cultured LLC-PK1 cells was due to the increases in hydrogen peroxide and lipid peroxide levels and not microsomal oxygen radical production, and that the mechanism of this cytotoxicity is very different from that of paraquat which induces microsomal oxygen radical production.     

Pharmacokinetics of zonisamide and drug interaction with phenobarbital in dogs

The purposes of the present study were to elucidate the pharmacokinetics of zonisamide, determine the presence of a drug interaction with phenobarbital, and evaluate how long any interaction lasted after discontinuation of phenobarbital in dogs. Five dogs received zonisamide (5 mg/kg, p.o. and i.v.) before and during repeated oral administration of phenobarbital (5 mg/kg, bid, for 30–35 days). Zonisamide (5 mg/kg, p.o.) was also administered 8, 10, and 12 weeks after discontinuation of phenobarbital. Blood was sampled until 24 h after each zonisamide administration and serum concentrations of zonisamide were determined. Repeated phenobarbital decreased the maximum serum concentration, area under the serum concentration vs. time curve, apparent elimination half-life, and bioavailability of zonisamide. Total clearance increased. Time to maximum serum concentration and volume distribution were not changed. The maximum serum concentration and area under the serum concentration vs. time curve of zonisamide continued to be low until 10 weeks after the discontinuation of phenobarbital. They were restored to the same serum concentration as before phenobarbital administration 12 weeks after the discontinuation of phenobarbital. These data suggested that repeated administration of a clinical dose of phenobarbital enhanced the clearance of zonisamide and the enhanced clearance lasted at least 10 weeks after the discontinuation of phenobarbital. Caution may be necessary when zonisamide is given with phenobarbital and when antiepileptic therapy is changed from phenobarbital to zonisamide.