Haruo Yoshimura

Mutagenicities of carbadox and olaquindox — Growth promoters for pigs

Carbadox and olaquindox were examined for mutagenicities in the repair tests with Bacillus subtilis (rec assay) and Salmonella typhimurium (uvr assay) and in the reverse mutation test (TA100 and TA98 of S. typhimurium). Both compounds were positive in the rec and uvr assays, and were highly mutagenic for strains TA100 and TA98. Carbadox was about 6 times move mutagenic than olaquindox in the absence of S9 mix. When incubated in S9 mix or bacterial cytosol (BC) mix for various times at 37 degree C, carbadox was found to lose its mutagenic activities easier than olaquindox. The mutagenicity of carbadox was almost inactivated at 10 min after incubation with S9 mix, but olaquindox still retained its activities even at 20 min. While carbadox required 20 min to be inactivated in BC mix, olaquindox was not completely inactivated even if incubated for 60 min.

Antimicrobial susceptibilities of enterococci isolated from faeces of broiler and layer chickens

Enterococci were isolated from faecal droppings of chickens in broiler and layer farms and the susceptibilities to nine therapeutic antimicrobial agents and six growth‐promoting antibiotics were determined by the agar dilution method. Resistance to therapeutic antimicrobial agents such as ampicillin, clindamycin, erythromycin, streptomycin, tetracycline or tylosin was more frequent in enterococcal isolates from broiler farms than in those from layer farms. Resistance to ofloxacin was rare, occurring in only one (0·7%) of the Enterococcus faecium isolates from broiler farms. Resistance to growth‐promoting antibiotics such as avilamycin, salinomycin and virginiamycin was common among isolates from broiler farms. Of the E. faecium isolates from broiler farms, 12·4% were resistant to avilamycin and 27·4% were resistant to virginiamycin. Resistance to salinomycin was detected in all enterococcal species, ranging from 12·4% of E. faecium isolates to 50% of E. hirae isolates.

Antimicrobial Susceptibility of Pasteurella multocida Isolated From Cattle and Pigs

Minimum inhibitory concentrations (MICs) of 10 antimicrobial agents were determined for Pasteurella multocida from cattle and pigs (72 and 68 isolates, respectively). Higher MICs were observed with oxytetracycline, doxycycline, tilmicosin and thiamphenicol for porcine isolates than for bovine isolates. Enrofloxacin was the most active, with an MIC for 90% of the isolates (MIC90) of 0.05 microg/ml for both bovine and porcine isolates. Aspoxicillin exhibited the same excellent activity against penicillin-susceptible isolates as ceftiofur, with MICs ranging from < or = 0.025 to 0.1 microg/ml. Aminoglycosides were less active, with an MIC90 of > 100 microg/ml for both bovine and porcine isolates.

Teratogenic assessment of carbadox in rats

Carbadox was administered by gavage once daily to pregnant rats at doses of 0 (control), 10, 25, 50 or 100 mg/kg on days 8 through 15 of pregnancy. The dams were killed on day 21 and the number of implantation sites, resorptions and live fetuses were counted. A significant dose-related decrease in maternal body weight gains during treatment (days 8 through 15 of pregnancy) occurred at doses of 10 mg/kg and above. There was a dose-related decrease in fetal body weights which was statistically significant at 25 mg/kg and above. This compound showed not only embryolethal but teratogenic effect. Resorption rates were 81.8% at 100 mg/kg, occurring complete resorptions in five dams, compared with 3.4% resorption rate in the control. In fetal examinations, a significant increase in the incidence of external, skeletal and internal malformations occurred at 100 mg/kg, where the surviving fetuses born to dams with 40-93% resorptions had any malformations, short tail; kinky tail; brachygnathia or ectrodactyly.

Comparative In Vitro Activity of 16 Antimicrobial Agents Against Actinobacillus Pleuropneumoniae

Sixteen antimicrobial agents were tested for their activity against 68 isolates of Actinobacillus pleuropneumoniae by determining the minimum inhibitory concentrations (MICs). Ceftiofur and the fluoroquinolones danofloxacin and enrofloxacin were the most active compounds, with a MIC for 90% of the isolates (MIC90) of ≤ 0.05 µg/ml. The MIC90 values of benzylpenicillin, amoxicillin and aspoxicillin were 0.78 units/ml, 0.39 µg/ml and ≤ 0.05 µg/ml, respectively. Three isolates (4.4%) were resistant to penicillins, but aspoxicillin was as active as ceftiofur against the susceptible isolates, with MICs of ≤ 0.05 µg/ml for all isolates. Resistance to oxytetracycline, chloramphenicol and thiamphenicol occurred in 22 (32.4%), 14 (20.6%) and 15 (22.1%) of the isolates, respectively. Doxycycline was more active than oxytetracycline, with a MIC90 of 1.56 µg/ml as against 25 µg/ml. Florfenicol was not only as active as thiamphenicol, with a MIC for 50% of the isolates (MIC50) of 0.39 µg/ml, but also active against thiamphenicol-resistant isolates. All the isolates were susceptible to florfenicol. All the isolates were also susceptible to gentamicin, spectinomycin, tilmicosin, colistin and tiamulin. Of these, spectinomycin was the least active, with a MIC50 of 25 µg/ml, followed by tiamulin, with a MIC50 of 6.25 µg/ml. Of the 68 isolates tested, 49 (72.0%) were of serotype 2; 14 (20.5%) were of serotype 1; 2 each (3.0

Antimicrobial Susceptibilities of Erysipelothrix rhusiopathiae Isolated from Pigs with Swine Erysipelas in Japan, 1988–1998

) were of serotypes 5 and 6; and one was of serotype 7. Of the isolates, 23 (33.8%) were resistant to one or more of the major antibiotics. Antibiotic resistance was found only infrequently among serotype 2, with 5 (10.2%) of 49 isolates being resistant to chloramphenicol and/or oxytetracycline, while it occurred in 18 (94.7%) of the 19 isolates of other serotypes.

Induction of chromosome aberrations by pyrimethamine in cultured Chinese hamster (CHL) cells

The susceptibility to 21 antimicrobial agents of 214 strains of Erysipelothrix rhusiopathiae isolated from pigs affected with swine erysipelas in Japan between 1988 and 1998 was determined. Ampicillin, cloxacillin, benzylpenicillin, ceftiofur, tylosin, enrofloxacin and danofloxacin were the most active agents [minimum inhibitory concentrations (MICs); < or = 0.025-0.78 microgram/ml], followed by cefazolin, virginiamycin, tiamulin, chloramphenicol, florphenicol and oxolinic acid (MICs; 0.1-25 micrograms/ml). Activity was poor or absent with kanamycin and sulfadimethoxine. Strains resistant to dihydrostreptomycin, erythromycin, clindamycin, lincomycin, oxytetracycline and doxycycline were detected. The susceptibilities to dihydrostreptomycin and oxytetracycline tended to decrease. Investigation of the differences in antimicrobial susceptibility of the 214 strains according to their serotypes, sources, isolation years and regions, showed that the strains resistant to dihydrostreptomycin were most frequently found in the strains of serotype 1a and in strains from septicaemic cases. Strains resistant to oxytetracycline were detected in all serotypes and all sources, and most of the strains resistant to erythromycin were detected in the strains of serotype 2. The frequency of strains resistant to dihydrostreptomycin gradually increased from 1988 to 1996, but then decreased between 1997 and 1998. The frequency of strains resistant to oxytetracycline was remained more than 38% from 1988 to 1998. It was suggested that the strains resistant to dihydrostreptomycin and oxytetracycline were distributed over almost all districts of Japan.

Mutagenicity screening of anesthetics for fishes

Induction of chromosome aberrations was investigated in cultured Chinese hamster cells treated with pyrimethamine. Pyrimethamine without metabolic activation strongly induced structural chromosome aberrations in a dose-dependent manner. Aberrant metaphase cells occurred at a frequency of 80%, when cells were treated at 1.6 microgram/ml for 48 h.

Effect of oral dosing vehicles on the developmental toxicity of flubendazole in rats

Abstract 3 fish anesthetics, eugenol, phenthiazamine and tricaine, were tested for mutagenicity in the rec assay (repair test) with Bacillus subtilis strains M45 (rec − ) and H17 (rec + ), and in the reverse mutation assay with Salmonella typhimurium strains TA100, TA98, TA1535, TA1537 and TA1538. The rec assay was negative for all the compounds. In the reverse mutation assay, phenthiazamine was mutagenic in strains TA100, TA98 and TA1537 after metabolic activation with rat hepatic S9 mix. Eugenol and tricaine were non-mutagenic in the presence and absence of S9 mix.

High-performance liquid chromatographic determination of pamaquine, primaquine and carboxy primaquine in calf plasma using electrochemical detection

Flubendazole was suspended in deionized water or olive oil and administered by gavage once daily to pregnant rats on Days 8-15 of pregnancy to examine if the embryolethal and teratogenic doses were affected by the vehicles used. Flubendazole in olive oil caused a statistically significant increase in embryolethality at doses of 7.83 mg/kg per day and higher, with complete resorption in all dams at 31.33 mg/kg per day. When flubendazole was suspended in deionized water, a significant increase in embryolethality occurred only at a maternal dose of 125.32 mg/kg per day. The proportion of litters with anomalous fetuses was significantly increased at doses of 31.33 mg/kg per day and above when flubendazole was administered in deionized water, but increased at doses at four times lower when flubendazole was administered as in olive oil. Administered as a single dose in olive oil on any one of Days 6-12 of pregnancy, a flubendazole dose of 31.33 mg/kg caused significant increases in embryolethality and decreased fetal body weights on Days 7-9, with an 82.7% incidence of embryolethality on Day 8, with complete resorption in 5 of the 8 dams. The critical periods for teratogenic effects were between Days 8 and 11 of pregnancy, with Day 9 being the most critical. Fetuses with gross, skeletal, or internal anomalies were seen in dams given a single dose of as low as 7.83 mg/kg.