In this report prevalence rates of rodent viruses in laboratory animals are presented based on routine serological screening of mouse and rat colonies from European institutes. The prevalences found during the period 2000-2003 are compared with those reported for 1981-1984 and 1990-1993. It is shown that some infections were eliminated from laboratory animal colonies (e.g. K-virus and polyomavirus) by taking preventative measures whereas other infections such as mouse hepatitis virus and parvoviruses remained at a high rate. Further decreases in prevalence rates in the last 10 years were found for infections such as pneumonia virus of mice, reovirus type 3, Sendai virus, sialodacryoadenitis/rat coronavirus and Mycoplasma pulmonis. The introduction of new detection methods showed that mouse parvovirus and rat parvovirus, both members of the Parvoviridae family, remain a major threat to laboratory mice and rats. Guinea pig cytomegalovirus and para-influenza virus appeared to be the most prevalent agents among laboratory guinea pigs. The importance of a standardized, up-to-date screening programme is discussed.

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A bstractThe following metabolites of sulfadiazine (S) were isolated from monkey urine by preparative HPLC: 5-hydroxysulfadiazine (50H), 4-hydroxysulfadiazine (40H) and the glucuronide (SOHgluc) and sulfate conjugate of 50H (50Hsulf). The compounds were identified by NMR, mass and infrared spectrometry and hydrolysis by /3-glucuronidase. The analysis of S, the hydroxymetabolites (40H, 50H) and conjugates N4-acetylsulfadiazine (N4), SOHgluc and 50Hsulf in human and monkey plasma and urine samples was performed using reversed-phase gradient HPLC with UV detection. In plasma, S and N4 could be detected in high concentrations, whereas the other metabolites were present in only minute concentrations. In urine, S, the metabolites and conjugates were present. The limit of quantification of the compounds in plasma varies between 0.2 and 0.6 /¿g/ml (S 0.31, N4 0.40, 40H 0.20, 50H 0.37, SOHgluc 0.33 and SOHsulf 0.57 ¿tg/ml). In urine it varies between 0.6 and 1.1 /¿g/ml (S 0.75, N4 0.80, 40H 0.60, 50H 0.80, SOHgluc 0.80 and SOHsulf 1.1 ¿¿g/ml). The method was applied to studies with healthy human subjects and Rhesus monkeys. The metabolites 5OH, SOHgluc and 50Hsulf were present in Rhesus monkey and not in man. Preliminary results of studies of metabolism and pharmacokinetics in Rhesus monkey and man are presented. Subject and monkeysA single oral dose of 500 mg S was adminis tered to one healthy human subject (male, 35 years old, 85 kg, slow acetylator of sulfonamides) with 100 ml of tap water after an overnight fast. The study had the approval of the hospital ethics committee and informed consent was obtained from the volunteer.Rhesus monkeys were obtained from the Cen tral Animal Laboratory, University of Nijmegen and the Laboratory Animals Breeding Ex perimental Farm of Shunde Guangdong (Beijing, China). One Rhesus monkey (female, 5 years old and weighing about 5 kg) was housed in a metabolic cage and fed orally with 50 mg/kg of sulfadiazine and serial plasma and urine samples were collected for 2 days. Three Rhesus monkeys (female, 4-5 years old and weighing about 5 kg) obtained from the Central Animal Laboratory, University of Nijmegen, were housed in a meta bolic cage and fed orally for 5 days with 50 mg/kg of sulfadiazine and all urine was collected for 6 days. The study had the approval of the ethics committee of the Animal Laboratory. SamplingBlood samples of 2 ml were drawn from the volunteer and collected in heparinized Eppendorf vials (2 ml) at regular time intervals during 2 days after administration by means of fingertip puncture with Monolet lancets (Monoject, St. Louis, MO, USA). After centrifuging at 3000 g for 5 min, plasma samples were stored at -20°C pending analysis.Urine was collected from untimed voiding. The total time of sample collection was 96 h. Three samples of 7 ml of each void were stored at -20°C pending analysis.Blood samples of 2 ml were drawn from the monkey by puncture of the vena mediana and collected in heparinized Eppendorf vials at 0.1, 2, 3, 4, 5, 6, 7, 8, 10, 12, 24 and 48 h ...

The aim of the present study was to determine the in-vitro susceptibility of Toxoplasma gondii to dihydrofolate reductase inhibitors and sulphonamides alone, and in combination. It was found that pyrimethamine had the most potent anti-Toxoplasma activity, while sulphadiazine, sulphamethoxazole and sulphametrole were approximately equally effective, but only at a high concentration. The 50% inhibitory concentration of sulphamethoxazole was determined using different fixed concentrations of pyrimethamine or trimethoprim. It was found that a ten-fold increment of the concentration of pyrimethamine, reduced the IC50 of sulphamethoxazole 1000 times. The influence of trimethoprim on the IC50 of sulphamethoxazole was less concentration dependent. Addition of dihydrofolate or tetrahydrofolate did not influence the IC50 of pyrimethamine. In conclusion, the present dose recommendations for sulphonamides, when combined with pyrimethamine, may be unnecessarily high. There may be a justification for dose reduction of sulphonamides in order to prevent side effects.

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