According to the ICH S3A Q&A, microsampling is applicable to pharmaceutical drugs and toxicological analysis. Few studies have reported the effect of microsampling on the toxicity of immunotoxicological drugs. The aim of this multicenter study was to evaluate the toxicological effects of serial microsampling on rats treated with azathioprine as a model drug with immunotoxic effects. Fifty microliters of blood were collected from the jugular vein of Sprague-Dawley rats at six time points from day 1 to 2 and 7 time points from day 27 to 28. The study was performed at three organizations independently. The microsampling effect on clinical signs, body weights, food consumption, hematological parameters, biochemical parameters, urinary parameters, organ weights, and tissue pathology was evaluated. Azathioprine-induced changes were observed in certain hematological and biochemical parameters and thymus weight and pathology. Microsampling produced minimal or no effects on almost all parameters; however, at 2 organizations, azathioprine-induced changes were apparently masked for two leukocytic, one coagulation, and two biochemical parameters. In conclusion, azathioprine toxicity could be assessed appropriately as overall profiles even with blood microsampling. However, microsampling may influence azathioprine-induced changes in certain parameters, especially leukocytic parameters, and its usage should be carefully considered.
A gelatin capsule is widely used as a device for oral administration of granular/powdered materials or small amounts of liquid materials in animal experiments. In this study, we investigated the insulin- and glucagon-related parameters following oral administration of gelatin capsules to beagle dogs since a gelatin capsule is made of protein composed of many amino acids as known to stimulate insulin or glucagon secretion. Gelatin capsules (1/2 ounces in size) were administered once orally to three male beagle dogs at the dose level of 0.29 and 1.67 g/kg as gelatin and the plasma levels of insulin, glucagon, glucose, non-esterified fatty acids (NEFA), total ketone bodies (KB) and alanine were determined before dosing and for up to 4 hr after dosing. Plasma insulin, glucagon and alanine levels increased immediately after dosing and subsequently plasma NEFA and total KB levels decreased. Most of these changes disappeared by 4 hr after dosing. No effects on plasma glucose levels were noted. In conclusion, a single oral administration of gelatin capsules increased plasma insulin and glucagon levels transiently and altered plasma levels of some biochemical parameters in dogs. These results might imply that attention should be paid to their own effect on the insulin and glucagon secretion at conducting animal experiments using a lot of gelatin capsules.
In six small renal angiomyolipomas (7-17 mm) the superiority of displaying the CT numbers of pixels within a lesion (pixel mapping) over the usual region of interest (ROI) measurement is described in the detection of small amounts of fat tissue. On precontrast 5 mm CT the ROI measurements were > 0 in four cases whereas pixel maps revealed pixels with values < 0 in six cases.
Abstract The food intake of households in 1,040 census tracts sampled in 1974, 1975, and 1976 for the nationwide nutrition survey of the Japanese Ministry of Health and Welfare, and the standardized mortality ratios (SMRs) of stomach and esophageal cancers from 1969 to 1974 for the cities, towns, and villages of the nutrition survey areas, were linked and their relationship was observed statistically by correlation analysis and multiple regression analysis. The results obtained are summarized as follows:
Abstract Objective To protect neonatal calves against fatal salmonellosis within the first 2 weeks after birth, using chicken egg yolk antibodies specific against Salmonella typhimurium or S dublin . Animals 38 neonatal Holstein calves from Salmonella -free farms. Procedure After removal of the lipid components with hydroxypropylmethylcellulose phthalate, egg yolk antibodies were spray dried. At 4 days of age, calves were challenge exposed by oral inoculation with 10 11 virulent S typhimurium (experiment 1) or S dublin (experiment 2). Starting from the challenge-exposure day, egg yolk antibody preparations were administered orally 3 times a day for 7 to 10 days. Results In passive immunization trials, the orally administered antibodies conferred dose-dependent protection against infection with each of the homologous strains of Salmonella . Within 7 to 10 days after challenge exposure, all control calves died, whereas low-titer antibody-treated calves had 60 to 100% mortality. Only fever and diarrhea, but no deaths ( P < 0.01), were observed in calves given the highest titer of antibody. Conclusions and Clinical Relevance Compared with that in control calves, survival was significantly higher among calves given antibodies with titers of 500 ( P < 0.05) and 1,000 ( P < 0.01) homotypic for S typhimurium and with titer of 5,000 ( P < 0.01) for S dublin . Egg yolk antibodies specific for whole cell S typhimurium or S dublin are protective against fatal salmonellosis when given in sufficiently high concentration, and may be clinically useful during a salmonellosis outbreak. ( Am J Vet Res 1998;59:416–420)
Although microsampling of blood is recommended to promote the 3Rs in toxicokinetic (TK) evaluation, there are few reports applying microsampling in actual toxicity evaluation. Here, we assessed the effects of microsampling on toxicological evaluation of methapyrilene hydrochloride, a hepatotoxic substance. Female SD rats received methapyrilene hydrochloride orally at dose levels of 0 (vehicle), 10, and 30 mg/kg BW, once daily for 4 weeks. Each dose level included a microsampling group and a non-microsampling group (n = 5). In the microsampling groups, blood sampling (50 µL/time point) was performed at 6 time points on day 1 of administration and 7 time points on day 27–28; all the animals underwent necropsy on day 29. Toxicity studies and TK analysis were performed, and through these studies in 2 organizations, cross-organization validation of the effect on toxicity evaluation was conducted. In one organization, microsampling obscured changes in some parameters in hematology due to the administration of methapyrilene hydrochloride. In the other organization, although the relationship between the developing pattern of histopathological findings in the liver and the blood sampling was suspected, it was associated with poor reproducibility; this was considered as a change within a variation range of biological reactions. Each of these phenomena was observed in only one organization without consistency. In both organizations, no effect of blood microsampling was observed in other endpoints. In conclusion, microsampling is considered to be a technique applicable to safety studies of drugs showing hepatotoxicity, as it did not show a marked influence on the toxicological evaluation of methapyrilene hydrochloride.
The protective effect of immunoglobulins derived from chicken egg yolk (IgY) against infection by Canine parvovirus 2 (CPV-2) was evaluated in 10 beagle dogs orally challenged with a strain of the virus. The 2-mo-old dogs were divided into 3 groups and treated with powders containing CPV-2 IgY or normal egg yolk for 7 d after the challenge. The 4 dogs receiving normal egg yolk (control group) demonstrated mild symptoms typical of CPV-2 infection, such as vomiting, diarrhea, and weight loss. No symptoms were observed by 16 d after challenge in the 3 dogs receiving 2 g of IgY powder. Of the 3 dogs receiving 0.5 g of IgY powder, 2 had clinical CPV-2 disease; however, the manifestations were less severe than in the control group. Furthermore, the IgY-treated groups had significantly greater weight gain and shorter duration of virus shedding than the control group. These results indicate that IgY is useful in protecting dogs from CPV-2-induced clinical disease.
