The influence of P-glycoprotein (P-gp) on intestinal absorption of drugs was investigated by comparison of the uptakes of two P-gp substrates, verapamil and vinblastine, using intestinal segments of wild-type and mdr1a/1b gene-deficient (mdr1a/1b(-/-)) mice, and Caco-2 cells. When [(3)H]vinblastine was injected into intestinal segments of wild-type mice, vinblastine was absorbed from duodenum and ileum, but not from jejunum. This difference among intestinal regions could not be explained by segmental differences of mdr1a mRNA expression. In Caco-2 cells, it was found that vinblastine had a high value of efflux/influx ratio (an index of affinity for P-gp) of 12.1, and a low permeability of less than 1 x 10(-6) cm/sec. The corresponding values for verapamil were 4.9 and 10.6 x 10(-6) cm/sec, respectively. After oral administration of [(3)H]vinblastine to mice, the maximum concentration (C(max)) and the area under the plasma concentration time-curve from time 0 to 24 hr (AUC(0-24 hr)) for mdr1a/1b(-/-) mice were 1.5 times greater than those for wild-type mice, while these parameters were not significantly different between the two strains in the case of [(3)H]verapamil. Therefore, P-gp substrates may be classified into at least two types, i.e., verapamil-type, for which the intestinal absorption is unaffected by P-gp, and vinblastine-type, for which the intestinal absorption is influenced by P-gp. Vinblastine-type P-gp substrates, with low permeability and high affinity for P-gp, would be unfavorable candidates for oral drugs.

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Huge vacuoles in the follicular epithelial cells distributing diffusely in the thyroid gland were seen in 2 out of 36 males and 8 out of 82 females of BrlHan: WIST@Jcl (GALAS) rats examined histopathologically. The vacuoles showed negative reactivity by periodic acid-Schiff reaction and thyroglobulin-immunohistochemistry. Corresponding to the vacuoles, remarkable dilatation of rough endoplasmic reticulum was seen in electron microscopic observation. The animals in which the thyroid lesion was found had shown no abnormalities in behavior, body weight, food consumption, or hematological and biochemical examinations. Plasma concentrations of thyroid-stimulating hormone (TSH) and thyroid hormones (T3 and T4) were not different from those of normal rats. From these results, thyroid functions seemed to be kept normal in spite of the severe morphological change. Based on the character and incidence of the thyroid lesion, it was presumed to be related with a certain genetic factor of one or several parents of breeding rats rather than food contamination or infection. ( BrlHan: WIST@Jcl (GALAS) rats, so called Wistar Hannover GALAS rats, have been used in toxicity studies in Europe. This strain has several beneficial characters such as a higher survival rate and a smaller body weight than those of other strains, for instance, Sprague-Dawley, Wistar, and Fischer 344 rats. A higher survival rate (about 80% for 2 years) is advantageous for long term-toxicity studies, and a smaller body weight is worthy to use in preliminary toxicity studies of new drugs when the quantity of compounds is limited. In our laboratory, this strain has been recently used in preliminary toxicity studies. In the studies, we found a lesion of the thyroid gland in 2 out of 36 males and 8 out of 82 females. One female bearing the lesion was from nontreated groups. We considered the lesion as a spontaneous change since the quality and the degree were similar to that in the non-treated animal.All animals were supplied from CLEA, Japan, Inc. at 5 weeks of age. Animals examined were from 6 lots (4 lots for 4 preliminary toxicity studies and 2 lots for the accumulation of background data at 8 weeks of age). They were housed in stainless steel cages in a room maintained at 23 ± 2°C, 55 ± 15% relative humidity and a 12-hr-light and -dark cycle, and had free access to a standard laboratory diet (CRF-1, Oriental Yeast Co., Ltd., Tokyo) and tap water. Blood samples were withdrawn from the abdominal aorta under sodium pentobarbital anesthesia and the animals were killed by exsanguination at 8 weeks of age.Many organs including the thyroid gland were removed and weighed (the organs of one rat was not weighed). The organs were fixed in 10% neutral-buffered formalin, embedded in paraffin, sectioned, and stained with hematoxylin and eosin (H.E.) for light microscopic observation. In addition, sections of the thyroid and pituitary glands were processed for periodic acid-Schiff (PAS) reaction. In 6 normal rats and 8 rats with thyroid lesion, immunohistochemi...

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SummaryObjectiveInconsistent results have been found in prior studies investigating the accuracy of self‐reported waist circumference, and no study has investigated the validity of self‐reported waist circumference among Japanese individuals. This study used the diagnostic standard of metabolic syndrome to assess the accuracy of individual's self‐reported height, weight and waist circumference in a Japanese sample.MethodsStudy participants included 7,443 Japanese men and women aged 35–79 years. They participated in a cohort study's baseline survey between 2007 and 2011. Participants' height, weight and waist circumference were measured, and their body mass index was calculated. Self‐reported values were collected through a questionnaire before the examination.ResultsStrong correlations between measured and self‐reported values for height, weight and body mass index were detected. The correlation was lowest for waist circumference (men, 0.87; women, 0.73). Men significantly overestimated their waist circumference (mean difference, 0.8 cm), whereas women significantly underestimated theirs (mean difference, 5.1 cm). The sensitivity of self‐reported waist circumference using the cut‐off value of metabolic syndrome was 0.83 for men and 0.57 for women.ConclusionsDue to systematic and random errors, the accuracy of self‐reported waist circumference was low. Therefore, waist circumference should be measured without relying on self‐reported values, particularly in the case of women.

The influence of ultraviolet (UV) irradiation on low frictional performance of CNx coatings with 100 nm thickness having nitrogen contents of 9%, 14% and 19% deposited on Si(100) substrate by ion beam mixing was investigated in N2 atmosphere environment. Three UV lights of 254, 312 and 365 nm were used to irradiate the surface of CNx / Si(100) for 60 min. The changes of N / C ratio and atomic binding energy in the coating were analysed using Auger electron spectroscopy and X‐ray photoelectron spectroscopy, respectively. The friction coefficient of Si3N4 ball sliding against CNx was measured by a pin‐on‐disc tribometer, and wear tracks were analysed by the transmission electron microscope image. The results showed that UV irradiation on CNx coating can decrease the critical frictional cycles for low friction coefficient and that the mechanism is due to the formation of graphite‐like structure in the topmost CNx coating. Copyright © 2012 John Wiley & Sons, Ltd.