Fetal and Neonatal Goiter in Cynomolgus Monkeys Following Administration of the Antithyroid Drug Thiamazole at High Doses to Dams During Pregnancy

To evaluate morphologic alterations in the thyroid gland in the second generation in cynomolgus monkeys, pregnant dams were exposed to high doses of thiamazole. In Experiment A, dams received thiamazole intragastrically via a nasogastric catheter from gestation day (GD) 50 to GD 150 or on the day before delivery. Initially, the dose level was 20 mg/kg/day (10 mg/kg twice daily); however, the dose level was subsequently decreased to 5 mg/kg/day (2.5 mg/kg twice daily), since deteriorated general conditions were observed in two dams. Six out of seven neonates died on the day of birth. The cause of neonatal death was tracheal compression and suffocation from goiter. The transplacental exposure to thiamazole affected the fetal thyroid glands and induced goiter in all neonates. The surviving neonate was necropsied 767 days after discontinuation of thiamazole exposure and showed reversibility of the induced changes. In Experiment B, dams were intragastrically administered thiamazole at 5 mg/kg/day (2.5 mg/kg twice daily) for treatment periods from GDs 51 to 70, 71 to 90, 91 to 110, 111 to 130 and 131 to 150. All fetuses showed enlarged thyroid glands but were viable. Histopathologically, hypertrophy and/or hyperplastic appearance of the follicular epithelium of the thyroid gland was observed at the end of each treatment period. The most active appearance of the follicular epithelium, consisting of crowded pedunculated structure, was demonstrated at end of the treatment period from GD 131 to 150. This is the first report on the morphology of fetal and neonatal goiter in the cynomolgus monkey

Val1483Ile polymorphism in the fatty acid synthase gene was associated with depressive symptoms under the influence of psychological stress

金沢大学医薬保健研究域薬学系Background: To study the association between lipid-metabolism and depressive symptoms, genetic polymorphisms in serotonin transporter linked promoter region (5-HTTLPR) and fatty acid synthase gene (FASN) were investigated. Method: A cross-sectional study was conducted on 177 women (n = 166) and men (n = 15) recruited from workers in a hospital and nursing homes in Japan. Depressive symptoms were assessed by the Center for Epidemiologic Studies Depression (CES-D) scale and perceived psychological stress was measured using visual analogue scale (VAS). The genotypes of 5-HTTLPR (insertion/deletion; L/S), and FASN (Val1483Ile) were determined by the PCR methods. Linear regression analysis was performed, in which CES-D scores served as a dependent variable, and VAS scores, gene polymorphism, and confounders as independent variables. Results: Under the influence of perceived stress, S/S carriers of the 5-HTTLPR gene showed significantly higher CES-D scores in comparison with L/L + L/S carriers (F = 8.2, standardised β = 0.15, p < 0.05). Regression analysis also confirmed that CES-D scores in participants with Ile/Ile + Val/Ile genotypes of the FASN gene were significantly higher than those with Val/Val genotype (F = 8.4, standardised β = 0.16, p < 0.05). In relation to physical features, BMI among participants with S/S genotype of 5-HTTLPR was significantly lower compared with those with L/L + L/S genotypes. Conclusions: The Val1483Ile polymorphism in the FASN was associated with depressive symptoms under the influence of psychological stress. The S variant of 5-HTTLPR was related with less obese. © 2011 Elsevier B.V. All rights reserved

Upper mantle electrical resistivity structure beneath the central Mariana subduction system

Author Posting. © American Geophysical Union, 2010. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Geochemistry Geophysics Geosystems 11 (2010): Q09003, doi:10.1029/2010GC003101.This paper reports on a magnetotelluric (MT) survey across the central Mariana subduction system, providing a comprehensive electrical resistivity image of the upper mantle to address issues of mantle dynamics in the mantle wedge and beneath the slow back-arc spreading ridge. After calculation of MT response functions and their correction for topographic distortion, two-dimensional electrical resistivity structures were generated using an inversion algorithm with a smoothness constraint and with additional restrictions imposed by the subducting slab. The resultant isotropic electrical resistivity structure contains several key features. There is an uppermost resistive layer with a thickness of up to 150 km beneath the Pacific Ocean Basin, 80–100 km beneath the Mariana Trough, and 60 km beneath the Parece Vela Basin along with a conductive mantle beneath the resistive layer. A resistive region down to 60 km depth and a conductive region at greater depth are inferred beneath the volcanic arc in the mantle wedge. There is no evidence for a conductive feature beneath the back-arc spreading center. Sensitivity tests were applied to these features through inversion of synthetic data. The uppermost resistive layer is the cool, dry residual from the plate accretion process. Its thickness beneath the Pacific Ocean Basin is controlled mainly by temperature, whereas the roughly constant thickness beneath the Mariana Trough and beneath the Parece Vela Basin regardless of seafloor age is controlled by composition. The conductive mantle beneath the uppermost resistive layer requires hydration of olivine and/or melting of the mantle. The resistive region beneath the volcanic arc down to 60 km suggests that fluids such as melt or free water are not well connected or are highly three-dimensional and of limited size. In contrast, the conductive region beneath the volcanic arc below 60 km depth reflects melting and hydration driven by water release from the subducting slab. The resistive region beneath the back-arc spreading center can be explained by dry mantle with typical temperatures, suggesting that any melt present is either poorly connected or distributed discontinuously along the strike of the ridge. Evidence for electrical anisotropy in the central Mariana upper mantle is weak.Japanese participation in the Marianas experiment was supported by Japan Society for the Promotion of Science for Grant-In-Aid for Scientific Research (15340149 and 12440116), Japan-U.S. Integrated Action Program and the 21st Century COE Program of Origin and Evolution of Planetary Systems, and by the Ministry of Education, Culture, Sports, Science, and Technology for the Stagnant Slab Project, Grant-in Aid for Scientific Research on Priority Areas (17037003 and 16075204). U.S. participation was supported by NSF grant OCE0405641. Australian support came from Flinders University. T. M. is supported by the Postdoctoral Scholar Program at the Woods Hole Oceanographic Institution, with funding provided by the Deep Ocean Exploration Institute

Omega-3 Eicosapentaenoic Acid Is Related to Happiness and a Sense of Fulfillment—A Study among Female Nursing Workers

Background: Omega (&omega;) 3 fatty acid (FA) is a polyunsaturated FA (PUFA) that can modulate some mental statuses. However, most studies have not considered the functional differences between eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). We investigated associations among happiness, a sense of fulfillment and serum &omega;3 PUFA levels. Methods: Participants were 133 female staff from a hospital and nursing homes. Happiness was measured using the Japanese version of the subjective happiness scale (SHS); a sense of fulfillment was assessed using a visual analogue scale. Serum FA concentrations were measured. A partial correlation test and a regression model were applied. Results: The SHS scores showed significantly positive correlations with a sense of fulfillment, DHA% and EPA% (p &lt; 0.05, &lt; 0.05 and &lt; 0.005, respectively), after controlling for age, BMI, menopause, snacking habits and leisure-time physical activities. A sense of fulfillment was significantly negatively correlated with &alpha;-linoleic acid%, and positively correlated with DHA% and EPA% (p &lt; 0.05, &lt; 0.05 and &lt; 0.005, respectively), after controlling for the confounders. A regression model showed that a sense of fulfillment, EPA, and not stopping menstruation explained happiness (standardised beta, B = 0.18, p &lt; 0.05; B = 0.24, p &lt; 0.01; and B = 0.32, and p &lt; 0.05, respectively), whereas age, BMI and snacking habits could not. Simultaneously, a regression model could not explain the association between DHA and happiness. Conclusion: Happiness was related with serum EPA%, a sense of fulfillment, and premenopause