Suitable Ovariectomy Age for Screening the Functional Agents by Femoral Bone Strength in Osteoporosis Model Rats

Abstract Osteoporosis is a major contributor to the high frequency of bone fracture in elderly women. The ovariectomized (OVX) rat is one of the excellent pre-clinical animal model of osteoporosis. Following ovariectomy, rapid loss of cancellous bone mass and strength occurs. Maximum breaking force of the femoral diaphysis is a major parameter to determine the severity of the osteoporosis directly. Although, the suitable age at ovariectomy remains obscure to evaluate the maximum breaking force of the femoral diaphysis. Accordingly, the suitable rat age at ovariectomy to evaluate the maximum breaking force of the femoral diaphysis for screening of therapeutic or functional agents was determined. Female Sprague-Dawley rats (6, 13 or 30 week-old) were used. Rats of each age were divided into two groups; underwent bilateral OVX and underwent bilateral laparotomy (sham). All rats were fed an AIN93G-based normal diet for further 10 weeks. Reduction of maximum bone strength in femur and increase of body weight gain were observed only in 6 week-old OVX rats after 10-week acclimatization, whereas the difference was obscure in 13 and 30 week-old OVX rats. Therefore, ovariectomy at 6 week-old was the suitable age for osteoporosis model to screen the effects of functional agents in rats

Exaggerated envy and guilt measured by economic games in Japanese women with anorexia nervosa

Background: Anorexia nervosa (AN) patients are assumed to express high levels of guilt and envy. Ultimatum game (UG) is a standard behavioral task that focuses on interpersonal behavior when splitting a sum of money between two players. UG studies consistently demonstrate that people tend to decrease their inequity in outcomes, one explanation being that economically irrational decision-making may partly arise from the emotions guilt and envy. We assumed that AN patients would perform excessively fair in UG, reflecting high guilt and envy. Methods: We utilized UG to investigate the characteristics of guilt and envy among 24 Japanese AN patients and 22 age-matched healthy controls (HC). The relation between the outcome of UG and decision strategy confirmed by post-experimental questionnaires was analyzed. Results: As proposer, AN offered a larger amount to the responder compared with HC (p = 0.002) while, on the other hand, as responder, AN demanded much higher allocation to accept the offer compared with HC (p = 0.026). Regarding the strategy as responder, AN put more emphasis on fairness and less emphasis on monetary reward compared with HC (p = 0.046, p = 0.042, respectively). Conclusions: The results indicate that Japanese AN patients demonstrate strong preference for fairness, with high guilt and high envy. High sensitivity to guilt and envy of AN patients can affect not only their own behavior concerning eating attitude and body shape, but also decision-making in interpersonal situations. Behavioral experimental settings among social situations will enable us to evaluate and help actual decision-making in the real life of patients

A soluble flavonoid-glycoside, alphaG-rutin, is absorbed as glycosides in the isolated gastric and intestinal mucosa.

We investigated the absorption and metabolism of the highly soluble quercetin glycoside αG-rutin, a glucose adduct of insoluble rutin, using the isolated mucosa of the rat stomach and intestines equipped with the Ussing chamber. αG-rutin and rutin appeared in the serosal sides of the gastric body and all the intestinal mucosa after the addition of αG-rutin (1 mM) to the mucosal fluid. The degree of αG-rutin appearance was much lower in the gastric fundus than in the other parts. Quercetin was not found in the mucosal fluid of any mucosal specimen. The concentrations (μM) of αG-rutin and rutin in the serosal fluid as a result of transport from the mucosal side increased time-dependently and linearly with mucosal αG-rutin concentration (1, 10 or 100 mM). The highest transport was shown in the ileal mucosa. These results indicate that αG-rutin is partly hydrolyzed to rutin through the intestine and absorbed as such

Leisure-time physical activity in youth as a predictor of adult leisure physical activity among Japanese workers: a cross-sectional study

Abstract Background Workers in Japan are not sufficiently active; however, it remains unclear how their leisure-time physical activity habits may be developed. This cross-sectional study investigated the relationship of age- and intensity-specific leisure-time physical activity in youth to adulthood leisure-time physical activity habits among Japanese workers. Methods In 2012, 968 workers (333 males and 635 females) from three companies and six hospitals in the Tokai region of Japan agreed to complete and submit a self-administered questionnaire. Intensity-specific leisure-time physical activity at ages 12 and 20 years was assessed retrospectively, and workers’ current participation in regular leisure-time physical activity was assessed as an outcome measure. Multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using logistic regression analysis. Results Mean ages for males and females were 40 and 37 years, respectively. Strenuous leisure-time physical activity at age 12 years was significantly positively associated with adulthood participation in leisure-time physical activity among male workers [adjusted OR (95% CI) = 2.29 (1.02, 5.14)]. Additionally, both strenuous and moderate physical activity at age 20 years was significantly positively associated with participation in regular leisure-time physical activity in adulthood among males and females. Conclusions Our results suggest that some leisure-time physical activity in youth may predict adult workers’ participation in regular leisure-time physical activity in Japan. Encouragement of leisure-time physical activity in youth could therefore be an effective measure to develop adult leisure-time physical activity habits among workers

Functional interaction between cyclooxygenase-2 and p53 in response to an endogenous electrophile

Cyclooxygenase-2 (Cox-2) is rapidly expressed by various stimuli and plays a key role in conversion of free arachidonic acid to prostaglandins. We have previously identified 4-hydroxy-2-nonenal (HNE), a lipid peroxidation-derived electrophile, as the potent Cox-2 inducer in rat epithelial RL34 cells and revealed that the HNE-induced Cox-2 expression resulted from the stabilization of Cox-2 mRNA that is mediated by the p38 mitogen-activated protein kinase signaling pathway. In the present study, we investigated an alternative regulatory mechanism of Cox-2 expression mediated by a transcription factor p53. In addition, to characterize the causal role for Cox-2, we examined the effects of Cox-2 overexpression in RL34 cells. To examine whether the HNE-induced Cox-2 expression was mechanistically linked to the p53 expression, we analyzed changes in Cox-2 and p53 expression levels in response to HNE and observed that the Cox-2 levels were inversely correlated with the p53 levels. Down-regulation of p53 followed by the activation of a transcription factor Sp1 was suggested to be involved in the HNE-induced Cox-2 gene expression. To characterize the effect of Cox-2 expression in the cells, we established the Cox-2-overexpressing derivatives of RL34 cells by stable transfection with Cox-2 cDNA. An oligonucleotide microarray analysis revealed a dramatic down-regulation of the proteasome subunit RC1 in the Cox-2 overexpressed cells compared to the empty-vector transfected control cells. Consistent with the Cox-2-mediated down-regulation of proteasome, a moderate reduction of the proteasome activities was observed. This proteasome dysfunction mediated by the Cox-2 overproduction was associated with the enhanced accumulation of p53 and ubiquitinated proteins, leading to the enhanced sensitivity toward electrophiles. These results suggest the existence of a causal link between Cox-2 and p53, which may represent a toxic mechanism of electrophilic lipid peroxidation products