ABSTRACT
Alzheimer's disease is an irreversible neurological disorder for which there are no effective small molecule therapeutics. A phosphodiesterase 5 (PDE5) inhibitor is a candidate medicine for the treatment of Alzheimer's disease. Rutaecarpine, an indole alkaloid found in Euodiae Fructus, has inhibitory activity for PDE5. Euodiae Fructus contains more evodiamine than rutaecarpine. Therefore, we performed molecular dynamics simulations of the complex of PDE5 and evodiamine. The results showed that the PDE5 and (-)-evodiamine complexes were placed inside the reaction center compared to the case of PDE5 and (+)-evodiamine complex. The binding of (-)-evodiamine to PDE5 increased the root-mean-square deviation and radius of gyration of PDE5. In the PDE5 with (-)-evodiamine complex, the value of the root-mean-square fluctuation of the M-loop, which is thought to be important for activity, increased. This result suggests that (-)-evodiamine may have inhibitory activity.
ABSTRACT
BACKGROUND: Anemia in infancy is still prevalent in developing countries. Commercial iron-fortified complementary foods or iron drops are not available in Japan, and breast-fed infants have a higher risk of anemia. We studied anemia screening in 10-month-old infants to determine whether breast-feeding is a risk factor for anemia. METHODS: Anemia screening was performed during regular health check for 10-month-old children at four local pediatric clinics in Shimane Prefecture, Japan. Venous blood was obtained for complete blood count. The clinical characteristics of each child were obtained via questionnaire. Anemia was defined as hemoglobin <11.0 g/dL. Children were categorized into anemia and no-anemia groups, and univariate analysis was conducted on comparison of the clinical variables. Multivariate logistic regression analysis for anemia was performed to adjust for several clinical variables. RESULTS: We analyzed data in 325 children. On univariate analysis, anemia was associated with breast-feeding, monthly bodyweight gain and gestational week. On multivariate logistic regression analysis, anemia was associated with feeding type and gestational week (OR of partial breast-feeding and formula feeding, 0.446; 95%CI: 0.208-0.957; and 0.223; 95%CI: 0.075-0.660, respectively, compared with exclusive breast-feeding, OR, 1.0; and gestational week, OR, 0.753; 95%CI: 0583-0.972). CONCLUSION: Breast-feeding is an important factor for anemia in 10-month-old Japanese infants. Breast-fed infants after 6 months of age may need iron supplements or iron-fortified complimentary foods.
