Oral administration of (-)catechin protects against ischemia-reperfusion-induced neuronal death in the gerbil

The effect of ad libitum oral-administration of (-)catechin solution on ischemia-reperfusion-induced cell death of hippocampal CA1 in the gerbil was histologically examined. When (-)catechin solution instead of drinking water was orally administered ad libitum for 2 weeks, dose-dependent protection against neuronal death following by transient ischemia and reperfusion was observed. To evaluate the involvement of reduction of reactive-oxygen-species (ROIs) by the antioxidant activity of (-)catechin in this protection, the superoxide scavenging activity of the brain in catechin-treated gerbils was measured by ESR and spin-trapping using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). The superoxide scavenging activities of the brains obtained from catechin-treated gerbils were significantly higher than those of catechin-untreated animals. From these results, it was suggested that orally administered (-)catechin was absorbed, passed through the blood-brain barrier and that delayed neuronal death of hippocampal CA1 after ischemia-reperfusion was prevented due to its antioxidant activities.     

Isolation and characterization of proteoglycans from growing antlers of wapiti (Cervus elaphus)

Proteoglycans were extracted with 4 M guanidine–HCl from the zone of maturing chondrocytes, the site of endochondral ossification of growing antlers of wapiti (Cervus elaphus). Proteoglycans were isolated by DEAE-Sephacel chromatography and separated by Sepharose CL-4B chromatography into three fractions. Fraction I contained a high molecular mass (>1000 kDa) chondroitin sulfate proteoglycan capable of interacting with hyaluronic acid. Its amino acid composition resembled that of the cartilage proteoglycan, aggrecan. Fraction II contained proteoglycans with intermediate molecular weight which were recognized by monoclonal antibodies specific to chondroitin sulfate and keratan sulfate. Fraction III contained a low molecular mass (<160 kDa) proteoglycan, decorin, with a glucuronate-rich glycosaminoglycan chain.     

Gas transport in serpentine microporous tubes under steady and pulsatile blood flow conditions

A serpentine gas exchange unit was built with cylindrical tubular microporous membranes featuring periodic arcs with a fixed curvature ratio (ratio of tube radius to radius of curvature) of 1/14 and circular angles between 30 and 360 deg. Oxygen transfer was measured under steady and pulsatile blood flow conditions in vitro and ex vivo to assess the design features which most effectively augment gas transfer. Under steady blood flow conditions, oxygen transfer increased with circular angles beyond 70 deg. Under pulsatile conditions, a wide range of geometrical and fluid mechanical parameters could be combined to enhance gas transfer performance, which eventually depended upon the secondary Reynolds number and the Womersley parameter.     

YCZ-18 Is a New Brassinosteroid Biosynthesis Inhibitor

Plant hormone brassinosteroids (BRs) are a group of polyhydroxylated steroids that play critical roles in regulating broad aspects of plant growth and development. The structural diversity of BRs is generated by the action of several groups of P450s. Brassinazole is a specific inhibitor of C-22 hydroxylase (CYP90B1) in BR biosynthesis, and the application use of brassinazole has emerged as an effective way of complementing BR-deficient mutants to elucidate the functions of BRs. In this article, we report a new triazole-type BR biosynthesis inhibitor, YCZ-18. Quantitative analysis the endogenous levels of BRs in Arabidopsis indicated that YCZ-18 significantly decreased the BR contents in plant tissues. Assessment of the binding affinity of YCZ-18to purified recombinant CYP90D1 indicated that YCZ-18 induced a typical type II binding spectrum with a K_d value of approximately 0.79 μM. Analysis of the mechanisms underlying the dwarf phenotype associated with YCZ-18 treatment of Arabidopsis indicated that the chemically induced dwarf phenotype was caused by a failure of cell elongation. Moreover, dissecting the effect of YCZ-18 on the induction or down regulation of genes responsive to BRs indicated that YCZ-18 regulated the expression of genes responsible for BRs deficiency in Arabidopsis. These findings indicate that YCZ-18 is a potent BR biosynthesis inhibitor and has a new target site, C23-hydroxylation in BR biosynthesis. Application of YCZ-18 will be a good starting point for further elucidation of the detailed mechanism of BR biosynthesis and its regulation.     

Japanese Lifestyle during Childhood Prevents the Future Development of Obesity among Japanese-Americans

Objective

To evaluate whether a Japanese lifestyle during childhood could protect against the future development of obesity-associated metabolic diseases by comparing native Japanese with Japanese-Americans in whom genetic factors are the same.

Methods

Study subjects were 516 native Japanese and 781 Japanese-Americans who underwent medical examinations between 2007 and 2010. Japanese-Americans were divided into 444 first-generation immigrants (JA-1), who were born in Japan, and 337 second- or later-generation descendants (JA-2), who were born in the United States. The JA-2 group was then divided into the kibei subgroup (N = 79), who had moved to Japan before the age of 18 years and later returned to the United States, and the non-kibei subgroup (N = 258), who had never lived in Japan.

Results

The JA-2 group had the highest percentages of obesity, metabolic syndrome, and type 2 diabetes compared with native Japanese and JA-1. Furthermore, among JA-2, the prevalence of obesity and metabolic syndrome in the kibei subgroup was significantly lower than that in the non-kibei subgroup. The prevalence of diabetes in the kibei subgroup also tended to be lower than in the non-kibei subgroup.

Conclusions

The prevalence of obesity and metabolic diseases differed with residence in Japan during childhood among Japanese-Americans. These findings indicate the possibility that Japanese lifestyle during childhood could reduce the future risks for obesity-associated metabolic diseases.     

Synergy of Omeprazole and Praziquantel In Vitro Treatment against Schistosoma mansoni Adult Worms

BackgroundTreatment and morbidity control of schistosomiasis relies on a single drug, praziquantel (PZQ), and the selection of resistant worms under repeated treatment is a concern. Therefore, there is a pressing need to understand the molecular effects of PZQ on schistosomes and to investigate alternative or synergistic drugs against schistosomiasis.MethodologyWe used a custom-designed Schistosoma mansoni expression microarray to explore the effects of sublethal doses of PZQ on large-scale gene expression of adult paired males and females and unpaired mature females. We also assessed the efficacy of PZQ, omeprazole (OMP) or their combination against S. mansoni adult worms with a survival in vitro assay.ConclusionsFunctional analysis of gene interaction networks is an important approach that can point to possible novel synergistic drug candidates. We demonstrated the potential of this strategy by showing that PZQ in combination with OMP displayed increased efficiency against S. mansoni adult worms in vitro when compared with either drug alone.     

Increase in Ultrasonic Intensity of Blood Speckle across Moderate Coronary Artery Stenosis Is an Independent Predictor of Functional Coronary Artery Stenosis Measured by Fractional Flow Reserve: Pilot Study

Background and Aims

The degree of coronary artery stenosis should be assessed both anatomically and functionally. We observed that the intensity of blood speckle (IBS) on intravascular ultrasound (IVUS) is low proximal to a coronary artery stenosis, and high distal to the stenosis. We defined step-up IBS as the distal minus the proximal IBS, and speculated that this new parameter could be used for the functional evaluation of stenosis on IVUS. The aims of this study were to assess the relationships between step-up IBS and factors that affect coronary blood flow, and between step-up IBS and fractional flow reserve (FFR).

Methods and Results

This study enrolled 36 consecutive patients with angina who had a single moderate stenosis in the left anterior descending artery. All patients were evaluated by integrated backscatter IVUS and intracoronary pressure measurements. FFR was calculated from measurements using a coronary pressure wire during hyperemia. Conventional gray-scale IVUS images were recorded, and integrated backscatter was measured in three cross-sectional slices proximal and distal to the stenosis. Step-up IBS was calculated as (mean distal integrated backscatter value) − (mean proximal integrated backscatter value). Stepwise multiple linear regression analysis showed that the heart rate (r = 0.45, P = 0.005), ejection fraction (r = −0.39, P = 0.01), and hemoglobin level (r = −0.32, P = 0.04) were independently correlated with step-up IBS, whereas proximal and distal IBS were not associated with these factors. There was a strong inverse correlation between step-up IBS and FFR (r = −0.84, P < 0.001), which remained significant on stepwise multiple linear regression analysis.

Conclusions

The newly defined parameter of step-up IBS is potentially useful for the functional assessment of coronary artery stenosis.     

A genome-wide association study for racing performances in Thoroughbreds clarifies a candidate region near the MSTN gene

Using 1400 microsatellites, a genome-wide association study (GWAS) was performed to identify genomic regions associated with lifetime earnings and performance ranks, as determined by the Japan Racing Association (JRA). The minimum heritability (h(2) ) was estimated at 7-8% based on the quantitative trait model, suggesting that the racing performance is heritable. Following GWAS with microsatellites, fine mapping led to identification of three SNPs on ECA18, namely, g.65809482T>C (P=1.05E-18), g.65868604G>T (P=6.47E-17), and g.66539967A>G (P=3.35E-14) associated with these performance measures. The haplotype of these SNPs, together with a recently published nearby SNP, g.66493737C>T (P=9.06E-16) in strong linkage disequilibrium, also showed a very clear association with the performance (P<1E-05). The candidate genomic region contained eight genes annotated by ENSEMBL, including the myostatin gene (MSTN). These findings suggest the presence of a gene affecting the racing performance in Thoroughbred racehorses in this region on ECA18.