Asian Science Citation Index is committed to provide an authoritative, trusted and significant information by the coverage of the most important and influential journals to meet the needs of the global scientific community.  
ASCI Database
308-Lasani Town,
Sargodha Road,
Faisalabad, Pakistan
Fax: +92-41-8815544
Contact Via Web
Suggest a Journal
 
Articles by K Maeda
Total Records ( 3 ) for K Maeda
  M Terashima , Y Ohashi , H Azumi , K Otsui , H Kaneda , K Awano , S Kobayashi , T Honjo , T Suzuki , K Maeda , M Yokoyama and N. Inoue
 

Background— Coronary arterial remodeling, which is a response to the growth of atherosclerotic plaques, is associated with plaque vulnerability. Oxidative stress induced by reactive oxygen species (ROS) via NAD(P)H oxidase in the vasculature also plays a crucial role in the pathogenesis of atherosclerosis-based cardiovascular disease. In this study, the relationship between coronary arterial remodeling and ROS generation was examined by comparing preinterventional intravascular ultrasound findings of atherosclerotic lesions to the histochemical findings of corresponding specimens obtained by directional coronary atherectomy.

Methods and Results— Predirectional coronary atherectomy intravascular ultrasound images of 49 patients were analyzed. The remodeling index was calculated by dividing the target-lesion external elastic membrane cross-sectional area by the reference-segment external elastic membrane cross-sectional area. Expansive remodeling was defined as a remodeling index of >1.0. ROS generation and NAD(P)H oxidase p22phox expression in directional coronary atherectomy specimens were evaluated using the dihydroethidium staining method and immunohistochemistry as the ratio of the positive area to the total surface area in each specimen, respectively. ROS generation and p22phox expression were significantly greater in lesions with expansive remodeling than in lesions without remodeling (0.18±0.12 versus 0.03±0.02, P<0.0001, 0.10±0.08 versus 0.04±0.05, P=0.0039, respectively). Both ROS generation and p22phox expression significantly correlated with the intravascular ultrasound-derived remodeling index (r=0.77, P<0.0001, r=0.53, P<0.0001, respectively).

Conclusions— Simultaneous examination with intravascular ultrasound and immunohistochemistry analyses suggests that NAD(P)H oxidase-derived ROS is related to the coronary arterial remodeling process associated with plaque vulnerability.

  T Watanabe , K Maeda , T Kondo , H Nakayama , S Horita , H Kusuhara and Y. Sugiyama
 

The clearance route and the absolute values for hepatic and renal clearance of drugs are important criteria for the selection of drug candidates. Based on pharmacokinetic theory, by assuming that uptake is the rate-determining process for the biliary excretion of drugs, organ intrinsic clearance should be simply estimated by the intrinsic uptake. In this study, to investigate whether organ clearance can be predicted from the in vitro uptake activity, we performed uptake experiments using isolated hepatocytes and kidney slices, integration plot analyses, and in vivo pharmacokinetic studies using 12 barely metabolized drugs in rats. The in vivo hepatic and renal clearance could be approximated by uptake clearance estimated from integration plot analyses, except for the renal clearance of some drugs that was relatively small. The comparison of intrinsic uptake clearance from in vitro experiments and integration plot studies revealed that in vivo hepatic uptake was well explained by uptake into isolated hepatocytes, whereas in kidney, in vivo uptake clearance was 10 to 100 times that in kidney slices and a scaling factor is required for its prediction from in vitro experiments. The organ clearance and the fraction excreted into urine could be predicted from in vitro studies except for drugs whose renal clearance was relatively small. This study suggests that the uptake process is the determining factor for organ clearance of minimally metabolized drugs, and uptake assays using isolated hepatocytes and kidney slices are useful for evaluating the uptake clearance.

  T Watanabe , K Maeda , T Kondo , H Nakayama , S Horita , H Kusuhara and Y. Sugiyama
 

The clearance route and the absolute values for hepatic and renal clearance of drugs are important criteria for the selection of drug candidates. Based on pharmacokinetic theory, by assuming that uptake is the rate-determining process for the biliary excretion of drugs, organ intrinsic clearance should be simply estimated by the intrinsic uptake. In this study, to investigate whether organ clearance can be predicted from the in vitro uptake activity, we performed uptake experiments using isolated hepatocytes and kidney slices, integration plot analyses, and in vivo pharmacokinetic studies using 12 barely metabolized drugs in rats. The in vivo hepatic and renal clearance could be approximated by uptake clearance estimated from integration plot analyses, except for the renal clearance of some drugs that was relatively small. The comparison of intrinsic uptake clearance from in vitro experiments and integration plot studies revealed that in vivo hepatic uptake was well explained by uptake into isolated hepatocytes, whereas in kidney, in vivo uptake clearance was 10 to 100 times that in kidney slices and a scaling factor is required for its prediction from in vitro experiments. The organ clearance and the fraction excreted into urine could be predicted from in vitro studies except for drugs whose renal clearance was relatively small. This study suggests that the uptake process is the determining factor for organ clearance of minimally metabolized drugs, and uptake assays using isolated hepatocytes and kidney slices are useful for evaluating the uptake clearance.

 
 
 
Copyright   |   Desclaimer   |    Privacy Policy   |   Browsers   |   Accessibility