著者

Kenta Mizoi Misako Kobayashi Arisa Mashimo Eiko Matsumoto Norio Masuda Manabu Itoh Toshiya Ueno Hidehisa Tachiki Seiichi Ishida Takuo Ogihara

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.45, no.1, pp.150-153, 2022-01-01 (Released:2022-01-01)

参考文献数

26

被引用文献数

1

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The aim of this work is to develop a new assay system for screening biliary excretion drugs. When monolayers of human liver-derived cell lines HepG2 and Huh-7 were grown on an insert membrane, the efflux ratio (ER: ratio of the apparent permeability coefficient in the basal-to-apical direction (Papp,B-to-A) to that in the apical to basal direction (Papp,A-to-B)) of sulfobromophthalein (BSP), a model substrate of multidrug resistance-associated protein 2 (MRP2), was greater than 1.0, indicating transport of BSP in the efflux direction. The efflux transport was significantly suppressed by MK-571, an inhibitor of MRPs, in both cell lines. Expression of MRP2 mRNA in HepG2 and Huh-7 was 3.5- and 1.4-fold higher, respectively, than in primary human hepatocytes, while expression of P-glycoprotein and breast cancer resistance protein mRNAs was markedly lower, supporting the idea that MRP2 is the main mediator of directional BSP transport in this assay system. The advantage of our system is the potential to quantitatively evaluate biliary excretion of MRP2 substrates in vitro.

著者

Risa Hayashi Kenji Nakai Akimune Fukushima Manabu Itoh Toru Sugiyama

出版者

一般社団法人 インターナショナル・ハート・ジャーナル刊行会

雑誌

International Heart Journal (ISSN:13492365)

巻号頁・発行日

vol.50, no.2, pp.161-171, 2009 (Released:2009-04-14)

参考文献数

26

被引用文献数

6 11

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Although ultrasonic diagnostic imaging and fetal heart monitors have undergone great technological improvements, the development and use of fetal electrocardiograms to evaluate fetal arrhythmias and autonomic nervous activity have not been fully established. We verified the clinical significance of the novel signal-averaged vector-projected high amplification ECG (SAVP-ECG) method in fetuses from 48 gravidas at 32-41 weeks of gestation and in 34 neonates. SAVP-ECGs from fetuses and newborns were recorded using a modified XYZ-leads system. Once noise and maternal QRS waves were removed, the P, QRS, and T wave intervals were measured from the signal-averaged fetal ECGs. We also compared fetal and neonatal heart rates (HRs), coefficients of variation of heart rate variability (CV) as a parasympathetic nervous activity, and the ratio of low to high frequency (LF/HF ratio) as a sympathetic nervous activity. The rate of detection of a fetal ECG by SAVP-ECG was 72.9%, and the fetal and neonatal QRS and QTc intervals were not significantly different. The neonatal CVs and LF/HF ratios were significantly increased compared with those in the fetus. In conclusion, we have developed a fetal ECG recording method using the SAVP-ECG system, which we used to evaluate autonomic nervous system development.

著者

Kenji Nakai Junichi Tsuboi Hitoshi Okabayashi Akimune Fukushima Manabu Itoh Hiroshi Kawata Fumihiko Miyake Hiroshi Kasanuki

出版者

International Heart Journal Association

雑誌

International Heart Journal (ISSN:13492365)

巻号頁・発行日

vol.48, no.6, pp.701-713, 2007 (Released:2007-12-27)

参考文献数

23

被引用文献数

15 18 13

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Noninvasive risk stratification is important for screening for lethal arrhythmia. We developed a 187-channel signal-averaged vector-projected high-resolution electrocardiograph (187-ch SAVP-ECG) for detecting abnormalities in the spatial location of ventricular high-frequency late potentials (HFLPs) and ventricular repolarization. The subjects consisted of 30 normal controls (CONTROL) and 13 patients with HFLPs (6 with myocardial infarction [MI], 6 with cardiomyopathy, and 1 with Brugada syndrome). The modified X, Y, Z-lead ECG and the synthesized signals from vector-projected 187-channel ECGs were amplified and passed through a digital filter. We calculated the integration of the HFLPs area between QRSend and 30 ms before QRSend. The integrated HFLPs map was superimposed on the corrected recovery time (RTc) and Tpeak-end dispersion maps composed by 187-ch SAVP-ECG. All patients received an examination by 64-channel magnetocardiography (64-ch MCG) on the same day. The spatial distribution of HFLPs by the 187-ch SAVP-ECG map was in agreement with the location of increased RT dispersion in MI. The spatial distribution of HFLPs in DCM demonstrated a wide variety of patterns. Interestingly, the spatial distribution of HFLPs in cases with ARVC was located at around a right ventricular outflow region. The spatial distribution of HFLPs by 187-ch SAVP-ECG was in agreement with those determined by 64-ch MCG. The 187-ch SAVP-ECG might be useful for evaluating the spatial distribution of nonuniform conduction and ventricular repolarization heterogeneity.

著者

Kenji Nakai Fumihiko Miyake Hiroshi Kasanuki Morio Shoda Keisuke Futagawa Atsushi Takahashi Yuko Matsuyama Takashi Nirei Junichi Tsuboi Hitoshi Okabayashi Manabu Itoh Hiroshi Kawata

出版者

International Heart Journal Association

雑誌

International Heart Journal (ISSN:13492365)

巻号頁・発行日

vol.49, no.2, pp.153-164, 2008 (Released:2008-05-13)

参考文献数

24

被引用文献数

14 16

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The purpose of this study was to verify the spatial distribution of myocardial repolarization heterogeneity using a newly developed 187-channel signal-averaged vector-projected ECG (187-ch SAVP-ECG). We constructed corrected recovery time (RTc) and Tpeak-end (corrected Tp-e) dispersion maps using a 187-ch SAVP-ECG based on vector-projection theory using a Mason-Likar lead system. We compared the spatial distribution and quantitative values of dispersion maps by 187-ch SAVP-ECG with those by 64-ch magnetocardiography (MCG) in 27 normal controls (control) and 16 patients (12 myocardial infarction (MI), and 4 dilated cardiomyopathy (DCM)). The wave pattern of the 187-ch SAVP-ECG in the representative cases was similar to those in 64-ch MCG. Spatial distribution increased RTc and corrected Tp-e dispersion maps defined by 187-ch SAVP-ECG were in agreement with those by 64-ch MCG. The value of RTc dispersion in MI was higher than that in control (41 ± 21 ms in MI versus 30 ± 12 ms in control, P < 0.05). The value of corrected Tp-e dispersion in DCM was higher than that in control (58 ± 12 ms in DCM versus 30 ± 13 ms in control, P < 0.001). There was a good correlation between RTc and corrected Tp-e dispersion values determined by 187-ch SAVP-ECG and 64-ch MCG modalities (y = 0.46x + 18, r = 0.62, P = 0.02 for RTc dispersion; y = 0.52x + 15, r = 0.63, P = 0.01 for corrected Tp-e dispersion). RTc and corrected Tp-e dispersion maps by 187-ch SAVP-ECG based on vector-projection theory can evaluate the spatial distribution of myocardial repolarization heterogeneity.