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2. Abstract 14148: Local Aldosterone Production via StAR in PAH and in Human IPS Cell-derived Cardiomyocytes: Efficacy of Spironolactone in Cardiac Remodeling and Mitochondrial Dynamics Under Hypoxic Stress

Author

Murai, Itsumi, Kaiami, Anyu, Kato, Ryuji, Imano, Hideki, Morihara, Hirofumi, Tomoda, Kiichiro, Asahi, Michio, Ijiri, Yoshio, Yamaguchi, Takehiro, Izumi, Yasukatsu, Yoshiyama, Minoru, Ohta-Ogo, Keiko, Ishibashi-Ueda, Hatsue, and Hayashi, Tetsuya

Published
2020
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3. Tissue Distribution of Cisplatin by Intra-arterial Infusion Route in Comparison to Systemic Route: Implication to Therapy for Node-positive Bladder Cancer

Author

ICHIHASI, ATSUSHI, primary, INAMOTO, TERUO, additional, UCHIMOTO, TAIZO, additional, NAKAMURA, KO, additional, KOMURA, KAZUMASA, additional, YANO, YUSUKE, additional, NISHIMURA, KAZUKI, additional, KINOSHITA, SHOKO, additional, NISHIO, KYOSUKE, additional, FUKUSHIMA, TATSUO, additional, NAKAMORI, KEITA, additional, MATSUNAGA, TOMOHISA, additional, TSUTSUMI, TAKESHI, additional, TSUJINO, TAKUYA, additional, UEHARA, HIROFUMI, additional, TAKAHARA, KIYOSHI, additional, YAMAMOTO, KAZUHIRO, additional, KATO, RYUJI, additional, IJIRI, YOSHIO, additional, HAYASHI, TETSUYA, additional, and AZUMA, HARUHITO, additional

Published
2023
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5. Rivaroxaban Attenuates Right Ventricular Remodeling in Rats with Pulmonary Arterial Hypertension

Author

Imano, Hideki, primary, Kato, Ryuji, additional, Nomura, Atsuo, additional, Tamura, Maki, additional, Yamaguchi, Yudai, additional, Ijiri, Yoshio, additional, Wu, Hong, additional, Nakano, Takashi, additional, Okada, Yoshikatsu, additional, Yamaguchi, Takehiro, additional, Izumi, Yasukatsu, additional, Yoshiyama, Minoru, additional, Asahi, Michio, additional, and Hayashi, Tetsuya, additional

Published
2021
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10. A Novel Analytical Method of Cisplatin Using the HPLC with a Naphthylethyl Group Bonded with Silica Gel (πNAP) Column

Author

Kato, Ryuji, primary, Sato, Takaji, additional, Kanamori, Michiko, additional, Miyake, Mizuho, additional, Fujimoto, Ayumi, additional, Ogawa, Kyohei, additional, Kobata, Daiki, additional, Fujikawa, Tomoya, additional, Wada, Yukari, additional, Mitsuishi, Rintaro, additional, Takahashi, Kodai, additional, Imano, Hideki, additional, Ijiri, Yoshio, additional, Mino, Yoshiki, additional, Chikuma, Masahiko, additional, Tanaka, Kazuhiko, additional, and Hayashi, Tetsuya, additional

Published
2017
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13. Hydrogen gas attenuates embryonic gene expression and prevents left ventricular remodeling induced by intermittent hypoxia in cardiomyopathic hamsters

Author

Kato, Ryuji, primary, Nomura, Atsuo, additional, Sakamoto, Aiji, additional, Yasuda, Yuki, additional, Amatani, Koyuha, additional, Nagai, Sayuri, additional, Sen, Yoko, additional, Ijiri, Yoshio, additional, Okada, Yoshikatsu, additional, Yamaguchi, Takehiro, additional, Izumi, Yasukatsu, additional, Yoshiyama, Minoru, additional, Tanaka, Kazuhiko, additional, and Hayashi, Tetsuya, additional

Published
2014
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14. O-LINKED N-ACETYL GLUCOSAMINE (O-GLCNAC) REGULATES AUTOPHAGY AND APOPTOSIS IN CARDIOMYOCYTES: A DOUBLE-EDGED SWORD IN INTERMITTENT HYPOXIA-INDUCED CARDIAC REMODELING

Author

Hayashi, Tetsuya, primary, Sasaki, Mizuho, additional, Watanabe, Akira, additional, Furukawa, Yuichi, additional, Nomura, Atsuo, additional, Uehashi, Waka, additional, Kato, Ryuji, additional, Ijiri, Yoshio, additional, Nakagawa, Takatoshi, additional, Asahi, Michio, additional, Yamaguchi, Takehiro, additional, Izumi, Yasukatsu, additional, and Yoshiyama, Minoru, additional

Published
2014
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24. Abstract 10404: Mineralocorticoid-Receptor Antagonists Regulate Mitochondrial Dynamics and Local Aldosterone Production Attenuating Right Ventricular Remodeling in Pulmonary Arterial Hypertension

Author

Hayashi, Tetsuya, Kato, Ryuji, Imano, Hideki, Ijiri, Yoshio, Nomura, Atsuo, Asahi, Michio, Wu, Hong, Nakano, Takashi, Yamaguchi, Takehiro, Izumi, Yasukatsu, Yoshiyama, Minoru, Ohta-Ogo, Keiko, and Ishibashi-Ueda, Hatsue

Abstract

Introduction:Pulmonary arterial hypertension (PAH) is a progressive disease that frequently leads to a fetal right ventricular (RV) remodeling. It has been known that the renin-angiotensin-aldosterone system is activated in patients with PAH. The aim of this study was to evaluate the impact ofmineralocorticoid receptor (MR) antagonists on mitochondrial dynamics in the RV myocardium and the expression of steroidogenic acute regulatory protein (StAR) associated with local aldosterone production.Methods:Autopsied heart samples (n=20) were obtained from patients with or without PAH. PAH model rats (n=46) were injected with semaxanib (20 mg/kg) and then exposed to hypoxia and reoxygenation for 4 weeks with/without treatment by spironolactone or eplerenone. Plasma aldosterone concentration was measured by enzyme-linked immunosorbent assay. After hemodynamic measurements, heart was examined by light and electron microscopy, immunohistochemistry, RT-PCR, and Western blot. Human umbilical vein endothelial cells (HUVECs) were cultured under hypoxic conditions (1% O2, 5% CO2) with/without treatment with spironolactone (SPL, 10 ?M).Results:In PAH patients, the expression of StAR and MR was significantly increased in cardiomyocytes and endothelial cells in the RV myocardium. In PAH rats, RV systolic pressure was over 60 mmHg with deteriorated RV function. Under electron microscopy, severe degeneration of mitochondria and capillaries with myofibrillar lysis in the RV myocardium were observed, which were compatible with those findings in PAH patients. The increased expression of MR and StAR in the heart of PAH rats was significantly decreased by MR antagonists. Histologically, SPL increased mitophagy, reducing mitofusin but not dynamin-related protein mRNA expression, preserved ultrastructure, and suppressed cardiomyocyte hypertrophy and interstitial fibrosis in the RV myocardium. In addition, MR antagonists decreased the phosphorylation of ERK-1/2, NF-?B, and Smad3 in HUVECs.Conclusions:MR antagonists attenuate cardiovascular remodeling in PAH through mitochondrial protection and suppression of MR and StAR. This could be a novel therapeutic strategy in patients with severe PAH when used in combination with standard treatment.

Published
2019
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25. Tissue Distribution of Cisplatin by Intra-arterial Infusion Route in Comparison to Systemic Route: Implication to Therapy for Node-positive Bladder Cancer.

Author

Ichihashi A, Inamoto T, Uchimoto T, Nakamura KO, Komura K, Yano Y, Nishimura K, Kinoshita S, Nishio K, Fukushima T, Nakamori K, Matsunaga T, Tsutsumi T, Tsujino T, Uehara H, Takahara K, Yamamoto K, Kato R, Ijiri Y, Hayashi T, and Azuma H

Subjects
Rats, Animals, Infusions, Intra-Arterial, Tissue Distribution, Platinum, Cisplatin therapeutic use, Urinary Bladder Neoplasms drug therapy, Urinary Bladder Neoplasms pathology
Abstract

Background/aim: In clinical practice, platinum-based systemic chemotherapy works to shrink pelvic lymph nodes. Intra-arterial (IA) bolus infusion may result in more favorable results than systemic chemotherapy. In the present study, we investigated the distribution of cisplatin administrated by IA infusion in varying organs, specifically focusing on the node tissue, in comparison with the intravenous (IV) route., Materials and Methods: Under anesthesia, cisplatin 0.42 mg/body was administrated by IA or IV infusion in rats to mimic a balloon-occluded arterial infusion model used in clinical practice. The kidney, bladder, lymphatic tissue, and peripheral blood were extracted to analyze the amount of cisplatin by inductively coupled plasma-mass spectrometry., Results: Concertation of cisplatin by IA infusion was higher than that by the IV route in the peripheral blood and kidney. IA infusion led to a significantly high concentration of cisplatin in the bladder compared to IV infusion (1.3±0.452 vs. 0.2 ppb/mg ± 0.055, p=0.050). Furthermore, the IA method led to an extremely high concentration of cisplatin in the lymphatic tissue compared to the IV method (0.1±0.036 vs. 13.3±5.36, p=0.048)., Conclusion: High cisplatin accumulation in the lymphatic tissue and bladder by IA administration may have a potential role for treating patients with node-positive bladder cancer., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Published
2023
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26. Hydrogen gas attenuates embryonic gene expression and prevents left ventricular remodeling induced by intermittent hypoxia in cardiomyopathic hamsters.

Author

Kato R, Nomura A, Sakamoto A, Yasuda Y, Amatani K, Nagai S, Sen Y, Ijiri Y, Okada Y, Yamaguchi T, Izumi Y, Yoshiyama M, Tanaka K, and Hayashi T

Subjects
Aldehydes pharmacology, Animals, Body Weight drug effects, Cardiomyopathies diagnostic imaging, Cardiomyopathies genetics, Cricetinae, Cysteine Proteinase Inhibitors pharmacology, Gases, Heart Ventricles drug effects, Mesocricetus, Organ Size drug effects, Superoxides metabolism, Ultrasonography, Cardiomyopathies pathology, Gene Expression Regulation, Developmental drug effects, Hydrogen pharmacology, Hypoxia pathology, Ventricular Remodeling drug effects
Abstract

The prevalence of sleep apnea is very high in patients with heart failure (HF). The aims of this study were to investigate the influence of intermittent hypoxia (IH) on the failing heart and to evaluate the antioxidant effect of hydrogen gas. Normal male Syrian hamsters (n = 22) and cardiomyopathic (CM) hamsters (n = 33) were exposed to IH (repeated cycles of 1.5 min of 5% oxygen and 5 min of 21% oxygen for 8 h during the daytime) or normoxia for 14 days. Hydrogen gas (3.05 vol/100 vol) was inhaled by some CM hamsters during hypoxia. IH increased the ratio of early diastolic mitral inflow velocity to mitral annulus velocity (E/e', 21.8 vs. 16.9) but did not affect the LV ejection fraction (EF) in normal Syrian hamsters. However, IH increased E/e' (29.4 vs. 21.5) and significantly decreased the EF (37.2 vs. 47.2%) in CM hamsters. IH also increased the cardiomyocyte cross-sectional area (672 vs. 443 μm(2)) and interstitial fibrosis (29.9 vs. 9.6%), along with elevation of oxidative stress and superoxide production in the left ventricular (LV) myocardium. Furthermore, IH significantly increased the expression of brain natriuretic peptide, β-myosin heavy chain, c-fos, and c-jun mRNA in CM hamsters. Hydrogen gas inhalation significantly decreased both oxidative stress and embryonic gene expression, thus preserving cardiac function in CM hamsters. In conclusion, IH accelerated LV remodeling in CM hamsters, at least partly by increasing oxidative stress in the failing heart. These findings might explain the poor prognosis of patients with HF and sleep apnea., (Copyright © 2014 the American Physiological Society.)

Published
2014
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