Papers - KAWAI Hiroshi
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Hiroshi Kawai, Naoki Takeda, Naoko Kojima, Reiko Iwadate, Naomi Kudo, , Atsushi Mitsumoto
8 86 - 91 2025.06
Authorship：Lead author, Corresponding author Language：English Publishing type：Research paper (scientific journal)
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Hiroshi Kawai, Akihiko Koizumi, Yu Kojima, Naohito Takahashi, Mari Okazaki, Hideshi Natsume, Toshinobu Seki
Japanese Journal of Pharmaceutical Education 8 2024.02
Authorship：Lead author Language：Japanese Publishing type：Research paper (scientific journal)
This study investigated the learning strategies employed by pharmacy students and their impact on academic performance, assessed through objective tests consisting of multiple-choice questions evaluating knowledge of pharmacy and pharmaceutical sciences. A questionnaire survey and factor analysis revealed four learning strategies employed by the students. They were “Overview” of learning content, incorporation of “Daily-life” events, “Construction” of knowledge, and “Memorization” of discrete facts. Overview and Construction strategies align closely with the well-established deep-processing strategies, namely organizational strategy and elaboration strategy. Overview and Daily-life strategies positively correlate with Construction, while Memorization negatively correlates with the other three strategies. These correlations may reflect a difference between the deep-processing and shallow-processing strategies. The adoption of these learning strategies differed for the top performers and lower graders. The top performers exhibited a higher factor score in Construction than the lower graders, whereas the lower graders displayed a higher factor score in Memorization. Construction exhibited a weak but positive correlation with examination scores, while Memorization exhibited a corresponding negative correlation. Daily study hours were slightly longer for top performers; however, the difference was insufficient to conclude that learning hours were crucial for the differences in academic performance. These results underscore the influence of learning strategies on the academic performance of pharmacy students. Deep-processing strategies such as Overview and Construction hold more significant promise for improving their academic performance.
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Clofibric acid increases molecular species of phosphatidylethanolamine containing arachidonic acid for biogenesis of peroxisomal membranes in peroxisome proliferation in the liver. Reviewed
Hiroaki Miura, Hiroki Mizuguchi, Mino Amano-Iwashita, Rie Maeda-Kogure, Akio Negishi, Ayako Sakai, Tomoaki Toyama, Hiroshi Kawai, Atsushi Mitsumoto, Naomi Kudo
Biochimica et Biophysica Acta – Molecular and Cell Biology of Lipids 1866 ( 8 ) 158963 2021.08
Language：English Publishing type：Research paper (scientific journal)
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A single pretreatment with clofibric acid attenuates carbon tetrachloride-induced necrosis, but not steatosis, in rat liver. Reviewed
Yoshihiro Yamakawa, Takaaki Doi, Yoshizumi Naitou, Hiroshi Kawai, Atsushi Mitsumoto, Naomi Kudo, Yoichi Kawashima
Food and Chemical Toxicology 145 111591 2020.11
Language：English Publishing type：Research paper (scientific journal)
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Urinary bile acid shows diurnal fluctuation and phase shift with daytime-restricted feeding in rats. Reviewed
Hiroshi Kawai, Ai Kurokawa, Takuya Ishibashi, Reiko Iwadate, Naomi Kudo, Yoichi Kawashima, Atsushi Mitsumoto
BPB Reports 3 ( 2 ) 60 - 64 2020.03
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)
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The efficacy of a mattress type sleep measuring device in analyzing sleep in healthy university students: comparison with actigraphy. Reviewed
Hiroshi Kawai, Yutaro Togashi, Takuya Ishibashi, Reiko Iwadate, Atsushi Mitsumoto
BPB Reports 2 ( 6 ) 125 - 129 2019.12
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)
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Antidepressants with different mechanism of action show different chronopharmacological profiles in the tail suspension test in mice. Invited
Hiroshi Kawai, Reiko Iwadate, Takuya Ishibashi, Naomi Kudo, Yoichi Kawashima, Atsushi Mitsumoto
Chronobiology International 36 ( 9 ) 1194 - 1207 2019.09
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)
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Reduction in secretion of very low density lipoprotein-triacylglycerol by a matrix metalloproteinase inhibitor in a rat model of diet-induced hypertriglyceridemia Reviewed
Yoichi Kawashima, Yoshihiro Eguchi, Tohru Yamazaki, Minako Karahashi, Hiroshi Kawai, Naomi Kudo
Journal of Pharmacology and Experimental Therapeutics 366 ( 1 ) 194 - 204 2018.07
Language：English Publishing type：Research paper (scientific journal) Publisher：The American Society for Pharmacology and Experimental Therapeutics
Matrix metalloproteinase inhibitors (MMPIs) reduced serum triacylglycerol (TAG) levels in streptozotocin-induced diabetic rats and Zucker fa/fa rats in our previous study. However, the mechanisms underlying TAG reduction by MMPIs remain unclear. The present study aimed to elucidate the mechanism by which F81-1144b, an MMPI, lowers serum TAG levels in an animal model of high-sucrose diet (HSD)-induced hypertriglyceridemia. F81-1144b was repeatedly administered to rats fed HSD, and its effects were evaluated on TAG levels in serum and the liver, very low density lipoprotein (VLDL) secretion, de novo fatty acid (FA) synthesis in the liver, and the expression of genes regulating the metabolism of FA, TAG, and VLDL in the liver and serum. F81-1144b lowered TAG levels in serum and the liver, VLDL-TAG secretion, de novo FA synthesis in the liver, and serum levels of insulin and glucose. F81-1144b suppressed the expression of genes related to the de novo synthesis of FA and TAG, key proteins (lipin 1 and apolipoprotein CIII) responsible for VLDL metabolism, and sterol regulatory element-binding protein-1c and carbohydrate response element-binding protein. F81-1144b little affected the expression of genes related directly to the degradation of TAG or FA, but it upregulated that of gene for uncoupling protein 2 in the liver. These results suggest that MMPIs are a novel type of therapeutic agent for the treatment of hypertriglyceridemia, because the metabolic effects of F81-1144b expected from changes in the expression of genes regulating lipid metabolism would alter metabolism differently from those induced by fibrates, niacin, or n-3 FAs.
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Time of administration of acute or chronic doses of imipramine affects its antidepressant action in rats Reviewed
Hiroshi Kawai, Natsumi Kodaira, Chika Tanaka, Takuya Ishibashi, Naomi Kudo, Yoichi Kawashima, Atsushi Mitsumoto
Journal of Circadian Rhythms 16 ( 1 ) 5 - 5 2018.05
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Ubiquity Press
The pathogenesis and therapeutics of depression are linked to the operation of the circadian system. Here, we studied the chronopharmacological action of a tricyclic antidepressant, imipramine. Male adult Wistar–Hannover rats were administered imipramine acutely or chronically in the morning or in the evening. The antidepressant action of imipramine was analyzed using the forced swim test (FST). A single dose of imipramine (30 mg/kg) in the morning, but not in the evening, reduced immobility and increased climbing in the FST. The plasma concentrations of imipramine and its metabolite, desipramine, were slightly higher in the morning than in the evening, which might explain the dosing time-dependent action of imipramine. Next, we analyzed the effect of chronic imipramine treatment. Rats received imipramine in the morning or in the evening for 2 weeks. The morning treatment resulted in larger effects in the FST than the evening treatment, and was effective at a dose that was ineffective when administered acutely. The levels of brain α-adrenergic receptors tended to decrease after chronic imipramine treatment. Imipramine might interact with noradrenergic neurons, and this interaction might chronically alter receptor expression. This alteration seemed greater in the morning than in the evening, which might explain the dosing time-dependent action of imipramine.
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Short and long photoperiods differentially exacerbate corticosterone-induced physical and psychological symptoms in mice Reviewed
Hiroshi Kawai, Jin Inabe, Takuya Ishibashi, Naomi Kudo, Yoichi Kawashima, Atsushi Mitsumoto
Biomedical Research (Tokyo) 39 ( 1 ) 47 - 55 2018.02
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：Biomedical Research Press
Circadian disruption affects the pathogenesis and development of various diseases. Depression is one of the most common diseases that relate to circadian rhythm. In this study, we analyzed the effects of daily light/dark (LD) conditions on depression and other symptoms, and also analyzed the mixed effects of LD conditions and corticosterone treatment. Male adult C57BL/6 mice were treated with corticosterone in a normal LD cycle of 12 hours light and 12 hours dark (LD12 : 12), short day conditions of 6 hours light and 18 hours dark (LD6 : 18), or long day conditions of 21 hours light and 3 hours dark (LD21 : 3). The activity rhythms of mice in aberrant LD conditions were entrained within 2 weeks. After 6 weeks of exposure, several behavioral tests were conducted. Corticosterone induced body weight gain and depression-like symptoms. The short or long LD conditions had little effect on vehicle-treated mice behavior. However, the aberrant LD conditions exacerbated the corticosterone-induced symptoms. Mice treated with corticosterone in LD6 : 18 showed exacerbated depression-like symptoms in a novelty suppressed feeding test. On the other hand, LD21 : 3 did not show any effects on mood, but enhanced corticosterone-induced body weight gain. These results indicated that aberrant LD conditions could act as an exacerbating factor for corticosterone-induced symptoms, and that short and long photoperiods induce different psychological and physiological changes. This corticosterone + aberrant LD model could be a useful animal model for investigating the effect of LD conditions on depression, obesity, and other symptoms in stressful circumstances.
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Chronopharmacological analysis of antidepressant activity of a dual-action serotonin noradrenaline reuptake inhibitor (SNRI), milnacipran, in rats Reviewed
Hiroshi Kawai, Megumi Machida, Takuya Ishibashi, Naomi Kudo, Yoichi Kawashima, Atsushi Mitsumoto
Biological and Pharmaceutical Bulletin 41 ( 2 ) 213 - 219 2018.02
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：日本薬学会
Biological rhythms are thought to be related to the pathogenesis and therapy of various diseases including depression. Here we investigated the influence of circadian rhythms on the antidepressant activity of the dual-action serotonin-noradrenaline reuptake inhibitor (SNRI) milnacipran. Rats administered milnacipran in the morning (8:00 a.m.; zeitgeber time [ZT]1) or in the evening (8:00 p.m.; ZT13) were analyzed in a forced swim test (FST). At ZT1, the rats' immobility was reduced and the swimming was increased, whereas at ZT13, their climbing was increased. These results suggest that the serotonergic and noradrenergic systems are preferentially affected at ZT1 and ZT13, respectively by milnacipran. We analyzed the plasma and brain levels of milnacipran after administration, and there were no differences between ZT1 and ZT13. The circadian rhythm of monoamine neurotransmitters was analyzed in several brain regions. The serotonin turnover showed rhythms with a peak during ZT18-ZT22 in hippocampus. The noradrenaline turnover showed rhythms with a peak during ZT22-ZT2. There was a difference of approx. 4 hr between the serotonergic and noradrenergic systems. This time difference might be one of the factors that affect the action of milnacipran and contribute to the dosing time-dependent behavioral pattern in the FST.
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Effects of essential oil inhalation on objective and subjective sleep quality in healthy university students Reviewed
Hiroshi Kawai, Saki Tanaka, Chika Nakamura, Takuya Ishibashi, Atsushi Mitsumoto
Sleep and Biological Rhythms 16 ( 1 ) 37 - 44 2018.01
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：日本睡眠学会
Aromatherapy with essential oils is one of the most popular complementary medical tools for improving sleep quality. However, only a few reports have objectively measured the effects of essential oils on sleep. Here, we used objective and subjective measures to analyze the effects of the essential oils of lavender (Lavandula angustifolia) and sweet orange (Citrus sinensis) on the sleep quality of healthy university students. The participants were monitored for 15 consecutive nights as they inhaled lavender oil, sweet orange oil, or neither in a crossover design. Their sleep was monitored objectively by actigraphy, and total sleep time (TST), sleep efficiency, sleep latency, and wake after sleep onset (WASO) were analyzed. Their sleep was analyzed subjectively using Oguri-Shirakawa-Azumi (OSA) sleep inventory scores. Inhalation of an essential oil improved sleep measures only in participants whose sleep quality was poor in the control condition. Lavender seemed more effective than sweet orange in objective measures, especially in improving sleep latency. In the subjective sleep analysis, the essential oils improved sleep maintenance, dreaming, and sleep length in subjects who had poor sleep quality. Sweet orange seemed more effective than lavender in the subjective sleep measures. The difference between the two oils suggests that expectancy bias had little effect on the hypnotic effect of lavender on objective sleep. Although no obvious effect was observed in good sleepers, the inhalation of lavender oil could be effective for helping poor sleepers improve objective sleep quality.
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Disposition of perfluorododecanoic acid in male rats after an oral administration. Reviewed
Kohei Kawabata, Suzuka Tamaki, Eri Kokubo, Yukari Kobayashi, Tomoya Shinohara, Ayako Sakai, Hiroshi Kawai, Atsushi Mitsumoto, Yoichi Kawashima, Naomi Kudo
Fundamental Toxicological Sciences 4 ( 4 ) 179 - 186 2017.07
Language：English Publishing type：Research paper (scientific journal) Publisher：日本毒性学会
The disposition of perfluorododecanoic acid (PFDoA), a perfluorocarboxylic acid with 12 carbon atoms, was studied in male rats. Rats received an oral administration of PFDoA at a dose of 50 mg/kg. The body weights of PFDoA-treated rats were slightly less than those of vehicle-treated control rats. PFDoA administration resulted in an increase in liver weight; it was highest at 5 days after the treatment and gradually decreased thereafter. Higher liver weight was observed until 70 days after the treatment. Concentrations of PFDoA in plasma and various tissues were estimated up to 70 days after dosing. A large amount of PFDoA was found in the liver. The PFDoA concentration was 263.94 ± 32.94 μg/g in the liver; the value was 7.93 times higher than that of serum 5 days after treatment. The hepatic PFDoA amount was found to be 29.63% of the dose. A certain amount of PFDoA was found in the brain and adipose tissues where perfluorocarboxylic acids with less than 11 carbon atoms were sparsely distributed. The half-life of PFDoA was 55.3, 49.3, 52.4, 57.1, and 49.8 days for serum, liver, kidneys, brain, and adipose tissue, respectively. PFDoA increased hepatic levels of mRNA for Cyp4A10, Acot1, and Acox1, target genes of PPARα, suggesting that PFDoA can activate PPARα, as was observed with other PFCAs. Elevated levels of these 3 genes were observed 70 days after treatment, and the levels were less than those at 7 days. The differences between PFDoA and PFCAs with less than 11 carbon atoms were discussed.
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Behavioral and biochemical characterization of rats treated chronically with thioacetamide: proposal of an animal model for hepatic encephalopathy associated with cirrhosis Reviewed
Hiroshi Kawai, Takuya Ishibashi, Naomi Kudo, Yoichi Kawashima, Atsushi Mitsumoto
Journal of Toxicological Sciences 2012.12
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)
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Impairment of heme biosynthesis induces short circadian period in body temperature rhythms in mice Reviewed
Reiko Iwadate, Yoko Satoh, Yukino Watanabe, Hiroshi Kawai, Nomi Kudo, Yoichi Kawashima, Tadahiko Mashino, Atsushi Mitsumoto
American Journal of Physiology Regulatory, Integrative Comparative Physiology 2012.07
Language：English Publishing type：Research paper (scientific journal)
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就寝前の牛乳摂取が睡眠の質に及ぼす影響 Reviewed
渡邉ゆきの、佐藤陽子、河合洋、光本篤史
FOOD FUNCTION 2010.11
Language：Japanese Publishing type：Research paper (scientific journal)
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Efficacy of urine bile acid as a non-invasive indicator of liver damage in rats Reviewed
Hiroshi Kawai, Naomi Kudo, Yoichi Kawashima, Atsushi Mitsumoto
Journal of Toxicological Sciences 2009.02
Authorship：Lead author Language：English Publishing type：Research paper (scientific journal)