著者

Tomoya Tachi Yoshihiro Noguchi Hitomi Teramachi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.43, no.1, pp.77-86, 2020-01-01 (Released:2020-01-01)

参考文献数

38

被引用文献数

2

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Utilization of community pharmacies/pharmacists is important for promoting appropriate self-medication; however, appropriate self-medication via pharmacies/pharmacists has not been well-implemented in Japan. Based on the transtheoretical model of health behavior change, we constructed an Educational Program for Promoting Appropriate Self-medication via Pharmacies and Pharmacists to inform the public about the assistive services of pharmacies/pharmacists regarding self-medication and the use of medication notebooks for self-medications. We then tested the efficacy of the program through a randomized controlled trial. The subjects were residents living around Gifu City, aged 20 years and above, and recruited through posters and pamphlets. The subjects were randomly allocated to a group that received only a medication/health class (control group) or one that received the medication/health class, as well as the educational program (intervention group). A questionnaire was administered immediately before the medication/health class (T1) and 2 months afterwards (T2), which allowed us to evaluate and compare the changes in the two groups’ behavior regarding performing appropriate self-medication via pharmacies/pharmacists. The percentage of people who began consulting with pharmacists concerning self-medication was significantly higher among the intervention group (38.2%, 13/34) than the control group (14.3%, 4/28) (p = 0.047). The percentage of people who began recording details of self-medication in their medication notebooks was significantly higher among the intervention group (38.2%, 13/34) than the control group (10.7%, 3/28) (p = 0.019). The educational program effectively encouraged the public to adopt appropriate self-medication practices to avail the services provided by pharmacies/pharmacists.

著者

Hiroshi Ueda

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.42, no.11, pp.1773-1782, 2019-11-01 (Released:2019-11-01)

参考文献数

67

被引用文献数

4 10

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Currently, only a few medicines have been approved for use in the clinical treatment of chronic pain, but they are not fully satisfying due to their side effects. From the view that radical treatment, rather than simply treating symptoms, is more important in addressing life-long chronic pain, we have been investigating translational research for a mechanism-based medicine to treat pain. Through the characterization of various types of peripheral and central neuropathic pain in mice, we discovered that lysophosphatidic acid (LPA) plays roles in definitive mechanisms of the development and maintenance of neuropathic pain. We found LPA1 receptor- and LPA3 receptor-mediated amplification of LPA production could be a key mechanism underlying the initiation and maintenance of this pain. We have developed stress-induced fibromyalgia models, and have revealed that LPA1 receptor-signaling also plays key roles in the mechanism. Throughout these studies, we found that LPA plays a key role in pain memory, and that LPA1 receptor- and LPA3 receptor-antagonists could reverse the established pain, and thereby cure the disease source of pain.

著者

Setsuo Kinoshita Tadahaya Mizuno Megumi Hori Michiaki Kohno Hiroyuki Kusuhara

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.42, no.12, pp.2069-2075, 2019-12-01 (Released:2019-12-01)

参考文献数

18

被引用文献数

3

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Proteome profiling based on two-dimensional (2D)-DIGE might be a useful tool for investigating drug-like compounds and the mode of action of drugs. However, obtaining data for profiling requires high labor costs, and it is difficult to control the reproducibility of spot positions because 2D-DIGE usually requires large-size glass plates and spot alignments are greatly affected by the quality of DryStrips and polyacrylamide gels (PAGs). Therefore, we have developed a novel platform by employing small size DryStrips and PAGs, and an image analysis strategy based on dual correction of spot alignment and volume. Our system can automatically detect a large number of consistent spots through all images. Cytosol fractions of HeLa cells treated with dimethyl sulfoxide (DMSO) or bortezomib were analyzed, 1697 consistent spots were detected, and 775 of them were significantly changed with the treatment. Deviations between different days and lot sets of DryStrips and PAGs were investigated by calculating the correlation coefficients. The mean values of the correlation between days and lot sets were 0.96 and 0.94, respectively. Clustering analysis of all the treatment data clearly separated the DMSO or bortezomib treated groups beyond day deviations. Thus, we have succeeded in developing an easy-to-handle 2D-DIGE system that can be a novel proteome profiling platform.

著者

Kentaro Ayada Masahiro Tsuchiya Hiroyuki Yoneda Kouji Yamaguchi Hiroyuki Kumamoto Keiichi Sasaki Takeshi Tadano Makoto Watanabe Yasuo Endo

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.40, no.8, pp.1326-1330, 2017-08-01 (Released:2017-08-01)

参考文献数

25

被引用文献数

4

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Recent studies suggest that histamine—a regulator of the microcirculation—may play important roles in exercise. We have shown that the histamine-forming enzyme histidine decarboxylase (HDC) is induced in skeletal muscles by prolonged muscular work (PMW). However, histological analysis of such HDC induction is lacking due to appropriate anti-HDC antibodies being unavailable. We also showed that the inflammatory cytokines interleukin (IL)-1 and tumor necrosis factor (TNF)-α can induce HDC, and that PMW increases both IL-1α and IL-1β in skeletal muscles. Here, we examined the effects (a) of PMW on the histological evidence of HDC induction and (b) of IL-1β and TNF-α on HDC activity in skeletal muscles. By immunostaining using a recently introduced commercial polyclonal anti-HDC antibody, we found that cells in the endomysium and around blood vessels, and also some muscle fibers themselves, became HDC-positive after PMW. After PMW, TNF-α, but not IL-1α or IL-1β, was detected in the blood serum. The minimum intravenous dose of IL-1β that would induce HDC activity was about 1/10 that of TNF-α, while in combination they synergistically augmented HDC activity. These results suggest that PMW induces HDC in skeletal muscles, including cells in the endomysium and around blood vessels, and also some muscle fibers themselves, and that IL-1β and TNF-α may cooperatively mediate this induction.

著者

Hironori Tsuchiya Maki Mizogami Takahiro Ueno Kenji Shigemi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.35, no.6, pp.988-992, 2012-06-01 (Released:2012-06-02)

参考文献数

26

被引用文献数

5 11

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The cardiotoxic effects of local anesthetics increase in cardiac ischemia which is characterized by the tissue pH lowering to 6.5 or less. Apart from the cardiac channel blockade, the membrane interaction has been referred to as another mode of their cardiotoxic action. By using biomimetic membranes, we verified the hypothesis that bupivacaine and lidocaine may increasingly interact with cardiac mitochondrial membranes under ischemia-like acidic conditions. Biomimetic membranes were prepared with different phospholipids and cholesterol to be unilamellar vesicles suspended in buffers of pH 7.4, 6.9, 6.4 or 5.9. Bupivacaine and lidocaine were reacted with the membrane preparations at cardiotoxically relevant concentrations and their membrane interactivities were determined by measuring fluorescence polarization. Both drugs interacted with 100 mol% 1,2-dipalmitoylphosphatidylcholine, peripheral nerve cell-mimetic and cardiomyocyte-mimetic membranes to increase membrane fluidity, although lowering the reaction pH from 7.4 to 5.9 decreased their membrane-fluidizing effects. In cardiomyocyte mitochondria-mimetic membranes containing 20 mol% cardiolipin, however, bupivacaine and lidocaine reversely increased their membrane interactivities at pH 5.9–6.4 compared with pH 7.4. Such increases were greater in anionic phospholipid membranes which consisted of substantial amounts of cardiolipin and phosphatidylserine. Positively charged bupivacaine and lidocaine would form ion-pairs with the negatively charged head-groups of anionic phospholipids under acidic conditions, thereby increasing the induced membrane fluidization. The mitochondrial membrane interactions depending on pH lowering may be, at least in part, responsible for local anesthetic cardiotoxicity enhanced in acidosis associated with cardiac ischemia.

著者

Shiro Hatakeyama Toshihiro Shida Hiroaki Yamaguchi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.42, no.11, pp.1891-1897, 2019-11-01 (Released:2019-11-01)

参考文献数

21

被引用文献数

5

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Onset of severe hyponatremia following cisplatin (CDDP) administration has been previously reported. However, the risk factors associated with hyponatremia still remain unclear. We conducted a retrospective, single-center, case-control study to identify independent risk factors of severe hyponatremia in patients with various types of cancers. Adult patients who received intravenous CDDP administration between January 2012 and December 2017 met the inclusion criteria. The investigators recorded patients’ demographics and clinical information retrospectively, and assessed the lowest serum sodium level within 21 d of the first CDDP administration. Risk factors for grade ≥3 hyponatremia were examined via a logistic regression analysis. Among a total of 472 patients, fifty patients (10.6%) developed grade ≥3 hyponatremia. Univariate analysis revealed that age (≥65 years), presence of small cell lung or esophageal cancer, and lower sodium concentrations in the serum (<138 mEq/L) were significantly associated with grade 3 and 4 hyponatremia. Additionally, multivariable logistic regression analysis showed that the presence of small cell lung cancer (adjusted odds ratio, 3.26; 95% confidence interval (CI), 1.07–10.00) and lower sodium concentrations in the serum (<138 mEq/L) (adjusted odds ratio, 6.18; 95%CI, 3.21–11.90) were independent risk factors of grade 3 and 4 hyponatremia. Thus, serum sodium concentrations in patients with these risk factors should be closely monitored after CDDP administration.

著者

Ken Konaka Takumi Sakurada Tatsuhiko Saito Sachiko Mori Masaki Imanishi Soji Kakiuchi Shuji Fushitani Keisuke Ishizawa

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.42, no.11, pp.1839-1845, 2019-11-01 (Released:2019-11-01)

参考文献数

22

被引用文献数

5

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Uridine 5′-diphospho-glucuronosyltransferase (UGT), a metabolic enzyme of irinotecan active metabolite, has two genetic polymorphisms (UGT1A1*6 and UGT1A1*28). In UGT1A1 homozygous or heterozygous patients, metabolism is delayed and the risk of developing adverse effects is increased, and therefore, dose reduction of irinotecan is considered. However, the specific dose reduction rate of irinotecan for heterozygous patients is uncertain. We studied the necessity of irinotecan dose reduction and its optimal dose in UGT1A1 heterozygous patients with lung cancer. Patients with lung cancer treated with irinotecan in the Tokushima University Hospital or Tokushima Municipal Hospital were included in this study. The dose of irinotecan was evaluated based on the relative dose intensity (RDI). The time to treatment failure (TTF) was defined as the period until treatment change, death, or progressive disease based on response evaluation criteria of solid tumors. We targeted 31 patients treated with irinotecan: 12 wild types (WT), 14 heterozygotes, and 1 complex heterozygote and 4 homozygotes. There was no significant difference in the TTF, but the mean RDI during the entire treatment period was significantly different in the wild type (79%), heterozygous (62%), and complex heterozygous and homozygous groups (46%). In addition, the proportion of patients who completed treatment without dose reduction in the WT group tended to be higher than that in the other groups. For lung cancer patients with UGT1A1 heterozygote types who start irinotecan therapy, reducing the initial dose by approximately 20% might be a safer chemotherapy without decreasing the therapeutic effect.

著者

Mari Hara Nakano Chihiro Udagawa Arata Shimo Yasuyuki Kojima Reiko Yoshie Hisamitsu Zaha Norie Abe Tokiwa Motonari Mikiko Unesoko Kenji Tamura Tatsunori Shimoi Masayuki Yoshida Teruhiko Yoshida Hiromi Sakamoto Ken Kato Taisei Mushiroda Koichiro Tsugawa Hitoshi Zembutsu

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

pp.b19-00527, (Released:2019-10-09)

参考文献数

42

被引用文献数

14

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Trastuzumab has been administered to patients with HER2-positive cancer, however, the cardiotoxicity is identified as one of the life-threatening toxicities. Clinically useful biomarker for trastuzumab-induced cardiotoxicity has been expected to be developed. To identify a novel genetic marker(s) determining the risk of trastuzumab-induced cardiotoxicity, we performed a first genome-wide association study (GWAS) in Japanese population. We enrolled 481 patients who had been treated with trastuzumab and carried out a GWAS using 11 cases (with cardiotoxicity) and 257 controls (without cardiotoxicity). Top 100 single nucleotide polymorphisms (SNPs) which revealed the smallest P values in GWAS (P = 7.60 x 10-7 - 2.01 x 10-4) were further examined using replication samples consisted of 14 cases and 199 controls. The combined analysis of the GWAS and replication study indicated possible association of five loci with trastuzumab-induced cardiotoxicity (rs9316695 on chromosome 13q14.3, rs28415722 on chromosome 15q26.3, rs7406710 on chromosome 17q25.3, rs11932853 on chromosome 4q25, and rs8032978 on chromosome 15q26.3, Pcombined = 6.00 x 10-6, 8.88 x 10-5, 1.07 x 10-4, 1.42 x 10-4, 1.60 x 10-4, respectively). Furthermore, we developed a risk prediction model for trastuzumab-induced cardiotoxicity using the five marker SNPs. The incidence of trastuzumab-induced cardiotoxicity in patients with risk score ≥ 5 was significantly higher (42.5%) compared to that in patients with score ≤ 4 (1.8%) (P = 7.82 x 10-15, odds ratio = 40.0). These findings suggest the potential to improve the ability of physicians to avoid the trastuzumab-induced cardiotoxicity for patients with HER2-positive cancer.

著者

Kaneyasu Nishimura Jun Takahashi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.36, no.2, pp.171-175, 2013-02-01 (Released:2013-02-01)

参考文献数

41

被引用文献数

27 37

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Parkinson’s disease (PD) is one of the candidate diseases for cell transplantation therapy, since successful clinical experiments have accumulated using human fetal tissue grafting for PD patients. Although some grafted PD patients have shown drastic improvements, several issues still remain with regard to using human fetal tissue. This review highlights the recent advances in stem cell technology toward clinical applications using human pluripotent stem cells. In particular, pluripotent stem cells, such as embryonic stem cells and induced pluripotent stem cells (iPSCs), are the focus as a source of cell transplantation therapy that can be used instead of human fetal tissues. Additionally, efficient methods for stem cell maintenance and differentiation have been developed and improved toward the clinical transition. These advances in the basic technologies have helped accelerate the realization of regenerative medicine. We also review the current topics regarding disease modeling and drug screening using iPSC technology. Finally, we also describe the future prospects of these stem cell research fields toward clinical application.

著者

Izumi Morita Hiroyuki Oyama Mayumi Yasuo Kazuhisa Matsuda Kengo Katagi Aya Ito Hiroka Tatsuda Hiroyuki Tanaka Satoshi Morimoto Norihiro Kobayashi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.40, no.2, pp.174-181, 2017-02-01 (Released:2017-02-01)

参考文献数

40

被引用文献数

10 17

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Law enforcement against illicit use of cannabis and related substances requires rapid, feasible, and reliable tools for on-site testing of cannabinoids. Notably, methods based on cannabinoid-specific antibodies enable efficient screening of multiple specimens. Antibody engineering may accelerate development of modern and robust testing systems. Here, we used in vitro affinity maturation to generate a single-chain Fv fragment (scFv) that recognizes with high affinity the psychoactive cannabinoid, Δ9-tetrahydrocannabinol (THC). A mouse monoclonal antibody against THC, Ab-THC#33, with Ka 6.2×107 M−1 (as Fab fragment) was established by the hybridoma technique. Then, a “wild-type” scFv (wt-scFv) with Ka, 1.1×107 M−1 was prepared by bacterial expression of a fusion gene combining the VH and VL genes for Ab-THC#33. Subsequently, random point mutations in VH and VL were generated separately, and the resulting products were assembled into mutant scFv genes, which were then phage-displayed. Repeated panning identified a mutant scFv (scFv#m1-36) with 10-fold enhanced affinity (Ka 1.1×108 M−1) for THC, in which only a single conservative substitution (Ser50Thr) was present at the N-terminus of the VH-complementarity-determining region 2 (CDR2) sequence. In competitive enzyme-linked immunosorbent assay (ELISA), the mutant scFv generated dose–response curves with midpoint 0.27 ng/assay THC, which was 3-fold lower than that of wt-scFv. Even higher reactivity with a major THC metabolite, 11-nor-9-carboxy-Δ9-tetrahydrocannabinol, indicated that the mutant scFv will be useful for testing not only THC in confiscated materials, but also the metabolite in urine. Indeed, the antibody fragment is potentially suitable for use in advanced on-site testing platforms for cannabinoids.

著者

Shunsuke Nakamori Jun Takahashi Sumiko Hyuga Jinwei Yang Hiroaki Takemoto Takuro Maruyama Naohiro Oshima Nahoko Uchiyama Yoshiaki Amakura Masashi Hyuga Takashi Hakamatsuka Yukihiro Goda Hiroshi Odaguchi Toshihiko Hanawa Yoshinori Kobayashi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.42, no.9, pp.1538-1544, 2019-09-01 (Released:2019-09-01)

参考文献数

34

被引用文献数

12

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The analgesic effect of Ephedra Herb (EH) is believed to be derived from the anti-inflammatory action of pseudoephedrine (Pse). We recently reported that ephedrine alkaloids–free EH extract (EFE) attenuates formalin-induced pain to the same level as that achieved by EH extract (EHE), which suggests that the analgesic effect of EH may not be due to ephedrine alkaloids (EAs). To examine the contribution of EAs to the analgesic effect of EH, mice were injected with formalin to induce a biphasic pain reaction (first phase, 0–5 min; second phase, 10–45 min) at various time points after oral administration of the following test drugs: ephedrine (Eph), Pse, “authentic” EHE from Tsumura & Co. (EHE-Ts), EFE, and EHE that was used as the source of EFE (EHE-To). Biphasic pain was suppressed at 30 min after administration of Eph, EHE-Ts, and EHE-To. At 6 h after administration of EFE, EHE-To, and Pse—and at 4 to 6 h after administration of EHE-Ts—only second-phase pain was suppressed; however, the effect of Pse at 6 h was not significant. These results suggested that EHE has a biphasic analgesic effect against biphasic formalin-induced pain: in the first phase of analgesia (30 min after administration), biphasic pain is suppressed by Eph; in the second phase of analgesia (4–6 h after administration), second-phase pain is alleviated by constituents other than EAs, although Pse may partially contribute to the relief of second-phase pain.

著者

Xiaoying Yu Xindi Zhang Hua Jin Zhiwei Wu Chunlu Yan Zhijun Liu Xinghua Xu Shuangfang Liu Feifei Zhu

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.42, no.9, pp.1482-1490, 2019-09-01 (Released:2019-09-01)

参考文献数

44

被引用文献数

23

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Zhengganxifeng decoction (ZGXFD) is a traditional Chinese medicinal formula, from “Medical Zhong parameter West recorded” by Xichun Zhang, which has been applied to the treatment of clinical essential hypertension. Besides its effect in blood pressure reduction, ZGXFD is also known to be a radical therapy with little or no side effects. Compared with western medicines, Chinese medicinal formulas have the advantage of simultaneously attacking multiple targets. However, such a property brings trouble to the pharmacological studies of Chinese medicines. This study investigated the composition of gut microbiota in spontaneously hypertensive rats (SHR) treated with ZGXFD. ZGXFD was shown to cause similar effects in the treatment group as benazepril: both were able to reduce in SHR the microbial diversity, Firmicutes to Bacteroidetes (F/B) ratio and coccus to bacillus (C/B) ratio. Meanwhile, ZGXFD can maintain the integrity of intestinal mechanistic barrier and elevate the percentage of bacteria producing short chain fatty acids (SCFA). By investigating renin–angiotensin system (RAS) system, we found that ZGXFD can decrease the expression of angiotensin-converting-enzyme (ACE) in lungs, which in turn causes a increase in AngI produces angiotensin1–7 (Ang1–7) and decrease in AngII. ZGXFD regulate blood pressure in SHR via RAS.

著者

Keita Hirai Toshihiro Shirai Yuya Suzuki Tatsuki Shimomura Kunihiko Itoh

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

pp.b19-00385, (Released:2019-09-03)

参考文献数

39

被引用文献数

2

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Vitamin D has an immune-modulating effect, related to the pathophysiology of asthma and chronic obstructive pulmonary disease (COPD). However, few studies have focused on the difference between patients with asthma and COPD in the association of circulating vitamin D levels with clinical outcomes. We sought to investigate the associations of circulating vitamin D levels with health-related quality of life (HR-QOL), severity, and exacerbations. Subjects included 152 asthma patients and 50 COPD patients. We measured plasma concentrations of 25-hydroxyvitamin D3 [25(OH)D3]. HR-QOL was assessed using the EuroQoL 5-Dimension (EQ-5D) and the 12-item Short Form Health Survey (SF-12) scales. Exacerbations were recorded during a one-year follow-up. Associations between plasma 25 (OH)D3 concentrations and outcome variables were evaluated using linear regression. Plasma concentrations of 25(OH)D3 were positively associated with the EQ-5D index value and the SF-12 physical component score in patients with asthma; however, such associations were not observed in patients with COPD. A significant association between severity and plasma concentrations of 25(OH)D3 was found only in patients with COPD. The hazard ratios (95% confidence interval) of plasma 25(OH)D3 concentrations (per 1 ng/mL decrease) for time to first exacerbation was 1.38 (1.10–1.75; p = 0.006) and 0.95 (0.87–1.03; p = 0.179) in patients with COPD and asthma, respectively. Lower concentrations of plasma 25(OH)D3 contributed to lower HR-QOL in patients with asthma, and were associated with severity and risk of future exacerbations in patients with COPD.

著者

Keita Hirai Toshihiro Shirai Yuuka Rachi Sekiko Uehara Megumi Ueda Eiji Nakatani Kunihiko Itoh

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

pp.b19-00476, (Released:2019-08-06)

参考文献数

33

被引用文献数

9

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Genetic variations in glucocorticoid-induced transcript 1 (GLCCI1) have been associated with the response to corticosteroid treatment. However, the associations of GLCCI1 polymorphisms or gene expression with the prognosis of asthma and pathophysiological factors related to steroid insensitivity remain unclear. We sought to investigate the associations of GLCCI1, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and histone deacetylase 2 (HDAC2) mRNA expression levels and the GLCCI1 rs37973 polymorphism with asthma severity and future exacerbation in patients with asthma. Subjects included 25 patients with severe asthma and 127 patients with nonsevere asthma. mRNA expression levels in peripheral blood mononuclear cells were measured and evaluated as predictors of severe asthma using receiver operating characteristic (ROC) analysis. The hazard ratios of the mRNA expression levels for time to first exacerbation in the 1-year follow-up period were calculated. GLCCI1, Nrf2, and HDAC2 mRNA expression levels were significantly lower in patients with severe asthma than in patients with nonsevere asthma and could predict severe asthma with an area under the ROC curve of 0.68, 0.71, and 0.65, respectively. In contrast, no relationship was found between the GLCCI1 rs37973 polymorphism and severe asthma. The hazard ratios for asthma exacerbation in patients with low GLCCI1, Nrf2, and HDAC2 mRNA expression levels were 3.24 (95% confidence interval, 1.42–7.40), 3.13 (1.37–7.16), and 2.98 (1.22–7.25), respectively. Patients with severe asthma could be distinguished by lower GLCCI1, Nrf2, and HDAC2 mRNA levels in peripheral blood cells, and all of these gene signatures could predict future asthma exacerbations.

著者

Tomoaki Ishida Michiro Iizuka Yanglan Ou Shunpei Morisawa Ayumu Hirata Yusuke Yagi Kohei Jobu Yasuyo Morita Mitsuhiko Miyamura

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.42, no.7, pp.1128-1133, 2019-07-01 (Released:2019-07-01)

参考文献数

33

被引用文献数

7

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In diabetic patients, skeletal muscle atrophy occurs due to increased oxidative stress and inflammation. Skeletal muscle atrophy reduces the QOL of patients and worsens life prognosis. Therefore, development of preventive therapy for muscle atrophy in hyperglycemic state is eagerly awaited. Juzentaihoto is a medicinal herb that has a function to supplement physical strength, and it is expected to prevent muscle atrophy. To determine the preventive effect of juzentaihoto on muscle atrophy in hyperglycemic state, streptozotocin (STZ) was administered to induce diabetes in mice and the preventive effect of juzentaihoto was evaluated. Mice that received juzentaihoto extract (JTT) showed that the decrease in muscle fiber cross-sectional area in the gastrocnemius muscle was reversed. Additionally, the expression level of tumor necrosis factor α (TNF-α), an inflammatory cytokine, in serum decreased, and that of ubiquitin ligase (atrogin-1, muscle RING-finger protein-1) mRNA in skeletal muscle decreased. An anti-inflammatory cytokine interleukin-10 showed increased levels in the serum and increased levels in spleen cell culture supernatant collected from mice that received JTT. JTT had no effect on the blood glucose level. These results suggest that prophylactic administration of JTT to STZ-induced diabetic mice affects immune cells such as in spleen, causing an anti-inflammatory effect and inhibiting excessive activation of the ubiquitin-proteasome system, to reverse muscle atrophy.

著者

Unno Keiko Kishido Takahiro Hosaka Maho OKADA Shoji

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.20, no.12, pp.1240-1244, 1997-12-15

被引用文献数

1 8

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To investigate the role of constitutive hsp70 in protein folding and to probe the supplementation by other hsps in this folding, yeast cells expressing reduced constitutive hsp70 proteins, ssa1ssa2,were transformed with a plasmid expressing a bacterial luciferase protein. With several independent clone cells of transformants, the levels of luciferase activity and some hsps, such as hsp104,hsp90,hsp70 and hsp26,were examined. The luciferase activity was significantly lower in ssa1ssa2 transformants than in the wild type (wt) cell transformed with the same plasmid. Among several clone cells of ssa1ssa2,the cells with higher luciferase activities exhibited higher amounts of Ssa4 which is known to be expressed instead of lacking Ssa1 and Ssa2. The luciferase activity closely correlated with the amount of Ssa proteins, more than with the amount of other hsps. It is suggested that consitutional Ssa "chaperones" are needed for the folding of proteins and, in cells lacking Ssa1 and Ssa2,the increased Ssa4 is thought to partly compensate for their role in the folding of luciferase in vivo.

著者

Unno Keiko Kishido Takahiro Okada Shoji

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.21, no.6, pp.631-633, 1998-06-15

被引用文献数

1 4

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Mammalian small heat shock protein (s-hsp) has been suggested to participate not only in stress tolerance but also in the growth regulation and differentiation of cells. To confirm the role of s-hsp in cell growth, we investigated the relationship between the expression of hsp26 and yeast cell growth. Cells lacking constitutive hsp70,ssa1ssa2,have been known to have a poor growth rate and to over-express hsp26 and some other hsps. We obtained several cell clones of ssa1ssa2 whose doubling times were different from one another. The amount of hsp26 was closely linked to the doubling time of ssa1ssa2 cells. This result suggests that the expression of hsp26 modulates the growth rate of yeast cells lacking constitutive hsp70,similarly to mammalian cells.

著者

Jeon Jeong-Ryae Kim Jong-Yeon

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.29, no.10, pp.2111-2115, 2006-10-01

参考文献数

19

被引用文献数

1 28

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The present study examined the anti-obesity effects of pine needle extract (PNE) in 3T3-L1 preadipocytes and <i>in vivo</i> studies. PNE treatment suppressed both glycerol-3-phosphate dehydrogenase activity and expression of peroxisome proliferator-activated receptor (PPAR) &gamma; in cultured 3T3-L1 adipocytes. To investigate the effect of PNE on obesity in rats fed high-fat diet, four types of diet, which included a normal diet (ND), high-fat diet (HFD), ND+PNE, and HFD+PNE diets, were fed to the rats <i>ad libitum</i> for 6 weeks. The PNE supplement significantly decreased body weight gain and visceral fat mass compared to the HFD group. The total cholesterol, TG, and leptin levels in the plasma were significantly reduced by PNE supplementation compared with those of the HFD group. Histological findings in liver tissue showed that PNE supplementation alleviated steatosis induced by HFD. In conclusion, PNE treatment suppressed differentiation of 3T-L1 adipocytes, in part by down-regulating expression of PPAP&gamma; mRNA, and reduced adipose tissue mass, hyperlipidemia, and hepatic steatosis in obese rats fed HFD. Therefore, pine needle water extract may be considered for use in therapy to control obesity.

著者

Harada Shigeyoshi Haneda Eiji Maekawa Toshiro MORIKAWA Yuko FUNAYAMA Shinji NAGATA Nobuyuki OHTSUKI Kenzo

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.22, no.10, pp.1122-1126, 1999-10-15

参考文献数

18

被引用文献数

7 33

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The physiological significance of the casein kinase II (CK-II)-mediated phosphorylation of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on its three enzymatic activities [RNA-dependent DNA polymerase (RDDP), DNA-dependent DNA polymerase (DDDP) and ribonuclease H (RNase H)] was investigated in vitro. It was found that (i) the purified recombinant RT (rRT) functioned as an effective phosphate acceptor for CK-II; (ii) the RDDP, DDDP and RNase H activity of rRT was stimulated about 2.8-, 4.1- and 3.9-fold, respectively, after full phosphorylation by CK-II; and (iii) this stimulation was selectively inhibited by potent CK-II inhibitors, such as neocarzinostatin-chromophore (NCS-chrom) and three polyphenol-containing anti-oxidant compounds [quercetin, epigallocatechin gallate (EGCG) and 8-chloro-3', 4', 5,7-tetrahydroxyisoflavone (8C-3', 4', 5,7-THI)]. These results suggest that (i) CK-II may be responsible for activation of RT in HIV-1-infected cells; and (ii) the selective inhibition of CK-II-mediated activation of HIV-1 RT by potent CK-II inhibitors may be involved in the mechanism of their anti-HIV-1 effects at the cellular level.

著者

尾崎 幸紘

出版者

公益社団法人日本薬学会

雑誌

Biological & pharmaceutical bulletin (ISSN:09186158)

巻号頁・発行日

vol.18, no.4, pp.559-562, 1995-04-15

参考文献数

23

被引用文献数

5 40

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This study was carried out to examine the antiinflammatory effect of aqueous extracts of Kakkon-to (K), Kakkon-oren-ogon-to (KO), Kikyo-to (KK), Haino-to (H), Haino-san (HS), Mao-to (M) and Senkinkeimei-san (SK), which have been used for the treatment of stomatitis, tonsillitis, cold and chronic inflammatory diseases, and to elucidate the mode of their effects. Oral administration of K, KO, KK, H, HS, M and SK inhibited dose-dependently the increase of dye leakage induced by acetic acid in mice. Further antiinflammatory study was carried out on KK, H and HS which showed potent inhibition. All three extracts significantly inhibited the carrageenin-induced edema and the cotton pellet-induced granuloma formation. From these results, it is suggested that KK, H and HS may inhibit both the early exudative stage and the late proliferative stage in inflammatory processes. These extracts are comprised of Platycodon root as do other crude drugs, and the root may be partly responsible for the antiinflammatory effects induced.