著者

Masashi Kitamura Masako Aragane Kou Nakamura Tatsushi Adachi Kazuhito Watanabe Yohei Sasaki

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.41, no.8, pp.1303-1306, 2018-08-01 (Released:2018-08-01)

参考文献数

15

被引用文献数

9

---

Cannabis sativa L. is cultivated worldwide for a variety of purposes, but its cultivation and possession are regulated by law in many countries, necessitating accurate detection methods. We previously reported a DNA-based C. sativa identification method using the loop-mediated isothermal amplification (LAMP) assay. Although the LAMP technique can be used for on-site detection, our previous protocol took about 90 min from sampling to detection. In this study, we report an on-site protocol that can be completed in 30 min for C. sativa identification based on a modified LAMP system. Under optimal conditions, the LAMP reaction started at approximately 10 min and was completed within 20 min at 63°C. It had high sensitivity (10 pg of purified DNA). Its specificity for C. sativa was confirmed by examining 20 strains of C. sativa and 50 other species samples. With a simple DNA extraction method, the entire procedure from DNA extraction to detection required only 30 min. Using the protocol, we were able to identify C. sativa from various plant parts, such as the leaf, stem, root, seed, and resin derived from C. sativa extracts. As the entire procedure was completed using a single portable device and the results could be evaluated by visual detection, the protocol could be used for on-site detection and is expected to contribute to the regulation of C. sativa.

著者

Tomoichiro Asano Midori Fujishiro Akifumi Kushiyama Yusuke Nakatsu Masayasu Yoneda Hideaki Kamata Hideyuki Sakoda

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.30, no.9, pp.1610-1616, 2007-09-01 (Released:2007-09-01)

参考文献数

44

被引用文献数

29 56

---

Inositol phospholipids phosphorylated on D3-position of their inositol rings (3-phosphoinositides) are known to play important roles in various cellular events. Activation of PI (phosphatidylinositol) 3-kinase is essential for aspects of insulin-induced glucose metabolism, including translocation of GLUT4 to the cell surface and glycogen synthesis. The enzyme exists as a heterodimer containing a regulatory subunit and one of two widely-distributed isoforms of the p110 catalytic subunit: p110α or p110β. Activation of PI 3-kinase and its downstream AKT has been demonstrated to be essential for almost all of the insulin-induced glucose and lipid metabolism such as glucose uptake, glycogen synthesis, suppression of glucose output and triglyceride synthesis as well as insulin-induced mitogenesis. Accumulated PI(3,4,5)P3 activates several serine/threonine kinases containing a PH (pleckstrin homology) domain, including Akt, atypical PKCs, p70S6 kinase and GSK.In the obesity-induced insulin resistant condition, JNK and p70S6K are activated and phosphorylate IRS-proteins, which diminishes the insulin-induced tyrosine phosphorylation of IRS-proteins and thereby impairs the PI 3-kinase/AKT activations. Thus, the drugs which restore the impaired insulin-induced PI 3-kinase/AKT activation, for example, by suppressing JNK or p70S6K, PTEN or SHIP2, could be novel agents to treat diabetes mellitus.

著者

Yuka Ono Yukitaka Fukaya Shoji Imai Tohru Yamakuni

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.31, no.6, pp.1199-1204, 2008-06-01 (Released:2008-06-01)

参考文献数

34

被引用文献数

10 20

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Extract of the whole plant, Ajuga decumbens (KE) has long been used in China as a medication for the relief of joint pain. Previously, we proved that KE up-regulated the synthesis of collagen in false aged model rats. In this paper we examined the effects of KE on nitric oxide (NO) production, expression of inducible nitric oxide synthase (iNOS), osteoblast and osteoclast activity. We also investigated whether KE had any anti-osteoporosis or anti-arthritic activity by using ovariectmized mice and adjuvant induced arthritic rats. KE exhibited down-regulation of differentiation into osteoclast and up-regulation of mineralization in osteoblast-like MC3T3-E1 cells in a concentration-dependent manner. NO synthesized by iNOS plays important roles in inflammatory disease and imbalance between bone resorption and bone formation caused by estrogen depletion. KE inhibited expression of iNOS which caused concentration dependent inhibition of NO production. Furthermore, KE prevented brittle bones in ovariectomized mice and swelling of the left hind ankle in adjuvant induced arthritic rats. Therefore, KE improved the balance of bone resorption and bone formation, showing anti-inflammatory effects. Consequently, KE is beneficial for sufferers of bone and joint disease.

著者

Takanori Miyoshi Nobuhiro Misumi Mikako Hiraike Yuki Mihara Takashi Nishino Minako Tsuruta Yosei Kawamata Yoichi Hiraki Aki Kozono Masao Ichiki

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.39, no.12, pp.2009-2014, 2016-12-01 (Released:2016-12-01)

参考文献数

42

被引用文献数

21

---

Cisplatin (CDDP) combination chemotherapy is widely administered to patients with advanced lung cancer. The dose depends on multiple factors, including whether the tumor is non-small-cell lung cancer (NSCLC) or small-cell lung cancer (SCLC). Although efficacy is limited by cisplatin-induced nephrotoxicity (CIN), little is known about the risk factors for this complication. The aim of this study was to identify the risk factors for CIN in patients with advanced lung cancer, both NSCLC and SCLC. We retrospectively reviewed clinical data for 148 patients who underwent initial chemotherapy including CDDP ≥50 mg/m2 per patient per day for the first course at Kyushu Medical Center between October 2010 and September 2013. All data were collected from the electronic medical record system. Nephrotoxicity was defined as an increase in serum creatinine concentration of at least grade 2 during the first course of CDDP chemotherapy, as described by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. CIN was observed in nine patients. Univariate analysis revealed that cardiac disease and lower baseline serum albumin (Alb) values conferred a higher risk of nephrotoxicity (p<0.05). The cut-off value of Alb was 3.8 g/dL, calculated by receiver operating characteristics (ROC) curves. Multivariable logistic regression analysis revealed that cardiac disease (odds ratio=11.7; p=0.002) and hypoalbuminemia (odds ratio=6.99 p=0.025 significantly correlated with nephrotoxicity. In conclusion, cardiac disease and low baseline Alb values are possible risk factors for CIN.

著者

Chao Yu Shanjun Tan Chunyu Zhou Cuilin Zhu Xin Kang Shuai Liu Shuang Zhao Shulin Fan Zhen Yu Ai Peng Zhen Wang

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.39, no.11, pp.1787-1792, 2016-11-01 (Released:2016-11-01)

参考文献数

39

被引用文献数

9

---

Berberine is one of the main active constituents of Rhizoma coptidis, a traditional Chinese medicine, and has long been used for the treatment of gastrointestinal disorders. The present study was designed to investigate the effects of berberine on the intestinal mucosal barrier damage in a rat uremia model induced by the 5/6 kidney resection. Beginning at postoperative week 4, the uremia rats were treated with daily 150 mg/kg berberine by oral gavage for 6 weeks. To assess the intestinal mucosal barrier changes, blood samples were collected for measuring the serum D-lactate level, and terminal ileum tissue samples were used for analyses of intestinal permeability, myeloperoxidase activity, histopathology, malondialdehyde (MDA) level, and superoxide dismutase (SOD) activity. Berberine treatment resulted in significant decreases in the serum D-lactate level, intestinal permeability, intestinal myeloperoxidase activity, and intestinal mucosal and submucosal edema and inflammation, and the Chiu’s scores assessed for intestinal mucosal injury. The intestinal MDA level was reduced and the intestinal SOD activity was increased following berberine treatment. In conclusion, berberine reduces intestinal mucosal barrier damage induced by uremia, which is most likely due to its anti-oxidative activity. It may be developed as a potential treatment for preserving intestinal mucosal barrier function in patients with uremia.

著者

Hiroaki Takahashi Takeshi Chiba Tomohiko Tairabune Yusuke Kimura Go Wakabayashi Katsuo Takahashi Kenzo Kudo

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.37, no.5, pp.853-857, 2014-05-01 (Released:2014-05-01)

参考文献数

12

被引用文献数

1 9

---

It is unknown whether nutritional status influences pain intensity in cancer patients receiving a transdermal fentanyl patch (FP). This study aimed to determine whether nutritional status is associated with pain intensity and to evaluate the influence of changes in nutritional status on pain intensity in cancer patients receiving transdermal FP treatment. We included 92 patients receiving transdermal FP treatment for the first time with switching from oxycodone. The patients were classified into low- and normal-nutrition groups based on their nutritional status, which was assessed according to the Nutrition Risk Screening 2002 (NRS 2002) parameters. The pain intensity of each patient was evaluated by a numeric rating scale (11-point scale from 0 to 10). NRS 2002 score and pain intensity were obtained on day 3 after the FP was applied to the skin. Pain intensities were significantly higher among patients in the low-nutrition group than among patients in the normal-nutrition group. NRS 2002 scores showed a significant positive correlation with the pain intensities. In 52 of 92 patients, who were evaluated using the NRS 2002 score and pain intensity on day 30 after FP application, the changes in NRS 2002 scores were significantly related to changes in pain intensities (odds ratio, 30.0; 95% confidence interval, 4.48–200.97; p=0.0005). These results suggest that an increase in the NRS 2002 score is a risk factor for an increase in pain intensity in cancer patients receiving FP treatment. Malnutrition may lead to poor pain management in cancer patients receiving FP treatment.

著者

Shogo Tokuyama Kazuo Nakamoto

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.34, no.8, pp.1174-1178, 2011-08-01 (Released:2011-08-01)

参考文献数

57

被引用文献数

17 41

---

Fatty acids, which are the essential nutrients for humans, are an important source of energy and an essential component of cell membranes. They also function as signal transduction molecules in a range of biological phenomena. Recently, an increasing number of physiologic and pharmacologic reports on fatty acids have improved our understanding of the association of fatty acids with certain diseases. It has also become apparent that functional properties of fatty acids are modulated by factors such as the amount of individual fatty acid intake and their distribution among organs. Recently, the functional relationship between polyunsaturated fatty acids and pain has been the focus of many studies. Both basic and clinical studies have shown that a dietary intake of n-3 series polyunsaturated fatty acids results in a reduction in the pain associated with rheumatoid arthritis, dysmenorrhea, inflammatory bowl disease, and neuropathy. In addition, levels of n-6 series polyunsaturated fatty acids are high in patients with chronic pain. These results indicate that polyunsaturated fatty acids play a vital role in pain regulation. In this review, we summarize a number of basic and clinical studies on polyunsaturated fatty acids and their association with pain.

著者

Kouji Kowari Iori Hirosawa Hirono Kurai Naoki Utoguchi Makiko Fujii Yoshiteru Watanabe

出版者

公益社団法人日本薬学会

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.25, no.5, pp.678-681, 2002 (Released:2002-05-10)

参考文献数

22

被引用文献数

3 9

---

To determine the effectiveness of human chorionic gonadotropin (hCG) administered rectally, we studied the pharmacokinetics and pharmacodynamics of hCG using a hollow-type suppository. HCG was not detected in plasma when only hCG was administered rectally, even at a higher dose (4000 IU/kg body weight) than intravenous injection, because of its low bioavailability due to high molecular weight or degradation by proteolytic activity. To enhance the rectal absorption of hCG, the effectiveness of its coadministration with α-cyclodextrin (α-CyD), an absorption-enhancing agent, was investigated in male rabbits. HCG was detected in plasma following coadministration of hCG and α-CyD (10 mg/kg body weight) into the rectum. The plasma hCG concentration increased with increasing dose of α-CyD. The AUC0→48 observed after coadministration of hCG and α-CyD at 30 mg/kg body weight was approximately four times higher than that of hCG and α-CyD at 10 mg/kg body weight. HCG at a high concentration induced a rapid increase in the plasma testosterone concentration (74.2±3.4 ng/ml) 2 h after intravenous administration. However, the testosterone concentration 24 h after intravenous administration decreased to the physiological level (approximately 20 ng/ml) which had been observed before such administration. On the other hand, the maximum level of testosterone concentration (40.0±12.6 ng/ml) was observed 24 h after rectal administration of hCG (400 IU/kg body weight) in combination with α-CyD (30 mg/kg body weight). Moreover, the plasma testosterone concentration (31.0±11.4 ng/ml) obtained 72 h after rectal administration tended to be maintained at a higher level than that (14.4±0.9 ng/ml) observed before the administration. These results suggest that the hollow-type suppository as a rectal delivery system of hCG is promising as a new mode of hCG therapy.

著者

Jun Ye Yuping Li Takeki Hamasaki Noboru Nakamichi Takaaki Komatsu Taichi Kashiwagi Kiichiro Teruya Ryuhei Nishikawa Takeshi Kawahara Kazuhiro Osada Kazuko Toh Masumi Abe Huaize Tian Shigeru Kabayama Kazumichi Otsubo Shinkatsu Morisawa Yoshinori Katakura Sanetaka Shirahata

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.31, no.1, pp.19-26, 2008-01-01 (Released:2008-01-01)

参考文献数

86

被引用文献数

57 62

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Vascular endothelial growth factor (VEGF) is a key mediator of tumor angiogenesis. Tumor cells are exposed to higher oxidative stress compared to normal cells. Numerous reports have demonstrated that the intracellular redox (oxidation/reduction) state is closely associated with the pattern of VEGF expression. Electrolyzed reduced water (ERW) produced near the cathode during the electrolysis of water scavenged intracellular H2O2 and decreased the release of H2O2 from a human lung adenocarcinoma cell line, A549, and down-regulated both VEGF transcription and protein secretion in a time-dependent manner. To investigate the signal transduction pathway involved in regulating VEGF expression, mitogen-activated kinase (MAPK) specific inhibitors, SB203580 (p38 MAPK inhibitor), PD98059 (ERK1/2 inhibitor) and JNKi (c-Jun N-terminal protein kinase inhibitor) were applied. The results showed that only PD98059 blocks VEGF expression, suggesting an important role for ERK1/2 in regulating VEGF expression in A549 cells. As well, ERW inhibited the activation of extracellular signal-regulated kinase (ERK) in a time-dependent manner. Co-culture experiments to analyze in vitro tubule formation assay revealed that A549 cell-derived conditioned medium significantly stimulated the formation of vascular tubules in all analyzed parameters; tubule total area, tubule junction, number of tubules, and total tubule length. ERW counteracted the effect of A549 cell-conditioned medium and decreased total tube length (p<0.01). The present study demonstrated that ERW down-regulated VEGF gene transcription and protein secretion through inactivation of ERK.

著者

Yurika Tahara Mikako Fujita Tianli Zhang Dongxing Wang Hiroshi Tateishi Akihiro Togami Perpetual Nyame Hiromi Terasawa Nami Monde Joyce Appiah-Kubi Wright Ofotsu Amesimeku Doaa Husham Majeed Alsaadi Mikiyo Wada Koji Sugimura Sevgi Gezici Halilibrahim Ciftci Faruk Karahan Nazim Sekeroglu Masami Otsuka Tomohiro Sawa Yosuke Maeda Takashi Watanabe Kazuaki Monde

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.11, pp.1535-1547, 2023-11-01 (Released:2023-11-01)

参考文献数

67

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The introduction of combined anti-retroviral therapy (cART) in 1996, along with a continual breakthrough in anti-human immunodeficiency virus-1 (HIV-1) drugs, has improved the life expectancies of HIV-1-infected individuals. However, the incidence of drug-resistant viruses between individuals undergoing cART and treatment-naïve individuals is a common challenge. Therefore, there is a requirement to explore potential drug targets by considering various stages of the viral life cycle. For instance, the late stage, or viral release stage, remains uninvestigated extensively in antiviral drug discovery. In this study, we prepared a natural plant library and selected candidate plant extracts that inhibited HIV-1 release based on our laboratory-established screening system. The plant extracts from Epilobium hirsutum L. and Chamerion angustifolium (L.) Holub, belonging to the family Onagraceae, decreased HIV-1 release and accelerated the apoptosis in HIV-1-infected T cells but not uninfected T cells. A flavonol glycoside quercetin with oenothein B in Onagraceae reduced HIV-1 release in HIV-1-infected T cells. Moreover, extracts from Chamerion angustifolium (L.) Holub and Senna alexandrina Mill. inhibited the infectivity of progeny viruses. Together, these results suggest that C. angustifolium (L.) Holub contains quercetin with oenothein B that synergistically blocks viral replication and kills infected cells via an apoptotic pathway. Consequently, the plant extracts from the plant library of Turkey might be suitable candidates for developing novel anti-retroviral drugs that target the late phase of the HIV-1 life cycle.

著者

Miya Urui Yasuyuki Yamada Akira Nakagawa Fumihiko Sato Hiromichi Minami Nobukazu Shitan

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.10, pp.1494-1497, 2023-10-01 (Released:2023-10-01)

参考文献数

15

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Advancements in synthetic biology have facilitated the microbial production of valuable plant metabolites. However, constructing complete biosynthetic pathways within a single host organism remains challenging. To solve this problem, modular co-culture systems involving host organisms with partial pathways have been developed. We focused on Escherichia coli, a general host for metabolite production, and Pichia pastoris (Komagataella phaffii), a novel synthetic biology host due to its high expression of biosynthetic enzymes. Previously, we reported the co-culture of E. coli cells, which produce reticuline (an important intermediate for various alkaloids) from glycerol, with P. pastoris cells, which produce the valuable alkaloid stylopine from reticuline. However, Pichia cells inhibited E. coli growth and reticuline production. Therefore, we aimed to improve this co-culture system. We investigated the pre-culture time before co-culture to enhance E. coli growth and reticuline production. Additionally, we examined the optimal concentration of Pichia cells inoculated for co-culture and methanol addition during co-culture for the continuous expression of biosynthetic enzymes in Pichia cells. We successfully established an improved co-culture system that exhibited an 80-fold increase in productivity compared to previous methods. This enhanced system holds great potential for the rapid and large-scale production of various valuable plant metabolites.

著者

Fukie Niijima-Yaoita Masahiro Tsuchiya Hiroshi Ohtsu Kazuhiko Yanai Shunji Sugawara Yasuo Endo Takeshi Tadano

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.1, pp.91-97, 2012-01-01 (Released:2012-01-05)

参考文献数

35

被引用文献数

29 30

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Exercise necessitates a large supply of O2 and nutrients and rapid removal of CO2 and waste products. Histamine is a regulator of the microcirculation (which performs these exchanges), suggesting a possible involvement of histamine in exercise. Histamine is released from either mast cells or non-mast cells. In the latter, histamine is newly formed via the induction of histidine decarboxylase (HDC) in response to an appropriate stimulus, and it is released without being stored. Here, in mice, we examined the role of histamine or HDC induction in exercise. Prolonged walking (PW) (in a cylindrical cage turned electrically) increased HDC mRNA and HDC activity in quadriceps femoris muscles. Mice given a histamine H1-receptor antagonist [fexofenadine (peripherally acting) or pyrilamine (peripherally and centrally acting)] or an irreversible HDC inhibitor (α-fluoromethylhistidine) displayed less PW endurance than control mice. Ranitidine (H2-receptor antagonist) tended to reduce endurance. Other histamine-receptor (H3 and H4) antagonists had no significant effects on endurance. Mice deficient in HDC or histamine H1-receptors displayed markedly less endurance than control mice, and HDC activity in the quadriceps femoris of H1-deficient mice was rapidly elevated by PW. Fexofenadine significantly reduced the muscle levels of nitric oxide (NO) metabolites and glycogen after PW. The results support the ideas that (i) histamine is involved in protecting against exercise-induced fatigue or exhaustion, (ii) histamine exerts its protective effect via H1 receptors and the ensuing production of NO in skeletal muscle, and (iii) histamine is provided, at least in part, by HDC induction in skeletal muscles during prolonged exercise.

著者

Deokbae Park

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.2, pp.184-193, 2022-02-01 (Released:2022-02-01)

参考文献数

44

被引用文献数

3

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Bendimidazole anthelmintics (BAs) have gained interest for their anticancer activity. The anticancer activity is mediated via multiple intracellular changes, which are not consistent under different conditions even in the same cells. We investigated the anticancer activity of fenbendazole (FZ, one of BAs) under two different growth conditions. The growth rate of H4IIE cells was dose-dependently decreased by FZ only in actively growing cells but not in fully confluent quiescent cells. Apoptosis-associated changes were also induced by FZ in actively growing cells. Markers of autophagy were not changed by FZ. The number of cells was markedly increased in sub-G1 phase but decreased in S- and G2/M phases by FZ. FZ up-regulated p21 (an inhibitor of cyclin-CDK) but suppressed the expression of cell cycle-promoting proteins (cyclin D1 and cyclin B1). FZ did not affect integrin αV or n-cadherin expression as well as cell migration. Glycolytic changes (glucose consumption and lactate production) and the generation of reactive oxygen species (ROS) were not affected by FZ. Although the activity of mitogen-activated protein kinases (MAPKs) was altered by FZ, the inhibition of MAPKs did not affect the pro-apoptotic activity of FZ. Taken together, FZ selectively suppressed the growth of cells via p21-mediated cell cycle arrest at G1/S and G2/M, and resulted in apoptosis only in actively growing cells but not in quiescent cells. Glucose metabolism, ROS generation, and MAPKs are unlikely targets of FZ at least in H4IIE rat hepatocellular carcinoma cells used in this study.

著者

Chul-Ho Yun Chun-Sik Bae Taeho Ahn

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.39, no.8, pp.1338-1346, 2016-08-01 (Released:2016-08-01)

参考文献数

42

被引用文献数

17 17

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Nanoparticles (NPs) containing cationic monovalent lipids such as 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and N-(1-[2,3-dioleyloxy]propyl)-N,N,N-trimethylammonium chloride (DOTMA), have been widely used for the delivery of nucleic acid such as small-interfering RNA and polypeptide to cells as cancer therapies and vaccine development. Several previous reports have suggested that cationic liposomes induce reactive oxygen species (ROS) and ROS-mediated toxicity in cells. Here, we systematically investigated the effects of DOTAP- or DOTMA-containing NPs without any cargo on the human carcinoma cells, HepG2. Treatment with NPs containing DOTAP or DOTMA increased the production of cellular ROS, such as H2O2 and lipid peroxidation, in HepG2 cells and concomitantly decreased cell viability. These effects were dependent on the lipid concentration, surface density of cationic lipids, and particle size of NPs. However, neutral NPs consisting of 1,2-dioleoyl-3-phosphocholine did not elicit the effective ROS generation or cell death regardless of the lipid concentration and particle size. The present study suggests that DOTAP- and DOTMA-NPs are able to induce cancer cell death through production of ROS in the absence of any therapeutic cancer reagents. These results also provide a rational background for the design of delivery systems using cationic lipid-based NP formulations.

著者

Honoka Fujimori Takuya Ohba Shinsuke Nakamura Masamitsu Shimazawa Hideaki Hara

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.8, pp.1032-1040, 2023-08-01 (Released:2023-08-01)

参考文献数

61

被引用文献数

2

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Parkinson’s disease (PD) is a neurodegenerative disorder characterized by motor symptoms and neuropathological features, such as loss of dopaminergic neurons in the substantia nigra pars compacta and accumulation of alpha-synuclein (α-Syn). Progranulin (PGRN) is a secreted growth factor that exhibits anti-inflammatory properties and regulates lysosomal function. Although autophagy-lysosome pathway is the main degradative pathway for α-Syn, the molecular mechanistic relationship between PD and PGRN remains unclear. In this study, we investigated the role of PGRN in PD pathology. PGRN protein expression in striatum was increased in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model mice. Intracerebroventricular (i.c.v.) administration of PGRN ameliorated the decrease in expression of tyrosine hydroxylase, a dopaminergic neuron marker, in MPTP-treated mice. Furthermore, i.c.v. administration of PGRN ameliorated 6-hydroxydopamine-induced motor deficits. In SH-SY5Y human neuroblastoma cells, 1-methyl-4-phenylpyridinium ion (MPP+), an active metabolite of MPTP, increased α-Syn expression. In contrast, PGRN ameliorated MPP+-induced increase in α-Syn expression. Although PGRN decreased the levels of autophagy-related proteins Sequestosome-1 (p62) and MAP1LC3 (LC3)-II, PGRN did not influence the phosphorylation of AMP-activated protein kinase and mechanistic target of rapamycin, which are also proteins that regulate autophagy. Immunostaining analysis showed that PGRN ameliorated MPP+-induced increase of LC3 puncta, indicator of autophagosome, and co-localization of LC3 and α-Syn. The DALGreen assay showed that PGRN ameliorated MPP+-induced decreasing trend of autolysosomes. These results suggest that PGRN participates in α-Syn degradation via acceleration of the autophagy-lysosome pathway and is a potential therapeutic target for PD.

著者

Koji Nishizawa Kosuke Torii Aya Kawasaki Masanori Katada Minoru Ito Kenzo Terashita Sadakazu Aiso Masaaki Matsuoka

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.30, no.9, pp.1758-1762, 2007-09-01 (Released:2007-09-01)

参考文献数

32

被引用文献数

17 23

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Cordyceps sinensis (CS) has been known as a component of traditional medicines that elicit various biological effects such as anti-fatigue, immunomodulatory, and hypoglycemic actions. Since it has been well-established that fatigue is closely related to depression, we used the tail suspension test (TST) in mice to examine the antidepressant-like effects of hot water extract (HWCS) and supercritical fluid extract (SCCS) of CS. Immobility time in the TST was reduced by administration of SCCS (2.5—10 ml/kg, p.o.) dose-dependently though it was not reduced by treatment with HWCS (500—2000 mg/kg, p.o.). Neither HWCS nor SCCS altered locomotor activity in the open field test, excluding the possibility that the effect of SCCS is due to activation of locomotion. Pretreatment with prazosin (an adrenoreceptor antagonist) or sulpiride (a dopamine D2 receptor antagonist) reduced the effect of SCCS on the immobility time. In contrast, pretreatment with p-chlorophenylalanine (p-CPA, a serotonin synthesis inhibitor) did not alter the anti-immobility effect of SCCS. The last finding is consistent with an additional observation that SCCS had no effect on head twitch response induced by 5-hydroxy-L-tryptophan in mice. Taken altogether, these results suggest that SCCS may elicit an antidepressant-like effect by affecting the adrenergic and dopaminergic systems, but not by affecting the serotonergic system.

著者

Tadahide Furuno Mamoru Nakanishi

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.2, pp.178-183, 2012-02-01 (Released:2012-02-01)

参考文献数

29

被引用文献数

21 30

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Kefir is a traditional fermented milk beverage produced by kefir grains in the Caucasian countries. Kefiran produced by Lactobacillus kefiranofaciens in kefir grains is an exopolysaccharide having a repeating structure with glucose and galactose residues in the chain sequence and has been suggested to exert many health-promoting effects such as immunomodulatory, hypotensive, hypocholesterolemic activities. Here we investigated the effects of kefiran on mast cell activation induced by antigen. Pretreatment with kefiran significantly inhibited antigen-induced Ca2+ mobilization, degranulation, and tumor necrosis factor-α production in bone marrow-derived mast cells (BMMCs) in a dose-dependent manner. The phosphorylation of Akt, glycogen synthase kinase 3β, and extracellular signal-regulated kinases (ERKs) after antigen stimulation was also suppressed by pretreatment of BMMCs with kefiran. These findings indicate that kefiran suppresses mast cell degranulation and cytokine production by inhibiting the Akt and ERKs pathways, suggesting an anti-inflammatory effect for kefiran.

著者

Seira Nishibe-Toyosato Yosuke Ando Nayu Nakasuji Takahiro Hayashi Kaori Ito Hidezo Matsuda Naho Tsujii Masahiro Tsuge Kazuyoshi Imaizumi Kenji Kawada Shigeki Yamada

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.3, pp.505-510, 2023-03-01 (Released:2023-03-01)

参考文献数

25

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Pharmaceutical consultation targeting outpatients at the Fujita Health University Hospital (Japan) provides support to patients undergoing anticancer drug treatment. This study aimed to explore factors that affect the comprehension of cancer chemotherapy among outpatients who received cancer treatment at our hospital. A questionnaire survey was conducted, and comprehension was scored on a scale of 1–5 (1, no comprehension; 5, full comprehension). When factors other than age and sex [the influence of which on comprehension has been reported in previous reports] were noted, differences in comprehension between the questionnaire items were comparatively analyzed according to the presence/absence of the relevant factors. Overall, 536 patients were included. Age (<70 years) and pharmacist interventions were identified as factors contributing to a comprehension score. The levels of comprehension regarding the name of the cancer chemotherapy, content/schedule of the treatment, purposes of the prescribed drugs, and objectives of blood tests were significantly higher in the group that received the pharmaceutical interventions; conversely, the level of comprehension for the self-management of adverse events was significantly lower in this group than in the group that did not receive any pharmaceutical interventions. Age and interventions by the pharmacist affected the comprehension of cancer chemotherapy by patients.

著者

Shunsuke Nashimoto Shungo Imai Mitsuru Sugawara Yoh Takekuma

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.2, pp.230-236, 2023-02-01 (Released:2023-02-01)

参考文献数

32

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The Child–Pugh score is widely used to assess liver function and estimate drug clearance in patients with liver cirrhosis. Recently, the albumin–bilirubin (ALBI) score, which objectively assesses liver function based only on albumin and total bilirubin levels, was developed as a new method. The purpose of this study was to analyze the relationship between the liver function assessment method and the plasma concentration of voriconazole (VRCZ), an antifungal drug for patients with liver cirrhosis. This single-center retrospective study enrolled 159 patients who received VRCZ between 2012 and 2020. In patients administered VRCZ orally, the median concentration to dose (C : D) ratio increased with the progression of Child–Pugh and ALBI grades. Positive correlations between the ALBI score and VRCZ C : D ratio were observed in patients with cirrhosis (r = 0.52 (95% confidence interval, 0.069–0.79); p < 0.05). In addition, a highly negative correlation was observed between the ALBI score and VRCZ daily maintenance dose (r=−0.79 (95% confidence interval, −0.92 to −0.50); p < 0.0001). In contrast, for patients administered VRCZ intravenously, no increase in C : D ratio was observed for both Child–Pugh and ALBI scores compared to the non-liver cirrhosis group. This may be because the injection is often used in severely ill patients, and factors other than impaired liver function may affect the plasma concentrations of VRCZ. In conclusion, the ALBI score was shown to be useful in predicting VRCZ clearance as well as the Child–Pugh score, and the initial dose of VRCZ might be determined according to the ALBI score.

著者

Nozomi Yamamoto Yuji Tanno Yoichi Tanaka Daiki Hira Tomohiro Terada Yoshiro Saito Yuya Yokozawa

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.46, no.3, pp.511-516, 2023-03-01 (Released:2023-03-01)

参考文献数

27

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Pharmacogenetics (PGx) enhances personalized care, often reducing medical costs, and improving patients’ QOL. Unlike single variant analysis, multiplex PGx panel tests can result in applying comprehensive PGx-guided medication to maximize drug efficacy and minimize adverse reactions. Among PGx genes, drug-metabolizing enzymes and drug transporters have significant roles in the efficacy and safety of various pharmacotherapies. In this study, a genotyping panel has been developed for the Japanese population called PGx_JPN panel comprising 36 variants in 14 genes for drug-metabolizing enzymes and drug transporters using a mass spectrometry-based genotyping method, in which all the variants could be analyzed in two wells for multiplex analysis. The verification test exhibited good concordance with the results analyzed using the other standard genotyping methods (microarray, TaqMan assay, or another mass spectrometry-based commercial kit). However, copy number variations such as CYP2D6*5 could not apply to this system. In this study, we demonstrated that the mass spectrometry-based multiplex method could be useful for in the simultaneous genotyping of more than 30 variants, which are essential among the Japanese population in two wells, except for copy number variations. Further study is needed to assess our panel to demonstrate the clinical use of pharmacogenomics for precision medicine in the Japanese population.