著者

津島 己幸 真岡 孝至 勝山 政明 小塚 睦夫 松野 隆男 徳田 春邦 西野 輔翼 岩島 昭夫

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.18, no.2, pp.227-233, 1995-02-15 (Released:2008-04-10)

参考文献数

26

被引用文献数

43 77

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As a screening study for anti-tumor promoters, 51 carotenoids with diverse structures were examined for their inhibitory effects on the Epstein-Barr virus activation activity of 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells. The results showed that most of the carotenoids exhibited inhibitory activity, and in general, no cytotoxicity on Raji cells was observed in the assay. Among the carotenoids, β-cryptoxanthin, lutein, and lactucaxanthin showed the strongest inhibitory activity, superior to the well known anti-tumor promoter, β-carotene. Heteroxanthin, peridinin, and halocynthiaxanthin showed cytotoxicity at the high concentration (1000 molar ratio per TPA), but indicated a strong inhibitory effect at the lower concentrations, which were only weakly toxic (500 and 100 molar ratios). Based on these results, the essential moiety for the activity of carotenoids was considered to be the 3-hydroxy-ε-end group.

著者

Hitomi Ozawa Atsushi Imaizumi Yoshihiko Sumi Tadashi Hashimoto Masashi Kanai Yuji Makino Takanori Tsuda Nobuaki Takahashi Hideaki Kakeya

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.40, no.9, pp.1515-1524, 2017-09-01 (Released:2017-09-01)

参考文献数

50

被引用文献数

35

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Curcumin, a polyphenol derived from the rhizome of the naturally occurring plant Curcuma longa, has various pharmacological actions such as antioxidant and anti-inflammatory effects. In this paper, we evaluated the role of its internal metabolite, curcumin β-D-glucuronide (curcumin monoglucuronide, CMG), by investigating curcumin kinetics and metabolism in the blood. Firstly, we orally administered highly bioavailable curcumin to rats to elucidate its kinetics, and observed not only the free-form of curcumin, but also, curcumin in a conjugated form, within the portal vein. We confirmed that curcumin is conjugated when it passes through the intestinal wall. CMG, one of the metabolites, was then orally administered to rats. Despite its high aqueous solubility compared to free-form curcumin, it was not well absorbed. In addition, CMG was injected intravenously into rats in order to assess its metabolic behavior in the blood. Interestingly, high levels of free-form curcumin, thought to be sufficiently high to be pharmacologically active, were observed. The in vivo antitumor effects of CMG following intravenous injection were then evaluated in tumor-bearing mice with the HCT116 human colon cancer cell line. The tumor volume within the CMG group was significantly less than that of the control group. Moreover, there was no significant loss of body weight in the CMG group compared to the control group. These results suggest that CMG could be used as an anticancer agent without the serious side effects that most anticancer agents have.

著者

Mitsuyoshi Okita Yuki Yayoshi Kousuke Ohara Akio Negishi Hayato Akimoto Naoko Inoue Sachihiko Numajiri Shigeru Ohshima Seiichi Honma Shinji Oshima Daisuke Kobayashi

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

pp.b17-00340, (Released:2017-08-04)

参考文献数

21

被引用文献数

3

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Kakkonto (KK), a traditional Japanese Kampo formulation for cold and flu, is generally sold as an over-the-counter (OTC) pharmaceuticals used for self-medication. Kampo formulations should be used according to the Sho-symptoms of Kampo medicine. These symptoms refer to the subjective symptoms themselves. Although with OTC pharmaceuticals, this is often not the case. We surveyed the relationship of agreement of Sho with the benefit feeling rate (BFR) of patients who took KK (n = 555), cold remedies with KK (CK, n = 315), and general cold remedies (GC, n = 539) using internet research. BFR of a faster recovery was greater in participants who took the medication early and who had confidence in their physical strength in all treatment groups. BFR was significantly higher in the GC group than in the KK group for patients with headache, runny nose, blocked nose, sneezing, and cough. BFR was also significantly higher in the GC group than in the CK group for headache (males) and cough (females). BFR was the highest in the KK group for stiff shoulders. All cold remedies were more effective when taken early, and the larger the number of Sho that a patient had, the greater the BFR increased. Therefore, a cold remedy is expected to be most effective when there are many cold symptoms and when it is taken at an early stage of the common cold.

著者

Mina Thon Toru Hosoi Chanbora Chea Koichiro Ozawa

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.40, no.8, pp.1161-1164, 2017-08-01 (Released:2017-08-01)

参考文献数

37

被引用文献数

6

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The lack of response to leptin’s actions in the brain, “leptin resistance,” is one of the main causes of the pathogenesis of obesity. However, although high-fat diets affect sensitivity to leptin, the underlying mechanisms of leptin resistance are still an enigma. Here we examined the effect of excess saturated fatty acids (SFAs) on leptin signaling in human neuronal cells. Palmitate, the principle source of SFAs in diet, induced leptin resistance in a human neuroblastoma cell line stably transfected with the Ob-Rb leptin receptor (SH-SY5Y-ObRb). We next investigated the function of stearoyl-CoA desaturase-1 (SCD1), an enzyme which converts SFAs into monounsaturated fatty acids (MUFAs), on leptin-induced signaling. We found that reduction of SCD1 activity, through SCD1 inhibition and knockdown, impairs leptin-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation in human neuronal cells. Our findings suggested that SCD1 plays a key role in the pathophysiology of leptin resistance in neuronal cells associated with obesity.

著者

Ryota Tanaka Yuhki Sato Koji Goto Norihisa Yasuda Yoshifumi Ohchi Yosuke Suzuki Tamio Ueno Kentaro Ito Tetsuya Kaneko Shusaku Kurogi Ko Nonoshita Hiroki Itoh

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.40, no.8, pp.1226-1231, 2017-08-01 (Released:2017-08-01)

参考文献数

28

被引用文献数

6

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Doripenem (DRPM) is a broad-spectrum antibacterial agent often used as empirical therapy for critically ill patients, although there is a lack of studies validating the recommended dosage regimen for patients admitted to intensive care unit (ICU), based on pharmacokinetic (PK)/pharmacodynamic (PD) index. In this study, we estimated the free time above minimum inhibitory concentration (fT>MIC (%)) of DRPM using population PK analysis of 12 patients in ICU, and evaluated the validity of the dosage regimen stratified by creatinine clearance. Using a 2-compartment population PK model reported previously, the mean total clearance or distribution volume of DRPM estimated by Bayesian estimation was significantly lower or higher than that of based on population PK model. The estimated fT>MIC (%) of the recommended standard (normal renal function: 0.5 g every 8 h, moderate: 0.25 g every 8 h, severe renal impairment: 0.25 g every 12 h) and higher doses (normal: 1.0 g every 8 h, moderate: 0.5 g every 8 h, severe: 0.25 g every 8 h) against MICs of 0.5, 1 and 2 µg/mL exceeded 40% in all patients. When stratified by creatinine clearance, the PK/PD breakpoints estimated by Monte Carlo simulation in three grades of renal function tended to be higher than the previously reported PK/PD breakpoints for patients with urinary tract infection, an infection of lesser severity than ICU patients. These results suggest that the dosage regimen stratified by renal function derived from Japanese package insert may be sufficient to achieve effective treatment in ICU patients.

著者

Renata Grespan Marcia Paludo Henrique de Paula Lemos Carmem Patrícia Barbosa Ciomar Aparecida Bersani-Amado Marcia Machado de Oliveira Dalalio Roberto Kenji Nakamura Cuman

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.35, no.10, pp.1818-1820, 2012-10-01 (Released:2012-10-01)

参考文献数

11

被引用文献数

8 37

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This study was designed to test the efficacy of eugenol, a compound obtained from the essential oil of cloves (Syzygium aromaticum) in collagen-induced arthritis (CIA), a well characterized murine model of rheumatoid arthritis. Macroscopic clinical evidence of CIA manifests first as periarticular erythema and edema in the hind paws. Treatment with eugenol starting at the onset of arthritis (day 25) ameliorated these clinical signs of CIA. Furthermore, eugenol inhibited mononuclear cell infiltration into the knee joints of arthritic mice and also lowered the levels of cytokines (tumor necrosis factor (TNF)-α, interferon (IFN)-γ and tumor growth factor (TGF)-β) within the ankle joints. Eugenol treatment did not affect the in vitro cell viability as assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Therefore, eugenol ameliorates experimental arthritis and could be useful as a beneficial supplement in treating human arthritis.

著者

Zheng Zhihui Yang Yi Shao Huayi Liu Zongying Lu Xinhua Xu Yanni He Xiaobo Jiang Wei Jiang Qin Zhao Baohua Zhang Hua Li Zhuorong Si Shuyi

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.10, pp.1631-1634, 2011

被引用文献数

6

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In our previous study, two synthetic thiophenes such as IMB-05 and IMB-15 were found as peroxisome proliferator-activated receptor gamma (PPARγ) agonists and exhibited beneficial effects on glucose tolerance of diabetic mice <i>in vivo</i>. In the present study, their effect on the transactivity of other nuclear receptors was further investigated. IMB-05 and IMB-15 could not only activated PPARγ but also efficiently activate PPARα in GAL4-hPPARα/γ (ligand binding domain (LBD)) chimeric receptor assay and PPAR response element (PPRE)-luc reporter gene assay with EC₅₀ values of 1.8—5.2 μ<small>M</small>, whereas no activity was observed in other nuclear receptor assays. In addition, the maximal efficacy of IMB-05 and IMB-15 in activating PPARα/γ was approximately 30% of that observed with Wy14643 and rosiglitazone. These data indicate that the two thiophene derivatives are novel class of partial PPARα/γ dual agonists, which may be the mechanism underlying their regulatory effects on glucose homeostasis.

著者

Joan Manjuh Tankam Michiho Ito

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.36, no.10, pp.1608-1614, 2013-10-01 (Released:2013-10-01)

参考文献数

44

被引用文献数

6 34

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The aromatherapeutical potential of Piper guineense essential oil was investigated in mice via inhalation administration, and the active compounds were identified. An open field test and light/dark transition test were used to evaluate the sedative and anxiolytic activities of this essential oil, respectively. P. guineense essential oil showed significant sedative activity at an effective dose of 4.0×10−5 mg per cage compared to the control group. It also showed potent anxiolytic effect at a dose of 4.0×10−6 mg per cage. The main compounds of P. guineense essential oil were linalool (41.8%) and 3,5-dimethoxytoluene (10.9%). These two main compounds were shown to play a major role in the sedative activity of P. guineense essential oil. These results suggest that inhalation of P. guineense essential oil might induce a mild tranquilizing effect.

著者

Nobuyuki Okamura Hidetoshi Miyauchi Tominari Choshi Takashi Ishizu Akira Yagi

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.26, no.5, pp.658-661, 2003 (Released:2003-05-01)

参考文献数

19

被引用文献数

7 9

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A method for semi-micro high-performance liquid chromatography (HPLC) has been established for the simultaneous determination of 3α-hydroxyglycyrrhetic acid and 3-dehydroglycyrrhetic acid together with glycyrrhizin, glycyrrhetic acid and glycyrrhetic acid mono-glucuronide formed by incubation of glycyrrhizin with rat feces. The analysis was accomplished within 25 min with a TSKgel ODS-80TsQA (150×2.0 mm i.d.) column by linear gradient elution using a mobile phase containing aqueous phosphoric acid and acetonitrile at a flow rate of 0.2 ml·min−1, a thermostatic oven at 25 °C, and detection at 254 nm. The detection limits of these compounds were 0.2 pmol per injection (5 μl). The metabolites of glycyrrhizin, by anaerobic or aerobic incubation with rat fecal suspension over 48 h, were determined. Glycyrrhizin was almost completely converted to metabolite glycyrrhetic acid, and metabolites 3α-hydroxyglycyrrhetic acid and 3-dehydroglycyrrhetic acid in negligible amounts in anaerobic conditions. However, the metabolic time courses of 3-dehydroglycyrrhetic acid when incubated in aerobic conditions revealed that it apparently continued increasing during the whole incubation period.

著者

Rie Naito Chihiro Tohda

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.29, no.9, pp.1892-1896, 2006 (Released:2006-09-01)

参考文献数

23

被引用文献数

31 52

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Although Polygala tenuifolia WILLD (PT) was classically mentioned as an anti-dementia drug in Chinese and Japanese traditional medicine, basic research showed only enhancement of the cholinergic function. In Alzheimer's disease, neuritic atrophy and synaptic loss occur prior to neuronal death event, and may be the first trigger of the memory impairment. Therefore, we studied effects of Polygala tenuifolia WILLD (PT) on Aβ(25—35)-induced neuronal damage using rat cortical neurons for characterization of activities of PT under Aβ-induced neuronal damage. Treatment with the water extract of PT enhanced axonal length dose-dependently after Aβ(25—35)-induced axonal atrophy. However, dendritic atrophy and synaptic loss induced by Aβ(25—35) were not recovered by treatment with PT extract. In contrast, Aβ(25—35)-induced cell damage was completely inhibited by PT extract. By characterization of PT effects on neuronal morphological plasticity and cell damage, usefulness as well as an insufficiency of PT as an anti-dementia drug was clarified.

著者

Maiko Akutagawa Kazuki Ide Yohei Kawasaki Mie Yamanaka Ryo Iketani Hiroshi Yamada Naohiko Masaki

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

pp.b17-00354, (Released:2017-06-09)

参考文献数

30

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To compare the rate of treatment discontinuation due to adverse events for telaprevir-based triple (T/PR) and pegylated interferon-alfa-2b and ribavirin (PR) therapy for the treatment of hepatitis C virus (HCV) infection in patients over the age of 65 years, in Japan.Retrospective analysis of the health data of patients over the age of 65 years treated for a HCV infection genotype 1 using T/PR or PR therapy, from 38 prefectures in Japan. The primary outcome was the rate of treatment discontinuation due to adverse events for T/PR and PR. The secondary outcome was to evaluate the prevalence and type of adverse events during the treatment period that resulted in treatment discontinuation for both therapies. For comparison, the T/PR and PR populations were matched using the propensity score method, and adjusted odds ratios (ORs) for treatment discontinuation calculated by multivariate logistic regression analysis.The study group included 1330 patients, 328 in the T/PR group and 1002 in the PR group. The rate of treatment discontinuation due to adverse events in the matched population was lower for T/PR (19.82%) than PR (35.98%) therapy, (adjusted OR, 0.418; 95% confidence interval, 0.292-0.599; p < 0.01). Malaise was the principal cause of treatment discontinuation in both groups (T/PR, 30.77%, and PR, 42.37%).Using real-world health data of elderly individuals in Japan, we identified a lower rate of treatment discontinuation for T/PR than PR. Our outcomes provide information for a segment of the population that is generally excluded for clinical trials.

著者

Nannan Zhang Zhongchi Li Kang Xu Yanying Wang Zhao 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.9, pp.1448-1454, 2016-09-01 (Released:2016-09-01)

参考文献数

48

被引用文献数

1 30

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Obesity-related renal diseases have been a worldwide issue. Effective strategy that prevents high fat-diet induced renal damage is of great significance. Resveratrol, a natural plant polyphenol, is famous for its antioxidant activity, cardioprotective effects and anticancer properties. However whether resveratrol can play a role in the treatment of renal diseases is unknown. In this study, we added resveratrol in normal glucose or high glucose medium and provide evidences that resveratrol protects against high-glucose triggered oxidative stress and cell senescence. Moreover, mice were fed with standard diet, standard diet plus resveratrol, high-fat diet or high-fat diet plus resveratrol for 3 months, and results show that resveratrol treatment prevents high-fat diet induced renal pathological damage by activating SIRT1, a key member in the mammalian sirtuin family that response to calorie restriction life-extension method. This research confirms the potential role of resveratrol in the treatment of renal diseases and may provide an effective and convenient method to mimic the beneficial effects of calorie restriction.

著者

Hiroko Makihara Yuka Koike Masatomi Ohta Emi Horiguchi-Babamoto Masahito Tsubata Kaoru Kinoshita Tomoko Akase Yoshio Goshima Masaki Aburada Tsutomu Shimada

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.7, pp.1137-1143, 2016-07-01 (Released:2016-07-01)

参考文献数

42

被引用文献数

19

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Visceral obesity induces the onset of metabolic disorders such as insulin resistance and diabetes mellitus. Adipose tissue is considered as a potential pharmacological target for treating metabolic disorders. The fruit of Terminalia bellirica is extensively used in Ayurvedic medicine to treat patients with diseases such as diabetes mellitus. We previously investigated the effects of a hot water extract of T. bellirica fruit (TB) on obesity and insulin resistance in spontaneously obese type 2 diabetic mice. To determine the active ingredients of TB and their molecular mechanisms, we focused on adipocyte differentiation using mouse 3T3-L1 cells, which are widely used to study adipocyte physiology. We show here that TB enhanced the differentiation of 3T3-L1 cells to mature adipocytes and that one of the active main components was identified as gallic acid. Gallic acid (10–30 µM) enhanced the expression and secretion of adiponectin via adipocyte differentiation and also that of fatty acid binding protein-4, which is the target of peroxisome proliferator-activated receptor gamma (PPARγ), although it does not alter the expression of the upstream genes PPARγ and CCAAT enhancer binding protein alpha. In the PPARγ ligand assay, the binding of gallic acid to PPARγ was undetectable. These findings indicate that gallic acid mediates the therapeutic effects of TB on metabolic disorders by regulating adipocyte differentiation. Therefore, TB shows promise as a candidate for preventing and treating patients with metabolic syndrome.

著者

Akira OKU Kiichiro UETA KENJI ARAKAWA Tomomi KANO-ISHIHARA Mamoru MATSUMOTO Tetsuya ADACHI Koichiro YASUDA Kinsuke TSUDA Akira SAITO

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.23, no.12, pp.1434-1437, 2000-12-01 (Released:2008-04-10)

参考文献数

24

被引用文献数

17 26

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T-1095, a derivative of phlorizin, is an orally active inhibitor of Na+ -glucose cotransporter (SGLT). We investigated the acute antihyperglycemic effect of T-1095 in streptozotocin-induced diabetic rats (STZ rats). T-1095 and its metabolite T-1095A inhibited the SGLT activity in brush border membranes prepared from kidneys of both normal and STZ rats, but the latter agent was approximately 10 times more potent than the former. Single oral administration of T-1095 (30-100 mg/kg) dose-dependently induced glycosuria in normal rats. The fed glucose levels in STZ rats were dose-dependently suppressed by single oral administration of T-1095 (3-100 mg/kg), whereas there was only marginal hypoglycemic effect in normal rats. Since there was no effect on blood glucose in nephrectomized STZ rats, inhibition of renal glucose reabsorption rather than intestinal glucose absorption mainly contributes to the antihyperglycemic effect of T-1095. In conclusion, T-1095 is the first orally active agent which has an acute antihyperglycemic action in the absence of endogeneous insulin secretion with a low risk of hypoglycemia and has therapeutic potential for treatment of diabetes mellitus.

著者

Tohru Sakai Miyuki Ohhata Misaki Fujii Sayaka Oda Yasuna Kusaka Miki Matsumoto Akiko Nakamoto Tomoyo Taki Mariko Nakamoto Emi Shuto

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.40, no.4, pp.391-395, 2017-04-01 (Released:2017-04-01)

参考文献数

27

被引用文献数

16

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Propolis is a bee product with various biological properties. C57BL/6 mice were fed a high-fat diet and treated with propolis for 14 weeks. Body weight in mice treated with 2% propolis was less than that in control mice from 3 weeks after the start of treatment until 14 weeks except for the 7th week. Mice treated with propolis showed significantly lower epididymal fat weight and subcutaneous fat weight. Infiltration of epididymal fat by macrophages and T cells was reduced in the propolis group. Supplementation of propolis increased feces weight and fat content in feces, suggesting that mechanisms of weight reduction by propolis partly include a laxative effect and inhibition of fat absorption.

著者

Mitsuhiro Machitani Fuminori Sakurai Keisaku Wakabayashi Kosuke Nakatani Kazuo Takayama Masashi Tachibana Hiroyuki Mizuguchi

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.40, no.3, pp.272-277, 2017-03-01 (Released:2017-03-01)

参考文献数

25

被引用文献数

7

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Clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-mediated genome engineering technology is a powerful tool for generation of cells and animals with engineered mutations in their genomes. In order to introduce the CRISPR/Cas9 system into target cells, nonviral and viral vectors are often used; however, such vectors trigger innate immune responses associated with production of type I interferons (IFNs). We have recently demonstrated that type I IFNs inhibit short-hairpin RNA-mediated gene silencing, which led us to hypothesize that type I IFNs may also inhibit CRISPR/Cas9-mediated genome mutagenesis. Here we investigated this hypothesis. A single-strand annealing assay using a reporter plasmid demonstrated that CRISPR/Cas9-mediated cleavage efficiencies of the target double-stranded DNA were significantly reduced by IFNα. A mismatch recognition nuclease-dependent genotyping assay also demonstrated that IFNα reduced insertion or deletion (indel) mutation levels by approximately half. Treatment with IFNα did not alter Cas9 protein expression levels, whereas the copy numbers of guide RNA (gRNA) were significantly reduced by IFNα stimulation. These results indicate that type I IFNs significantly reduce gRNA expression levels following introduction of the CRISPR/Cas9 system in the cells, leading to a reduction in the efficiencies of CRISPR/Cas9-mediated genome mutagenesis. Our findings provide important clues for the achievement of efficient genome engineering using the CRISPR/Cas9 system.

著者

Kazuki Ide Yohei Kawasaki Ryo Iketani Naohiko Masaki

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

pp.b16-00941, (Released:2017-02-17)

参考文献数

23

被引用文献数

2

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In this study, a nationwide database was used to identify the risk factors for treatment discontinuation due to adverse events during telaprevir, peginterferon, and ribavirin (T/PR) treatment, and estimate the increase in the occurrence of adverse events when patients have multiple risk factors at the same time. The risk factors were identified using univariate logistic regression analysis, and a Cochran–Armitage trend test was used to analyze the correlation between the number of risk factors and treatment discontinuation due to adverse events. Of the 25,989 individuals registered in the database, 1,668 (age, mean ± SD: 58.0 ± 9.9) were included in the study. Of these, 188 (11.27%) discontinued T/PR therapy due to adverse events. In the univariate logistic regression analysis, sex, age, AST level, and platelet count were found to significantly affect the incidence of T/PR treatment discontinuation (P < 0.05). Furthermore, the incidence of treatment discontinuation gradually increased from 4.6% to 27.2% as the number of risk factors increased from 0 to 4, and the Cochran–Armitage trend test showed a significant correlation (P < 0.001). In conclusion, this study not only revealed the risk factors for treatment discontinuation but also showed that patients with multiple risk factors are more likely to discontinue treatment due to adverse events compared to patients with fewer risk factors.

著者

Takashi Nakamura Yosuke Noma Yu Sakurai Hideyoshi Harashima

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.40, no.2, pp.234-237, 2017-02-01 (Released:2017-02-01)

参考文献数

12

被引用文献数

17

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Intravesical drug delivery by cationic liposomes (Cat-LPs) represents a potent nanotechnology for enhancing therapeutic effects against bladder disorders. However, preventing the aggregation of Cat-LPs in urine poses a significant barrier. We report on an examination of the effect of modifying liposomes with polyethylene glycol (PEG) lipids to prevent Cat-LPs from aggregating in human urine. Although Cat-LPs underwent significant aggregation in human urine, introducing 5 mol% of PEG2k lipid or 2 mol% of PEG5k lipid completely inhibited the aggregation of the Cat-LPs. When 2 mol% of PEG2k lipids were introduced, the lipid structures of 1,2-distearoly-sn-glycero-3-phosphoethanolamine (DSPE) and 1,2-distearoyl-sn-glycerol (DSG) greatly prevented aggregation compared with cholesterol. By contrast, when Cat-LPs, after incubation in urine, were exposed to bladder cancer cells, only introducing cholesteryl-PEG into the Cat-LPs showed a significant enhancement in cellular uptake. These results offer the potential for incorporating cholesteryl-PEG into Cat-LPs for achieving both stability in urine and effective cellular uptake.

著者

Mitsumasa Kaneta Wataru Ochiai Marina Nagae Wataru Suto Mika Hanagata Haruka Suzuki Satoshi Kitaoka Jo Hatogai Nobutomo Ikarashi Kiyoshi Sugiyama

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.1809-1814, 2016-11-01 (Released:2016-11-01)

参考文献数

56

被引用文献数

2

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Approximately 30% of patients with cancer pain experience concurrent neuropathic pain. Since these patients are not sufficiently responsive to morphine, the development of an effective method of pain relief is urgently needed. Decreased function of the μ opioid receptor, which binds to the active metabolite of morphine M-6-G in the brain, has been proposed as a mechanism for morphine resistance. Previously, we pharmacokinetically examined morphine resistance in mice with neuropathic pain, and demonstrated that the brain morphine concentration was decreased, expression level of P-glycoprotein (P-gp) in the small intestine was increased, and expression level and activity of uridine diphosphate glucuronosyltransferase (UGT)2B in the liver were increased. In order to clarify the mechanism of the increased expression of UGT2B, we examined the phase of neuropathic pain during which UGT2B expression in the liver begins to increase, and whether this increased expression is nuclear receptor-mediated. The results of this study revealed that the increased expression of UGT2B in the liver occurred during the maintenance phase of neuropathic pain, suggesting that it may be caused by transcriptional regulation which was not accompanied by increased nuclear import of pregnane X receptor (PXR).

著者

Shigehiro Yanagihara Yuya Taniguchi Mareto Hosono Eiji Yoshioka Rika Ishikawa Yoshihiro Shimada Toshihiko Kadoya Kazuhiro Kutsukake

出版者

The Pharmaceutical Society of Japan

雑誌

Biological and Pharmaceutical Bulletin (ISSN:09186158)

巻号頁・発行日

vol.33, no.9, pp.1596-1599, 2010-09-01 (Released:2010-09-01)

参考文献数

22

被引用文献数

10 11

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Assessment of biological potency and its comparison with clinical effects are important in the quality control of therapeutic glycoproteins. Animal models are usually used for evaluating bioactivity of these compounds. However, alternative methods are required to simplify the bioassay and avoid ethical issues associated with animal studies. Negatively charged sialic acid residues are known to be critical for in vivo bioactivity of recombinant human erythropoietin (rhEPO). In this study, we used capillary zone electrophoresis, a charge-based separation method, to estimate the sialic acid content for predicting in vivo bioactivity of rhEPO. In vivo bioactivities of rhEPO subfractions were measured and compared with sialylation levels. The results obtained indicated that in vivo bioactivity of rhEPO is not simply correlated with the sialylation level, which suggests that it is difficult to predict biological potency from the sialic acid content alone. N-Glycan moieties as well as sialic acid residues may have a significant impact on in vivo bioactivity of rhEPO.