巻号一覧
130 巻, 7 号
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総説
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服部 喜之2010 年 130 巻 7 号 p. 917-923
発行日: 2010/07/01
公開日: 2010/07/01
ジャーナル フリーCancer gene therapy has been intensively developed using non-viral vectors, among which cationic liposomes and nanoparticles are the most investigated. Optimal gene therapy for tumors must deliver plasmid DNA (pDNA) or synthetic small interfering RNA (siRNA) to tumor cells with high efficiency and minimal toxicity. We developed new cationic nanoparticles (NP) composed of cholesteryl-3β-carboxyamidoethylene-N-hydroxyethylamine (OH-Chol) and Tween 80, and evaluated the transfection efficiencies of pDNA and siRNA into human prostate tumor PC-3 xenografts. NP showed effective transfection of pDNA and siRNA when directly injected into the xenografts. For targeted delivery to tumors, vitamin folic acid has been utilized for folate receptor (FR)-mediated drug delivery since FR is frequently overexpressed on many types of human tumors. We developed folate-linked nanoparticles (NP-F) composed of OH-Chol, Tween 80 and folate-poly(ethylene glycol)-distearoylphosphatidylethanolamine conjugate. Tumor growth of FR-positive human nasopharyngeal tumor KB xenografts was significantly inhibited when a complex of NP-F and a therapeutic gene was intratumorally injected. These findings suggested that cationic cholesterol-based nanoparticles are potential non-viral pDNA and siRNA vectors for local tumor treatment.
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太田 悠介2010 年 130 巻 7 号 p. 925-936
発行日: 2010/07/01
公開日: 2010/07/01
ジャーナル フリーA copper-catalyzed synthesis of 2-(aminomethyl)indole through domino three-component coupling-cyclization has been developed. This reaction proceeds through Mannich-type coupling of 2-ethynylanilines, aldehydes, and secondary amines, followed by hydroamination. This indole formation was applicable to the synthesis of 4-methylene-2,3,4,9-tetrahyro-1H-pyrido[3,4-b]indoles and 5,6,7,8-tetrahydrobenzo[e]indolo[2,3-c]azepines via palladium-catalyzed C-H functionalization at the 3-position of indole. A combination of the three-component indole formation with nucleophilic cyclization promoted by t-BuOK or MsOH provides an effective access to β-carboline scaffolds. Indole-fused 1,4-diazepines were also synthesized through deprotection/N-arylation at the nitrogen atom of indole by one-pot addition of MeONa after the formation of 2-(aminomethyl)indoles. In relation to the three-component indole formation, a novel four-component synthesis of isoquinolines has been developed. This isoquinoline formation includes Mannich-type reaction of 2-ethynylbenzaldehyde with (HCHO)n and secondary amine, imine formation with t-BuNH2, isoquinoline formation, and elimination of t-butyl group to directly afford 3-(aminomethyl)isoquinolines in good yields. By the use of an alkane diamine instead of t-BuNH2, fused 3-(aminomethyl)isoquinoline derivatives were obtained by cascade cyclization and oxidation.
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一般論文
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Munish AHUJA, Sumit KUMAR, Monika YADAV原稿種別: Regular Article
2010 年 130 巻 7 号 p. 937-944
発行日: 2010/07/01
公開日: 2010/07/01
ジャーナル フリーIn the present study, buccal discs of fluconazole were prepared by direct compression method employing Mimosa pudica seed mucilage as bucoadhesive polymer. The formulation of buccal discs was optimised using 3-factor, 3-level central composite design, using polymer/excipient ratio, drug concentration and compression force as the independent variables and bioadhesion time and percentage release as dependent variables. The results revealed that polymer/excipient ratio and compression force are the significant factors affecting the bioadhesion time and percentage release, with the effect of polymer/excipient ratio being more pronounced. A quadratic model with backward elimination fitted to the data was used to predict the responses in the optimal region. The optimised formulation of buccal discs provided bioadhesion time and percentage release close to the predicted values. The proposed mathematical model is found to be robust and accurate for optimisation of buccal discs of fluconazole, consistent with the goals of bioadhesion time of 10 h and more than 85% release in 10 h.
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中島 晴信, 富山 健一, 河上 強志, 伊佐間 和郎2010 年 130 巻 7 号 p. 945-954
発行日: 2010年
公開日: 2010/07/01
ジャーナル フリーIn preparing for the revision of the authorized analytical method for tributyltin (TBT) and triphenyltin (TPT), which are banned from using according to the “Act on the Control of Household Products Containing Harmful Substances”, an examination was conducted on the detection method of these substances using gas chromatography/mass spectrometry (GC/MS), after derivatizing them (ethyl-derivatizing method and hydrogen-derivatizing method). Ethyl-derivatized compounds had stability, which enabled the detection of TPT with a higher sensitivity. In addition, a preparation suitable for the following analytical objects was established: (1) textile products, (2) water-based products (such as water-based paint), (3) oil-based products (such as wax), and (4) adhesives. Addition-recovery experiments were conducted using the prescribed pretreatment method, when each surrogate substances (TBT-d27, TPT-d15) were added and the data were corrected, good recovery rates (94.5-118.6% in TBT, and 86.6-110.1% in TPT) were obtained. When TBT and TPT in 31 commercially available products were analyzed based on the developed analytical method, an adhesive showed 13.2 μg/g of TBT content, which exceeded the regulatory criterion (1 μg/g as tin). Next, when the same products with different manufacturing date were analyzed, TBT (10.2-10.8 μg/g), which exceeded the regulatory criterion, was detected in 4 products among 8 products, and simultaneously, a high concentration (over 1000 μg/g) of dibutyltin (DBT) was detected. It was suggested that TBT as an impurity of DBT remained, and the manufacturer chose the voluntary recall of the product. The new method is considered sufficiently applicable as a revised method for the conventionally authorized method.
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山田 孝明, 渡邉 裕之, 矢野 貴久, 野中 敏治, 高田 敦史, 園田 正信, 窪田 敏夫, 江頭 伸昭, 大石 了三2010 年 130 巻 7 号 p. 955-960
発行日: 2010/07/01
公開日: 2010/07/01
ジャーナル フリーAlthough S-1 is frequently used in cancer chemotherapy, the drug interaction with warfarin, an anticoagulant agent, is not fully paid attention. In the present study, we investigated retrospectively the timing of expression of blood coagulation abnormality in nine patients treated with warfarin and S-1 concomitantly. In five patients, the dose of warfarin was reduced or interrupted after concomitant use of S-1. The International Normalized Ratio (INR) was significantly increased after combination with S-1 compared with the former value. In all patients, the INR was increased in three weeks after combination with S-1. On the other hand, serum creatinine, aspartate aminotransferase, alanine aminotransferase or serum albumin was not different before and after combination with S-1. These results suggest that the careful monitoring of the blood coagulation ability is necessary in all patients receiving warfarin and S-1 concomitantly.
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朝比奈 泰子, 堀 里子, 澤田 康文2010 年 130 巻 7 号 p. 961-969
発行日: 2010/07/01
公開日: 2010/07/01
ジャーナル フリーOur objective was to clarify the current understanding of the definition and safety of oral health products among patients and health professionals, and patients’ perception about their communication with physicians and pharmacists regarding those products. Self-administered questionnaires were completed by patients at 17 community pharmacies in 14 prefectures of Japan. For health professionals, we sent a questionnaire to pharmacists and physicians who were registered as members of the Internet-based Medical Doctor's and Pharmacist's Information-Sharing System. The respondents were 242 patients, 158 physicians and 407 pharmacists. Some patients did not categorize dietary supplements as health products, while they did so categorize conventional foods (e.g., fermented soybeans, yogurt). Their understanding of the definition of health products was different from that of health professionals. Less than half of the patients considered that health products might potentiate or attenuate the effects of concomitant drugs, and this view was especially common among the elderly. The percentage of patients who reported that they rarely or never asked for advice from a pharmacist about their use of health products was significantly higher among those who had an incorrect understanding about health products. In conclusion, some patients’ recognition of oral health products was different from that of health professionals, and most patients do not discuss their use of such products unless they are asked. Therefore, it is important for health professionals to check a patient's use of health products and be sure what he or she means when using the term ‘health product’.
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ノート
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平川 宣幸, 矢ノ下 良平, 吉井 大, 矢野 博子2010 年 130 巻 7 号 p. 971-975
発行日: 2010/07/01
公開日: 2010/07/01
ジャーナル フリーSix allergic conjunctivitis patients (12 eyes) and 4 healthy volunteers (8 eyes) were investigated in terms of the effect of cooling sheets on eye itching and tear histamine concentration, before and 5 min after cooling the eyelids with cooling sheets. The severity of itching was evaluated with a five-level itching score. The combination treatment of levocabastine with cooling sheets significantly reduced eye itching, while no significant change in tear histamine concentration was observed before and after cooling sheet use. The cooling sheets are useful for reducing eye itching in the therapy of allergic conjunctivitis. The tear histamine concentration did not correlate with the antiitching effect of cooling sheets in this study.
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芝口 浩智, 山本 知佳, 黒木 政秀, 二神 幸次郎2010 年 130 巻 7 号 p. 977-982
発行日: 2010/07/01
公開日: 2010/07/01
ジャーナル フリーCytomegalovirus (CMV) remains the most important pathogen following solid organ transplantation and is the major cause of recipient morbidity and mortality during the first 6 months posttransplantation. To prevent CMV infection and/or to prevent symptomatic CMV disease, immunoglobulin (Ig) G including hyperimmune CMV IgG are used alone or in combination with antiviral medications. The CMV IgG titer, however, has a wide range and frequently depends on the company supplying the Ig preparation even if the preparations come from the plasma pool of a national blood donation agency. In the present study, we therefore simultaneously measured and evaluated the CMV IgG titers in various Ig preparations using two common methods: the neutralizing antibody (NT) and enzyme immunoassay (EIA). The CMV IgG titer in the present study indicated different values using both methods among Ig preparations that were made from the plasma pool of a national blood donation agency (about 3.5- or about 1.7-fold difference using the NT or EIA methods, respectively). Furthermore, there were no correlations in the CMV IgG titer between our findings and published data from the manufacturers, or between the two methods tested here. These findings suggest the importance and necessity of a standard method and/or sample for the measurement and assessment of CMV IgG in Ig preparations.
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森元 康夫, 柴田 裕次郎2010 年 130 巻 7 号 p. 983-987
発行日: 2010/07/01
公開日: 2010/07/01
ジャーナル フリーAlthough fragrances are often used in aromatherapy for the treatment of edema, few studies on their diuretic and/or antiedematous activities have been performed. In this study, the effects of four types of fragrant ingredients (d-limonene, piperitone, α-pinene, and cinnamaldehyde) were examined in a mouse model of fluid retention. The mice were loaded with water after treatment with desmopressin (an antidiuretic hormone). In addition, zingerone, a pungent component of ginger which is considered to be effective in the treatment of edema, was examined. Moreover, their effects were compared with those of furosemide, a representative diuretic. Among the five types of fragrant ingredients examined, all except for cinnamaldehyde increased the urine volume in the fluid retention mouse model when administered at a dose of 100 mg/kg. In particular, d-limonene and zingerone significantly increased the urine volume. Thus the effects of these two ingredients were further examined at lower doses of 10 and 30 mg/kg. d-Limonene significantly increased the urine volume in a dose-dependent manner. Zingerone resulted in a significant increase in the urine volume only at a dose of 30 mg/kg. In normal mice, d-limonene did not affect the urine volume at the same doses. In contrast, zingerone significantly increased the urine volume in normal mice at a dose of 30 mg/kg. Furosemide significantly increased the urine volume in both the fluid-retentive and normal mice. These results indicate that both d-limonene and zingerone exhibit diuretic actions; however, the former fragrance only exerted an action in the fluid-retentive state. This different action suggests that d-limonene might be promising for the treatment of edema.
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遠野 弘美, 堀井 周文, 布施 貴史, 小此木 明, 与茂田 敏2010 年 130 巻 7 号 p. 989-997
発行日: 2010/07/01
公開日: 2010/07/01
ジャーナル フリーThe bark of Prunus jamasakura Siebold (Pruni Cortex) has long been used in Japan as a folk remedy and is one of ingredients of the Kampo formula, Jumi-haidoku-to (JHT). JHT is used for treatment of skin diseases such as acne (acne vulgaris). According to Kampo medicinal sources, Quercus Cortex can be used in place of Pruni Cortex. In this study, we found that water extracts of Pruni Cortex, not Quercus Cortex showed a binding effect on estrogen receptor β (ERβ). Thus, their chemical analysis was carried out by GC-MS and found that five unique constituents (i.e., sakuranetin, naringenin, genistein, genkwanin and arctigenin) were detected in Pruni Cortex. The ERβ binding capacity of these constituents was examined using 70 ng/ml 17β-estradiol, as the positive control with 100% ERβ binding. Among them, genistein (60% at 10 ng/ml) showed the strongest binding capacity than naringenin (60% at 1000 ng/ml) and sakuranetin (40% at 1000 ng/ml). These results suggested that Pruni Cortex in JHT could play an important role in treatment of acne. In addition, those of Pruni Cortex from different harvest places were also examined in their chemical contents and ERβ binding capacity. The extracts of Pruni Cortex from Kyushu in Japan and Anhui Province in China showed higher contents of genistein and stronger ERβ binding capacity than that of Pruni Cortex from Tokushima Prefecture in Japan.
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