YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
132 巻, 5 号
選択された号の論文の15件中1~15を表示しています
誌上シンポジウム
  • 杉森 裕樹, 折井 孝男
    原稿種別: Foreword
    2012 年 132 巻 5 号 p. 531
    発行日: 2012/05/01
    公開日: 2012/05/01
    ジャーナル フリー
  • 山本 美智子
    原稿種別: Review
    2012 年 132 巻 5 号 p. 533-548
    発行日: 2012/05/01
    公開日: 2012/05/01
    ジャーナル フリー
      In pharmacovigilance, it has been recognized that it is essential to share the information regarding the risk of drugs among stakeholders and to have risk communication (RC) which enables consumers to make their own judgments regarding the risk. In particular, RC between the governmental agencies and consumers is given a high priority. Hence, its provisions and initiatives should be considered thoroughly. I present a brief overview of current proactive approaches for RC to protect the patient's rights, to increase openness and transparency and to share information in the US and EU. Following the Food and Drug Administration Amendment Act (FDAAA), Institute of Medicine of the National Academies (IOM) recommended that FDA makes efforts for RC. The RC Advisory Committee was established and consumers are involved as its members. FDA published “Guidance Drug Safety Information” in 2007 and “Strategic Plan for RC” in 2009. Thus, its framework has been developed. European Medicines Agency (EMA) issued “Work programme 2010” and “EMA Communication on safety related issues”, which indicated its policies and measures. EMA is promoting development of the framework for Patient Involvement (e.g., members of scientific committees). Regarding the direct patient reporting of adverse drug reactions, FDA began that in 2003 and EMA recommends to encourage it for EU Member States, and it has already started in some countries. RC has important roles to take safety measures for drugs and to protect patient's rights, therefore such an approach for it be implemented is expected in Japan.
  • 中山 健夫
    原稿種別: Review
    2012 年 132 巻 5 号 p. 549-554
    発行日: 2012/05/01
    公開日: 2012/05/01
    ジャーナル フリー
      The concept of evidence-based medicine (EBM) has promulgated among healthcare professionals in recent years, on the other hand, the problem of underuse of useful clinical evidence is coming to be important. This is called as evidence-practice gap. The major concern about evidence-practice gap is insufficient implementation of evidence-based effective treatment, however, the perspective can be extended to measures to improve drug safety and prevention of drug related adverse events. First, this article reviews the characteristics of the database of receipt (healthcare claims) and the usefulness for research purpose of pharmacoepidemiology. Second, as the real example of the study on evidence-practice gap by using the receipt database, the case of ergot-derived anti-Parkinson drugs, of which risk of valvulopathy has been identified, is introduced. The receipt analysis showed that more than 70% of Parkinson's disease patients prescribed with cabergoline or pergolide did not undergo echocardiography despite the revision of the product label recommendation. Afterwards, the issues of pharmaceutical risk management and risk communication will be discussed.
  • 小島 正美
    原稿種別: Review
    2012 年 132 巻 5 号 p. 555-559
    発行日: 2012/05/01
    公開日: 2012/05/01
    ジャーナル フリー
      A lot of healthcare professionals experienced annoyance with biased mass media news regarding medical and health issues. In this paper, I propose “news profiling method” and “media guideline” to improve the medical and health journalism.
  • 広瀬 誠
    原稿種別: Review
    2012 年 132 巻 5 号 p. 561-562
    発行日: 2012/05/01
    公開日: 2012/05/01
    ジャーナル フリー
      Recently, the Ministry of Health, Labour and Welfare has made efforts toward the strengthening of dissemination of appropriate drug and safety information through information service for healthcare professionals. Furthermore, Pharmaceuticals and Medical Devices Agency (PMDA) enforced webpages regarding drug safety information tools, such as PMDA “MediNavi”. In European Medicines Agency (EMA), during the preparation of information (such as patient leaflets), the Agency interacts and cooperates with patients' and consumers' organizations to ensure that it is adequately formulated and comprehensible to the target audience. To disseminate information that is of real good service to patients, further risk communication with patients (patient involvement) is expected.
総説
  • 加藤 晃一
    原稿種別: Review
    2012 年 132 巻 5 号 p. 563-573
    発行日: 2012/05/01
    公開日: 2012/05/01
    ジャーナル フリー
      A majority of proteins encoded in genomes of limited size are post-translationally diversified by covalent modifications such as glycosylation and ubiquitination. Although recent advances in structural proteomics have enabled high-throughput structure determination of proteins, structural analyses of post-translationally modified proteins remain challenging because of the lack of appropriate determination methods. Therefore, we developed methodologies for characterizing the post-translational modifications of proteins from the structural viewpoint, focusing especially on glycosylation and ubiquitination. For instance, we established a systematic method for structural glycomics to address broader issues, including glycosylation profiling and 3D structure analyses of glycoproteins. Our stable-isotope-assisted NMR techniques in conjunction with X-ray crystallographic approach provide valuable information at the atomic level on conformations, dynamics, and interactions of glycoproteins such as antibody and proteins involved in the ubiquitin-proteasome system. These studies provide the structural basis for improved efficacy of therapeutic antibodies on defucosylation of their Fc glycans and mechanistic insights into ubiquitination reactions in glycoprotein-fate determination in cells. These approaches will allow new possibilities for structural studies on post-translationally modified proteins of clinical, pathological, and pharmaceutical interests.
  • 上杉 志成
    原稿種別: Review
    2012 年 132 巻 5 号 p. 575-586
    発行日: 2012/05/01
    公開日: 2012/05/01
    ジャーナル フリー
      In human history, small organic molecules have been utilized for improving human health and for revealing secrets of life. Discovery or design of small organic molecules with unique biological activity permits small-molecule-initiated exploration of biology. Our laboratory has been discovering and designing bioactive small synthetic molecules to use them as tools to analyze or modulate biological processes. This personal perspective summarizes our contributions to chemical biology, particularly in the fields of gene transcription, cell therapy, growth factor signaling, and target identification.
  • 白川 久志
    原稿種別: Review
    2012 年 132 巻 5 号 p. 587-593
    発行日: 2012/05/01
    公開日: 2012/05/01
    ジャーナル フリー
      Astrocytes, the most abundant cells in the central nervous system (CNS), play diverse roles in the regulation of neuronal activity, vascular function and gliotransmitter release. In neurodegenerative diseases, pathologically activated astrocytes show astrogliosis, which is clinically characterized by an abnormal cell morphology and excessive astrocyte proliferation. Thrombin, a crucial factor for brain injury after intracerebral hemorrhage, activates astrocytic Ca2+ signaling through a specific subtype of the thrombin receptor, termed the proteinase-activated receptor (PAR). In this study, we demonstrate a novel pathophysiological role for transient receptor potential canonical 3 (TRPC3) Ca2+-permeable nonselective cation channels in thrombin-activated astrocytes. In 1321N1 human astrocytoma cells and cultured rat cortical astrocytes, thrombin induced heterogeneous Ca2+ responses with asynchronous repetitive peaks. These oscillations were found to be the result of repetitive Ca2+ release from intracellular stores followed by replenishment of the stores with Ca2+ from the extracellular region. The oscillations occurred without a direct [Ca2+]i increase and were inhibited by the selective TRPC3 inhibitor pyrazole-3. Pharmacological manipulation with BAPTA-AM, cyclopiazonic acid, 2-aminoethoxydiphenyl borate and pyrazole-3 indicated that Ca2+ mobilization through TRPC3 was involved in thrombin-induced changes in the morphology of astrocytes. Moreover, thrombin-induced upregulation of S100B, a marker of reactive astrocytes, at 20 h and increased astrocytic proliferation at 72 h were inhibited by Ca2+ signaling blockers and knockdown of TRPC3 with specific siRNA. Taken together, these results suggest that TRPC3 may constitute a new therapeutic target for brain injury after intracerebral hemorrhage.
  • 上田 真史
    原稿種別: Review
    2012 年 132 巻 5 号 p. 595-600
    発行日: 2012/05/01
    公開日: 2012/05/01
    ジャーナル フリー
      In solid tumors, hypoxic regions arise because of an imbalance between oxygen supply and consumption. The transcription factor hypoxia-inducible factor-1 (HIF-1), which is overexpressed in hypoxic regions, was recently reported to be a master transcriptional activator of various genes (such as those involved in glucose metabolism, vascularization, invasion, and metastasis) related to malignant phenotypes. Therefore, the development of techniques for the noninvasive detection of HIF-1-active hypoxic tumor cells is of great interest. Although various modalities are used for molecular imaging in vivo, nuclear medical imaging, which can give information about organ functions, plays a central quantitative role in molecular imaging. However, because radioactive probes become attenuated due to the nuclide-specific half-life, an appropriate probe design and/or imaging method is required to obtain a high-contrasted image within a limited time. My colleagues and I have developed a probe and a method for the rapid detection of HIF-1-active hypoxic regions in tumors. Because the α subunit of HIF-1 (HIF-1α) controls the transcriptional activity of HIF-1 and is unique in that its degradation is regulated by the oxygen partial pressure, we first developed a fusion protein probe that is degraded similarly as HIF-1α. Then, to control the biodistribution of radioactivity, we utilized a “pretargeting method” that uses a combination of the fusion protein and a small-molecule radioactive probe that can bind to the protein and is rapidly cleared from the blood. Rapid and high-contrast imaging of HIF-1-active tumors can be achieved with this pretargeting method.
一般論文
  • 舟越 亮寛, 横山 晴子, 河合 典子, 小林 健二, 上野 文昭, 山田 安彦
    原稿種別: Regular Article
    2012 年 132 巻 5 号 p. 601-607
    発行日: 2012/05/01
    公開日: 2012/05/01
    ジャーナル フリー
      The urea breath test (UBT) is used widely for assessment of Helicobacter pylori (H. pylori) eradication after treatment. A false-negative UBT is common during administration of anti-ulcer drugs and immediately after their discontinuation. It was thought that the pharmaceutical care by the pharmacists was necessary for the diagnostic accuracy of UBT after H. pylori eradication therapy. Therefore, we investigated the effect of pharmaceutical care on diagnosis based on assessment of UBT. The patients who performed UBT were classified into two groups according to the pharmacists' intervention. From 2008 April to 2009 September, the number of the patients taken pharmaceutical care was 57 (intervention group) and that of the patients taken no pharmaceutical care was 62 (control group). When drugs for H. pylori infection and anamnestic therapy were same, the percentage that avoided administration of double drugs was significantly increased by the pharmaceutical care (93.3% in intervention group versus 21.4% in control group, p<0.05). Therefore, the percentage of noncompliance that performed UBT 4 weeks after treatment onward was significantly decreased by the pharmaceutical care (1.6% in intervention group versus 17.5% in control group, p<0.05). Moreover, the percentage of recurrence after treatment was significantly decreased, there were 3.3% in the intervention group and 14.0% in the control group. In conclusion, it was very important that the pharmacists take care in the management of treatment and UBT for H. pylori eradication therapy.
  • 小林 正紀, 日高 和宏, 知嵜 郁美, 高橋 夏子, 小倉 次郎, 板垣 史郎, 平野 剛, 山口 浩明, 井関 健
    原稿種別: Regular Article
    2012 年 132 巻 5 号 p. 609-615
    発行日: 2012/05/01
    公開日: 2012/05/01
    ジャーナル フリー
      The aim of this study was to determine the effects of α-cyano-4-hydroxycinnamic acid (CHC), a lactate efflux inhibitor, and citrate, an alkaline reagent, on statin-induced muscle injury using a human prototypic embryonal rhabdomyosarcoma cell line (RD) as a model of in vitro skeletal muscle and on statin-induced muscle damage in an in vivo study. Statin-induced reduction of cell viability and apoptosis was measured by the 3-(4,5-dimethylthiazol-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) assay and caspase assay. In an in vivo study, plasma creatine phosphokinase (CPK) level was examined in cerivastatin-treated rats. CHC increased growth inhibition of RD cells induced by cerivastatin, a lipophilic statin, but not these induced by pravastatin, a hydrophilic statin. On the other hand, citrate suppressed cerivastatin-, simvastatin- and atorvastatin-induced reduction of cell viability and caspase activation in RD cells. Moreover, citrate prevented cerivastatin-induced increase in CPK concentration in a concentration-dependent manner. This is first study to evaluate CHC or citrate-induced exacerbation or improvement of statin-induced muscle damage.
  • 泉 太郎, 堀 里子, 佐藤 宏樹, 三木 晶子, 澤田 康文
    原稿種別: Regular Article
    2012 年 132 巻 5 号 p. 617-627
    発行日: 2012/05/01
    公開日: 2012/05/01
    ジャーナル フリー
      Aggravation of asthmatic response (asthmatic attack, 2 cases) and adverse events (tremor, 1 case) due to a switch from a brand-name tulobuterol tape to a generic tape were recently reported. These changes disappeared after reformulation from generic to the brand-name tape. To investigate this issue, we conducted a questionnaire survey on changes of asthmatic response, adverse events and product usability due to a switch between tulobuterol tapes. We identified 44 cases (18 from doctors, 26 from pharmacists) in which changes of asthmatic response or adverse events had occurred due to a switch between tulobuterol tapes. Aggravation of asthmatic response had occurred in 30 cases and adverse events in 21 cases due to switch from brand-name tulobuterol tape to generic tape. As regards change of product usability, we obtained 96 relevant responses (18 from doctors, 78 cases pharmacists), and the major response was that generic tulobuterol tape peeled off the skin more easily than did the brand-name tape (60 cases). These results suggest that changes of asthmatic response, adverse events and product usability should be carefully monitored when switching tulobuterol tapes.
  • 吉松 嘉代, 河野 徳昭, 川原 信夫, 穐山 浩, 手島 玲子, 西島 正弘
    原稿種別: Regular Article
    2012 年 132 巻 5 号 p. 629-674
    発行日: 2012/05/01
    公開日: 2012/05/01
    ジャーナル フリー
      Developments in the use of genetically modified plants for human and livestock health and phytoremediation were surveyed using information retrieved from Entrez PubMed, Chemical Abstracts Service, Google, congress abstracts and proceedings of related scientific societies, scientific journals, etc. Information obtained was classified into 8 categories according to the research objective and the usage of the transgenic plants as 1: nutraceuticals (functional foods), 2: oral vaccines, 3: edible curatives, 4: vaccine antigens, 5: therapeutic antibodies, 6: curatives, 7: diagnostic agents and reagents, and 8: phytoremediation. In total, 405 cases were collected from 2006 to 2010. The numbers of cases were 120 for nutraceuticals, 65 for oral vaccines, 25 for edible curatives, 36 for vaccine antigens, 36 for therapeutic antibodies, 76 for curatives, 15 for diagnostic agents and reagents, and 40 for phytoremediation (sum of each cases was 413 because some reports were related to several categories). Nutraceuticals, oral vaccines and curatives were predominant. The most frequently used edible crop was rice (51 cases), and tomato (28 cases), lettuce (22 cases), potato (18 cases), corn (15 cases) followed.
  • 本橋 慎也, 堀 雄史, 小野 孝明, 大西 一功, 川上 純一
    原稿種別: Regular Article
    2012 年 132 巻 5 号 p. 675-681
    発行日: 2012/05/01
    公開日: 2012/05/01
    ジャーナル フリー
      Granisetron is a selective 5-hydroxy tryptamine3 receptor antagonist and widely used for chemotherapy-induced nausea and vomiting (CINV). Recommended dose of intravenous granisetron in the USA and Europe has been set at 0.01 mg/kg (1 mg/body) in the antiemetic treatment guidelines established by the American Society of Clinical Oncology and National Comprehension Cancer Network. In contrast, the approved dose in Japan is 0.04 mg/kg (3 mg/body). Randomized controlled trials (RCTs) which compared 1 mg/body with 3 mg/body of intravenous granisetron for CINV had been reported in Japan. In these RCTs, however, hematological malignancy patients were excluded. We performed observational retrospective study to compare 1 mg/body with 3 mg/body of intravenous granisetron for the prevention of CINV and adverse events in hematological malignancy patients. Number of the patients and chemotherapy courses were 15 and 30 in the 1 mg/body group, and 15 and 27 in the 3 mg/body group, respectively. No nausea rates in the 1 and 3 mg/body group were 83% and 89% of courses, respectively. No vomiting rates in the 1 and 3 mg/body group were 97% and 100% of courses, respectively. The incidences of constipation in the 1 and 3 mg/body group were 34% and 45% of courses, respectively. Anaphylaxis and headache did not occur in both groups. Our findings suggested that 1 mg/body of intravenous granisetron can prevent from CINV in hematological malignancy patients, as well as 3 mg/body.
ノート
  • 榎屋 友幸, 村木 優一, 岩本 卓也, 川瀬 亮介, 長谷川 正裕, 須藤 啓広, 内田 淳正, 奥田 真弘
    原稿種別: Note
    2012 年 132 巻 5 号 p. 683-687
    発行日: 2012/05/01
    公開日: 2012/05/01
    ジャーナル フリー
      Deep venous thrombosis (DVT) is a life-threatening postoperative complication and occurs frequently after total-knee-replacement arthroplasty (TKA) and total-hip-replacement arthroplasty (THA). Fondaparinux (FPX) has been used to treat and prevent DVT, however interindividual difference of the drug efficacy exists. Therefore, this chart review was retrospectively conducted to research risk factors for a residual DVT after FPX treatment. Total of 112 patients undergone TKA or THA were treated with 2.5 mg FPX once a day between postoperative day (POD) 1 and 14 from July 2007 through December 2008. Among these patients, 30 patients who were detected DVT on POD 4 were enrolled in this study. Thirty patients were divided into two groups according to the presence (n=11) or absence (n=19) of DVT on POD14. The DVT (−) group had a significantly longer activated partial thromboplastin time (APTT, median 31.4 s) on POD 1 than the DVT (+) group (28.5 s) (p<0.02). Multivariate logistic regression analysis revealed that APTT lower than 28.5 seconds on POD1 was considered to be independent risk factor significantly contributing to residual DVT (odds ratio 17.5, 95% confidential interval 2.0-295.4, p=0.02). These findings should provide useful information for understanding the interindividual difference of the efficacy of FPX after TKA or THA.
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