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138 巻, 5 号
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受賞総説
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畠山 浩人2018 年 138 巻 5 号 p. 591-598
発行日: 2018/05/01
公開日: 2018/05/01
ジャーナル フリーNucleic acid therapy is expected to be a next generation medicine. We recently developed a multifunctional envelope-type nano device (MEND) for use as a novel delivery system. The modification of polyethylene glycol (PEG), i.e., PEGylation, is useful for achieving the delivery of MENDs to tumors via an enhanced permeability and retention (EPR) effect. However, PEGylation strongly inhibits the cellular uptake and endosomal escape of MEND, which results in significant loss of action, and therefore lost effectiveness, of the cargo therapeutic. For successful nucleic acid delivery in cancer treatment, the crucial problem associated with the use of PEG, known as the “PEG dilemma”, must be solved. In this review, we describe the development and application of MEND in overcoming the PEG dilemma based on manipulating both the pharmacokinetics and intracellular trafficking of cellular uptake and endosomal release using a cleavable PEG lipid, a pH-sensitive fusogenic peptide, and a pH-sensitive cationic lipid. We also developed dual-ligand liposomes with a controlled diameter of around 300 nm, then modified these with a specific ligand and a cell penetrating peptide designed to target the neovasculature of tumors. Dual-ligand liposomes could induce an anti-tumor effect in drug resistant tumors by delivering drugs to tumor blood vessels, rather than to the cancer cells themselves. Here, we review our recent efforts to develop a novel liposomal drug delivery system (DDS) by manipulating pharmacokinetics and intracellular trafficking for drug therapy and nucleic acid medicine.
抄録全体を表示Editor's pickThe modification of polyethylene glycol (PEG), i.e. PEGylation is commonly used approach for increasing stability of drug delivery systems (DDSs), but results in loss of activity simultaneously. This article describes the trade-off relationship between activity and stability as PEG dilemma and strategies to overcome PEG dilemma. The authors developed a cleavable PEG lipid in response to tumor microenvironment, a pH-sensitive fusogenic peptide, and pH-sensitive cationic lipids in response to endosome/lysosome, which balanced activity and stability of DDSs and exerted therapeutic effect of nucleic acid cargos.
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誌上シンポジウム
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鈴木 順子, 今津 嘉宏2018 年 138 巻 5 号 p. 599-600
発行日: 2018年
公開日: 2018/05/01
ジャーナル フリーPDF形式でダウンロード (187K) -
今津 嘉宏, 米田 吉位, 内田 恵美子, 山浦 克典, 鈴木 順子2018 年 138 巻 5 号 p. 601-605
発行日: 2018年
公開日: 2018/05/01
ジャーナル フリーOnychomycosis often remains undiagnosed by physicians during patient home visits. Prescriptions of antifungal medications require blood tests because of possible side effects, especially in patients with liver dysfunction. However, the general condition of onychomycosis patients in home care is often unstable; thus, antifungal use may be contraindicated. Although onychomycosis is a dermatological disease, visiting physicians should perform initial treatment as a part of home medical care. In general, home-visting physicians should be prepared to respond to initial treatment in areas other than their specialized field of medical training. This study revealed problems in: 1)methods of recording the course of treatment; 2）recognition of differences in needs among medical professionals; and 3）changes in the burdens experienced by patients. In aging societies, the focus continues to shift from hospital-based to home-based medical care and treatment delivery has changed from specialists to medical care teams. Healthcare should provide continuous treatment for various medical issues such as hypertension, hyperlipidemia, cardiovascular disease, nutritional management, and palliative care to patients and their families. Teams of physicians, visiting nurses, and pharmacists play important roles in home-based professional medical care. Using the treatment of onychomycosis as an example, it was possible to identify methods to improve the lifestyles of home-based patients.
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米田 吉位, 今津 嘉宏, 内田 恵美子, 山浦 克典, 鈴木 順子2018 年 138 巻 5 号 p. 607-609
発行日: 2018/05/01
公開日: 2018/05/01
ジャーナル フリーPatients usually consult a dermatologist for the treatment of onychomycosis. However, in the case of home care, visiting nurses may assist with bathing, which offers the opportunity to observe patients' feet for possible signs of onychomycosis without causing anxiety. It is estimated that more than 30% of patients receiving home care have onychomycosis. Before the approval of efinaconazole, healthcare personnel hesitated to treat onychomycosis because of: 1) possible side effects, especially liver dysfunction and pain due to repeated blood collection, as a major goal of home care is to minimize pain; and 2) the questionable efficacy of previously available antifungal medications. In addition, many patients report fear of “transmitting athlete's foot to others” and “do not want to show my dirty toenails”. On the other hand, caregivers reportedly worry about “athlete's foot being transmitted to them”.
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内田 恵美子, 今津 嘉宏, 米田 吉位, 山浦 克典, 鈴木 順子2018 年 138 巻 5 号 p. 611-613
発行日: 2018/05/01
公開日: 2018/05/01
ジャーナル フリーThe aim of this study was to assess the effects of cooperation by visiting nurses and physicians experienced in general patient care, dermatology, and podiatry for the treatment of ringworm. Questionnaires were delivered to 1184 patients receiving home-based care by one of 14 participating visiting nursing establishments with a combined capacity of 3273 patients throughout five wards of the Tokyo metropolitan area. Responses were obtained from 691 patients (participation rate, 60.2%; average age, 80.2 years). The onychomycosis morbidity rate among home care patients was 22.7%. The results showed a significant reduction in the incidence of ringworm in the intervention group, from 79.5% to 54.5% (p=0.022), and in the incidence of “foot skin infection”, from 100.0% to 31.6% (p<0.001). Although the level of care deteriorated in the control group (p=0.008), there was no significant change in the intervention group. The incidence of leg pain also remained unchanged in the control group (p=0.285) but decreased in the intervention group (p=0.003). While the “degree of satisfaction with foot cleanliness” did not change significantly in the control group (p=0.260), patients in the intervention group were generally satisfied with foot cleanliness. It is necessary to take into account foot care and the effect of onychomycosis treatment vearsusu no treatment and to ensure that visiting nurses and caregivers master foot care-related treatment regimens. We suggest the need to improve the maintenance of foot care and ringworm intervention/treatment performed by physicians, nurses, and caregivers.
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山浦 克典, 林 直子, 今津 嘉宏, 米田 吉位, 内田 恵美子, 鈴木 順子2018 年 138 巻 5 号 p. 615-619
発行日: 2018/05/01
公開日: 2018/05/01
ジャーナル フリーThere is an urgent need to promote home medical care in Japan because of the country's superaging society. Community pharmacists are expected to play an important role as part of home medical care teams. The prevalence of nail ringworm is high among home-care patients and can cause decreases in the quality of life, including difficulty in walking due to pain caused by nail deformation and inflammation around infected nails. Nail ringworm is typically treated with oral medication. However, the condition is left untreated in many elderly patients because of the risk of drug-drug interactions or concerns about severe liver damage. Efinaconazole, a novel triazole antifungal agent, has recently become available in Japan, enabling patients with nail ringworm to be treated with a topical medication. In topical treatment, the method of application is important because of its major impact on the therapeutic effect. Therefore, pharmacists should take special care to instruct patients and caregivers on the proper use of topical efinaconazole. Adherence to oral medication can be easily monitored by checking the number of tablets or capsules remaining, but adherence to topical medication regimens is more difficult to assess because the remaining amount cannot be determined precisely by checking the outer appearance of the container. The aim of this study was to determine and improve home-care patients' adherence to topical efinaconazole treatment regimens by measuring amounts remaining in the containers using a portable electronic scale. We found that this method is useful for determining the status of topical efinaconazole use.
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鈴木 順子, 今津 嘉宏, 米田 吉位, 山浦 克典, 内田 恵美子2018 年 138 巻 5 号 p. 621-628
発行日: 2018/05/01
公開日: 2018/05/01
ジャーナル フリーIn a superaging society, the medical paradigm should include both less coverage of medical-care work flow by human resources and high-quality care for patients. Strategies such as establishing medical-care teams and community medicine systems mainly for home medical care should be implemented. However, a well-organized system for home-based medical treatment of elderly patients is not yet in place, as evidenced by the lack of care, problems with long-term polypharmacy resulting from visits to multiple healthcare providers, and declines in their physical strength. It is assumed that care might not be provided in association with treatment because planning based on the paradigm of “home medical care” has not been fully established. Therefore, in this study, we aimed to determine the “paradigm shift in home medical care” based on the treatment of onychomycosis. We also hoped to identify the types of medical support required to improve the general well-being of individuals and what needs to be done to ensure a high quality of life for patients. All those (including patients themselves) involved in patient care should together formulate a protocol for medical treatment and cooperate based on the role each can play. Although it may be difficult to maintain cooperation among healthcare workers, improvements in the medical quality of an entire region can be achieved by planning a life design including medical treatment for each patient.
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清水 忠, 安原 智久2018 年 138 巻 5 号 p. 629
発行日: 2018/05/01
公開日: 2018/05/01
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佐々木 順一, 北澤 京子, 中山 健夫2018 年 138 巻 5 号 p. 631-635
発行日: 2018/05/01
公開日: 2018/05/01
ジャーナル フリーThis research aimed to clarify the present status and challenges of evidence-based medicine (EBM) education in schools of pharmacy. We sent a questionnaire to 268 faculty members in August 2015, and a total of 192 were completed. The educational contents by respondents differed considerably. Only about 30% of respondents self-assessed the current EBM courses they taught as “fulfilling”. Challenges such as “time deficits”, “lack of exercise lessons and practical training”, “limited awareness and skills of teachers”, “lack of appropriate educational tools”, and “insufficient academic ability of students” were mentioned.
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小川 竜一2018 年 138 巻 5 号 p. 637-644
発行日: 2018/05/01
公開日: 2018/05/01
ジャーナル フリーTraining pharmacy students to become future clinical pharmacists is an important mission in the 6-year school of pharmacy curriculum in Japan. Since 2014, we have conducted an on-campus practical training program to develop basic skills in clinical pharmacy for third-year pharmacy students at Meiji Pharmaceutical University. This training program includes searching for and retrieving drug information; interpretation of laboratory findings, vital signs, and physical examinations; literature appraisal; and professional writing. These training sections are arranged in the above-mentioned order to facilitate effective understanding of each. In the literature appraisal section, each student group is assigned a report on a prospective controlled study of a given drug published in English and reads it critically according to the literature appraisal worksheet. Then the group writes a monograph on the drug described in the report based on the literature and other information. Thereafter, all students are reshuffled into new groups so that students who were assigned different drugs are placed together, in the so-called jigsaw learning method. Students then discuss which two or three drugs in a specific pharmacological class should be adopted in the hospital formulary according to the knowledge gained through this training program series. The themes were novel oral anticoagulants in the 2014 academic year, dipeptidyl peptidase 4 inhibitors in 2015, and 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors in 2016. Although there are some problems that need to be resolved in the future, this approach appears effective in helping students build drug information skills as a basic competence of clinical pharmacists.
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恩田 光子, 高垣 伸匡2018 年 138 巻 5 号 p. 645-647
発行日: 2018/05/01
公開日: 2018/05/01
ジャーナル フリーOsaka University of Pharmaceutical Sciences has included an evidence-based medicine (EBM) exercise in the introductory education for clinical practice for 4th-year pharmacy students since 2015. The purpose of this exercise is to learn the process of practice and basic concepts of EBM, especially to cultivate the practical ability to solve patients' problems and answer their questions. Additionally, in 2016, we have attempted flipped teaching. The students are instructed to review the basic knowledge necessary for active learning in this exercise by watching video teaching materials and to bring reports summarizing the contents on the flipped teaching days. The program includes short lectures [overview of EBM, document retrieval, randomized controlled trials (RCTs), and systematic review], exercises [patient, intervention, comparison, outcome (PICO) structuring, critical appraisal of papers in small groups with tutors], and presentations. The program includes: step 1, PICO structuring based on scenarios; step 2, critical appraisal of English-language papers on RCTs using evaluation worksheets; and step 3, reviewing the results of the PICO exercise with patients. The results of the review are shared among groups through general discussion. In this symposium, I discuss students' attitudes, the effectiveness of small group discussions using flipped teaching, and future challenges to be addressed in this program.
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江角 悟, 河崎 陽一, 猪田 宏美, 北村 佳久, 千堂 年昭2018 年 138 巻 5 号 p. 649-653
発行日: 2018/05/01
公開日: 2018/05/01
ジャーナル フリーPharmacists are required to contribute to evidence-based medicine (EBM) by providing drug information, which can be collected from various sources such as books, websites, and original articles. In particular, information from original articles is needed in some situations. For example, original articles by international researchers are used to aid the management of novel in-hospital preparations on which little knowledge is available. We introduced an information evaluation program, the Okayama University Hospital EBM Model, into the clinical training of 5th-year pharmacy students. It aims to enable students to evaluate the validity of novel in-hospital preparations using original articles. This program has improved students' knowledge of EBM, and the satisfaction level of those enrolled was high. In addition, customer satisfaction analysis revealed that the overall degree of student satisfaction was related to their understanding of the necessity for EBM and the difficulty of practical training. In addition, students' achievements were evaluated using rubrics, and that method allowed the achievements of each student to be assessed appropriately. We hope to revise this program with the aim of improving students' understanding of EBM.
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清水 忠, 上田 昌宏, 豊山 美琴, 大森 志保, 高垣 伸匡2018 年 138 巻 5 号 p. 655-666
発行日: 2018/05/01
公開日: 2018/05/01
ジャーナル フリーPracticing evidence-based medicine (EBM) is likely to gain importance for clinical pharmacists in the relatively near future in Japan. An educational program including research and the critical appraisal of literature was required for pharmacy students as of 2015. We organized a six-month practical EBM course for pharmacy students at Hyogo University of Health Sciences. To evaluate its effectiveness, students took a 10-question test after completing the course. The mean score of six students was 8.33±1.79 points. We also conducted a 1-day practical EBM workshop for pharmacists. Changes in knowledge and skills related to EBM were evaluated based on the responses to 10 questions. Knowledge and skills related to several variables improved significantly after the workshop (6.36 points before versus 9.09 points after the workshop; p=0.023). The results suggested that our EBM educational course is effective in improving EBM-related knowledge and skills of pharmacists and pharmacy students.
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小坂田 文隆, 小池 千恵子2018 年 138 巻 5 号 p. 667-668
発行日: 2018/05/01
公開日: 2018/05/01
ジャーナル フリーPDF形式でダウンロード (191K) -
恩田 将成, 三澤 幸樹, 小坂田 文隆2018 年 138 巻 5 号 p. 669-678
発行日: 2018/05/01
公開日: 2018/05/01
ジャーナル フリーThe mammalian retina consists of five classes of neurons: photoreceptor, horizontal, bipolar, amacrine, and ganglion cells. Based on cell morphology, electrophysiological properties, connectivity, and gene expression patterns, each class of retinal neurons is further subdivided into many distinct cell types. Each type of photoreceptor, bipolar, and ganglion cell tiles the retina, collectively providing a complete representation across the visual scene. Visual signals are processed by at least 80 distinct cell types and at least 20 separate circuits in the retina. These circuits comprise parallel pathways from the photoreceptor cells to ganglion cells, each forming a channel of visual information. Feed-forward and feedback inhibition of horizontal and amacrine cells shape these parallel pathways. However, the cell-type-specific roles of inhibitory circuits in retinal information processing remain unknown. Here we summarize parallel processing strategies in the retina, and then introduce our viral and electrophysiological approaches that reveal the roles of genetically defined subtypes of amacrine cells in retinal circuits.
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竹内 晴紀, 坪 泰弘, 北野 勝則, 小池 千恵子2018 年 138 巻 5 号 p. 679-684
発行日: 2018/05/01
公開日: 2018/05/01
ジャーナル フリーThe vertebrate retina is one of the most sophisticated parts of the nervous system. It comprises five classes of neurons and one glial type cell. During development, but prior to a vertebrate's eyes opening, retinal circuits are refined by endogenous neural activity. Characteristic patterns of activity, including oscillatory activity, occur in the normal retina, whereas distinctive alternative patterns occur in abnormal retinas. In this paper, we first describe the electrophysiological and spike sorting methods used to study retinal oscillations. Next, we describe the mechanisms and functions of oscillation in the normal retina. Finally, we characterize the distinctive oscillations and abnormal spontaneous activities in the degenerative retina.
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谷口 佳那子, 小池 千恵子, 北野 勝則2018 年 138 巻 5 号 p. 685-692
発行日: 2018/05/01
公開日: 2018/05/01
ジャーナル フリーRhythmic neural activities are observed in many brain regions, and these are considered to play an important role in neural information processing. On the other hand, distinct rhythmic neural activities emerge under several pathological conditions, suggesting that rhythmic neural activity has a close relation to brain function and dysfunction. In many pathological cases, the intrinsic property of unusual rhythm generation in a neuron or a neuronal network is prevented under normal conditions, but released by the pathological condition. Therefore, it may be useful to explore which conditions determine rhythm generation in order to understand the mechanisms of brain function/dysfunction. The pathological retina in retinal degeneration exhibits rhythmic neural activity not observed in the healthy retina. In this review, we first provide a brief introduction to the possible mechanisms of rhythm generation in a neural system. Then we introduce experimental evidence of rhythm generation in the pathological retina, as well as two hypotheses regarding this mechanism. Finally, we raise several issues to be solved for the further understanding of pathological rhythm generation.
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総説
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北村 繁幸2018 年 138 巻 5 号 p. 693-713
発行日: 2018/05/01
公開日: 2018/05/01
ジャーナル フリーThe endocrine-disrupting activities of various environmental chemicals are metabolically activated. For example, diphenyls, styrene oligomers, chalcones, trans-stilbene and 2-nitrofluorene are not estrogens, but after incubation with liver microsomes, their metabolites show estrogenic activities. Thus, these chemicals are estrogenically activated by the cytochrome P450 system. In contrast, the antiandrogenic activity of fenthion, an organophosphorus insecticide, is abolished after metabolism to sulfoxide and sulfone derivatives. Structural requirements of twenty bisphenol A related compounds, as well as various benzophenones, for estrogenic and antiandrogenic activities have been investigated. The estrogenic and antiandrogenic activities of Benzophenone 3, a representative UV absorbant, are activated by oxidative metabolism. Parabens (used as antimicrobial agents) exhibit estrogenic activity, and their potency shows a bell-shaped curve between C1 (methylparaben) and C12 (dodecylparaben) parabens. The AhR ligand activity of indirubin is decreased by metabolism. Polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDE) are activated by hydroxylation to show estrogenic and thyroid hormone-disrupting activities. Halogen adjacent to a hydroxyl group is essential for thyroid hormone-disrupting activity. Tetrabromobisphenol A, tetrachlorobisphenol A and tetramethylbisphenol A also exhibit thyroid hormone-disrupting activity. Amphibian metamorphosis of tadpoles to frogs is affected by hydroxylated PCB, hydroxylated PBDE and bisphenol A derivatives. These chemicals suppress thyroid hormone-dependent metamorphosis, acting as antagonists of thyroid hormone. Thus, metabolic modification can have a dramatic impact on the endocrine-disrupting activities of environmental chemicals.
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ノート
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炭 昌樹, 長谷川 千晶, 森井 博朗, 星野 伸夫, 奥貫 裕美, 金本 賢枝, 堀江 美弥, 岡本 陽香, 藪田 直希, 松田 雅史, ...2018 年 138 巻 5 号 p. 715-722
発行日: 2018年
公開日: 2018/05/01
ジャーナル フリーThe importance of community-based care systems has increased due to the highly aging population and diversity of disease. To enhance the cooperation among healthcare professionals in community-based care systems, a two-day on-site training program for community pharmacists based on a multidisciplinary team approach was conducted at the Medical Science Hospital of Shiga University from April 2015 to March 2017. There were two professional courses in this training program: the palliative care course and nutrition support course. Both courses consisted of common pharmaceutical care training as follows: regional cooperation among healthcare professionals, pharmacist's clinical activities in the ward, pressure ulcer care, infection control, and aseptic technique for parenteral solutions. Each course was limited to 2 participants. A questionnaire was given to participants in the training program. Seventy-five pharmacists participated in the training and all of them answered the questionnaire. According to the questionnaire, 86% of participants felt that 2 days was an appropriate term for the training program. Positive answers regarding the content of each program and overall satisfaction were given by 100% and 99% of the participants, respectively. In the categorical classification of free comments regarding the expected change in pharmacy practice after the training, both “support for patients under nutritional treatment” and “cooperation with other medical staff” were answered by 24 participants. These results suggested that the 2-day on-site training for community pharmacists facilitated cooperation among healthcare professionals in the community.
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前田 直人, 庄司 雅紀, 橋本 萌, 荒川 行生, 恩田 光子2018 年 138 巻 5 号 p. 723-729
発行日: 2018/05/01
公開日: 2018/05/01
ジャーナル フリーThe objective of this survey is investigating pharmacists' recognition of and belief in the importance of doing PRE-AVOID using the drug profile book (DPB). The main survey items were: 1. Awareness and self-confidence concerning PRE-AVOID using DPB, 2.Status of educating patients of the merits of the DPB, 3. Status of educating patients of the utilities of the DPB, 4. Status of educating patients of the roles of the DPB, 5. Guidance provided on methods of DPB usage, and 6. Interactions with patients. A multiple regression analysis was performed using “Awareness and self-confidence concerning PRE-AVOID using DPB” as a dependent variable. A regression equation including three items (“Educating the roles”, “Blood test”, and “Not using multiple DPBs at same time”) was derived for “Self-confidence in PRE-AVOID work” (R2=0.20). The item most affecting “Self-confidence in PRE-AVOID work” was “Educating the roles” (R=0.28). A regression equation with “Awareness of PRE-AVOID work” as a dependent variable was not derived. The results of the study suggest that “Educating the roles” or “Not using multiple DPBs at same time” for patients, and asking the results of “Blood test” in a medication consultation may increase pharmacists belief in doing PRE-AVOID.
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