YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
134 巻, 3 号
選択された号の論文の24件中1~24を表示しています
誌上シンポジウム
  • 内田 享弘, 都甲 潔
    2014 年 134 巻 3 号 p. 305-306
    発行日: 2014年
    公開日: 2014/03/01
    ジャーナル フリー
  • 都甲 潔
    2014 年 134 巻 3 号 p. 307-312
    発行日: 2014/03/01
    公開日: 2014/03/01
    ジャーナル フリー
      Anyone talks about the taste using different taste scale. Since how to feel the taste is different from one to other people, we sometimes lead to inconsistency when speaking about the taste of food. The present study aims at development of electronic tongue (taste sensor) and electronic nose (odor sensor). There are two important properties about the taste sensor. One, each sensor electrode (lipid/polymer membrane) is specific to each taste. Another is that the sensor can measure the aftertaste such as richness, which is the aftertaste of umami. In the case of, e.g., bitterness electrode (BT0), it responds well to bitter taste substances such as quinine, cetirizine, hydroxyzine and bromhexine. For other taste qualities, on the other hand, it shows no response. A taste sensor is now sold by Intelligent Sensor Technology, Inc., and utilized in pharmaceutical and food companies. An electronic nose to detect lingering scent is composed of surface plasmon resonance (SPR) sensor, which is a sensing device with high sensitivity, and antigen-antibody interaction. A self-assembled monolayer was constructed on the reception surface of SPR device. The experimental result on benzaldehyde, a typical peach flavor, shows the sensor sensitivity 4 ppb, which is superior to the human sensitivity of about 350 ppb. Our developed taste sensor and electronic nose play the role of gustatory and olfactory senses, respectively.
  • 池崎 秀和
    2014 年 134 巻 3 号 p. 313-316
    発行日: 2014/03/01
    公開日: 2014/03/01
    ジャーナル フリー
      In pharmaceutical fields, the palatability of drug formulation has been attracted, especially for children. It is excellent that pediatric medicines are delivered to a famine-stricken area on volunteer work. However, children cannot take extremely bitter drug because they are said to be highly sensitive to bitterness. Therefore, we contribute to the development of formulation palatable to children by providing pharmaceutical industry with “the measure of taste”. In taste sensing technology, we established two methods to control the sensor's characteristics by optimizing both electric density and hydrophobicity of membrane. These innovative approaches enable the development advanced taste sensors to fulfill the 4 types of requirements: (1) The threshold of taste sensors must be the same as the human taste threshold; (2) Taste sensors must respond consistently to the same taste like the human tongue; (3) There must be a clearly defined unit of information from taste sensors; and (4) Taste sensors must detect interactions between taste substances.
  • 内田 享弘
    2014 年 134 巻 3 号 p. 317-323
    発行日: 2014/03/01
    公開日: 2014/03/01
    ジャーナル フリー
      The bitterness of 10 basic medicines was evaluated using a multichannel taste sensor (Intelligent Sensor Technology). Three variables were obtained from the taste sensor data: sensor output (S), the change of membrane potential caused by adsorption, corresponding to aftertaste (C), and the ratio C/S. These variables were used to predict an estimated bitterness score in multiple regression analysis. There was correlation between the bitterness score predicted by the taste sensor and the score obtained by human gustatory sensation. The method showed quantitative predictability for the evaluation of bitterness. Secondly, bitterness intensities of eight H1-antihistamines were assessed by comparing the Euclidean distances between the drug and water using taste sensing system Astree II (α-MOS). Two sensors were ultimately selected as best suited to bitterness evaluation, and the data obtained from the two sensors depicted the actual taste map of the eight drugs. Also the bitterness masking efficiency of epinastine hydrochloride with acesulfame potassium was successfully predicted. Finally, Vesicare® tablets, whose main component is solifenacin succinate, are known to be extremely bitter. Recently, Vesicare® orally disintegrating tablets (ODTs), which contain a salting-out taste-masking system, have appeared on the market. To evaluate the effect of crushing on the bitterness of the tablets, Vesicare® ODTs and conventional Vesicare® tablets (CTs) were crushed either heavily or lightly. The bitterness scores of sample solutions were predicted using taste sensor. The lightly crushed ODT was predicted to be less bitter than CT. When tablets must be crushed, it is strongly recommended that ODT be crushed gently.
  • 原田 努, 櫻井 真帆, 本藤 聡子, 安井 将展, 大脇 孝行
    2014 年 134 巻 3 号 p. 325-331
    発行日: 2014/03/01
    公開日: 2014/03/01
    ジャーナル フリー
      Using a taste sensor in the field of medical products has the following four main purposes: (1) Ensuring that investigational product and placebo are indistinguishable; (2) Formulation design; (3) Quality control; (4) Benchmark test. Unlike evaluating a taste of food, roughly predicting a taste of drug without human sensory test and quantitative evaluation using small quantity of drug sample are more important than evaluation of the nuances of homogeneous taste and preference. Here are some examples of using taste sensor for these purposes. (1) We predicted a taste of suspension of phosphatic drug substance in an early phase of development using a taste sensor. As a result, the suspension seemed to have sour and bitter taste. Then we made placebo solution of citric acid similar taste as much like active suspension to ensure indistinguishable taste from each other. (2) A taste of orally disintegrating tablet (ODT) in the mouth is important to drug adherence. The taste of an ODT was then evaluated in chronological order by combining the taste sensor with the new disintegration testing apparatus to design easy-to-take formulation. (3) We evaluated taste variation of a commercial product in batch-to-batch and identified the cause of the variation. (4) We did benchmark test for easy-to-take of commercial ODTs in vitro. There is great variability among these products in the disintegrating profile and the taste.
  • 中本 高道
    2014 年 134 巻 3 号 p. 333-338
    発行日: 2014/03/01
    公開日: 2014/03/01
    ジャーナル フリー
      In this review, an odor sensing system and an olfactory display are introduced into people in pharmacy. An odor sensing system consists of an array of sensors with partially overlapping specificities and pattern recognition technique. One of examples of odor sensing systems is a halitosis sensor which quantifies the mixture composition of three volatile sulfide compounds. A halitosis sensor was realized using a preconcentrator to raise sensitivity and an electrochemical sensor array to suppress the influence of humidity. Partial least squares (PLS) method was used to quantify the mixture composition. The experiment reveals that the sufficient accuracy was obtained. Moreover, the olfactory display, which present scents to human noses, is explained. A multi-component olfactory display enables the presentation of a variety of smells. The two types of multi-component olfactory display are described. The first one uses many solenoid valves with high speed switching. The valve ON frequency determines the concentration of the corresponding odor component. The latter one consists of miniaturized liquid pumps and a surface acoustic wave (SAW) atomizer. It enables the wearable olfactory display without smell persistence. Finally, the application of the olfactory display is demonstrated. Virtual ice cream shop with scents was made as a content of interactive art. People can enjoy harmony among vision, audition and olfaction. In conclusion, both odor sensing system and olfactory display can contribute to the field of human health care.
  • 喜多 純一
    2014 年 134 巻 3 号 p. 339-347
    発行日: 2014/03/01
    公開日: 2014/03/01
    ジャーナル フリー
      The design concept of flavor and fragrance analyzer “FF-2020” was descried; at first how to recognize the quantification of odor, introducing traditional quantification of odor and how to compose the analyzer. At last two analysis of the medical goods were described. The most important thing to quantify the odor is to recognize the three faced of odor that is chemical component face, subjective feeling and objective feeling. For the electronic nose like a flavor and fragrance analyzer, objective feeling should be quantified by the analyzer. Then the original mode of analysis was made to realize the quantification of the objective feeling.
  • 山本 美智子, 折井 孝男
    2014 年 134 巻 3 号 p. 349-350
    発行日: 2014/03/01
    公開日: 2014/03/01
    ジャーナル フリー
  • 渡邊 伸一
    2014 年 134 巻 3 号 p. 351-353
    発行日: 2014/03/01
    公開日: 2014/03/01
    ジャーナル フリー
      Various information on pharmaceuticals is provided to healthcare professionals in order to ensure the safe use of pharmaceuticals. In addition to package inserts that contain information on indication, dosage, and administration, some review reports of new drugs which contain the summary of the results of clinical trials submitted for new drug application and review process as well as manuals for handling disorders due to adverse drug reactions which contain early symptoms and information on treatment of serious adverse reactions are provided. Information on drugs is renewed based on drug reactions reported to the authority. It is important that pharmacists comprehend this information and have the updated information on drugs, and disseminate this information to other healthcare professionals such as doctors, nurses etc. for the safe use of pharmaceuticals. Pharmacists who have completed a six-year course are expected to utilize all this information and contribute to the safe use of pharmaceuticals.
  • 山本 美智子
    2014 年 134 巻 3 号 p. 355-362
    発行日: 2014/03/01
    公開日: 2014/03/01
    ジャーナル フリー
      It is necessary to offer the proper information about prescription drugs for appropriate use of them in clinical practice. However, a lot of time and labor is required to comprehensively collect the information necessary for clinical application and it could be extremely difficult. If the clinical experience and other information is derived solely on a commercial basis, then it may lead to improper prescription practices. “Academic detailing” is a form of interactive educational outreach to physicians to provide unbiased, non-commercial, evidence-based information about medications and other therapeutic decisions, with the goal of improving patient care. In Western countries, the public funds are used to support universities and other research institution programs. The experience from such programs spreads to a broader scientific community. In US, “Academic detailing” was pioneered 30 years ago. National Resource Center for Academic Detailing (NaRCAD) is an initiative supported by Agency for Healthcare Research and Quality (AHRQ) grant. Clinical pharmacists are acting as Detailers in Europe and America, and this improves medical quality. The importance of Academic Detailing activity would be also recognized in Japan, and fully-trained (with six-years of specialized training) pharmacists with evaluative and communication skills can be expected to act as such a specialist.
  • 錦織 淳美
    2014 年 134 巻 3 号 p. 363-366
    発行日: 2014/03/01
    公開日: 2014/03/01
    ジャーナル フリー
      In 2012, a new medical fee system was introduced for the clinical activities of hospital pharmacists responsible for in-patient pharmacotherapy monitoring in medical institutions in Japan. The new medical system demands greater efforts to provide the most suitable and safest medicine for each patient. By applying the concept of academic detailing to clinical pharmacists' roles in hospitals, I present drug use evaluation in three disease states (peptic ulcer, insomnia, and osteoporosis). To analyze these from multiple aspects, we not only need knowledge of drug monographs (clinical and adverse drug effects), but also the ability to evaluate a patient's adherence and cost-effectiveness. If we combine the idea of academic detailing with a clinical pharmacist's role, it is necessary to strengthen drug information skills, such as guideline or literature search skills and journal evaluation. Simultaneously, it is important to introduce new pharmaceutical education curriculums regarding evidence-based medicine (EBM), pharmacoeconomics, and professional communication in order to explore pharmacists' roles in the future.
  • 中山 健夫
    2014 年 134 巻 3 号 p. 367-370
    発行日: 2014/03/01
    公開日: 2014/03/01
    ジャーナル フリー
      Academic detailing, interactive information services by pharmacists for clinicians, has been getting interests in the US and European countries. A systematic review of randomized controlled trials supported the effectiveness of academic detailing. Knowledge of evidence-based medicine and clinical practice guidelines is one of the essential bases for pharmacists to promote these activities. In addition, pharmacists need to understand attitudes and ways of thinking of clinicians toward medicines. Through communications and information sharing between clinicians and pharmacists, collaborations to modify and improve the use of medicines should be facilitated. On these grounds, academic detailing will be able to play an important role in real healthcare circumstances.
  • 徳山 尚吾, 前田 武彦
    2014 年 134 巻 3 号 p. 371-372
    発行日: 2014/03/01
    公開日: 2014/03/01
    ジャーナル フリー
  • 前田 武彦, 尾髙 昌宣
    2014 年 134 巻 3 号 p. 373-378
    発行日: 2014/03/01
    公開日: 2014/03/01
    ジャーナル フリー
      Transient receptor potential protein (TRP) channels are distributed in pain pathways including primary afferent neurons and function as transduction of various noxious stimuli to innocuous stimuli. TRP channels are considered as molecular basis of chronic pain. Targeting TRPs may lead to novel class of analgesics, and so drug-discovery efforts are focused on TRP agonists and its antagonists. Few products have, however, been placed on the market, because most of candidates have adverse effects. A lesion or disease of the somatosensory nervous system causes neuropathic pain, a type of chronic pain. Neuropathic pain is intolerable and obstinate and therefore, debilitates the affected patients. A great deal of effort has been made to develop medicine targeting molecules involved in neuropathic pain, whereby the promising therapeutically targeted molecules have been identified. Neuroinflammation, based on pathological alteration in crosstalk between nervous system and immune system, has been a focus of attention as pathological mechanism involved in development of neuropathic pain. Recently, we used an animal model for neuropathic pain to find the possibility that neuropathic pain was exacerbated by adipokines derived from perineural adipocytes distributed in injured peripheral neurons. A working hypothesis is therefore proposed that the perineural adipocytes interacts with the immune cells, which also have TRPV1, in injured peripheral nerve, followed by a paracrine loop involving proinflammatory cytokines, chemokines and adipokines derived from them which aggravates and prolongs pain. Here, we overview the developmental status in TRPV1-targetting analgesics and illustrate our recent findings in terms of neuroinflammation.
  • 中川 貴之, 勇 昂一, 原口 佳代, 宗 可奈子, 朝倉 佳代子, 白川 久志, 金子 周司
    2014 年 134 巻 3 号 p. 379-386
    発行日: 2014/03/01
    公開日: 2014/03/01
    ジャーナル フリー
      Neuropathic pain is a pathological pain condition that often results from peripheral nerve injury. Several lines of evidence suggest that neuroinflammation mediated by the interaction between immune cells and neurons plays an important role in the pathogenesis of neuropathic pain. Transient receptor potential melastatin 2 (TRPM2) is a nonselective Ca2+-permeable cation channel that acts as a sensor for reactive oxygen species. Recent evidence suggests that TRPM2 expressed on immune cells plays an important role in immune and inflammatory responses. In this study, we examined the roles of TRPM2 expressed on immune and glial cells in neuropathic pain. TRPM2 deficiency attenuated pain behaviors (mechanical allodynia, thermal hyperalgesia and spontaneous pain behaviors) in various kinds of inflammatory and neuropathic pain, but not in nociceptive pain models. In peripheral nerve injury-induced neuropathic pain models, TRPM2 deficiency diminished infiltration of neutrophils mediated through CXCL2 production from macrophages around the injured peripheral nerve and activation of spinal microglia, suggesting that TRPM2 expressed on macrophages and microglia aggravates peripheral and spinal pronociceptive inflammatory responses. Furthermore, we examined the infiltration of peripheral immune cells into the injured nerve and spinal cord using bone marrow chimeric mice by crossing wildtype and TRPM2-knockout mice. The results suggest that TRPM2 plays an important role in the infiltration of peripheral immune cells, particularly macrophages, into the spinal cord, rather than into the injured nerves. The spinal infiltration of macrophages mediated by TRPM2 may contribute to the pathogenesis of neuropathic pain.
  • 大澤 匡弘, 山本 昇平, 小野 秀樹
    2014 年 134 巻 3 号 p. 387-395
    発行日: 2014年
    公開日: 2014/03/01
    ジャーナル フリー
      Central sensitization in the spinal cord is well known to be involved in chronic pain. Recent investigations indicated that the protein expressions involving the synaptic plasticity are changed in several brain areas under a chronic pain condition. These changes in supraspinal neural function might cause the emotional and memory dysfunction. It is also possible that these changes are involved in the chronic pain. Indeed, since the improvement of spinal and peripheral sensitization showed limited relief in the neuropathic pain, the sensitization of supraspinal nociceptive transmission might be involved in the expression of chronic pain. We recently found that intra-thalamic treatment with excitatory neurotransmitter glutamate caused hyperalgesia, which is mediated by the stimulation of glutamate N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. Moreover, intracerebroventricular treatment with gabapentin, a calcium channel alpha2delta-1 subunit blocker, attenuated the hyperalgesia in the nerve-injury model of mice. These results suggest that the sensitization of supraspinal nociceptive transmission is involved in neuropathic pain. It is also indicated that neuropathic pain is resulted from the activations of spinal glial cells. Likewise, the supraspinal glial activation was observed in the neuropathic pain. Therefore, the sensitization of supraspinal nociceptive transmission might be important for a chronic pain. In this review, we would like to discuss the possible involvement of the supraspinal sensitization in neuropathic pain and in its application for the curative treatment in chronic pain.
  • 中本 賀寿夫, 西中 崇, 里 尚也, 万倉 三正, 小山 豊, 徳山 尚吾
    2014 年 134 巻 3 号 p. 397-403
    発行日: 2014/03/01
    公開日: 2014/03/01
    ジャーナル フリー
      Fatty acids, one class of 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 variety of biological phenomena. The important functional role of fatty acids in both onset and suppression of pain has become increasingly apparent in recent years. Recently, we have also demonstrated that the release of an endogenous opioid peptide, β-endorphin, plays an important role in the induction of docosahexaenoic acid (DHA)-induced antinociception. It is well known that fatty acids affect intracellular and intercellular signaling as well as the membrane fluidity of neurons. In addition to intracellular actions, unbound free fatty acids (FFAs) can also carry out extracellular signaling by stimulating the G protein-coupled receptor (GPCR). Among these receptors, G protein-coupled receptor 40 (GPR40) has been reported to be activated by long-chain fatty acids such as DHA, eicosapentaenoic acid (EPA) and arachidonic acid. In the peripheral area, GPR40 is preferentially expressed in pancreatic β-cells and is known to relate to the secretion of hormone and peptides. On the other hand, even though this receptor is widely distributed in the central nervous system, reports studying the role and functions of GPR40 in the brain have not been found. In this review, we summarize the findings of our recent study about the long-chain fatty acid receptor GPR40 as a novel pain regulatory system.
  • 田辺 光男
    2014 年 134 巻 3 号 p. 405-412
    発行日: 2014/03/01
    公開日: 2014/03/01
    ジャーナル フリー
      Recent studies have revealed considerable evidence for our understanding of the mechanisms underlying the development and maintenance of chronic pain including neuropathic and inflammatory pain. It is considered that plastic changes in the spinal dorsal horn contribute to the amplification of pain signaling. Moreover, persistent pain affects brain function and also the endogenous descending pain regulatory system. To characterize these pathophysiological changes and pharmacological properties in chronic pain conditions at the synaptic level, we have employed in vitro electrophysiology in slices of the spinal cord and supraspinal regions such as brainstem and hippocampus of adult mice and in vivo electrophysiology in anesthetized rats. In particular, we have successfully prepared spinal slices with an attached dorsal root, where A-fiber- or C-fiber-evoked monosynaptic excitatory postsynaptic currents or miniature excitatory postsynaptic currents were recorded from voltage-clamped dorsal horn neurons. In anesthetized rats, C-fiber-evoked field potentials were recorded from the spinal dorsal horn in response to electrical stimulation of the sciatic nerve fibers, and their long-term potentiation was elicited to mimic increased synaptic efficacy after peripheral nerve injury. Of interest is the finding that some drugs exerted the injury-specific effects on synaptic transmission, thus strongly suggesting the importance of pharmacological analysis at the synaptic level combined with electrophysiological techniques to obtain pathophysiological information and new insights into drug research in this field.
総説
一般論文
  • 菅原 隆文, 村上 礼隆, 植竹 宣江, 松本 俊治, 宮森 伸一, 岡本 良一, 開 浩一
    2014 年 134 巻 3 号 p. 433-438
    発行日: 2014/03/01
    公開日: 2014/03/01
    ジャーナル フリー
      The Guidelines for Management of Deep-seated Mycoses 2007 recommend the use of micafungin as a first-line agent for the treatment of candidemia. On the package insert, the recommended dose of micafungin is 50 mg/d. However, the Guidelines recommend a micafungin dose of 100-150 mg/d. In the present study, we evaluated the relationship between the effectiveness and dose of micafungin in 42 patients with candidemia who underwent treatment with micafungin. We found that the efficacy rate of micafungin at a dose of 50 mg/d was 40%, whereas that at ≥100 mg/d was 87.5%. Moreover, the treatment was more effective in patients who received ≥100 mg/d of micafungin as compared to those who received 50 mg/d of micafungin. Furthermore, we assessed the efficacy of micafungin according to the Candida species. Among all patients, the efficacy rate of micafungin was found to be lower in patients infected by Candida parapsilosis as compared to those infected by other Candida species. However, among the patients who received ≥100 mg/d of micafungin, the efficacy rate in patients infected by Candida parapsilosis was equivalent to that of patients who were infected by other Candida species. Thus, based on the results of the present study, the optimal micafungin dose for the treatment of candidemia appears to range from 100 to 150 mg/d, as recommended by the Guidelines.
ノート
  • 白井 義啓, 篠島 俊史, 内山 周, 竹腰 昌広, 津島 永吉, 田端 俊英
    2014 年 134 巻 3 号 p. 439-445
    発行日: 2014年
    公開日: 2014/03/01
    [早期公開] 公開日: 2013/12/04
    ジャーナル フリー
      The cerebellar cortex, the brain region responsible for motor coordination and learning expresses a high density of B-type γ-aminobutyric acid receptor (GABAbR). Previous in vitro and in situ studies indicated that cerebellar GABAbR may mediate multiple forms of inhibitory and excitatory modulation of cerebellar circuits. Nevertheless, the in vivo influence of cerebellar GABAbR activation is unclear. As the first step in addressing this issue, we examined how pharmacological activation of cerebellar GABAbR modulates optokinetic reflex (OKR), an involuntary cerebellum-dependent eye movement for stabilizing the retinal image against the drift of the visual scene. We injected baclofen, a GABAbR-selective agonist, or control saline into the cerebellar flocculi of adult mice and then performed 1-h OKR measurement sessions on two consecutive days. In the day 1 session, the baclofen (5 nM)-injected mice and control mice showed similar initial OKR gains and similar training-induced increases in the OKR gain (OKR adaptation). This result suggests that GABAbR activation does not affect cerebellar computation for executing OKR and formation of short-term memory for OKR adaptation. At the beginning of the day 2 session, the baclofen (5 nM or 50 μM)-injected mice showed an OKR gain higher than that achieved in the day 1 session while the control mice did not. This result suggests that GABAbR activation may facilitate the formation of OKR adaptation-related long-term memory. These findings provide a new insight into the functional architecture of the cerebellar circuits and indicate GABAbR to be a new target of pharmacological therapy against diseases with cerebellar dysfunction.
  • 相良 英憲, 川手 結梨, 田中 守, 田中 亮裕, 出石 文男, 荒木 博陽
    2014 年 134 巻 3 号 p. 447-453
    発行日: 2014/03/01
    公開日: 2014/03/01
    [早期公開] 公開日: 2013/12/11
    ジャーナル フリー
      The clinical training curriculum for fifth-year students of a school of medicine (Department of Medicine) includes training in clinical pharmacy, which is conducted by the Department of Pharmacy. Following training involving the simple suspension method, a survey was conducted to examine its effects to improve medical students' knowledge on the proper use of drugs. Forty-eight 5th-year students of Ehime University School of Medicine, Department of Medicine, underwent training that employed the simple suspension method, and examinations were conducted prior to and following it to assess its effects. Following the training, the questionnaire results were analyzed using Quantification Theory Class II to examine whether knowledge acquired from it had motivated the students to use the simple suspension method. A correspondence structural analysis was also conducted to identify improvements in the training. The correct answer rate increased from 55.2±2.4% before to 83.8±1.7% after training, which supports its learning effects. The presence or absence of changes in disposition and the efficacy of the method for patients with dysphagia strongly motivated the medical students to use the method. As a future improvement, it is necessary to describe differences between the crushing and simple suspension methods during training. The results of a survey on training involving medical students conducted based on the simple suspension method suggested its learning effects and knowledge that motivated them to use the method.
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