著者

田中 喜秀 鳴石 奈穂子

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.128, no.11, pp.1595-1604, 2008 (Released:2008-11-01)

参考文献数

15

被引用文献数

5 5 1

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Psychological stress is of major importance to all age groups in recent years, and may lead to mental disorder and various diseases. An objective and quantitative method for measuring salivary stress-related substances is highly desired because saliva collection is easy, stress free and noninvasive. We have developed a rapid and easy-to-use analytical tool for the measurement of cortisol and secretory immunoglobulin A (sIgA) based on microchip technology, immunoselectivity and electrophoretic separation technique. Performing immunoreaction and capillary electrophoresis (CE) separation on microchips is a promising technique for on-site determination of biogenic substances, and has a few advantages over conventional immunoassay methods: reduced sample size, shortening analysis times, high separation efficiency, reduced cost, and downsizing of analytical system. At this stage of our research, some preliminary prototypes of a high-sensitive microchip CE instrument were constructed to determine the stress-related substances in real saliva samples. However, there is not enough detection sensitivity for cortisol analysis. On the other hand, sIgA was successfully analyzed using a laboratory-built microchip CE system and optimal analytical conditions. The sIgA determination is rapid compared with a conventional immunoassay method, and provides an acceptable degree of repeatability and recovery. In the future, microchip technologies will enable total automation and integration of sample preparation. This research has widespread future potential for monitoring multiple stress-related markers within minutes from a trace of saliva, and can contribute to disease prevention and overall good health.

著者

嶋根 卓也

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.136, no.1, pp.79-87, 2016 (Released:2016-01-01)

参考文献数

16

被引用文献数

6

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The non-medical use or abuse of prescription drugs, including benzodiazepines, is a growing health problem in Japan. An association between prescription drug overdose and suicide risk has also been reported. The Japanese Ministry of Health, Labour and Welfare has expected pharmacists to act as “gatekeepers”, facilitating early identification of individuals at high risk of prescription drug abuse including overdose, supplying medication counseling to patients, and helping to introduce these patients to appropriate medical care. Prescription drugs such as benzodiazepines are widely used in psychiatry. However, these drugs are prescribed not only by psychiatrists but also by other healthcare professionals including primary care physicians. Moreover, in recent years, the dispensing of prescriptions has moved rapidly from inside to outside hospitals, with prescription drugs being dispensed mainly at community pharmacies. Although all healthcare professionals including hospital pharmacists can play a role in preventing prescription drug abuse, the role of the community pharmacist is vital in addressing this problem. Formerly, community pharmacists were recognized as “community scientists”, low-threshold accessible healthcare advisors. Now, community pharmacists should return to the role of community scientists to prevent prescription drug abuse. This article begins by reviewing the current situation of prescription drug abuse and dependence in Japan. The role of pharmacists as gatekeepers in preventing prescription drug abuse is then examined. Finally, this article discusses the effect of intervention in the form of gatekeeper training for community pharmacists.

著者

野村 渉

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.135, no.3, pp.405-414, 2015 (Released:2015-03-01)

参考文献数

79

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Artificial zinc finger proteins (ZFPs) consist of Cys2-His2-type modules composed of approximately 30 amino acids that adopt a ββα structure and coordinate a zinc ion. ZFPs recognizing specific DNA target sequences can substitute for the binding domains of various DNA-modifying enzymes to create designer nucleases, recombinases, and methylases with programmable sequence specificity. Enzymatic genome editing and modification can be applied to many fields of basic research and medicine. The recent development of new platforms using transcription activator-like effector (TALE) proteins or the clustered regularly interspaced short palindromic repeats/CRISPR-associated protein (CRISPR/Cas) system has expanded the range of possibilities for genome-editing technologies. These technologies empower investigators with the ability to efficiently knockout or regulate the functions of genes of interest. In this review, we discuss historical advancements in artificial ZFP applications and important issues that may influence the future of genome editing and engineering technologies. The development of artificial ZFPs has greatly increased the feasibility of manipulating endogenous gene functions through transcriptional control and gene modification. Advances in the ZFP, TALE, and CRISPR/Cas platforms have paved the way for the next generation of genome engineering approaches. Perspectives for the future of genome engineering are also discussed, including applications of targeting specific genomic alleles and studies in synthetic biology.

著者

栗田 かほる 望月 優花 国分 秀也 厚田 幸一郎

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.135, no.11, pp.1307-1315, 2015 (Released:2015-11-01)

参考文献数

14

被引用文献数

2

---

The dose of a transdermal fentanyl patch is proportional to its application site area. Therefore, the absorption of fentanyl may decrease if the patch detaches, leading to insufficient analgesia. Sixteen healthy volunteers were enrolled in a study to investigate the appropriate application sites and clinical utility of three transdermal fentanyl patches available in Japan. Three placebos, Fentanyl 1-day (Fentos; Fen), Fentanyl 3-day (Durotep; Dur), and Generic Fentanyl 3-day (HMT) were administered using a crossover study design. The placebos were applied to 11 different sites, including both sides of the upper arm, abdomen, back, thigh, chest, and the middle of the chest. We determined the patch detachment area and incidence of patch-induced itching every 24 h and evaluated differences between each application site using the Wilcoxon signed-rank test. Significant patch detachment was observed on the abdomen and upper arms with Fen, on the abdomen and chest with Dur, and on the chest with HMT compared with that at other sites (p<0.005). Although no significant difference in itching was observed between regions when administering Fen, itching significantly increased on the chest and back when using Dur and on the abdomen when using HMT as compared with that at other sites (p<0.05). Our results indicate that the three transdermal Fen patches exhibit different adhesive properties and local adverse events, indicating that the application site should be cautiously selected for each patch type.

著者

古川 昭栄

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.135, no.11, pp.1213-1226, 2015 (Released:2015-11-01)

参考文献数

71

被引用文献数

1 3

---

The author has studied nerve growth factor (NGF) and its family of neurotrophic factors (neurotrophins) for over 40 years. During the first 20 years, my laboratory established a highly sensitive enzyme immunoassay for NGF and analyzed the regulatory mechanism of NGF synthesis in cultured primary cells. Fibroblast cells cultured from peripheral organs such as the heart and astrocytes from the brain produced a substantial amount of NGF in a growth-dependent manner. Furthermore, synthesis of NGF in these cells could be upregulated by catechol compounds including catecholamines. This observation might explain a physiological relation between the level of NGF mRNA and the density of innervation in the peripheral sympathetic nervous systems. Over the subsequent 20 years, my laboratory investigated the physiological functions of neurotrophic factors, including neurotrophins, during development or post-injury and found that brain-derived neurotrophic factor (BDNF) plays a role in the formation of the laminar structure of the cerebral cortex. In addition, my laboratory discovered that endogenous glial cell line-derived neurotrophic factor (GDNF) contributes to the amelioration of motor activity after spinal cord injury. Therefore we aimed to develop low-molecular weight compounds that generate neurotrophic factor-like intracellular signals to protect or ameliorate neurological/psychiatric diseases. 2-Decenoic acid derivatives and other similar molecules could protect or ameliorate in animal models of mood disorders such as depression and enhance recovery from spinal cord injury-induced motor paralysis. Compounds that can generate neurotrophin-like signals in neurons are expected to be developed as therapeutic drugs for certain neurological or psychiatric disorders.

著者

五郎丸 毅 古田 隆 馬場 茂雄 野田 敦子 井口 定男

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.101, no.6, pp.544-547, 1981-06-25 (Released:2008-05-30)

参考文献数

11

被引用文献数

3

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The kinetic isotope effects in the in vivo metabolism of three kinds of deuterated aminopyrine (AM), i.e., AM-3-CD3, AM-2-CD3 and AM-4-N (CD3)2, were investigated. In order to evaluate the effect of deuterium labeling on the metabolic rate of AM, an equimolar mixture of AM and AM-3-CD8 (AM : AM-3-CD3), AM : AM-2-CD3 or AM : AM-4-N (CD3)2, was orally administered to rats. Urinary metabolites were extracted with chloroform and the extracts were subjected to gas chromatograph-mass spectrometer after trimethylsilylation. AM metabolites were measured by using selected ion monitoring focused on their molecular ions. The kinetic isotope effect was estimated from the ratio of the amount of the metabolite excreted from deuterated AM to that excreted from AM (D/H ratio). After the administration of AM : AM-3-CD3, D/H ratios of 3-hydroxymethyl metabolites were in the range of 0.347 to 0.403. On the contrary, D/H ratios of 4-demethylamino metabolites were in the range of 1.22 to 1.30. These values indicated that the deuterium labeling of AM shifted the initial step of AM metabolism from oxidation of the 3-methyl group to demethylation of the 4-dimethylamino group. This isotope effect is well-known as a "metabolic switching". In the case of AM-4-N (CD3)2, D/H ratio of 4-formylaminoantipyrine indicated the effect on the oxidative formylation by deuterium labeling.

著者

七海 陽子 恩田 光子 坪田 賢一 田中 理恵 向井 裕亮 的場 俊哉 田中 有香 荒川 行生

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.135, no.9, pp.1057-1067, 2015 (Released:2015-09-01)

参考文献数

24

被引用文献数

5

---

In Japan the prevalence of dementia has increased considerably, and pharmacists are involved in addressing these patients' medication-related problems. Here, we determined whether pharmacists' comprehensive assessment of medication profiles could reduce the burden of dementia patients' medication-related problems. In this historical cohort study 120 community pharmacies were randomly selected, and participating pharmacists completed questionnaires concerning comprehensive assessment of patient medication profiles, using a “start” questionnaire for patients prescribed medication prior to or during the study period and a “follow-up” questionnaire for patients who subsequently visited pharmacies for prescriptions. Numbers and details of problems and solutions implemented by pharmacists and identified in the start and follow-up questionnaires were compared. Changes in start and follow-up scores were also compared between patients whose problems were identified by pharmacists (identified group) and those whose problems were not (non-identified group). Data were collected for 349 patients issued medication by 60 pharmacies. The most common medication-related problems identified in the start survey were key person's understanding of donepezil (60 cases) and other dementia treatments (60 cases), and adherence to treatment (53 cases). Solutions implemented by pharmacists included gathering information regarding drug administration and dementia awareness from the key person and providing pharmaceutical counseling and instruction. Subsequently, problems related to understanding of dementia treatment, understanding donepezil, and adherence were resolved by 70.0%, 65.0%, and 58.5%, respectively. Pharmacists' comprehensive assessment of medication profiles could effectively solve dementia patients' medication-related problems.

著者

梅津 亮冴 阿部 純子 上田 夏実 加藤 大和 中山 蓉子 紀ノ定 保臣 中村 光浩

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.135, no.8, pp.991-1000, 2015 (Released:2015-08-01)

参考文献数

19

被引用文献数

3 7

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Over-the-counter (OTC) drugs play an important role in self-medication. To ensure patient safety, pharmacists should ask patients to pay attention to possible adverse events (AE) associated with OTC drugs and educate patients about the symptoms related to those AEs. The aims of the present study were as follows: (1) to assess the tendency of AEs to occur with OTC drug use in Japan; (2) to detect a safety signal for OTC drugs using the reporting odds ratio (ROR); and (3) to evaluate clustery features, which include suspected drugs and therapeutic classifications, and safety signal indices (number of reports and the ROR), using cluster analysis. The number of reports of AEs following use of combination cold remedy, antipyretic and analgesic remedy, and herbal medicine was 1007, 566, and 221, respectively. We set the cluster number at five; clustery features obtained were as follows: (1) high reporting rate for skin and subcutaneous tissue disorder AEs was the largest group related to combination cold remedy; (2) high reporting rate for nervous system disorder AEs including dizziness was the second largest group. The same medicinal ingredient may demonstrate similar tendencies of the occurrence of AEs and similar clustery features in the Japanese Adverse Drug Event Report database. Our analysis of AEs associated with OTC drugs may be useful for pharmacists and patients alike. Further studies are required to draw better-informed conclusions.

著者

永井 純也

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.126, no.5, pp.327-335, 2006 (Released:2006-05-01)

参考文献数

14

被引用文献数

5 13

---

Aminoglycoside antibiotics, such as gentamicin and amikacin, are a class of clinically important antibiotics used worldwide in the treatment of infections caused by Gram-positive and Gram-negative bacteria. However, nephrotoxicity and ototoxicity are serious problems in the use of aminoglycosides and are the major dose-limiting side effects. Most of the intravenously administered dose is excreted into the urine, whereas some of the aminoglycoside injected (about 10% of the dose) is selectively accumulated in the renal cortex, leading to renal injury. Aminoglycosides are taken up into the epithelial cells of the renal proximal tubules by an endocytic pathway. Acidic phospholipids, broadly distributed in the plasma membranes in various tissues, were considered to be the binding site of aminoglycosides. Recently, megalin, a giant endocytic receptor abundantly expressed in renal proximal tubules, has been reported to bind aminoglycosides. Therefore we first examined whether megalin plays an important role in the renal accumulation of aminoglycosides under in vivo and in vitro conditions. We then attempted to develop new strategies for preventing the nephrotoxicity of aminoglycosides based on the molecular mechanisms of aminoglycoside accumulation in the kidney. This review summarizes our recent findings ol the role of megalin in the renal accumulation of aminoglycosides and our approach to develop nonnephrotoxic aminoglycoside therapy.

著者

皆川 信子 上原 麻理子 関 志織 新田 あゆみ 古河原 健人

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.130, no.2, pp.247-251, 2010 (Released:2010-02-01)

参考文献数

24

被引用文献数

2 4

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Atovaquone, an analog of ubiquinone, binds tightly to the ubiquinol oxidation site (Qo site) of parasite cytochrome bc1 complex to inhibit electron transport at concentrations far lower than those at which the mammalian system is affected. The mode of action is thought similar to that of myxothiazol. To treat Pneumocystis jirovecii and Plasmodium falciparum infections, atovaquone has been used worldwide whereas it is unapproved in Japan. Since the pathogenic Candida species fungi seem resistant to atovaquone, this drug is not clinically available for candidosis, particularly deep mycosis. We examined the effects of atovaquone on cellular respiration and in vitro growth of C. albicans to explore a new therapeutic possibility for fungal infections. Atovaquone strongly inhibited glucose-dependent cellular respiration similarly to antimycin A, stigmatellin, and myxothiazol, specific bc1 complex inhibitors. However, atovaquone suppressed glucose-dependent cell growth to a much lesser extent versus the comparator agents. When added alone, lithium exerted slight growth inhibition. The combined addition of lithium with atovaquone showed a significant increase in inhibition of growth. Although the way lithium acts synergistically with atovaquone remains to be elucidated, our results suggest a new therapeutic possibility of this combination for the treatment of candidosis.

著者

角田 慎一 石井 明子

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.135, no.7, pp.841-842, 2015 (Released:2015-07-01)

著者

水上 元

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.135, no.7, pp.867-882, 2015 (Released:2015-07-01)

参考文献数

55

被引用文献数

1

---

Plant secondary product glycosyltransferases belong to family 1 of the glycosyltransferase superfamily and mediate the transfer of a glycosyl residue from activated nucleotide sugars to lipophilic small molecules, thus affecting the solubility, stability and pharmacological activities of the sugar-accepting compounds. The biotechnological application of plant glycosyltransferases in glycoside synthesis has attracted attention because enzymatic glycosylation offers several advantages over chemical methods, including (1) avoiding the use of harsh conditions and toxic catalysts, (2) providing strict control of regio-and stereo-selectivity and (3) high efficiency. This review describes the in vivo and in vitro glycosylation of natural organic compounds using glycosyltransferases, focusing on our investigation of enzymatic synthesis of curcumin glycosides. Our current efforts toward functional characterization of some glycosyltransferases involved in the biosynthesis of iridoids and crocin, as well as in the sugar chain elongation of quercetin glucosides, are described. Finally, I describe the relationship of the structure of sugar chains and the intestinal absorption which was investigated using chemoenzymatically synthesized quercetin glycosides.

著者

錦織 淳美

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.134, no.3, pp.363-366, 2014 (Released:2014-03-01)

参考文献数

4

---

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.

著者

中山 健夫

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.134, no.3, pp.367-370, 2014 (Released:2014-03-01)

参考文献数

16

---

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.

著者

内田 彰子

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.131, no.12, pp.1751-1753, 2011 (Released:2011-12-01)

被引用文献数

1

---

I am a team doctor of three competition groups including professional cycling team for ten years. The most troublesome issue as a sports doctor is the problem about doping. I cope thanks to a mobile telephone and an e-mail regardless of place and time, but introduce some examples because I still experience many doping “near miss” cases. In addition, there are problems in road competition spots as follows; 1) There are few team doctors. I am pressed by the consultation from plural teams, 2) An unexperienced doctor of the doping knowledge often prescribes prohibited drugs, 3) There are problems with no understanding of the medicine made in foreign countries, Chinese medicine, a generic drug, and supplements which obtained on the internet. I hope that anti-doping education in faculty of pharmaceutical sciences is made mandatory, sports pharmacists taken to the sports spot along increase, and a system and a database to teach local doctors and players quickly will be achieved in future.

著者

池谷 裕二

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.128, no.9, pp.1251-1257, 2008 (Released:2008-09-01)

参考文献数

18

被引用文献数

3 3

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Functional multineuron calcium imaging (fMCI) is a large-scale optical technique that records the suprathreshold activity from large neuron populations. fMCI has several advantages, including: i) simultaneous recording from hundreds of neurons, ii) single-cell resolution, iii) identifiable location of neurons, and iv) detection of non-active neurons during the observation period. I review the principle and detailed method of fMCI and also describe the effect of oseltamivir on neuronal network as an example for practical application of fMCI.

著者

石橋 祐子 村上 照夫 湯元 良子 酒井 正彦 新谷 洋通 板羽 秀之 神辺 眞之 益田 慎 夜陣 紘治 木平 健治 高野 幹久

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.124, no.11, pp.833-840, 2004 (Released:2004-11-01)

参考文献数

15

被引用文献数

6 6

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Burow's solution, or aluminum acetate solution, is effective in inhibiting various microorganisms including methicillin-resistant Staphylococcus aureus (MRSA) that are commonly observed in chronic suppurative otitis media. It takes several days to prepare Burow's solution using aluminum sulfate, and the pharmaceutical properties of the solution are not fully understood. In this study, the effect of storage (5 months) of Burow's solution prepared according to the Teine-Keijin Hospital manual on its pharmaceutical properties and antibacterial activities was examined. We also attempted to develop a rapid preparation method of aluminum acetate (or 1.7% aluminum) solution using two commercially available compounds of aluminum acetate basic (Al2O(CH3CO2)4, Al(OH)(CH3CO2)2). The properties of Burow's solution, pH, osmolarity and antibacterial activity, were the same among different preparations and its storage for 5 months at 4°C had no effect on these properties. The antibacterial potency of Burow's solution was dependent on aluminum concentration and its antibacterial potency against S. aureus and several MRSA strains was of the same magnitude. In a rapid preparation, aluminum acetate basic was mixed with appropriate amounts of tartaric acid and acetic acid, and the suspension was boiled for 2—2.5 hr until dissolved. The rapidly prepared aluminum acetate solution showed the same pharmaceutical properties and antibacterial activities as those of Burow's solution. The newly developed preparation method for aluminum acetate solution is expected to be convenient and feasible for hospital treatment of chronic suppurative otitis media.

著者

伊佐間 和郎 河上 強志 西村 哲治

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.132, no.8, pp.959-968, 2012 (Released:2012-08-01)

参考文献数

30

被引用文献数

2

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The International Standard ISO 8124-3:2010 “Safety of toys—Part 3: Migration of certain elements” controls the levels of migrated eight harmful elements (antimony, arsenic, barium, cadmium, chromium, lead, mercury and selenium) from infants toys. Moreover, the Japanese Food Sanitation Law controls the levels of migrated lead from metal accessory toys. However, the levels of migrated harmful elements from metal accessories that are not infants toys are not controlled, since they are not covered by the ISO Standard or the Food Sanitation Law. Therefore, we investigated the level of eight harmful elements migrated from metal accessories that infants may swallow by mistake. The extraction test of ISO 8124-3:2010 was executed in 117 products (total 184 specimens), and the concentration of these eight elements was measured by inductively coupled plasma mass spectroscopy (ICP-MS). As a result, 28 and one products released lead and cadmium beyond the maximum acceptable levels of the ISO standard, respectively. Metal accessories that infants may swallow by mistake should ideally not release harmful elements such as lead and cadmium.

著者

一番ヶ瀬 智子 今井 一洋

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.135, no.2, pp.197-203, 2015 (Released:2015-02-01)

参考文献数

11

被引用文献数

1

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It is routine to search for and recognized genetic defects in human disorders to provide knowledge for diagnosis, treatment, and protection against diseases. It is also important to investigate and demonstrate the cause of a disease from the proteomic perspective, because intracellular signaling systems depend on protein dynamics. Demonstrating changes in protein levels enables us to understand biochemical events during the initiation and progression of a disease. To understand changes in protein levels in tissues and cells, we have developed a novel proteomics approach, FD-LC-MS/ MS. This consists of fluorogenic derivatization (FD), HPLC separation and detection/quantification of proteins in a biological sample, followed by the isolation and tryptic digestion of target proteins, and then their identification using HPLC and tandem mass spectrometry (MS/MS) with a database-searching algorithm. The method is highly sensitive (femtomole-level detection) through the use of less noisy fluorogenic rather than fluorescence derivatization, and enables precise and comprehensive relative quantitation of protein levels (between-day relative standard deviation of peak heights of ca. 20%) by combining FD with HPLC separation. In this paper, after a simple review of differential profiling using FD-LC-MS/MS, for example the analysis of stimulated vs. unstimulated samples, we introduce the development and application of the FD-LC-MS/MS method for comprehensive differential proteomics of several tissues, including mouse liver, mouse brain, and breast cancer cell lines, to reveal protein levels and biochemical events in tissues and cells.

著者

安原 智久 曽根 知道 河野 武幸 荻田 喜代一

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.135, no.1, pp.99-105, 2015 (Released:2015-01-01)

参考文献数

18

被引用文献数

2 2

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A revised core curriculum model for pharmaceutical education, developed on the basis of the principles of outcome-based education, will be introduced in 2015. Inevitably, appropriate assessments of students' academic achievements will be required. Although evaluations of the cognitive domain can be carried out by paper tests, evaluation methods for the attitude domain and problem-solving abilities need to be established. From the viewpoint of quality assurance for graduates, pharmaceutical education reforms have become vital to evaluation as well as learning strategies. To evaluate student academic achievements on problem-solving abilities, authentic assessment is required. Authentic assessment is the evaluation that mimics the context tried in work and life. Specifically, direct evaluation of performances, demonstration or the learners' own work with integrated variety knowledge and skills, is required. To clarify the process of graduate research, we obtained qualitative data through focus group interviews with six teachers and analyzed the data using the modified grounded theory approach. Based on the results, we clarify the performance students should show in graduate research and create a rubric for evaluation of performance in graduate research.