著者

王子田 彰夫 高嶋 一平

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.3-7, 2016 (Released:2016-01-01)

参考文献数

7

---

Fluorescence probes are now widely used as indispensable tools in many cell functional analyses. At present, the design of fluorescent probes largely depends on the limited numbers of established sensing mechanisms such as photo-induced electron transfer (PET), photo-induced charge transfer (PCT), and fluorescence resonance energy transfer (FRET). Although these mechanisms are versatile in metal ion sensing, introduction of a new sensing mechanism is highly desirable not only to design a more sophisticated probe with high selectivity and sensitivity but also to expand the diversity of the sensing targets to unveil biological phenomena. In this article, we report the design of dual emission fluorescent probes for metal ions based on a unique fluorescence-sensing mechanism. The fluorescent probes incorporating this sensing mechanism displayed a large emission red-shift on complexation with metal ions such as CdII and AgI. X-ray crystallography and theoretical computational calculations of the CdII and AgI complexes revealed that the emission shift was induced by non-coordination contact between the aromatic ring of fluorophore and the metal ion (arene-metal ion contact; AM-contact), which modulates the energy levels of molecular orbitals. The fluorescent probe was successfully applied to in cell ratiometric bioimaging of bioactive hydrogen sulfide (H2S). These successful applications highlight the usefulness of this sensing mechanism in biological fluorescence analysis.

著者

齋藤 侑也

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.12, no.5, pp.387-390, 1976

著者

玉木 啓文 佐藤 宏樹 堀 里子 澤田 康文

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.4, pp.525-529, 2012 (Released:2012-04-01)

参考文献数

4

被引用文献数

1 2

---

Confusion of drug names is one of the most common causes of drug-related medical errors. A similarity measure of drug names, “vwhtfrag”, was developed to discriminate whether drug name pairs are likely to cause confusion errors, and to provide information that would be helpful to avoid errors. The aim of the present study was to evaluate and improve vwhtfrag. Firstly, we evaluated the correlation of vwhtfrag with subjective similarity or error rate of drug name pairs in psychological experiments. Vwhtfrag showed a higher correlation to subjective similarity (college students: r=0.84) or error rate than did other conventional similarity measures (htco, cos1, edit). Moreover, name pairs that showed coincidences of the initial character strings had a higher subjective similarity than those which had coincidences of the end character strings and had the same vwhtfrag. Therefore, we developed a new similarity measure (vwhtfrag+), in which coincidence of initial character strings in name pairs is weighted by 1.53 times over coincidence of end character strings. Vwhtfrag+ showed a higher correlation to subjective similarity than did unmodified vwhtfrag. Further studies appear warranted to examine in detail whether vwhtfrag+ has superior ability to discriminate drug name pairs likely to cause confusion errors.

著者

山添 康 永田 清

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.25, no.4, pp.333-336, 1989

著者

北 潔 山田 陽城

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.2, pp.203-204, 2016 (Released:2016-02-01)

参考文献数

5

著者

安藤 陽子

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.49, no.9, pp.886-888, 2013

参考文献数

4

著者

長谷川 一子

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.49, no.9, pp.844-848, 2013

参考文献数

8

著者

服部 信孝

出版者

公益社団法人 日本薬学会

雑誌

ファルマシア (ISSN:00148601)

巻号頁・発行日

vol.49, no.9, pp.829-829, 2013

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

---

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

Maki Kinoyama Hayami Nitta Shinsuke Hara Akiharu Watanabe Kunihisa Shirao

出版者

公益社団法人 日本薬学会

雑誌

Journal of Health Science (ISSN:13449702)

巻号頁・発行日

vol.53, no.5, pp.608-614, 2007 (Released:2007-10-01)

参考文献数

32

被引用文献数

2 3 7

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We examined what changes occurred in the activity and content of superoxide dismutase (SOD) in the blood and the amount of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the urine as a consequence of oral administration of antioxidant health foods including plant-based SOD, vitamin C and vitamin E to seven healthy subjects every day for 15 days. Although there was a significant increase in the concentration of vitamins C and E in serum, there was a significant decrease in SOD (extracellular type) activity and Mn-SOD (mitochondrial type) content and a narrower range of variation therein. In contrast, there was a tendency toward an increase in the amount of 8-OHdG in the urine (observed in 6 of 7 subjects). We looked into the possibility that SOD activity was being inhibited by pycnogenol (water extract of the bark of the French maritime pine) as the main ingredient of the antioxidant health foods, and it became clear that SOD activity is included in pycnogenol. These results suggest that oral administration of antioxidant health foods containing SOD originating in plants has the effect of lowering the activity and content of SOD in the blood.

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

---

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

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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)