YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
136 巻 , 12 号
選択された号の論文の11件中1~11を表示しています
総説
  • 髙橋 成周
    2016 年 136 巻 12 号 p. 1585-1590
    発行日: 2016年
    公開日: 2016/12/01
    ジャーナル フリー
     Phenylboronic acid (PBA) derivatives have been used as alternatives to enzymes in the development of sugar-sensitive systems because the optical and electrochemical properties of these derivatives are significantly modulated upon sugar binding. This article reviews the voltammetric properties of sugar sensors prepared using dithiobis (4-butyrylamino-m-phenylboronic acid) (DTBA-PBA)-modified electrodes and PBA-appended layer-by-layer film-modified electrodes. In addition, the redox properties of reduced graphene oxide (rGO)-modified glassy carbon electrodes (GCEs) are discussed. The surface of a gold electrode was modified with a monolayer of DTBA-PBA to prepare sugar-sensitive electrodes. The modified electrodes exhibited attenuated cyclic voltammograms for Fe(CN)63−/4− in the presence of sugars at neutral pH as a result of their binding to DTBA-PBA on the electrode. Useful calibration curves were obtained for determining 3-300 mM D-glucose and 0.3-30 mM D-fructose. Similarly, gold electrodes coated with multilayer films composed of PBA-modified poly(allylamine hydrochloride) and carboxymethylcellulose exhibited a sugar-dependent response at neutral pH. The dynamic range of these modified electrodes was 0.1-300 mM for D-glucose and D-fructose. The surface of GCE was modified with rGO to evaluate the electrochemical response of the modified GCE to hydrogen peroxide (H2O2). The rGO-modified electrodes exhibited significantly higher responses in the redox reactions of H2O2 compared with the response of an unmodified GCE.
  • 重野 真徳
    2016 年 136 巻 12 号 p. 1591-1600
    発行日: 2016/12/01
    公開日: 2016/12/01
    ジャーナル フリー
     Molecular switching is the phenomenon in which a molecular structural change occurs reversibly in response to an external stimulus or energy. It plays an important role in biology, in which it is used for sensing environmental changes. In contrast to well-studied equilibrium molecular switching involving thermodynamically stable states, nonequilibrium molecular switching involving a metastable state is a notable chemical phenomenon and is the theme of this study. Sulfonamido- and aminomethylenehelicene oligomers show a reversible structural change from a double helix to a random coil in dilute solution. A metastable state consisting of random coils can be generated by heating, which shows various nonequilibrium thermodynamic properties. Molecular phenomena including molecular thermal hysteresis, molecular memory effect, and one-directional three-state molecular structural change occur, none of which is observed in an equilibrium molecular switching system. They can be applied to sensing environmental changes such as temperature increases/decreases, temperature change rates, and concentration increases, and for counting the numbers 1 and 2.
  • 久松 洋介
    2016 年 136 巻 12 号 p. 1601-1611
    発行日: 2016/12/01
    公開日: 2016/12/01
    ジャーナル フリー
     In this review, we introduce the development of supermolecules, host-guest complexes, and metal complexes formed from the combination of non-covalent interactions and/or coordination bonds, as well as their biological applications. An adenine selective host molecule 1 provides a correctly oriented array of complementary hydrogen bonding sites for the adenine nucleobase. Furthermore, the new DDAA (D: hydrogen bond donor, A: hydrogen bond acceptor) module 4 and ADDA module 7 have been developed as quadruple hydrogen-bonding modules. A quadruple zwitterion 8 forms supramolecular gel in dimethyl sulfoxide, driven by the formation of ion-paired dimers between the zwitterionic units. The obtained supramolecular gel exhibits reversible gel-sol transitions in response to both acid, base, and heating. Self-assembly of a dimeric zinc(II) complex, dianion of cyanuric acid (CA) or 5,5-diethylbarbituric acid (Bar), and copper(II) ion (Cu2+) in an aqueous solution provides 4 : 4 : 4 and 2 : 2 : 2 supermolecules 10 and 11, respectively. These supermolecules possess Cu2(μ-OH)2 centers, and accelerate the hydrolysis of a phosphate monoester dianion, mono(4-nitrophenyl)phosphate (MNP), at neutral pH. Regioselective substitution reactions of tris-cyclometalated iridium (Ir) complexes at the 5′-position on 2-phenylpyridine type ligands, and their subsequent conversions to a variety of functional groups are described. For example, pH-sensitive Ir complexes having basic functional groups have been developed. Tris-cyclometalated Ir complexes containing cationic peptides, such as Lys-Lys-Gly-Gly (KKGG) peptides, work as inducers and detectors of cancer cell death. Mechanistic studies suggest that the Ir complex interacts with anionic molecules on the cell surface and/or membrane receptors to trigger an intracellular Ca2+ response, resulting in necrosis accompanied by membrane disruption.
  • 浅川 倫宏
    2016 年 136 巻 12 号 p. 1613-1621
    発行日: 2016/12/01
    公開日: 2016/12/01
    ジャーナル フリー
     This article describes the development of various probes and immunogens for chemical-biological investigations of food flavonoids. We accomplished a large (gram)-scale asymmetric synthesis of a key intermediate, 5-aminopentyl deoxy epigallocatechin-3-gallate (APDOEGCg; 3), an analogue of green tea polyphenol EGCg, in which the key step was cationic cyclization utilizing neighboring group participation of the gallate carbonyl group. The synthetic APDOEGCg (3) was efficiently converted to a fluorescent probe 18 and an immunogen 19 by utilizing the high reactivity of the amine functional group. We confirmed the usefulness of these probes for imaging studies and the generation of antibodies, respectively. We also describe the efficient synthesis of a positron emission tomography (PET) probe [11C]20 by incorporation of 11C into EGCg (1), for which synthetic 4″-Me-EGCg (20) was utilized as an authentic sample. Our synthetic strategy was also applied for the practical synthesis of nobiletin (21), a polymethoxylated flavone from citrus. Synthetic nobiletin was readily converted to various probes by selective demethylation and incorporation of fluorescein, biotin or 11C. These probes should be useful for a range of biological applications. Detailed examination of the mechanisms and further applications are in progress.
  • 金子 雪子
    2016 年 136 巻 12 号 p. 1623-1629
    発行日: 2016年
    公開日: 2016/12/01
    ジャーナル フリー
     Pancreatic β-cell dysfunction is a major feature of type 2 diabetes. Therefore maintenance of β-cell function is essential to preventing the onset and progression of type 2 diabetes. To elucidate the mechanisms underlying the regulation of insulin secretion and β-cell survival, we particularly focused on the roles of gasotransmitters in pancreatic β-cells. Nitric oxide (NO) and hydrogen sulfide (H2S) are recognized as toxic gases. However, they are also vital physiological and pathophysiological mediators in various cell types. NO, generated from L-arginine by reactions catalyzed by NO synthases, is a well-known neurotransmitter and smooth muscle relaxation factor. In pancreatic β-cells, induction of nitric oxide synthase 2 (NOS2) by inflammatory cytokines generates a large amount of NO, which contributes to the impairment of β-cell function and induction of β-cell apoptosis, which are, in turn, involved in the development of type 1 diabetes. In contrast, a physiological level of NO, generated by constitutive NOS (cNOS), acts as a positive or negative regulator of insulin secretion and β-cell survival, depending on concentration. H2S generated from L-cysteine has been shown to play a role of neuromodulator, and this gas possesses cytoprotective properties. In pancreatic β-cells, H2S functions as a potent suppressor of insulin secretion. Furthermore, chronic exposure to high glucose induces H2S production by increasing the expression of a H2S-producing enzyme, cystathionine γ-lyase (CSE). H2S generated by CSE prevents β-cell apoptosis via an antioxidant mechanism. Here, we describe the current understanding of the function of gasotransmitters in regulating insulin secretion and pancreatic β-cell survival.
  • 上田 善弘
    2016 年 136 巻 12 号 p. 1631-1639
    発行日: 2016/12/01
    公開日: 2016/12/01
    ジャーナル フリー
     The first total syntheses of multifidosides A-C are reported. The prominent feature is an unconventional retrosynthesis based on organocatalytic site-selective acylation of unprotected glycosides at the final stage of synthesis. A notable advantage of this strategy is that it avoids the risks of undesired side reactions during the removal of the protecting groups at the final stage of total synthesis. The proposed synthetic strategy has another advantage in terms of efficient late-stage derivatization of natural products. Due to the predictability and reliability of the catalytic site-selective introduction of various functionalized acyl groups, the present synthetic strategy could provide a general synthetic route to 4-O-acylglycosides, such as phenylethanoid glycosides and ellagitannins, which are of biological interest.
一般論文
  • 山下 良子, 神山 秀一, 山本 明日香, 加納 宏樹, 結城 祥充, 上田 晃, 川本 由加里, 後藤 仁和, 山本 聡
    2016 年 136 巻 12 号 p. 1641-1649
    発行日: 2016年
    公開日: 2016/12/01
    ジャーナル フリー
     The efficacy of cefepime (CFPM) is known to depend on the ratio of the time that the serum levels exceed the minimum inhibitory concentration (MIC) to the dosing interval (%T>MIC). The objective of this study was to clarify the relation between %T>MIC and clinical outcome of CFPM, and to identify the optimal dosage regimen. We investigated the outcome of CFPM treatment for febrile neutropenia (FN) patients with normal renal function. Treatment success was defined as the completion of FN therapy with CFPM only. And we calculated %T>MIC for each case based on population pharmacokinetic parameters. The MIC value for simulation was set as 8 μg/mL. In logistic regression analysis, treatment success was significantly associated with the elevation of %T>MIC in the group with persistent neutropenia, yielding a receiver operating characteristic curve with an optimal cutoff value of 73.1%. Next, we simulated %T>MIC for each case under various dosing regimens. For patients whose creatinine clearance (CLcr) exceeded 100 mL/min, it was found to be difficult to attain the objective under the current regimen. In contrast, it was calculated that treatment with 2 g three times a day (t.i.d.) could attain the objective for most of the patients with 3 h of infusion. These results suggest that CFPM treatment under the current regimen is ineffective for FN patients with normal or augmented renal function, and that 2 g t.i.d. is necessary in quite a lot cases, although such use is off-label.
  • 北山 友也, 籠田 智美, 吉川 紀子, 河井 伸之, 西村 奏咲, 三浦 健, 安井 菜穂美, 篠塚 和正, 中林 利克
    2016 年 136 巻 12 号 p. 1651-1656
    発行日: 2016/12/01
    公開日: 2016/12/01
    ジャーナル フリー
     The Pharmaceutical Education Support Center was established in the Department of Pharmacy at the School of Pharmacy and Pharmaceutical Science of Mukogawa Women's University in 2014. We started teaching first and second years students according to proficiency from the 2014 academic year. Students were divided into two classes: the regular class (high proficiency class) and the basic class (low proficiency class), based on achievement in several basic subjects related to the study of pharmacy. The staffs in the Pharmaceutical Education Support Center reinforce what is taught to students in the basic class. In this reinforcement method of education, the class size is small, consisting of about 15 students, a quiz to review the previous lesson is given at the beginning of each lecture, and an additional five lectures are conducted, compared to the high proficiency class, which receives 15 lectures. In this study, we evaluated the effects of the reinforcement method of physiology education on achievement in pharmacology that was not conducted in the proficiency-dependent teaching method. The students in the basic class in physiology education were chosen based on achievement levels in anatomy. Achievement levels of pharmacology students in the basic class of physiology improved compared with those of students who had the same achievement levels in physiology but were not taught according to proficiency-dependent teaching in the 2013 academic year. These results suggest that the reinforcement method for education in basic subjects in pharmacy, such as physiology, can improve achievement in more advanced subjects, such as pharmacology.
ノート
  • 溝口 優, 桑野 紗子, 鈴木 育子, 重山 昌人
    2016 年 136 巻 12 号 p. 1657-1666
    発行日: 2016/12/01
    公開日: 2016/12/01
    ジャーナル フリー
     Although the removal of bacteria in the oral cavity is regarded as an important preventive measure against pneumonia, the majority of elderly individuals are rarely provided with oral care-related information. This study examined the usefulness of oral care-related information provision for the elderly by pharmacists working at drugstores. A questionnaire survey was conducted, involving 387 pharmacists working at drugstores and 51 elderly individuals who visited such stores. Oral care-related information had been actively provided by 14.5% of the pharmacists, and 62.5% of all oral care products were being sold as care products. When focusing on the elderly, 70.6% showed interest in oral care, but the proportion of those who had performed self-care to promote such health was limited to 5.9%. After being provided with oral care-information, 97.6% answered “I wish to regularly perform oral self-care”, and 86.3% regarded oral care-related information provision by pharmacists as “very useful”. The results of this study demonstrate the usefulness of information provision by pharmacists at drugstores to promote oral self-care among the elderly.
  • 一木 裕子, 小林 大介, 窪田 敏夫, 大園 沙保子, 村上 綾, 山川 裕介, 是木 一也, 島添 隆雄
    2016 年 136 巻 12 号 p. 1667-1674
    発行日: 2016/12/01
    公開日: 2016/12/01
    [早期公開] 公開日: 2016/08/29
    ジャーナル フリー
     The number of patients with diabetes continues to increase in Japan, which means that education in disease management is important. However, there have been few investigations into the importance of hospital pharmacists performing outpatient education for diabetes mellitus in Japan. In the diabetes outpatient department of Kitakyushu City Moji Hospital, a pharmacist commenced patient education using check sheets before patients saw the physicians from 2012. We divided the patients into groups with an increase or decrease of hemoglobin A1c (HbA1c) level after 6 months from the start of patient education. To assess the factors related to a decrease of HbA1c level, we compared background factors, and laboratory values between these two groups. In the patients whose HbA1c level decreased, the level was high at the start of patient education and they had less knowledge about their medications. To evaluate the impact of this patient education, we compared HbA1c values before patient education and after 6 months to determine the effect of providing education in the diabetes outpatient department. In the HbA1c≥8% group, the HbA1c level decreased significantly during 6 months of patient education. These results suggest that patient education by hospital pharmacists can be effective if HbA1c level is high at the start of education. This is the first report about the usefulness of patient education by a hospital pharmacist for improvement of HbA1c level in diabetic outpatients in Japan.
ケースレポート
  • 輿石 徹, 奥山 清
    2016 年 136 巻 12 号 p. 1675-1679
    発行日: 2016/12/01
    公開日: 2016/12/01
    ジャーナル フリー
     A 70-year-old woman, residing in a nursing home, was admitted to our hospital because of cerebral hemorrhage. She had excessive sweating, a temperature above 37°C, and intermittent muscle spasm such as myoclonus, since the time of admission. We suspected that these symptoms were related to side effects caused by the milnacipran she was taking for depression, prior to hospitalization. After we discontinued milnacipran, the patient began exhibiting withdrawal symptoms such as excitement and insomnia. When we substituted milnacipran with mianserin, the withdrawal symptoms diminished and the excessive sweating and involuntary movement disappeared. Serotonin-norepinephrine reuptake inhibitor (SNRI) and selective serotonin reuptake inhibitor (SSRI) have been widely utilized in the clinic to treat depression; serious side effects such as serotonin syndrome and withdrawal syndrome associated with their discontinuation, have been reported. However, it is unlikely that serotonin syndrome and withdrawal syndrome due to a precedent use of milnacipran would have been reported. This case was suspected to be related to serotonin syndrome and withdrawal syndrome from the course of treatment. This case provides valuable information for addressing new similar cases caused by milnacipran.
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