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137 巻, 12 号
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誌上シンポジウム
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石澤 啓介, 入江 利行2017 年 137 巻 12 号 p. 1425
発行日: 2017年
公開日: 2017/12/01
ジャーナル フリーPDF形式でダウンロード (145K) -
今井 徹2017 年 137 巻 12 号 p. 1427-1430
発行日: 2017/12/01
公開日: 2017/12/01
ジャーナル フリーCritically ill patients who receive high-level invasion show physiological changes different from those under more normal conditions, along with variable therapeutic effects and pharmacokinetics. The concept of systemic inflammatory response syndrome (SIRS) has been introduced to describe the clinical state resulting from invasive actions taken under acute circumstances, resulting in an acute-phase systemic response. In particular, dosages of vancomycin (VCM) and phenytoin (PHT) need to be adjusted by therapeutic drug monitoring (TDM) because of their narrow therapeutic concentration windows. However, there are few reports on the pharmacokinetics of VCM and PHT in patients with SIRS. We performed a retrospective cohort study of patients treated with VCM and PHT. These studies suggest that the pharmacokinetics of VCM are affected by SIRS score and duration. Furthermore, the concentration of PHT was also shown to be higher in SIRS patients compared with non-SIRS patients. These findings suggest that the pharmacokinetics of VCM and PHT may be affected by the pathology of SIRS, rather than by other patient characteristics. Modifying dosing according to SIRS will improve the prediction accuracy of drug concentration based on TDM. In this review, I introduce work conducted by pharmacists in the clinical study of critically ill patients, and will be discussing the evaluation of pharmacotherapy in emergency and intensive care medicine.
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今浦 将治2017 年 137 巻 12 号 p. 1431-1437
発行日: 2017/12/01
公開日: 2017/12/01
ジャーナル フリーThe pathological conditions of patients who require intensive care are usually complex and extremely severe; their health and life are in a critical state. Therefore, correct, rapid treatment of these conditions is indispensable. Furthermore, the selection of drugs and adjustment of their dosage for an immediate effect are important. Moreover, most patients are immunocompromised and present an extremely high level of risk for complications involving infectious diseases. Since such complications may lead to life-threatening outcomes, a rational dosage regimen to achieve sufficient antimicrobial activity from the initial stage of treatment is essential. However, most critically ill cases are complicated by several factors: fluid retention including edema, pleural effusion, and ascites; increased vascular permeability and hypoalbuminemia; and dysfunction of various organs. These factors cause significant changes in the pharmacokinetics of antimicrobials, making it particularly difficult to design a dosage regimen at the time of initial administration. Thus, we focused on the importance of a rational dosage regimen for antimicrobial drugs in the treatment of infectious diseases. We conducted a retrospective study of severe cases of pneumonia with a high death rate; patients were divided into two groups according to the pharmacist intervention procedures and a comparative study of treatment efficacy was performed. Furthermore, for antimicrobial agents to exert a sufficient effect from the initial stage of treatment, we examined the theoretical methodology underlying the initial administration.
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座間味 義人, 新村 貴博, 武智 研志, 今西 正樹, 小山 敏広, 石澤 啓介2017 年 137 巻 12 号 p. 1439-1442
発行日: 2017年
公開日: 2017/12/01
ジャーナル フリーApproximately 100000 people suffer cardiopulmonary arrest in Japan every year, and the aging of society means that this number is expected to increase. Worldwide, approximately 100 million develop cardiac arrest annually, making it an international issue. Although survival has improved thanks to advances in cardiopulmonary resuscitation, there is a high rate of postresuscitation encephalopathy after the return of spontaneous circulation, and the proportion of patients who can return to normal life is extremely low. Treatment for postresuscitation encephalopathy is long term, and if sequelae persist then nursing care is required, causing immeasurable economic burdens as a result of ballooning medical costs. As at present there is no drug treatment to improve postresuscitation encephalopathy as a complication of cardiopulmonary arrest, the development of novel drug treatments is desirable. In recent years, new efficacy for existing drugs used in the clinical setting has been discovered, and drug repositioning has been proposed as a strategy for developing those drugs as therapeutic agents for different diseases. This review describes a large-scale database study carried out following a discovery strategy for drug repositioning with the objective of improving survival rates after cardiopulmonary arrest and discusses future repositioning prospects.
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総説
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棚橋 孝雄2017 年 137 巻 12 号 p. 1443-1482
発行日: 2017/12/01
公開日: 2017/12/01
ジャーナル フリーStudies on the structural determination, biosynthesis, and biological activities of secondary metabolites from natural sources are significant in the field of natural products chemistry. This review focuses on diverse secondary metabolites isolated from medicinal plants and cultivated mycobionts of lichens in our laboratory. Monoterpene-tetrahydroisoquinoline glycosides and alkaloids isolated from Cephaelis acuminata and Alangium lamarckii gave important information on the biosynthesis of ipecac alkaloids. A variety of glycosides linked with a secologanin unit and indole alkaloids were obtained from medicinal plants belonging to the families of Rubiaceae, Apocynaceae, and Loganiaceae. Plant species of the four genera Fraxinus, Syringa, Jasminum, and Ligustrum of the family Oleaceae were chemically investigated to provide several types of secoiridoid and iridoid glucosides. The biosynthetic pathway leading from protopine to benzophenanthridine alkaloids in suspension cell cultures of Eschscholtzia californica was elucidated. The structures and biological activities of the bisbenzylisoquinoline alkaloids of Stephania cepharantha and Nelumbo nucifera were also investigated. In addition, the mycobionts of lichens were cultivated to afford various types of metabolites that differ from the lichen substances of intact lichens but are structurally similar to fungal metabolites. The biosynthetic origins of some metabolites were also studied. These findings suggest that cultures of lichen mycobionts could be sources of new bioactive compounds and good systems for investigating secondary metabolism in lichens.
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齋藤 望2017 年 137 巻 12 号 p. 1483-1490
発行日: 2017/12/01
公開日: 2017/12/01
ジャーナル フリーBiological systems exhibit dynamic phenomena at the macroscopic level as a result of the hierarchical integration of phenomena at the molecular level. For example, a number of amino acids compose actin proteins, which form three-dimensional structures determined by the sequence of amino acids. They form fibers by self-assembly, which then form ordered structures such as meshes, lyotropic liquid crystals (LCs), and bundles. The dynamic and reversible polymorphism between these nano- to centimeter-sized ordered structures is essential for biological functions such as cell division, contraction, and locomotion. To understand biological systems and create new functional materials, it is essential to develop a methodology to integrate phenomena at the molecular level into those at the macroscopic level using synthetic molecules. In this research, synthetic oligomers containing helicenes, which exhibit reversible structural transitions between cylindrical double helices and random coils in response to thermal stimuli, were employed as building blocks for the development of such a methodology. The properties of homo- and hetero-double helices at the molecular level were first controlled by taking advantage of the diversity of their molecular structures. Then, nano- to micrometer-sized structures were constructed by the self-assembly of hetero-double helices, which include fibers/gels, vesicles, and lyotropic LCs, and their dynamic properties were controlled by molecular design.
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中妻 彩2017 年 137 巻 12 号 p. 1491-1496
発行日: 2017/12/01
公開日: 2017/12/01
ジャーナル フリーVitamin A (VA) plays critical roles in gut homeostasis. Dendritic cells in mesenteric lymph nodes (MLN-DCs) can metabolize VA to retinoic acid (RA), thereby inducing gut-tropic lymphocytes and enhancing peripheral differentiation of regulatory T cells expressing forkhead box P3. We found that MLN-DCs from VA-deficient mice induced a distinct inflammatory T helper type 2 (Th2)-cell subset that produced abundant interleukin-13 (IL-13) and expressed receptors for homing to skin and inflammatory sites but not to the intestine. IL-6-neutralizing antibodies or RA abrogated the induction of this subset. On the other hand, RA receptor antagonists allowed MLN-DCs from VA-sufficient mice to induce a similar T-cell subset. IL-6 induced the differentiation of this subset from naive CD4+ T cells upon activation with antibodies against CD3 and CD28, and RA receptor antagonists enhanced this induction. It has been considered that VA deficiency reduces Th2-dependent antibody responses. However, oral administration of an antigen to VA-deficient mice failed to induce immune tolerance but primed strong IL-13-dependent immunoglobulin G1 (IgG1) responses and IgE responses that caused skin allergy. These results suggest that MLN-DCs possess the latent ability to induce IL-13-producing inflammatory Th2 cells and that RA prevents them from inducing IL-13-dependent allergic or inflammatory responses to orally administered antigens.
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冨田 隆志2017 年 137 巻 12 号 p. 1497-1504
発行日: 2017/12/01
公開日: 2017/12/01
ジャーナル フリーSeveral issues concerning medicines remain unclear, including the availability of known, but not easily recognizable information. This review evaluates the mechanisms of side effects and the various risk indications included in package inserts. The results can be summarized as follows. 1) Short-term exposure to gatifloxacin significantly induced insulin secretion and increased the cytosolic Ca2+ concentration of islet cells by augmenting extracellular Ca2+ influx and its release from the endoplasmic reticulum. Alternatively, there was a decline in the cellular insulin level and reactivity to sulfonylurea after prolonged exposure. The insulin depletion was greater than that produced by other fluoroquinolones. 2) The elution of di(2-ethylhexyl)phthalate (DEHP) from the infusion set could be associated with the solubilizers in the injection medicines. The package inserts of several products containing polysorbate or ethanol had no warning about DEHP. Although there was a slight correlation between polysorbate content and descriptions on package inserts, the use of DEHP-containing devices was prohibited for some products, even with limited amounts of polysorbate. Therefore, the package insert statements should be reviewed to reflect appropriately the extent of DEHP elution. 3) Risk management plan consists of strategies to minimize the potential risks of medicines. One approach could be to introduce reminders on package inserts; however, of 268 potential risks associated with 81 products, 56 were not mentioned in package inserts. Because most postmarketing pharmacovigilance plans depend on spontaneous reporting by healthcare personnel, the descriptions on package inserts should be reexamined.
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中尾 允泰2017 年 137 巻 12 号 p. 1505-1516
発行日: 2017/12/01
公開日: 2017/12/01
ジャーナル フリーThis article focuses on our investigation of the molecular structure characteristics of diketopiperazines (DKPs), and application of these findings to the development of novel functional molecules. DKPs bearing a benzyl moiety are known to adopt a folded conformation, in which the benzyl moiety is folded over the DKP ring. In order to investigate the driving force behind the folded conformation, we synthesized DKPs bearing a benzyl moiety with different para-substituents, and demonstrated that the folded conformation likely arose from intramolecular CH/π interactions, based on the electronic effects of para-substituents on the benzyl group in 1H NMR spectroscopy. On the other hand, N4-methylation of DKPs bearing a benzyl moiety was found to change their folded conformation to an extended conformation, based on single crystal X-ray crystallography and 1H NMR spectroscopy analysis. Next, we attempted to synthesize both hydroxamate-type siderophores containing the DKP ring: rhodotorulic acid and erythrochelin. Facile synthesis of rhodotorulic acid and its N,N′-dimethylated derivative was achieved by microwave-assisted cyclization of the corresponding dipeptide precursors. Interestingly, N,N′-dimethylated rhodotorulic acid was found to be more soluble in various organic solvents than rhodotorulic acid. Moreover, erythrochelin was synthesized for the first time, and its metal-chelating ability with not only Fe(III) but also Mg(II) was confirmed based on electrospray ionization mass spectrometry (ESI-MS) analysis. Finally, we synthesized DKPs bearing a primary amino group, and found that they could catalyze the asymmetric aldol reaction between hydroxyacetone and p-nitrobenzaldehyde.
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一般論文
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池田 佳代, 春日 真由, 細井 徹, 吉井 美智子, 杉山 政則, 若生 あき, 小澤 光一郎2017 年 137 巻 12 号 p. 1517-1531
発行日: 2017年
公開日: 2017/12/01
ジャーナル フリーA seminar titled “Implementation and evaluation of genetic testing of lifestyle-related disease genes” was held for pharmacists, medical clerks, and clerks of pharmacy insurance, with the aim of holding seminars led by pharmacists for the general public (including patients) in the future. The subject of the seminar was single nucleotide polymorphisms in obesity-related genes and alcohol metabolism-related genes. The purpose of the seminar was to contribute to the prevention of lifestyle-related diseases of the general public. We evaluated it by administering a questionnaire to the participants before and after the seminar. After the seminar, 55% of pharmacists answered that they would like to or would strongly like to participate in genetic testing (for lifestyle-related diseases and drug metabolism-related genes) of the general public. However, some participants did not wish to do so. A customer satisfaction (CS) analysis found that this was mainly because they did not want to know the results of genetic testing of others, which they felt should be private. Most (82%) of the pharmacists answered that assistance and advice was “very necessary” or “necessary” in the participation of genetic testing. These findings show that collaboration between pharmacies and universities will be important for future seminars to the general public.
抄録全体を表示Editor's pickThe authors held a seminar for pharmacists about genetic testing for lifestyle-related disease genes, with the aim of contributing to the prevention of lifestyle-related diseases. The authors showed that collaboration between pharmacies and universities is important for developing future seminars for the general public. This is because some pharmacists do not wish to know the results of private genetic testing, and most believe that the support of universities is necessary for the genetic testing of customers.
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ノート
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岸本 桂子, 竹内 智重, 福島 紀子2017 年 137 巻 12 号 p. 1533-1541
発行日: 2017/12/01
公開日: 2017/12/01
[早期公開] 公開日: 2017/09/05ジャーナル フリーIn Japan, a pharmacy or drug store license is required for selling pharmaceutical products. However, civilians without a pharmacy or drug store license are displaying pharmaceutical products for sale on a flea market application, which is illegal dealing. This study discussed the modality for implementing countermeasures for the illicit selling of pharmaceutical products. We extracted pharmaceutical products displayed for sale on three flea market applications (Mercari, Rakuma, Fril) on one day. One hundred and eighty-one pharmaceutical products were displayed (49 on Mercari, 86 on Rakuma, and 46 on Fril). There were 6.1% (11/181) domestically prescribed drugs, 69.1% (125/181) domestic OTC drugs, 23.8% (43/181) foreign-made prescribed drugs, and 1.1% (2/181) foreign-made OTC drugs. The seller could display the product for sale without confirming whether it is prohibited. We alerted the service providers of this illicit selling at flea markets at three different instances. The pharmaceutical product displays were deleted by the service providers at a rate of 55.1% (27/49) for Mercari and 51.2% (44/86) for Rakuma. The average number of drugs that were displayed for sale by each seller was 1.4 and the average number of total products that were displayed for sale by each seller was 100. The seller could have unintentionally displayed the pharmaceutical products for sale, without the knowledge that it is illegal. The service providers of flea market applications should create mechanisms to alert the sellers that displaying pharmaceutical products for sale is an illicit act and regulate these violations.
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三浦 亨, 杉本 直樹, 渡邊 龍一, 末松 孝子, 高柳 庸一郎, 伊藤 喜之, 斎藤 直樹, 澤 竜一, 加藤 毅, 藤峰 慶徳, 小池 ...2017 年 137 巻 12 号 p. 1543-1553
発行日: 2017/12/01
公開日: 2017/12/01
[早期公開] 公開日: 2017/09/29ジャーナル フリー1H quantitative NMR (1H qNMR) is known as a powerful tool for determination of analytes without the need for their identical standards, which is eligible to a primary rate method. 1H qNMR has been already stipulated to an assay for purity determination in Japanese Pharmacopoeia (JP), and then this technique has been also applied in several fields such as pharmaceutical and food sciences. However, there is little information about the accuracy of 1H qNMR so that the further applications into other fields such as industrial chemistry could be constricted. In this study, in order to assess the reliability of 1H qNMR, we designed the round-robin test of 1H qNMR under the basis of the measurement conditions described in JP. 1,4-Bis(trimethylsilyl)benzene-d4 [1,4-BTMSB-d4, 99.9±0.6% (w/w)] and 3,5-bis(trifluoromethyl)benzoic acid [3,5-BTMFBA, 99.96±0.06% (w/w)], which are certified reference materials (CRMs), were adopted to analyte and qNMR reference standard respectively for the accurate evaluation in this test. Six NMR instruments in 5 institutions optimized to 1H qNMR conditions provided the purity 1,4-BTMSB-d4 within acceptable error range. This result represented that 1H qNMR has the capability to determine precisely the value of analyte in practical analytical field and to be set as official analytical method for purity determination or assay of concentration of organic compounds.
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