YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
140 巻, 2 号
選択された号の論文の21件中1~21を表示しています
受賞総説
  • 佐野 紘平
    2020 年 140 巻 2 号 p. 117-122
    発行日: 2020/02/01
    公開日: 2020/02/01
    ジャーナル フリー

    Water-soluble macromolecules, such as polymers and monoclonal antibodies, have some advantages, including high water solubility, high biocompatibility, a wide range of molecular weights, and amenability to easy modification through the terminal attachment of functional groups. Although there are many instances in which water-soluble polymers are used as solubilizers and stabilizing agents in the medical sciences, the possibility of water-soluble polymers themselves serving as drug carriers in cancer-targeting theranostics (therapeutic+diagnostic) remains to be elucidated. We developed water-soluble polymers labeled with radioisotopes and fluorescence dyes, and elucidated their usefulness as cancer-targeting imaging probes by evaluating their biodistribution with in vivo molecular imaging techniques including nuclear medicine, fluorescence imaging, and photoacoustic imaging. Many water-soluble polymers have some physicochemical properties, such as lower critical solution temperature (LCST), which must be considered as well. We developed cancer-targeting therapeutic compounds by controlling the tumor accumulation of water-soluble polymers based on these physicochemical properties. In this paper, details of the development of cancer-targeting theranostics probes will be discussed.

  • 林 周作
    2020 年 140 巻 2 号 p. 123-128
    発行日: 2020/02/01
    公開日: 2020/02/01
    ジャーナル フリー

    The breakdown of the intestinal mucosal barrier has been shown to play a key role in the pathogenesis of intestinal immune-related disorders such as inflammatory bowel disease (IBD). IBD is a chronic inflammatory disorder with intermittent episodes of remission and relapse, and the incidence of IBD in Japan has risen dramatically in recent decades. Although sustained clinical remission has recently been recognized as an important goal of IBD therapy, there are not many treatment options to maintain long-term remission. Intestinal macrophages play pivotal roles in the regulation of immune homeostasis and inflammation in the intestine. Resident intestinal macrophages can regulate themselves and other immune cells, primarily through the spontaneous secretion of interleukin-10 (IL-10). We reported that the enhancement of IL-10 production by intestinal macrophages has the potential to be a novel therapeutic mechanism for maintaining the remission of IBD. Thus, to develop new therapeutic medicines for IBD, we screened the Wakanyaku Library derived from medicinal herbs for the ability to enhance IL-10 production by intestinal macrophages. Some compounds were identified with the potential to enhance IL-10 production by intestinal macrophages and thereby maintain long-term remission in IBD. This review focuses on our recent findings on the role of intestinal macrophages in the pathogenesis of IBD and developing a novel therapeutic strategy aimed at maintaining remission in IBD.

  • 原田 研一
    2020 年 140 巻 2 号 p. 129-137
    発行日: 2020/02/01
    公開日: 2020/02/01
    ジャーナル フリー

    (−)-2S,3S,4S,5S-Talaumidin (1) exhibits potent neurotrophic activities such as neurite-outgrowth promotion and neuroprotection in primary cultured rat cortical neurons and in nerve growth factor (NGF)-differentiated PC12 cells. To examine the stereochemistry-activity relationship of 1, systematic syntheses of seven stereoisomers of 1 were accomplished via Evans aldol reaction, diastereoselective hydroboration, and Mitsunobu reaction. All stereoisomers showed moderate-to-potent neurite-outgrowth promotion in NGF-differentiated PC12 cells. In particular, (−)-2S,3R,4S,5R-1e having all-cis-substituted configuration exhibited the most significant neurite-outgrowth promotion. Subsequently, we developed a short-step synthetic route for talaumidin derivatives so as to explore new neurotrophic compounds that could be obtained on a large scale. First, we synthesized derivative 2a, which is a racemic compound of (−)-1e, and compared its neurotrophic activity with (−)-1e. It was found that the neurotrophic activity of racemic 2a was similar to that of (−)-1e. Using the same synthetic route, several talaumidin derivatives were synthesized to optimize the oxy-functionality on aromatic rings. Thereby, bis(methylenedioxybenzene) derivative 2b was found to exhibit the highest neurotrophic activity. In addition, examination of the structure-activity relationship of 2b indicated that the 2,5-diphenyl structure was crucial moiety, and the two methyl groups on the tetrahydrofuran (THF) ring could enhance the neurotrophic activity. Furthermore, 2a and 2b were found to induce mouse optic nerve regeneration in vivo.

誌上シンポジウム
  • 異島 優, 田口 和明
    2020 年 140 巻 2 号 p. 139-140
    発行日: 2020/02/01
    公開日: 2020/02/01
    ジャーナル フリー
  • 田口 和明, 松元 一明, 丸山 徹, 小田切 優樹
    2020 年 140 巻 2 号 p. 141-146
    発行日: 2020/02/01
    公開日: 2020/02/01
    ジャーナル フリー

    Bioactive gas molecules, including oxygen, nitric oxide and carbon monoxide (CO), exhibit a variety of physiological activities, and are associated with the onset and progress of some disorders. These facts have led researchers to the development of bioactive gas donors for the treatment of intractable disorders. Hemoglobin is likely an ideal carrier of bioactive gases, since hemoglobin in red blood cells innately carries oxygen in the form of oxyhemoglobin, nitric oxide in the form of S-nitrosohemoglobin, and CO in the form of carbonylhemoglobin. In this study, we attempted to develop a biomimetic CO delivery system using a preparation of hemoglobin. Our strategy for the preparation of this hemoglobin-based CO carrier involves CO being exogenously bound to red blood cells or hemoglobin-encapsulated liposomes, called hemoglobin-vesicles (HbV), which mimic the structure and function of red blood cells. We accumulated evidence that the CO donors—CO-bound red blood cells and CO-bound HbV—showed therapeutic efficacy against intractable disorders in animal models. Here, we describe the potential of hemoglobin-based CO donors, especially CO-bound red blood cells and CO-bound HbV, for the treatment of certain disorders. Hemoglobin-based strategies for the delivery of other bioactive gases for novel drug development are also discussed.

  • 曽宮 正晴, 黒田 俊一
    2020 年 140 巻 2 号 p. 147-152
    発行日: 2020/02/01
    公開日: 2020/02/01
    ジャーナル フリー

    Viruses are natural nanocarriers that deliver various biological cargos, such as DNA, RNA, and proteins. We are developing a new nanocarrier by mimicking the early mechanism of infection by hepatitis B virus (HBV). When the HBV envelope L protein is overexpressed in yeast cells, hollow nanoparticles displaying L proteins are synthesized. This nanoparticle, namely a bio-nanocapsule (BNC), can specifically attach to, and then internalize into, human hepatic cells by implementing the early mechanism of infection by HBV. In this review, we outlined the cellular uptake mechanism of HBV/BNC linking to L protein function. The L protein contains several functional domains in the pre-S1 region, including the fusogenic domain and the heparin-binding domain. The fusogenic domain corresponding to the pre-S1(9-24) region is responsible for the low pH-dependent membrane fusion of BNC. The heparin-binding domain corresponding to the pre-S1(30-42) region has a strong affinity to heparin as compared to that of known heparin-binding peptides, such as vitronectin and gp120 in human immunodeficiency virus-1. This heparin-binding domain binds to heparan sulfate proteoglycan (HSPG) at the cell surface of human hepatic cells. These functional domains are present in any virus, thus, these viral envelope proteins are very useful in designing novel DDS nanocarriers.

  • 奥平 桂一郎
    2020 年 140 巻 2 号 p. 153-157
    発行日: 2020/02/01
    公開日: 2020/02/01
    ジャーナル フリー

    Atherosclerosis is a vascular disease responsible for acute heart attacks and stroke, which are leading causes of death not only in industrialized countries but also worldwide, and the number of patients afflicted by this disease has been increasing in Japan. High-density lipoprotein (HDL) is the plasma lipoprotein that carries what is often called your “good cholesterol” through the blood. This good cholesterol moniker is associated with HDL because higher circulating levels of this lipoprotein are associated with a well-known reduction in the risk of arteriosclerosis. Moreover, many protective mechanisms by which HDL could reduce atherosclerosis are described, including reverse cholesterol transport, along with anti-oxidant, anti-inflammatory and anti-thrombosis activities. However, HDL-modulating therapies to lower cardiovascular risk are not yet available. It has recently been proposed that apolipoprotein A-I (apoA-I) binding protein (AIBP) enhances HDL function by accelerating lipid release from cells and reducing associated inflammatory processes. In this context, our research is focused on the function of HDL-related proteins, such as proteins that regulate HDL production (ATP-binding cassette transporters), and HDL-binding proteins. We expect that these studies could eventually help in the development of HDL-related prognostic and therapeutic strategies to reduce the burden of cardiovascular disease in the future.

  • 門之園 哲哉, 近藤 科江
    2020 年 140 巻 2 号 p. 159-162
    発行日: 2020/02/01
    公開日: 2020/02/01
    ジャーナル フリー

    Small proteins that have a high affinity for cancer cell surface markers can be promising cheap alternatives to antibodies (antibody mimetics). Various types of antibody mimetics have thus been extensively developed. We recently found that a target-binding peptide binds to its target molecule more strongly when it is structurally constrained. To apply this finding to the development of chemically synthesizable small antibody mimetics, we have established an efficient method of creating such proteins, named fluctuation-regulated affinity proteins (FLAPs). To identify desirable scaffolds, first, 13 human proteins (46-104 aa) were selected from the Protein Data Bank. Then, thirteen graft acceptor (GA) sites that efficiently immobilize the grafted peptide structure were identified from six small protein scaffolds using molecular dynamics simulation. To assess the designed antibody mimetics in vitro, human epidermal growth factor receptor 2 (HER2)-binding peptides were selected from the anti-HER2 antibody drugs trastuzumab and pertuzumab by calculating the binding energy, and these were then grafted into the GA sites of scaffolds to create 65 FLAP candidates. The FLAP candidates were expressed in bacteria as fusion proteins with Renilla luciferase (Rluc), and their relative binding affinity to HER2 was easily determined by measuring the Rluc bioluminescence intensity without protein purification. Finally, four out of the 65 showed specific binding to HER2 with a dissociation constant (KD) of 24-65 nM, and these were used for the detection of HER2-expressing cancer cells. Our design strategy will promote the development of antibody mimetics for the effective treatment of cancers and other diseases.

  • 清水 太郎, 異島 優, 石田 竜弘
    2020 年 140 巻 2 号 p. 163-169
    発行日: 2020/02/01
    公開日: 2020/02/01
    ジャーナル フリー

    Modification of proteins with polyethylene glycol (PEG) (PEGylation) is a gold standard technique that improves the solubility, pharmacokinetics, and immunogenicity of modified proteins. To date more than 10 PEGylated protein formulations have been approved, and more than 20 PEGylated drugs are entering clinical trials. PEG has been considered non-immunogenic and non-toxic, but several studies have shown that PEG acquires immunogenicity following attachment to nanoparticles. The administration of PEGylated liposomes, micelles and proteins induces the production of antibodies against PEG (anti-PEG antibodies) in animals and human subjects. Indeed, approximately 20% of healthy human subjects possess pre-existing anti-PEG antibodies prior to treatment with PEGylated therapeutics. The induced and pre-existing anti-PEG antibodies cause not only the elimination of PEGylated proteins from blood circulation, but also allergic responses via the release of anaphylatoxins. Consequently, therapeutic outcomes for PEGylated proteins are impaired. The utility of PEGylated proteins could be improved by attenuating the PEG-related immune response. On the other hand, anti-PEG immune responses might be exploited for vaccine applications. Our recent studies demonstrated that anti-PEG antibodies mediate the delivery of antigens encapsulated in PEGylated liposomes, and enhance antigen-specific immune responses. In this review, we summarize anti-PEG antibody induction by PEGylated proteins and alterations in anti-PEG IgM-mediated pharmacokinetics and pharmacodynamics. These findings extend our knowledge of PEG-related immune responses.

  • 舩田 正彦, 三島 健一
    2020 年 140 巻 2 号 p. 171-172
    発行日: 2020/02/01
    公開日: 2020/02/01
    ジャーナル フリー
  • 嶋根 卓也, 邱 冬梅, 和田 清
    2020 年 140 巻 2 号 p. 173-178
    発行日: 2020/02/01
    公開日: 2020/02/01
    ジャーナル フリー

    This study aimed to review the current state and trends in cannabis use in Japan, using data from several national epidemiological surveys. The number of cannabis users in the general population was estimated approximately 1.3 million people. Cannabis use increased between 2015 and 2017. In 2017, the lifetime prevalence of cannabis use was greater than that of inhalants, and cannabis had become the most abused drug in Japan. The increase in cannabis users is thought influenced by increased access to illegal cultivation and positive thinking about cannabis use among many people, especially younger individuals.

  • 富山 健一, 舩田 正彦
    2020 年 140 巻 2 号 p. 179-192
    発行日: 2020/02/01
    公開日: 2020/02/01
    ジャーナル フリー

    In most countries marijuana is regulated by the Single Convention on Narcotic Drugs. In Japan marijuana use is illegal under the Marijuana Control Law. In USA, marijuana is also classified as a schedule I drug, which is the most stringent regulation category under federal law. On the other hand, California became the first state to legalize marijuana for medical uses in 1996. Since then, several other US states have approved marijuana for medical or recreational use. However, marijuana remains completely illegal in most states, while some allow only cannabidiol (CBD) extracted from marijuana for medical use. In June 2018, the US Food and Drug Administration approved Epidiolex, the first marijuana-derived drug, containing purified CBD, to treat certain rare childhood seizure syndromes. Therefore the situation surrounding control of marijuana in USA is complex. Recently, a definite trend toward reconsidering marijuana regulation has been seen around the world, which could have a major impact on marijuana policy in Japan. In this review, we investigated existing medical and recreational marijuana laws in various US states, with a focus on California, which approved recreational use in 2018. Here, we describe the current state of marijuana regulation in terms of both medical and recreational use. In addition, we discuss public safety issues associated with marijuana, including crime, traffic accidents, and emergency department visits from possible marijuana exposure, as well as generated tax revenues, from official marijuana-related reports in Colorado, which legalized marijuana use in 2012.

  • 三島 健一, 入江 圭一
    2020 年 140 巻 2 号 p. 193-204
    発行日: 2020/02/01
    公開日: 2020/02/01
    ジャーナル フリー

    Cannabis contains over 700 known cannabinoids, terpenoids, flavonoids, and so on; however, the roles and importance of these components have yet to be fully understood. Δ9-Tetrahydrocannabinol (THC) is believed the most psychoactive component in cannabis, whereas cannabidiol (CBD), cannabinol, and cannabigerol are the most well-known non-psychoactive components. THC, but not CBD, has been shown to produce abnormal behavior in animals; these effects are caused, at least in part, by binding to cannabinoid receptor type 1 (CB1) in the brain. Regarding the risks associated with cannabis use, acute effects of THC, such as a “high”, cognitive deficits, and irritability, are considered more important than potential dependence. On the other hand, CBD has shown anticonvulsant, anti-inflammatory, immunosuppressive, analgesic, and anticancer effects. However, CBD has very low affinity (in the micromolar range) for the CB1 receptor, as well as for the CB2 receptor, and its underlying mechanism remains obscure. In this review, we demonstrate that THC induces abnormal behavior such as catalepsy-like immobilization, spatial memory impairment, and high and low sensitivity to ultrasonic vocalization after an aversive air-puff stimulus. Moreover, we demonstrate that THC and CBD improve brain injury in middle cerebral artery occlusion in a mouse model through different mechanisms. These findings suggest the need to discuss the recent development of “THC and CBD pharmacology” in animal studies, as well as the utility and risk of various cannabis components in humans.

  • 舩田 正彦, 富山 健一
    2020 年 140 巻 2 号 p. 205-214
    発行日: 2020/02/01
    公開日: 2020/02/01
    ジャーナル フリー

    Cannabis use among the younger population in Japan has been steadily increasing. The aim of the present review is to highlight recent knowledge regarding the molecular mechanisms of action and health risks associated with cannabis and synthetic cannabinoid consumption. We investigated the effects of Δ9-tetrahydrocannabinol (THC) and synthetic cannabinoids on place conditioning in ICR mice. Both Δ9-THC and synthetic cannabinoids produce a significant conditioned place preference. These rewarding effects were completely suppressed by the cannabinoid CB1 receptor type antagonist AM251. The cytotoxicological effects of Δ9-THC and synthetic cannabinoids were also characterized in the limbic forebrain of mice in primary culture in vitro. Δ9-THC and synthetic cannabinoids caused cell death in a dose-dependent manner. The rank order of cytotoxicological potency was synthetic cannabinoids>Δ9-THC and related to the agonistic activities of the CB1 receptor. A recent review on the harmful effects of cannabis use in humans reported that behavioral impairments, especially in terms of attention, memory, and complex information-processing ability, can last for many weeks after cessation of cannabis use among heavy users. In addition, cannabis use could be a risk factor for drug dependence and later psychosis among adolescents. The results of animal and human studies suggest that CB1 receptors play an important role in the expression of harmful effects of cannabis and synthetic cannabinoid use. Moreover, concern regarding increasing concentrations of Δ9-THC in cannabis in many countries has been noted, because more potent cannabis may be associated with worse adverse effects.

総説
  • 髙畠 亨
    2020 年 140 巻 2 号 p. 215-228
    発行日: 2020/02/01
    公開日: 2020/02/01
    ジャーナル フリー

    Aromatic furazan has numerous pharmacologic and industrial applications. As part of our work on aromatic furazan chemistry and biochemistry, benzofurazan N-oxides, on irradiation using a high-pressure mercury lamp with a Pyrex filter in acetonitrile containing a little water, afforded 1H-azepine-2,7-dione. Mechanistic studies on the photoreaction using a low-pressure mercury lamp and photosensitizer suggest that photosensitized formation of 1H-azepine-2,7-dione with the aromatic hydrocarbon may be carried out by reabsorption of fluorescence. Quinoxaline 1,4-dioxide, phenazine 5,10-dioxide, and pyrido[2,3-b]pyrazine derivatives were synthesized from the corresponding aromatic or heteroaromatic furazan N-oxides by silica gel or molecular sieves under solvent-free conditions using microwave irradiation. The toxicities of some benzofurazans were examined on Escherichia coli; these may due to their reduction within the E. coli cell and their reoxidization by molecular dioxygen to form superoxide and hydrogen peroxide. The formation of 4,7-dicyanobenzofurazan anion radical in the E. coli cell suspension-4,7-dicyanobenzofurazan-glucose system in the absence of O2 was followed by ESR spectroscopy. 4,7-Dimethylbenzofurazan was transformed by 1O2 produced by irradiation of C60 into 4,7-dimethylbenzofurazan 4,7-endoperoxide. The endoperoxide decomposed back to 4,7-dimethylbenzofurazan at room temperature. 4,7-Dimethylbenzofurazan was transformed by irradiation with the third harmonic of a Quanta-Ray Nd:YAG laser (355 nm) into (2Z,4Z)-2,5-dimethylhexa-2,4-dienedinitrile monoxide. Irradiation of 4,7-dimethylbenzofurazan yielded a photoproduct with a quantum yield 0.48 and chemical yield 99%.

  • 鈴木 孝
    2020 年 140 巻 2 号 p. 229-271
    発行日: 2020/02/01
    公開日: 2020/02/01
    ジャーナル フリー

    Outcomes of treatment for malignant pediatric tumors including leukemia are improving by conventional multimodal treatment with strong chemotherapy, surgical resection, radiotherapy, and bone marrow transplantation. However, patients with advanced neuroblastoma, metastatic Ewing's sarcoma family of tumor (ESFT), and metastatic osteosarcoma continue to have an extremely poor prognosis. Therefore novel therapeutic strategies are urgently needed to improve their survival. Apoptotic cell death is a key mechanism for normal cellular homeostasis. Intact apoptotic mechanisms are pivotal for embryonic development, tissue remodeling, immune regulation, and tumor regression. Genetic aberrations disrupting programmed cell death often underpin tumorigenesis and drug resistance. Moreover, it has been suggested that apoptosis or cell differentiation proceeds to spontaneous regression in early stage neuroblastoma. Therefore apoptosis or cell differentiation is a critical event in this cancer. We extracted many compounds from natural plants (Angelica keiskei, Alpinia officiarum, Lycaria puchury-major, Brassica rapa) or synthesized cyclophane pyridine, indirubin derivatives, vitamin K3 derivatives, burchellin derivatives, and GANT61, and examined their effects on apoptosis, cell differentiation, and cell cycle in neuroblastoma and ESFT cell lines compared with normal cells. Some compounds were very effective against these tumor cells. These results suggest that they may be applicable as an efficacious and safe drug for the treatment of malignant pediatric tumors.

  • 東山 公男
    2020 年 140 巻 2 号 p. 273-287
    発行日: 2020/02/01
    公開日: 2020/02/01
    ジャーナル フリー

    Our investigations of various aspects of organic chemistry over the past 43 years are reviewed in this paper. The following subjects are discussed: 1) the diastereoselective addition reaction to chiral imines and oxazolidines of organometallic reagents and its applications and 2) the reaction and synthesis of fluorine-containing compounds.

一般論文
  • 永田 実沙, 田中 映里, 落合 千波, 串畑 太郎, 安原 智久, 曽根 知道, 池内 淳子
    2020 年 140 巻 2 号 p. 289-300
    発行日: 2020/02/01
    公開日: 2020/02/01
    ジャーナル フリー

    In this paper, as a program targeting school pharmacists engaged in health counseling and health guidance at elementary and junior high schools, which are often evacuation centers, we have rebuilt the disaster evacuation shelter support chart program for community pharmacists. As a result of the questionnaire survey, there were seen 4 groups. There were a group that was conscious of shelter support, a group who felt that they did not have aptitude for disaster relief, a group that was conscious of general support and logistical support, and a group that showed a negative attitude towards disaster relief. From this, it was suggested that this training program worked enlighteningly to support affected area by school pharmacists, and at the same time participants themselves could lead to consideration of aptitude for support at the time of disaster.

  • 上田 昌宏, 高垣 伸匡, 恩田 光子, 荒川 行生, 庄司 雅紀, 大森 志保, 清水 忠
    2020 年 140 巻 2 号 p. 301-312
    発行日: 2020/02/01
    公開日: 2020/02/01
    ジャーナル フリー

    In Japanese pharmaceutical education, the Model Core Curriculum was revised in 2013 to train pharmacists who can appropriately evaluate literature and use evidence-based medicine (EBM). However, in the investigation of EBM education at pharmaceutical universities in 2015, it was found that literature evaluation was hardly performed in the education of undergraduate students. One of the reason is the lack of EBM lecturers at each universities. Therefore, we adopted team-based learning (TBL) to educate more than 50 undergraduate students on the practical evaluation of literatures and the understanding of EBM concepts. The learning outcomes of this strategy were evaluated using the scores of individual tests before and after the class. As a result, the mean scores on the post-test significantly improved from 4.34 to 6.42 out of 10 total points (p<0.001). We further administered a questionnaire survey regarding the understanding of EBM (the mean score was 4.12). In conclusion, it was suggested that TBL for a large number was effective in EBM education for providing knowledge of literature evaluation and the understanding of fundamental concepts.

    Editor's pick

    Much less education has been done on literature evaluation in the Japanese education of pharmaceutical sciences. The authors adopted team-based learning (TBL) to educate undergraduate students on the practical evaluation of literature and the understanding of evidence-based medicine (EBM) concepts. The mean scores on the post-test significantly improved from 4.34 to 6.42 out of 10 total points. These results suggested that TBL was effective in EBM education for providing knowledge of literature evaluation and the understanding of fundamental concepts.

ノート
  • 出口 昌孝, 上瀬 英彦, 西田 圭吾, 大井 一弥
    2020 年 140 巻 2 号 p. 313-318
    発行日: 2020/02/01
    公開日: 2020/02/01
    ジャーナル フリー
    電子付録

    In recent years, it has become clear that zinc deficiency is closely related in several skin disorders. In elderly people, chronic itch and dry skin are common. In addition, the zinc concentrations are known to decrease with age. Therefore, we examined the beneficial effects of oral zinc supplementation on dry skin and itch in elderly people. Patients 65 years of age or older who visited the Jose Clinic (Odai-town, Mie Pref.) with serum zinc concentrations below 80 μg/dL were enrolled in the study (low zinc group). The participants were administered zinc acetate hydrate for 12 weeks from the start of the study, and transepidermal water loss (TEWL) and stratum corneum moisture content measurements, blood collection, and itch evaluation were performed every 4 weeks. Patients in the control group had serum zinc concentrations of ≥80 μg/dL (the normal zinc group). Results showed that TEWL was significantly higher in the low zinc group than in the normal zinc group, indicating that skin barrier function is impaired in the low zinc group. Serum zinc concentrations increased and TEWL decreased significantly over the 12 weeks of treatment. In addition, a negative correlation was observed between serum zinc concentrations and TEWL. Our results indicate that zinc supplementation is effective to improve the skin barrier function in elderly people.

  • 小田原 真希, 山科 卓也, 入江 健司, 山下 克也, 鶴田 南奈子, 塚田 寛子, 鶴山 萌子, 金内 弘志, 原 利宝, 児玉 真由子 ...
    2020 年 140 巻 2 号 p. 319-328
    発行日: 2020/02/01
    公開日: 2020/02/01
    ジャーナル フリー
    電子付録

    In this study, antimicrobial stewardship team (AST) intervention was evaluated by comparing patient outcomes and consumption of broad-spectrum antibiotics [carbapenem antibiotics and tazobactam/piperacillin (TAZ/PIPC)] before and after the intervention. There was no fluctuation in the consumption rate of carbapenem, TAZ/PIPC and other antibiotics, but there was a decreased annual consumption of antibiotics after AST intervention compared to before intervention. For the carbapenems, antimicrobial use density (AUD) of meropenem (MEPM) was highest in both periods, at 20.1 and 20.4 before and after AST intervention, respectively, with no significant change after AST intervention. However, the days of therapy (DOT) for MEPM were 27.4 and 24.8 d, respectively, with a decreasing trend after AST intervention. AUD and DOT for TAZ/PIPC after AST intervention were 6.5 and 8.1 d, respectively, which were lower than the pre-intervention values. Rapid identification of the causative strain enables early de-escalation and may improve the economics of antibiotic use, but there was no difference from before to after AST intervention. Compared with before and after strain identification, the carbapenem administration rate after AST intervention was significantly lower than the pre-intervention rate (p<0.01). There was no difference in 28-day mortality and treatment period before and after AST intervention, and there were no differences in outcomes such as resolution of bacteremia, mortality, exacerbation and no change from before to after AST intervention. Based on these results, we suggest that AST intervention can reduce consumption of antibiotics without altering patient outcomes.

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