[Development of Cancer-targeted Theranostics Probes Based on the Physicochemical Properties of Water-soluble Macromolecules].
Abstract 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 polyme...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - February 6, 2020 Category: Drugs & Pharmacology Authors: Sano K Tags: Yakugaku Zasshi Source Type: research

[Unraveling the Pathogenesis of Inflammatory Bowel Disease and Search for New Therapeutic Medicines].
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 developi...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - February 6, 2020 Category: Drugs & Pharmacology Authors: Hayashi S Tags: Yakugaku Zasshi Source Type: research

[Development of New Neurotrophic Compounds Based on Talaumidin].
Abstract (-)-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 configu...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - February 6, 2020 Category: Drugs & Pharmacology Authors: Harada K Tags: Yakugaku Zasshi Source Type: research

[The Charm of Protein for Drug Development].
PMID: 32009034 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - February 6, 2020 Category: Drugs & Pharmacology Authors: Ishima Y, Taguchi K Tags: Yakugaku Zasshi Source Type: research

[Strategy of Drug Development Based on the Bioactive Gas-carrying Capacity of Hemoglobin].
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-bo...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - February 6, 2020 Category: Drugs & Pharmacology Authors: Taguchi K, Matsumoto K, Maruyama T, Otagiri M Tags: Yakugaku Zasshi Source Type: research

[DDS Nanocarriers Mimicking Early Infection Machinery of Viruses].
Abstract 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...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - February 6, 2020 Category: Drugs & Pharmacology Authors: Somiya M, Kuroda S Tags: Yakugaku Zasshi Source Type: research

[Challenges in Drug Development Targeting Anti-atherosclerotic Proteins].
Abstract 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...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - February 6, 2020 Category: Drugs & Pharmacology Authors: Okuhira K Tags: Yakugaku Zasshi Source Type: research

[Semi-rational Design of Target-binding Small Proteins for Cancer Treatment].
Abstract 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 pr...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - February 6, 2020 Category: Drugs & Pharmacology Authors: Kadonosono T, Kizaka-Kondoh S Tags: Yakugaku Zasshi Source Type: research

[Induction of Anti-PEG Immune Responses by PEGylation of Proteins].
Abstract 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 antibodi...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - February 6, 2020 Category: Drugs & Pharmacology Authors: Shimizu T, Ishima Y, Ishida T Tags: Yakugaku Zasshi Source Type: research

[Trends in Drug Abuse: Cannabis in the Era of Post-new Psychoactive Substances].
PMID: 32009040 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - February 6, 2020 Category: Drugs & Pharmacology Authors: Funada M, Mishima K Tags: Yakugaku Zasshi Source Type: research

[Current Situation of Cannabis Use in Japan: Based on Data from the Nationwide General Population Survey on Drug Use in Japan 2017].
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. PMID: 32...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - February 6, 2020 Category: Drugs & Pharmacology Authors: Shimane T, Qiu D, Wada K Tags: Yakugaku Zasshi Source Type: research

[Present Conditions of Marijuana Regulation in USA: Medical and Recreational Use].
Abstract 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 u...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - February 6, 2020 Category: Drugs & Pharmacology Authors: Tomiyama KI, Funada M Tags: Yakugaku Zasshi Source Type: research

[Central Effect of Components of Cannabis: Utility and Risk].
Abstract 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 effec...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - February 6, 2020 Category: Drugs & Pharmacology Authors: Mishima K, Irie K Tags: Yakugaku Zasshi Source Type: research

[Dependence and Cytotoxicity of Components of Cannabis].
Abstract 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 cytoto...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - February 6, 2020 Category: Drugs & Pharmacology Authors: Funada M, Tomiyama KI Tags: Yakugaku Zasshi Source Type: research

[Chemical and Biochemical Reactions of Aromatic Furazan Compounds].
Abstract 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-...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - February 6, 2020 Category: Drugs & Pharmacology Authors: Takabatake T Tags: Yakugaku Zasshi Source Type: research

[Research on Analysis of Final Diagnosis and Prognostic Factors, and Development of New Therapeutic Drugs for Malignant Tumors (Especially Malignant Pediatric Tumors)].
Abstract 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...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - February 6, 2020 Category: Drugs & Pharmacology Authors: Suzuki T Tags: Yakugaku Zasshi Source Type: research

[Overview of 43 Years of Studies on Asymmetric Synthesis].
Abstract 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. PMID: 32009047 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - February 6, 2020 Category: Drugs & Pharmacology Authors: Higashiyama K Tags: Yakugaku Zasshi Source Type: research

[Implementation and Verification of Tabletop Training Program for Disaster Evacuation Shelter Support for School Pharmacist].
Abstract 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. ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - February 6, 2020 Category: Drugs & Pharmacology Authors: Nagata M, Tanaka E, Ochiai C, Kushihata T, Yasuhara T, Sone T, Ikeuchi J Tags: Yakugaku Zasshi Source Type: research

[Introduction of Team-based Learning to Evidence-based Medicine Educational Course for Pharmacy Students].
Abstract 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 EB...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - February 6, 2020 Category: Drugs & Pharmacology Authors: Ueda M, Takagaki N, Onda M, Arakawa Y, Shoji M, Ohmori S, Shimizu T Tags: Yakugaku Zasshi Source Type: research

[Transepidermal Water Loss (TEWL)-decreasing Effect by Administration of Zinc in the Elderly People].
Abstract 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 t...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - February 6, 2020 Category: Drugs & Pharmacology Authors: Deguchi M, Jose H, Nishida K, Ooi K Tags: Yakugaku Zasshi Source Type: research

[Evaluation of Intervention by an Antimicrobial Stewardship Team for Patients with Bacteremia].
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, respective...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - February 6, 2020 Category: Drugs & Pharmacology Authors: Odawara M, Yamashina T, Irie K, Yamashita K, Tsuruta M, Tsukada H, Tsuruyama M, Kaneuchi H, Hara R, Kodama M, Kubo N, Hiraki Y Tags: Yakugaku Zasshi Source Type: research

[Roles of TRPA1 in Painful Dysesthesia].
This study assessed the roles of transient receptor potential ankyrin 1 (TRPA1) in dysesthesia by utilizing three animal models of dysesthesia characterized by reductions in blood flow to the skin: a transient hindlimb ischemia/reperfusion model, characterized by spontaneous licking and tactile hypoesthesia of the ischemic hindpaw; a streptozotocin-induced diabetic neuropathy model in mice, characterized by cold hypersensitivity, which is likely parallel to the reduced skin blood flow of the hindpaw; and a hindlimb ischemia model. TRPA1 inhibition or deficiency blocked spontaneous licking in the transient hindlimb ischemia...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 8, 2020 Category: Drugs & Pharmacology Authors: So K Tags: Yakugaku Zasshi Source Type: research

[Approaches for Class Preparation Using Qualitative Analysis by Coding-Survey in Technical English Course "Yakugaku-Eigo Nyumon"].
[Approaches for Class Preparation Using Qualitative Analysis by Coding-Survey in Technical English Course "Yakugaku-Eigo Nyumon"]. Yakugaku Zasshi. 2020;140(1):107-111 Authors: Hosokawa M, Kodama N, Tanaka M, Takeuchi A, Koyama J Abstract The purpose of this study was to examine how students prepare for the pharmaceutical technical English course "Yakugaku-Eigo Nyumon" by qualitative analysis. A sub-text, supplemental material was used to assist students with class preparation. Qualitative questionnaires on understanding and approaches for class preparation as well as review of cla...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 8, 2020 Category: Drugs & Pharmacology Authors: Hosokawa M, Kodama N, Tanaka M, Takeuchi A, Koyama J Tags: Yakugaku Zasshi Source Type: research

[Investigation of Drug-induced Lung Injury for the Development of a Novel Therapeutic Approach].
In conclusion, the present study elucidated mechanisms underlying drug-induced EMT and highlighted a potential novel therapeutic approach to drug-induced lung diseases. PMID: 31902879 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 8, 2020 Category: Drugs & Pharmacology Authors: Kawami M Tags: Yakugaku Zasshi Source Type: research

[Diversity-oriented Symposium: Diversity Experiences through Study Abroad].
PMID: 31902880 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 8, 2020 Category: Drugs & Pharmacology Authors: Yakushiji F, Nakayama A Tags: Yakugaku Zasshi Source Type: research

[Efficient Discovery of Ligands Targeting Poor Lipid-signaling Metabolic Enzymes, as Facilitated by Activity-based Protein Profiling].
Abstract Despite a continuous increase in R&D spending on potential new medicines, the success rate of drug development has not improved. The pharmaceutical industry is now facing a major challenge. As a college student who was studying pharmaceutical sciences in Japan, I became passionate about developing a new technology that would allow us to efficiently discover novel drug targets and selective chemical ligands for these targets. This realization encouraged me to join the PhD program at The Scripps Research Institute (TSRI) in 2013, where I carried out thesis research focusing on ligand discovery for poorl...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 8, 2020 Category: Drugs & Pharmacology Authors: Ogasawara D Tags: Yakugaku Zasshi Source Type: research

[New Research Development and Connection with Fellow Scholars through Study Abroad].
Abstract After completing my doctoral training, I joined the Ronald Davis Laboratory at The Scripps Research Institute, Florida. At Scripps, I extended my research and worked to understand the mechanisms of age-related memory impairment. Three and a half years in Florida passed very quickly while I worked with a multi-national multi-cultural team of scientists. Since returning to Japan, I now lead my own research team. My research experience abroad helped me to expand my scope of research, and allowed me to combine the fields of aging and neurosciences to discover solutions for many newly emerging challenges to hu...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 8, 2020 Category: Drugs & Pharmacology Authors: Tonoki A Tags: Yakugaku Zasshi Source Type: research

[Consideration of Occupational Diversity via Academia through Studying Abroad in the UK].
Abstract Studying abroad may prove an attractive opportunity for young Japanese scientists, as it would allow them to broaden their perspectives regarding occupational diversity as a scientist. This is the first observation I made after studying abroad at the University of Oxford for two and a half years as a postdoctoral fellow. Many young scientists in the UK have got occupations not only in academia or in manufacturing industries, but also in various other business fields. Their occupational diversity seems to be considerably wider than that found among young Japanese scientists. The second feature I observed w...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 8, 2020 Category: Drugs & Pharmacology Authors: Ogura Y Tags: Yakugaku Zasshi Source Type: research

[Looking Back on My Time as a Postdoc in Germany].
Abstract After finishing my Ph.D., I had the opportunity to work as a postdoc in the Division of Redox Regulation (laboratory of Tobias Dick) at the German Cancer Research Center in Heidelberg for almost three years. Although cultural differences between Japan and Germany made my time in Germany hectic, the experience expanded my worldview as well as my research expertise. Here I would like to share my experience in conducting research abroad and give my opinion about its significance. I hope that this symposium review will be helpful to students interested in researching abroad and will give them a positive impre...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 8, 2020 Category: Drugs & Pharmacology Authors: Fujikawa Y Tags: Yakugaku Zasshi Source Type: research

[The Challenges of a Female Scientist Studying Abroad with Her Children at the University of Geneva].
Abstract My dream was to study abroad someday. Just after earning my Ph.D., I married and soon had children. I have had a busy life since then, balancing work with childcare, and thus had almost given up on my dream. How lucky-a chance suddenly came to me! I had an opportunity to study at the University of Geneva. In my case, the issue to overcome for this study abroad was how my family would be dealt with. After consulting with my family, I decided to take two daughters with me to Switzerland. Although I had a bit of a hard time, I managed to lead a fruitful life thanks to a good environment for bringing up child...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 8, 2020 Category: Drugs & Pharmacology Authors: Kubo M Tags: Yakugaku Zasshi Source Type: research

[Elucidation of New Function in Endothelial Cells for Efficient Delivery Strategy of Drug to Tissues].
Abstract The author has described two new functions of endothelial cells for efficient delivery of drugs to tissues. First, it was indicated that tight junction (TJ)-associated protein, claudin-1, exerts potent paracellular barrier function in cultured mouse lung microvascular endothelial cells (LMECs). This barrier was instantly and reversibly opened by reduction of TJ proteins expression via histamine H1 and H2 receptors. Histamine was biosynthesized by l-histidine decarboxylase from uptaken l-histidine, and biotransformed by type B of monoamine oxidase, suggesting that histamine concentration is controlled in r...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 8, 2020 Category: Drugs & Pharmacology Authors: Sakurai E Tags: Yakugaku Zasshi Source Type: research

[Basic Studies on the Mechanism, Prevention, and Treatment of Osteonecrosis of the Jaw Induced by Bisphosphonates].
Abstract Since the first report in 2003, bisphosphonate-related osteonecrosis of the jaw (BRONJ) has been increasing, without effective clinical strategies. Osteoporosis is common in elderly women, and bisphosphonates (BPs) are typical and widely used anti-osteoporotic or anti-bone-resorptive drugs. BRONJ is now a serious concern in dentistry. As BPs are pyrophosphate analogues and bind strongly to bone hydroxyapatite, and the P-C-P structure of BPs is non-hydrolysable, they accumulate in bones upon repeated administration. During bone-resorption, BPs are taken into osteoclasts and exhibit cytotoxicity, producing ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 8, 2020 Category: Drugs & Pharmacology Authors: Endo Y, Funayama H, Yamaguchi K, Monma Y, Yu Z, Deng X, Oizumi T, Shikama Y, Tanaka Y, Okada S, Kim S, Kiyama T, Bando K, Shima K, Suzuki H, Takahashi T Tags: Yakugaku Zasshi Source Type: research

[Development of Novel Nuclear Medical Imaging Probes for Quantification of Matrix Metalloproteinases in Diseases].
Abstract Matrix metalloproteinases (MMPs) regulate various cellular functions, such as motility, invasion, differentiation, and apoptosis. Precise in vivo quantification of MMPs in disease can provide beneficial information for both basic and clinical research studies. To this end, various types of probes have been developed for imaging MMPs in vivo. In this review, representative MMP-targeted probes, such as binding probes and activatable probes, are outlined, including highlights of our own research. In addition, strategies for the development of probes that apply "theranostics," a concept that integra...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 8, 2020 Category: Drugs & Pharmacology Authors: Kondo N Tags: Yakugaku Zasshi Source Type: research

[Factors Resulting Correlation and Differences in Renal Function Evaluation Index Using the Serum Cystatin C and Creatinine as Measured by an Enzymatic Method].
Abstract We previously reported the association of the estimated glomerular filtration rate (eGFRcreat) calculated from the serum creatinine level (S-Cr) measured using the Jaffe method with the GFR (eGFRcys) estimated from the serum cystatin C level (CysC). However, few studies have compared the eGFRcreat using the enzymatic method with the eGFRcys. It is unclear whether there are differences in the results of renal function assessment. The purpose of this study was to compare the eGFRcreat calculated from the S-Cr with the eGFRcys calculated from the CysC in patients in whom the S-Cr and CysC were simultaneously...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 8, 2020 Category: Drugs & Pharmacology Authors: Takahashi M, Takayama S, Suga H, Kadomura S, Kojima M, Iwao K, Takeda K, Sato H, Kobayashi M, Saitoh H Tags: Yakugaku Zasshi Source Type: research

[Examination of the Usefulness of Health Consultations in Community Pharmacies for Elderly People].
In this study, we conducted a web-based survey of 800 elderly people to clarify sex and regional differences in the usefulness of individual health consultations in community pharmacies for improving the health of elderly people. The results demonstrated that the health consultations were more useful for those with high health consciousness than those with low health consciousness and men living alone had the greatest need for health consultations. Among residents of urban areas, "physical activity and exercise" affected the usefulness of the health consultations for both men and women. In contrast, among residen...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 8, 2020 Category: Drugs & Pharmacology Authors: Osanai Y, Sakurai H Tags: Yakugaku Zasshi Source Type: research

[Translational Research Based on Understanding the Regulatory Mechanisms of in Vivo Behaviors of Fat-soluble Compounds].
Abstract Several fat-soluble compounds such as cholesterol and fat-soluble vitamins have important physiological activities in the body, and their excess and/or deficiency have been reported to be closely associated with the onset and progression of several conditions such as lifestyle-related diseases. It is important to clarify not only the physiological activities but also in vivo kinetics of fat-soluble compounds to understand their in vivo activity (toxicity). This review introduces our recent (reverse) translational research in a combination of basic and clinical studies to reveal the regulatory mechanisms o...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 5, 2019 Category: Drugs & Pharmacology Authors: Yamanashi Y Tags: Yakugaku Zasshi Source Type: research

[Hereditary Skeletal and Skin Disorders Caused by Defects in the Biosynthesis of Chondroitin/Dermatan Sulfate, and Molecular Mechanisms of Pulmonary Metastasis].
Abstract The roles of chondroitin sulfate (CS) and dermatan sulfate (DS) have been demonstrated in various biological events such as the construction of the extracellular matrix, tissue development, and cell signaling through interactions with extracellular matrix components, morphogens, and growth factors. Human genetic diseases, including skeletal abnormalities, connective tissue diseases, and heart defects, were reported to be caused by mutations in the genes encoding glycosyltransferases, epimerases, and sulfotransferases that are responsible for the biosynthesis of CS and DS. Glycobiological approaches reveal...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 5, 2019 Category: Drugs & Pharmacology Authors: Mizumoto S Tags: Yakugaku Zasshi Source Type: research

[Development of a Whole-brain Imaging System at Subcellular Resolution for Analysis of Animal Models of Neuropsychiatric Disorders].
Abstract Brain functions are performed by highly interconnected neurons distributed across the whole brain. Imaging of the whole brain at subcellular resolution is crucial for precise understanding of the pathological and therapeutic mechanisms of neuropsychiatric disorders; however, microscopic imaging of the whole brain remains a challenge due to the trade-offs between imaging speed and spatial resolution. To overcome this, we have recently developed block-face serial microscopy tomography (FAST), which is a novel serial-section imaging system using high-speed spinning-disk confocal microscopy. FAST enables high...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 5, 2019 Category: Drugs & Pharmacology Authors: Seiriki K Tags: Yakugaku Zasshi Source Type: research

[Generation of Zone-specific Hepatocyte-like Cells from Human Induced Pluripotent Stem Cells for Accurate Prediction of Drug-induced Hepatotoxicity].
Abstract Human induced pluripotent stem (iPS) cell-derived hepatocyte-like cells (iPS-HLCs) are expected to be applicable to large-scale in vitro hepatotoxicity screening systems. Accordingly, methods for generating HLCs from human iPS cells have been improved over the past decade. However, although human hepatocytes have zone-specific characteristics in vivo, there is currently no technique to generate zone-specific HLCs from human iPS cells. Therefore, to generate HLCs with zone-specific properties from human iPS cells, we cultured iPS-HLCs using a parenchymal or nonparenchymal cell-conditioned medium (CM). The ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 5, 2019 Category: Drugs & Pharmacology Authors: Mitani S Tags: Yakugaku Zasshi Source Type: research

[Development of a Novel Affinity Labeling Method for Target Identification of Bioactive Small Molecules].
Abstract Target identification (target-ID) is an important step in elucidating the mechanisms of action of bioactive small molecules. In the past few decades, a number of target-ID methods have been developed. Among these, affinity labeling has been reliably used for specific modifications, as well as for the identification of weakly interacting protein targets, membrane-associated protein targets, and target-interacting proteins under native cellular conditions, which are generally difficult to achieve by conventional pull-down methods. In general, affinity labeling utilizes chemical probes composed of a bioactiv...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 5, 2019 Category: Drugs & Pharmacology Authors: Yamaguchi T Tags: Yakugaku Zasshi Source Type: research

[Analyzing the Redox Status of Intracellular Glutathione and Its Application to an Intestinal Bowel Disease Model].
Abstract Oxidative stress, including reactive oxygen species (ROS) generation and resulting glutathione oxidation, have been implicated in numerous aspects of cell physiology and human pathology such as cell senescence, cell differentiation, and inflammation. Significant effort has been made to establish methods of analyzing ROS levels and glutathione oxidation within a living cell. The recent development of redox-sensitive green fluorescent protein (GFP) variants enables a robust and accurate estimation of ROS level and glutathione oxidation at subcellular resolution. We created membrane-targeted versions of glut...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 5, 2019 Category: Drugs & Pharmacology Authors: Hatori Y Tags: Yakugaku Zasshi Source Type: research

[Development of Molecular Probes for Live Imaging of Cancer and Infectious Diseases].
Abstract Positron emission tomography (PET) and single photon emission computed tomography (SPECT) are powerful molecular imaging methods for examining disease-related factors in the whole body using specific imaging probes. Recently, we tried to develop molecular imaging probes that specifically visualize pathological factors associated with cancers and infectious diseases. Although survivin is highly expressed in several cancers, its expression is undetectable in non-dividing tissues. Thus, we developed several small molecular imaging probes that target survivin. These ligands not only showed high affinity for s...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 5, 2019 Category: Drugs & Pharmacology Authors: Fuchigami T Tags: Yakugaku Zasshi Source Type: research

[Preparation and Evaluation of Fullerene Based Nanomedicine].
Abstract Fullerenes, large spherical molecules composed solely of carbon atoms, have gathered much attention for practical applications that take advantage of their unique spherical structure, physical properties, and biological activities. For example, fullerene C60 can function as a photosensitizer, an antioxidant, a bioimaging agent, and as a gene or drug carrier. However, the practical use of C60 for these potential biomedical applications has been hampered by the fact that it is only sparingly soluble in water. In this review, we focus on the development of hydrophilic C60 nanoparticles, the surface of which ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 5, 2019 Category: Drugs & Pharmacology Authors: Iohara D Tags: Yakugaku Zasshi Source Type: research

[Pharmaceutical Strategy to Protect Skin Barrier Function].
PMID: 31787642 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 5, 2019 Category: Drugs & Pharmacology Authors: Ooi K, Yamaura K Tags: Yakugaku Zasshi Source Type: research

[Improvement of the Skin Barrier Function with Physiologically Active Substances].
In this study, the ability of CER precursors to increase the level of CERs in the SC and improve the skin barrier function was examined. Glucosylceramide and sphingomyelin liposomes were used as CER precursors and prepared with a thin-film method. The particle diameter and surface potential of glucosylceramide liposomes were 120.0 nm and -20 mV, while those of sphingomyelin liposomes were 153.3 nm and -11.4 mV, respectively. Transmission electron microscopy images showed that both liposomes were closed vesicles having a lamellar structure. These liposomes were applied from the SC side of a three-dimensional cultured human ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 5, 2019 Category: Drugs & Pharmacology Authors: Tokudome Y Tags: Yakugaku Zasshi Source Type: research

[Protection of the Skin Barrier Function in Inflammatory Disease].
Abstract The skin is the largest human organ, comprising the epidermis that is composed of epithelial tissue, the dermis composed of connective tissue, and the innermost subcutaneous tissue. Generally, skin conditions are due to aging and the influence of the external environment, but empirically patients with gastrointestinal diseases are more prone to pruritus and inflammation caused by dry skin. A decrease in the skin barrier function, involving immunocompetent mast cells and oxidative stress, was noted in indomethacin-induced small intestine inflammation, dextran sodium sulfate (DSS)-induced ulcerative colitis...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 5, 2019 Category: Drugs & Pharmacology Authors: Ooi K Tags: Yakugaku Zasshi Source Type: research

[Mechanisms of Severe Cutaneous Adverse Reactions and a New Treatment Strategy].
Abstract Severe cutaneous adverse reactions (SCARs) are important in postmarketing drug safety because SCAR patients were highest in the adverse drug reaction relief system of Japan. The SCAR symptoms of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) include high fever, severe mucosal impairment, and epidermal necrosis-induced erosions and blisters. Approximately 600 cases of SJS and 300 cases of TEN are reported annually in Japan. Many suspected drugs such as acetaminophen, lamotrigine, allopurinol, and carbamazepine have been reported. Over the last 15 years, an association between human leu...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 5, 2019 Category: Drugs & Pharmacology Authors: Saito Y, Nakamura R Tags: Yakugaku Zasshi Source Type: research

[Topical Treatment of Pruritic Skin Disease and the Role of Community Pharmacists].
Abstract Itching, or pruritus, can be defined as an unpleasant sensation that evokes the desire to scratch. Pruritus is most commonly associated with a primary skin disorder such as atopic dermatitis (AD), psoriasis, etc., and can have a major impact on the quality of life of those patients. Itch-induced scratching can further damage the skin barrier, leading to a worsening of symptoms. For that reason, it is important to manage pruritus. Topical glucocorticoids are commonly the first-line therapy in the management of AD and psoriasis patients. We found that topical glucocorticoids induce pruritus in mice under ce...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 5, 2019 Category: Drugs & Pharmacology Authors: Yamaura K Tags: Yakugaku Zasshi Source Type: research

[Adherence to Oral Antihyperglycemic Agents (Dipeptidyl Peptidase-4 Inhibitors and Biguanides) and Its Associated Factors in Patients with Type 2 Diabetes].
Abstract To investigate medication adherence to oral antihyperglycemic agents and its associated factors in Japanese type 2 diabetic patients, a questionnaire survey was conducted in 983 adult patients receiving once-daily (QD) or twice-daily (BID) dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitor) or BID biguanides (BG) as monotherapy at 502 pharmacies in Japan. The percentage of patients with good adherence (the proportion of days in which patients took all pills as prescribed in the past 7 days ≥80%) was high (≥90%) in any dosing regimen with no significant difference among the groups. The following fact...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 5, 2019 Category: Drugs & Pharmacology Authors: Hayashi A, Kubo T, Okuyama K, Tokita S, Kamei M Tags: Yakugaku Zasshi Source Type: research

[Evaluation of the Collaboration between Community Interprofessionals and Pharmacists for Early Detection of Dementia].
Abstract The purpose of this study is to evaluate the collaboration system between Muscat Pharmacy and community general support center by verifying the results of tests for early detection of dementia, and the early support response for the participants with suspected dementia by the center. From December 2016 to November 2018, we conducted measurement sessions using a touch panel-type test, MSP-1100 at 23 events that included health promotion classes and local community events directed by community general support center. At a later date, a visit survey was administered by the center to the participants with sus...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 5, 2019 Category: Drugs & Pharmacology Authors: Akura H, Takahashi M, Hayashi T, Egawa T Tags: Yakugaku Zasshi Source Type: research