[Prion-like Propagation of Pathological α-Synuclein in Vivo].
[Prion-like Propagation of Pathological α-Synuclein in Vivo]. Yakugaku Zasshi. 2019;139(7):1007-1013 Authors: Masuda-Suzukake M, Hasegawa M Abstract α-Synuclein (αS) is the major component of the filamentous inclusions that constitute the defining characteristic of neurodegenerative synucleinopathies, including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. αS is deposited in a hyperphosphorylated and ubiquitinated form with a β-sheet-rich fibrillar structure in diseased brains. In 2008, some researchers reported that embryonic neurons transpl...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 3, 2019 Category: Drugs & Pharmacology Authors: Masuda-Suzukake M, Hasegawa M Tags: Yakugaku Zasshi Source Type: research

[Prion-like Properties of Misfolded Cu/Zn-superoxide Dismutase in Amyotrophic Lateral Sclerosis: Update and Perspectives].
Abstract Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease that is characterized by the loss of motor neurons, which results in progressive muscle atrophy. The pathology spreads from the initial site of onset to contiguous anatomic regions. Mutations in the gene encoding Cu/Zn-superoxide dismutase (SOD1) have been identified in a dominantly inherited form of ALS (ALS-SOD1). A major hallmark of ALS-SOD1 is the abnormal accumulation of conformationally aberrant SOD1 protein (i.e., misfolded SOD1) within motor neurons. Emerging experimental evidence has suggested that misfolded proteins associ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 3, 2019 Category: Drugs & Pharmacology Authors: Tokuda E, Marklund SL, Furukawa Y Tags: Yakugaku Zasshi Source Type: research

[Prion-like Propagation Model of Tau].
Abstract Abnormal proteins such as tau or α-synuclein that accumulate in brains with dementia have been shown to propagate like prion proteins. However, the expression patterns of tau in the mouse brain are different from those in humans, and the pathogenesis in the animal model of abnormal tau propagation remains incompletely understood. To overcome this problem, a novel mouse showing tau expression patterns similar to those of humans was developed using genome editing techniques. We inoculated the brain of this mouse with a sarkosyl-insoluble fraction containing abnormal tau derived from tauopathy patients...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 3, 2019 Category: Drugs & Pharmacology Authors: Hosokawa M, Hasegawa M Tags: Yakugaku Zasshi Source Type: research

[Complementary and Alternative Medicine for Breast Cancer Patients: An Overview of Systematic Reviews].
In conclusion, since most SRs were at moderate or high quality levels, CAM could be helpful for treating specific symptoms related to breast cancer. PMID: 31257250 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 3, 2019 Category: Drugs & Pharmacology Authors: Sasaki Y, Cheon C, Motoo Y, Jang S, Park S, Ko SG, Jang BH, Hwang DS Tags: Yakugaku Zasshi Source Type: research

[Improvements in Lifestyle from a Lifestyle Consecutive Self-Review at a Pharmacy].
This study tests such a service at a pharmacy. We prepared a lifestyle self-review test. From September 2015 to February 2016, pharmacists interviewed members of the community using the test, and pharmacists at 50 pharmacies in Aichi prefecture, Japan, set goals for lifestyle improvement. We analyzed 289 tests. The number of people who had a dietary goal concerning snacking was reduced from 19 people who snacked every day to 11. The number of people who had a goal to reduce their drinking was reduced from 7 people who drank every day to 4. The number of people who had an exercise goal was reduced from 17 people who did not...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 3, 2019 Category: Drugs & Pharmacology Authors: Suzuki R, Suzuki T, Kikuchi C Tags: Yakugaku Zasshi Source Type: research

[Verification of Relationship between Administration of Linezolid and Vomiting].
In this study, we aimed to verify the relationship between LZD administration and vomiting. Patients administered LZD at the Department of Orthopedic Surgery of Hokkaido University Hospital between November 2008 and December 2017 were enrolled in the study. The primary endpoint was the comparison of the vomiting rate between patients administered LZD (LZD group) and those administered other antibiotics (non-LZD group). For the secondary endpoint, to verify the risk factors of vomiting, a univariate logistic regression analysis was performed. In total, 130 patients were included in this study; 77 patients in the LZD group, ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 3, 2019 Category: Drugs & Pharmacology Authors: Tsutsumi T, Imai S, Yamada K, Yamada T, Kasashi K, Kobayashi M, Iseki K Tags: Yakugaku Zasshi Source Type: research

[Contributions to the Establishment and Promotion of Pharmacy Education Reform].
Abstract In 2006, four-year pharmacist training courses in Japanese pharmacy schools were extended to a six-year course. Around that time, I participated in a committee related to pharmacy education reform within the Ministry of Education, Culture, Sports, Science and Technology. I also joined the pharmacist division of the medical council of the Ministry of Health, Labour and Welfare, to reform the national pharmacist examination system. In addition, I was part of the Pharmacy Education Council responsible for developing the contents of the new six-year curriculum, especially for clinical training. In the process...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 3, 2019 Category: Drugs & Pharmacology Authors: Hirai M Tags: Yakugaku Zasshi Source Type: research

[Structural Basis of the Multifunctional Hub Protein and Identification of a Small-molecule Compound for Drug Discovery].
Abstract Translesion DNA synthesis (TLS) is an emergency system activated to inhibit cell death caused by DNA damage-induced replication arrest. Thus, TLS enables cancer cells to acquire resistance to alkylate anticancer drugs. REV7 functions as the hub protein that interacts with both the inserter DNA polymerase REV1 and the extender DNA polymerase REV3 in TLS. REV7-mediated protein-protein interactions (PPIs) are essential for the activation of TLS, and are therefore attractive targets for anticancer drug development. To clarify the REV7-REV3 and REV7-REV1 PPIs, we determined the structures of REV7-REV3 and REV7...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 3, 2019 Category: Drugs & Pharmacology Authors: Hara K Tags: Yakugaku Zasshi Source Type: research

[Development of External Stimuli-responsive Organic π Molecules and the Creation of Novel Photo-functions].
[Development of External Stimuli-responsive Organic π Molecules and the Creation of Novel Photo-functions]. Yakugaku Zasshi. 2019;139(7):975-986 Authors: Kamino S Abstract We have found that the spiro form of aminobenzopyranoxanthene (ABPX) exhibits dual solvatochromic and nanoaggregate fluorescence in organic solvents by spectrophotometric and theoretical analyses. The dual fluorescence properties of ABPX were adjustable in response to water content, and served as a new detection principal for naked-eye visualization (above 0.5 wt%) and quantification (0.010-0.125 wt%) of water in tetrahydrofuran....
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 3, 2019 Category: Drugs & Pharmacology Authors: Kamino S Tags: Yakugaku Zasshi Source Type: research

[Prion and Prion-like Proteins].
PMID: 31257256 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 3, 2019 Category: Drugs & Pharmacology Authors: Sano K, Hosokawa M Tags: Yakugaku Zasshi Source Type: research

[Elucidation of the Molecular Basis of Abnormal Prion Protein (PrP) Formation in a Cell-Free System Using Baculovirus and Insect Cell-derived Recombinant PrP].
Abstract The molecular basis underlying the conversion of normal prion protein (PrPC) into abnormal prion protein (PrPSc) has not been fully elucidated. The protein-misfolding cyclic amplification (PMCA) technique, which can amplify PrPSc in vitro with the use of intermittent sonication, mimics the process of in vivo PrPSc replication. Accumulating evidence suggests that co-factors other than PrP may play a crucial role in the faithful replication of PrPSc. In conventional PMCA, brain homogenates (BHs) from normal animals are used as the PrPC substrate. Since BHs contain many impurities, it is difficult to identif...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 3, 2019 Category: Drugs & Pharmacology Authors: Imamura M, Mori T, Takatsuki H, Iwamaru Y, Atarashi R Tags: Yakugaku Zasshi Source Type: research

[Protective Role of the Host Innate Immune System in Prion Pathogenesis].
Abstract Prion diseases, including human Creutzfeldt-Jakob disease, are infectious, intractable central neurodegenerative diseases, which are also zoonoses that commonly infect not only higher organisms but also a wide variety of animals. Pathogenic prions induce abnormal prion protein (PrP), which is produced by structural conversion of normal PrP, a beta-sheet-rich structure with high aggregation propensity. Thus, it is believed that the host is immunotolerant against prions because there is no difference in the primary structure of normal and abnormal PrP, and prions do not induce a marked immune response. Rece...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 3, 2019 Category: Drugs & Pharmacology Authors: Ishibashi D Tags: Yakugaku Zasshi Source Type: research

[Real-time Quaking-induced Conversion Analysis of Prion-like Seeding Activity of Pathological α-Synuclein].
We examined whether brain tissues from cases of dementia with Lewy bodies (DLB), which contain serine 129 (Ser129)-phosphorylated insoluble aggregates of αSyn, exhibit prion-like seeding activity in vitro using the real-time quaking-induced conversion (RT-QuIC) seeding assay. Brain tissues from cases of diffuse neocortical DLB yielded a 50% seeding dose of 107.3-109.8/g brain. The RT-QuIC assay could discriminate between DLB and other neurological and neurodegenerative disorders, suggesting its potential applicability for differential diagnosis. Insoluble aggregates of αSyn>250 kDa detected only in DLB brain...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 3, 2019 Category: Drugs & Pharmacology Authors: Sano K Tags: Yakugaku Zasshi Source Type: research

[Clinical Research on the Effects of Differences in Properties of External Preparations for Skin on Application Amount: An Exploratory Investigation of the Relationship between the Base Usability and Application Amount by Questionnaire in Adult Subjects].
In this study, we investigated the usability and application amount of three bases with different properties (ointment base, cream base, and lotion base) in 62 adult subjects and exploratively examined the effect of the different base properties on the application amount. The results of this clinical study showed that the usability and preference for the base used for external preparations varies, and poor usability and low preference may lead to a reduction in the application amount. Even with good usability and high preference, there were many cases in which an adequate amount was not applied due to lack of specific inst...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 21, 2019 Category: Drugs & Pharmacology Authors: Nakahigashi H, Numazaki T, Nakamura H, Yoshioka D, Ashizuka Y, Yoshimune R, Honda N Tags: Yakugaku Zasshi Source Type: research

[Comparison of the Pharmaceutical Characteristics of Brand-name and Generic Pramipexole Extended-release Tablets and their PTP Package Usability].
In this study we examined the stability of tablets in the ODP (25℃ RH75%) while also comparing the ease of handling of the seven products currently marketed in Japan. In the tablets' ODP, changes such as swelling and decreases in tablets hardness were observed in six formulations. Differences were found among the products in comparison of packaging material, required tablet extrusion strength, and ease of removal. Given the differences in PTP materials and hygroscopicity it is suggested that pharmacists must not only consider the drug formulations of products but also contribute to improvements in medication adherence fo...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 13, 2019 Category: Drugs & Pharmacology Authors: Akiyama S, Maida C, Miyamoto E, Doi N Tags: Yakugaku Zasshi Source Type: research

[The Involvement of Src in Airway Inflammation Induced by Repeated Exposure to Lipopolysaccharide in Mice].
Abstract Corticosteroid insensitive airway inflammation is one of major barrier to effective managements of chronic airway diseases, such as obstructive pulmonary airway disease (COPD) and severe asthma. The role of nonreceptor tyrosine kinase Src is important in airway inflammation in mice models of atopic asthma and COPD. Thus, in this study, we determined the effects of Src inhibitor, dasatinib, on airway inflammation induced by repeated intranasal exposure to lipopolysaccharide (LPS). Male mice (A/J strain, 5 weeks old) were intranasally exposed to LPS twice daily for 3 days, and dasatinib was intranasally tre...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 13, 2019 Category: Drugs & Pharmacology Authors: Nishimoto Y, Yasuda H, Masuko K, Usui Y, Ueda K, Kimura G, Ito K, Kizawa Y Tags: Yakugaku Zasshi Source Type: research

[Elucidation of the Mechanisms Underlying Regulation of Somatic Stem Cell Function: Possible Application to the Treatment of Neuropsychiatric, Metabolic Bone, and Lifestyle Diseases].
PMID: 31155523 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 4, 2019 Category: Drugs & Pharmacology Authors: Nakamichi N, Takarada T Tags: Yakugaku Zasshi Source Type: research

[Possible Treatment of Neuropsychiatric Disorders by Promotion of Neuronal Differentiation through Organic Cation Transporters].
Abstract Neurons differentiated from neural stem cells mature to form a neuronal network. Neuronal maturation enables neurotransmission that regulates brain function. Therefore, abnormal neuronal differentiation causes dysfunction in neurotransmission, and is involved in the onset of various neuropsychiatric disorders. Most of the drugs currently available for the treatment of neuropsychiatric disorders act on membrane receptors and reuptake transporters of neurotransmitters, and control neurotransmission. These membrane proteins have a high affinity for a specific neurotransmitter, and are highly expressed in syn...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 4, 2019 Category: Drugs & Pharmacology Authors: Nakamichi N, Masuo Y, Kato Y Tags: Yakugaku Zasshi Source Type: research

[Adult Neurogenesis-activating Signals as Therapeutic Targets for Neurodegenerative Disorders].
Abstract In most mammalian species, adult neurogenesis appears to occur only in the olfactory bulb and hippocampal dentate gyrus, where neural stem/progenitor cells exist to create new neurons. The discovery of multi-potential neural stem/progenitor cells (NPCs) in the adult brain has precipitated a novel therapeutic strategy for harnessing these endogenous cells to aid in recovery from neurodegenerative disorders. During neurodegeneration, a plethora of endogenous factors, including cytokines, chemokines, neurotransmitters, blood-derived factors, and reactive oxygen species, are released by the activation of resi...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 4, 2019 Category: Drugs & Pharmacology Authors: Yoneyama M, Ogita K Tags: Yakugaku Zasshi Source Type: research

[Evaluation of Naturally Occurring Compounds Regulating Brown/Beige Adipocyte Differentiation].
Abstract Brown adipose tissue is a critical regulator of metabolic health, and contributes to thermogenesis by uncoupling oxidative phosphorylation through the action of mitochondrial uncoupling protein 1 (Ucp1). Recent studies have shown that cold exposure and the stimulation of β3-adrenergic receptors induce the development of brown cell-like "beige" adipocytes in white adipose tissue. Brown and/or beige adipocyte-mediated thermogenesis suppresses high-fat diet-associated obesity. Therefore, the development of brown/beige adipocytes may prevent obesity and metabolic diseases. In the present study,...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 4, 2019 Category: Drugs & Pharmacology Authors: Hirai T, Takagi M, Nakashima KI, Inoue M Tags: Yakugaku Zasshi Source Type: research

[Dissecting the Hierarchy and Lineage of Mesenchymal Stem Cells Using Mouse Genetics as a Step toward Drug Discovery and Regenerative Medicine].
Abstract The mesenchymal stem cell (MSC) is a type of tissue stem cell. In clinical studies, cultured MSCs have shown important therapeutic effects on diseases via both the reduction of neurological defects and the regulation of immune responses. However, in vivo MSC localization, function, and properties are poorly understood; therefore, the molecular understanding of MSC hierarchy is less advanced compared to hematopoietic stem cell hierarchy. Runt-related transcription factor 2 (Runx2) is an essential transcriptional regulator of osteoblast differentiation from MSCs. Runx2 deficiency in Paired-related homeobox ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 4, 2019 Category: Drugs & Pharmacology Authors: Takarada T Tags: Yakugaku Zasshi Source Type: research

[Towards Further Sharing of Knowledge and Activities on Standards of Quality Assurance (QA) across Industry, Academia and Government to Promote Research Integrity and Accelerate Drug Discovery].
PMID: 31155528 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 4, 2019 Category: Drugs & Pharmacology Authors: Kakuta H, Sudo H Tags: Yakugaku Zasshi Source Type: research

[Good Laboratory Practice: Initial Development, Necessity, and Issues of Data Reliability in Basic Research].
Abstract This review describes the initial development of good laboratory practice (GLP) and follows the discoveries of quality control problems in labs that conducted tests in U.S. pharmaceutical companies. In addition to introducing the essence of the GLP standards, how the GLP ensures the reconstructability and reproducibility of study results is explained in detail. Issues in nonclinical safety studies in drug development and approaches of the Japanese Pharmaceuticals and Medical Devices Agency to overcome them are also described. It is hoped that this review is helpful not only to those who work on drug devel...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 4, 2019 Category: Drugs & Pharmacology Authors: Ito K, Someya H Tags: Yakugaku Zasshi Source Type: research

[Conducting Assured Nonclinical Studies in the Pharmaceutical Industry: Good Laboratory Practice (GLP) Study, GLP Inspection, and Standards for Assurance].
Abstract Many nonclinical and clinical studies are conducted to submit new drug applications for chemical entities. Nonclinical studies cover pharmacology, pharmacokinetic, and toxicology aspects and provide pharmacologic evidence as well as kinetic and toxicologic profiles of the compounds. The risks and benefits of compounds are evaluated based on these nonclinical studies, especially before initiation of the first human trials. Therefore, using adequate procedures, highly controlled, quality nonclinical data should be obtained. This section shares and discusses items required of good laboratory practice (GLP)-c...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 4, 2019 Category: Drugs & Pharmacology Authors: Fujikawa Y Tags: Yakugaku Zasshi Source Type: research

[Problems with Laboratory Notebooks in Academia and How to Resolve Them].
Abstract There is currently a major effort to promote drug discovery in academia as a way to seed new drug development in the pharmaceutical industry. However, there are concerns in industry about the quality of drug candidates generated in academic institutions. These concerns encompass culture and perceptions with respect to intellectual property management, the process of product development, and the reliability of scientific data. Questions about data reliability underscore the particularly serious problem of mistrust in academic research. Therefore, the author became interested in the topic of industry standa...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 4, 2019 Category: Drugs & Pharmacology Authors: Kakuta H Tags: Yakugaku Zasshi Source Type: research

[Research Reliability Required in Academia].
Abstract The Bridging Research Accelerating Network Program of the Japan Agency for Medical Research and Development has increased academic research on nonclinical studies to acquire proof of concept for pharmaceuticals, and recently some universities with special technological knowledge have started collaborative research with pharmaceutical companies. In such joint research, companies often repeat studies conducted by academic institutions to ensure that the study data meet the reliability requirements for new drug applications (NDAs). Conducting repeated studies is costly and time consuming and delays the R&...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 4, 2019 Category: Drugs & Pharmacology Authors: Sudo H Tags: Yakugaku Zasshi Source Type: research

[The 2nd Symposium "Current Status of Reverse Translational Research Conducted by Hospital Pharmacists" ~Challenges for Screening of Therapeutic Molecular Target and Personalized Medicine~].
[The 2nd Symposium "Current Status of Reverse Translational Research Conducted by Hospital Pharmacists" ~Challenges for Screening of Therapeutic Molecular Target and Personalized Medicine~]. Yakugaku Zasshi. 2019;139(6):899-900 Authors: Masuda S, Itoh H, Ikeda R, Jono H PMID: 31155533 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 4, 2019 Category: Drugs & Pharmacology Authors: Masuda S, Itoh H, Ikeda R, Jono H Tags: Yakugaku Zasshi Source Type: research

[Clinical Pharmacology Research for Promoting Individualized Cancer Chemotherapy].
Abstract Cancer chemotherapy has progressed remarkably with conventional and molecular-targeted anticancer drugs as well as immune checkpoint inhibitors. However, adverse drug reaction (ADR) management remains a challenge in cancer chemotherapy. Therefore, improving the quality of medical care through clinical pharmacology research is warranted. Intravenous injection of bendamustine in patients with follicular or mantle cell lymphoma frequently causes venous irritation. Because the underlying mechanisms are not clear, we investigated the factors responsible for bendamustine-induced venous irritation. Based on the ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 4, 2019 Category: Drugs & Pharmacology Authors: Watanabe H, Uchida M, Masuda S Tags: Yakugaku Zasshi Source Type: research

[Toward Personalized Cancer Therapy with Oral Molecular-targeted Agents].
We examined the relationship between the plasma concentration of drugs and clinical findings, such as side effects and treatment effects, at our hospital. In this symposium review, we introduce our results based on the treatment of patients with renal cell carcinoma. PMID: 31155535 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 4, 2019 Category: Drugs & Pharmacology Authors: Yamaguchi H, Takasaki S, Kikuchi M, Kawasaki Y, Arai Y, Mano N Tags: Yakugaku Zasshi Source Type: research

[Clinical Approach to Individualization of Antimicrobial Therapy Based on Pharmacokinetic/Pharmacodynamic Analysis and Therapeutic Drug Monitoring].
Abstract The use of a drug administration plan and therapeutic drug monitoring (TDM) based on pharmacokinetic-pharmacodynamic (PK-PD) analysis is important for the effective use of antimicrobial agents to treat infections. We focused on the use of beta-lactam agents, anti-methicillin-resistant Staphylococcus aureus (MRSA) agents, and an antifungal agent as antimicrobial agents and examined their efficacy in patients under special clinical conditions from the viewpoint of safety and TDM. Our PK-PD analysis of the use of an administration plan to set an optimum serum level for beta-lactam agents or anti-MRSA drugs f...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 4, 2019 Category: Drugs & Pharmacology Authors: Sato Y, Suzuki Y, Tanaka R, Kaneko T, Itoh H Tags: Yakugaku Zasshi Source Type: research

[Exploring Molecular Targets for Epilepsy Treatment from the Perspective of Neuronal Homeostasis].
Abstract Brain function is controlled by the balance between the excitatory and inhibitory systems. If this balance is disrupted and the excitatory system dominates, convulsions or epileptic seizures are induced. Neuronal hyperexcitability in the brain leads to marked changes in the function of the neurons, which adversely affect the stability of the neural network. Many of the currently used antiepileptic drugs are symptomatic treatments that suppress the electrical hyperexcitability of the cerebrum. Although patients with epilepsy should continuously take antiepileptic drugs to control their seizures, approximat...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 4, 2019 Category: Drugs & Pharmacology Authors: Nagai T, Shan W, Yamada K Tags: Yakugaku Zasshi Source Type: research

[Effectiveness of Pharmacist-convened Multidisciplinary Clinical Team Meetings in Promoting Appropriate Benzodiazepine Receptor Agonist Use].
This study aimed to investigate whether the pharmacists at multidisciplinary clinical team meetings can help reduce BZRA use and promote appropriate use of these drugs. The psychiatric unit of the Tokyo Women's Medical University Hospital occupies two floors, with 31 beds on Floor A and 34 beds on Floor B. The multidisciplinary clinical team meetings were held once a week in each ward. During the meetings, the pharmacists comprehensively assessed the number of BZRA doses administered and the equivalent diazepam doses, presented their prescription recommendations aimed at dosage reduction, and shared their views with the en...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 4, 2019 Category: Drugs & Pharmacology Authors: Geka M, Inada K, Shimizu S, Geka Y, Takahashi Y, Hamada Y, Nishimura K, Kimura T Tags: Yakugaku Zasshi Source Type: research

[Development of Synthetic Strategies for Densely Oxygenated Natural Products: Total Synthesis of Lactacystin and Zaragozic Acid C Using Photochemical C(sp3)-H Functionalization].
Abstract This review describes two novel synthetic routes from (S)-pyroglutaminol to (+)-lactacystin, a potent inhibitor of the 20S proteasome and from d-gluconolactone derivative to zaragozic acid C, a potent squalene synthase inhibitor. In lactacystin synthesis, the photoinduced intermolecular C(sp3)-H alkynylation and intramolecular C(sp3)-H acylation chemoselectively and stereoselectively constructed the tetrasubstituted and trisubstituted carbon centers, respectively. In the synthesis of zaragozic acid C, the stereoselective installation of the two contiguous tetrasubstituted carbons was achieved by the photo...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 8, 2019 Category: Drugs & Pharmacology Authors: Nagatomo M Tags: Yakugaku Zasshi Source Type: research

[Search for Protein Tyrosine Phosphatase 1B Inhibitors from Marine Organisms and Induced Production of New Fungal Metabolites by Modulating Culture Methods].
Abstract Marine environments offer a rich source of natural products with potential therapeutic applications because the ocean covers 70% of the earth's surface and approximately 80% of all living organisms live in the sea. Therefore we have investigated bioactive compounds from marine organisms such as marine sponges, ascidians, and marine-derived microorganisms. This review consists of two topics based on marine natural product chemistry. (1) Protein tyrosine phosphatase (PTP) 1B plays a key role as a negative regulator in the insulin and leptin signaling pathways. Accordingly, the development of PTP1B inhibitor...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 8, 2019 Category: Drugs & Pharmacology Authors: Yamazaki H Tags: Yakugaku Zasshi Source Type: research

[Approach for Producing New 3,3,3-Trifluoropropenylation Reagents: Introduction of a 3,3,3-Trifluoroprop-1-enyl Group for Drug Development].
Abstract The chemistry of the 3,3,3-trifluoroprop-1-enyl (TFPE) group has attractive characteristics in medicinal chemistry as a new fluorine motif. However, there are no reports on the properties of this group because it is difficult to construct molecules with it. For the convenient construction of the TFPE group, a new fluorination reagent, CF3CH=CHTMS (1), was developed from commercially available chemicals with easy purification processes and excellent yields. The utility of 1 as a trifluoropropenylation reagent was exhibited in several types of reaction such as the Sonogashira cross-coupling reaction. Furthe...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 8, 2019 Category: Drugs & Pharmacology Authors: Ikeda A Tags: Yakugaku Zasshi Source Type: research

[Cutting-edge Science and Technology of Forensic Criminal Investigation and Identification].
PMID: 31061335 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 8, 2019 Category: Drugs & Pharmacology Authors: Seto Y, Inoue H Tags: Yakugaku Zasshi Source Type: research

[Forensic Science and Scientific Investigation].
Abstract The precise proof of a crime using objective evidence is becoming increasingly important as Japan's crime rate climbs. This need arises not only from the current high rate of anonymous crime, but also the introduction of a Saiban-in (citizen judge) system, and the increased silence of suspects following investigation visualization. Forensic science is an academic field that investigates legal (and illegal) matters using science, and subsequently applies research results to resolving real crime cases. Materials examined during forensic practice include both common specimens, such as fingerprints, footprint...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 8, 2019 Category: Drugs & Pharmacology Authors: Inoue H Tags: Yakugaku Zasshi Source Type: research

[Current Status of Drug Problems and Drug Analysis].
Abstract The number of persons arrested in Japan for drug-related offenses in 2016 increased from the previous year. Especially, cannabis offenses have increased since 2014, with more than 2000 persons arrested in 2015. As a feature of the year 2017, we analyzed many cannabis concentrates, called "Cannabis wax", in the process of analyzing cannabis in the Narcotics Control Department. "Cannabis wax" refers to concentrates of the hallucinogenic component of cannabis, tetrahydrocannabinol (THC). Increasingly, cannabis wax containing 50 times higher THC than general dry cannabis has been confiscat...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 8, 2019 Category: Drugs & Pharmacology Authors: Akutsu M Tags: Yakugaku Zasshi Source Type: research

[Study of the Metabolism of New Drugs of Abuse].
Abstract Human hepatocytes possess a wider range of phase I and II drug-metabolizing enzyme activities than other liver tissue-derived products, such as human liver microsomes. Thus, hepatocytes may be useful for predicting the in vivo metabolic fate of new drugs of abuse in humans. Recently, new types of human hepatocytes have been made commercially available for use in drug metabolism studies, such as a liver tumor-derived cell line (HepaRG), and a human induced pluripotent stem cell-derived hepatocyte (h-iPS-HEP). In our laboratory, HepaRG has been used to elucidate the metabolic pathways of XLR-11, a synthetic...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 8, 2019 Category: Drugs & Pharmacology Authors: Kanamori T Tags: Yakugaku Zasshi Source Type: research

[Hair Testing for Drugs in the Field of Forensics].
Abstract Hair testing for drugs has been used extensively in the field of forensics since the 1990s as a means of obtaining firm evidence of drug ingestion. In addition to its longer detection windows, hair is the only specimen that can provide chronological information on individual drug use. Illicit drugs and hypnotics account for the majority of substances involved in crimes; they are usually analyzed to prove an addictive use or an exposure to drugs in drug-facilitated crimes. The mechanism of drug incorporation into hair has been intensively investigated to properly interpret the results of hair analysis. How...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 8, 2019 Category: Drugs & Pharmacology Authors: Shima N, Sasaki K, Kamata T, Miki A, Katagi M Tags: Yakugaku Zasshi Source Type: research

[Analysis of Countermeasures against Chemical Terrorism].
Abstract As a countermeasure against terrorism involving highly toxic chemical warfare agents, the rapid identification of the causative toxic substances is extremely important. This symposium review describes analytical methods the author's group has developed for detecting nerve gases after either high level or low level exposure. As a method for assessing human exposure to high levels of nerve gases, a technology that detects nerve gas hydrolysis products, i.e., strong anion exchange extraction-tert-butyldimethylsilyl derivatization-selectable one-dimensional or two-dimensional GC-MS, is explained. As a method ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 8, 2019 Category: Drugs & Pharmacology Authors: Seto Y Tags: Yakugaku Zasshi Source Type: research

[DNA Typing for Individual Identification].
Abstract As criminal cases have become more complicated, Japan's law enforcement officials are promoting the use of more sophisticated technologies, such as DNA analysis, in the course of criminal investigations in order to verify facts with objective evidence. The primary DNA analysis method employed by law enforcement officials is short tandem repeat (STR) analysis, a method for identifying individuals utilizing individual differences in the number of repeat units of characteristic DNA sequences. Presently, STR analysis can discriminate between individuals with the probability of one in approximately 4.7 trillio...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 8, 2019 Category: Drugs & Pharmacology Authors: Kitamura M Tags: Yakugaku Zasshi Source Type: research

[Innovative Cancer Therapeutics Propelled by Model Organisms: Paradigm Shift in Drug Discovery and Diagnosis for Cancer].
PMID: 31061342 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 8, 2019 Category: Drugs & Pharmacology Authors: Sugiura R Tags: Yakugaku Zasshi Source Type: research

[Live-imaging Analyses Using Small Fish Models Reveal New Mechanisms That Regulate Primary Tumorigenesis].
Abstract Since the 1980s, zebrafish (Danio rerio) have been used as a valuable model system to investigate developmental processes because they: 1) grow outside their mothers; 2) are transparent during the embryonic stage; and 3) have organs similar to those in humans. Recently, zebrafish have emerged as a powerful model animal for studying not only developmental biology but also human diseases, especially cancer. Owing to the significant advantages of zebrafish, such as low-cost breeding, high efficiency of transgenesis, and ease of in vivo imaging and oncogenic/tumor cell induction, zebrafish offer a unique oppo...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 8, 2019 Category: Drugs & Pharmacology Authors: Haraoka Y, Akieda Y, Ishitani T Tags: Yakugaku Zasshi Source Type: research

[Functional Analysis of Apoptosis Signal-regulating Kinase Family in a Murine Model of Tumor Metastasis].
Abstract Stress-responsive signaling pathways convert cellular stresses into various physiological responses, such as cell proliferation, apoptosis, and inflammation. Signal pathway dysfunction thus induces abnormal cellular behaviors that may lead to tumorigenesis and tumor progression, including metastasis. Tumor metastasis is the spread of tumor cells from primary lesions to other distant tissues/organs. Several types of murine model which mimic the progression of human cancer have been established for preclinical studies to understand the biology of cancer. Mitogen-activated protein kinase (MAPK) cascades are ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 8, 2019 Category: Drugs & Pharmacology Authors: Kamiyama M, Naguro I, Ichijo H Tags: Yakugaku Zasshi Source Type: research

[Fission Yeast as a Model System for Studying Cancer Signaling and Drug Discovery: Discovery of ACA-28 as a Novel Inducer of ERK-dependent Apoptosis Reveals a New Cancer Therapy].
Abstract Mitogen-activated protein kinase (MAPK) pathways are evolutionarily conserved kinase modules that link extracellular signals to the machinery that controls fundamental cellular processes such as growth, proliferation, differentiation, and apoptosis. The Ras/Raf/MEK/ERK MAPK pathway is one of the most studied of the mammalian MAPK pathways and has attracted intense research interest because of its critical involvement in the regulation of cell proliferation. The mutational activation of upstream signaling components that constitutively activate ERK MAPKs as seen in various primary tumor samples has validat...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 8, 2019 Category: Drugs & Pharmacology Authors: Sugiura R Tags: Yakugaku Zasshi Source Type: research

[Development of an Early Cancer Detection Method Using the Olfaction of the Nematode Caenorhabditis elegans].
In this study, we developed a Nematode-Nose (N-NOSE) test using Caenorhabditis elegans to provide a novel, highly accurate cancer detection system that is economical, painless, rapid, and convenient. We demonstrated that wild-type C. elegans displayed attractive chemotaxis toward human cancer cell secretions, cancer tissues, and urine from cancer patients but avoided control urine. In parallel, C. elegans olfactory neurons showed a significantly stronger response to urine from cancer patients than to control urine. In contrast, G protein α mutants and animals with ablated olfactory neurons were not attracted to urine...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 8, 2019 Category: Drugs & Pharmacology Authors: Uozumi T, Hirotsu T Tags: Yakugaku Zasshi Source Type: research

[Hypothermic Action of Oseltamivir Not Dependent on Its Anti-influenza Virus Action].
Abstract Although the anti-influenza virus drug oseltamivir ameliorates the fever of influenza, adverse events related to its hypothermic effect have been reported. We found that oseltamivir causes dose-dependent hypothermia in normal mice, and have been studying the pharmacological mechanisms responsible for 12 years. Oseltamivir blocks nicotinic cholinergic transmission at sympathetic ganglia and reduces sympathetic modulation of brown adipose tissue (BAT), a heat generator. Oseltamivir was found to target the ion channels of nicotinic acetylcholine receptors, as demonstrated by patch clamp experiments with cell...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 8, 2019 Category: Drugs & Pharmacology Authors: Ono H Tags: Yakugaku Zasshi Source Type: research

[Improving Effects of Peptides on Brain Malfunction and Intranasal Delivery of Those Derivatives to the Brain].
Abstract This review focuses on the anti-dementia and antidepressant-like effects of peptides including glucagon-like peptide (GLP)-1, GLP-2, neuromedin U (NmU), and oxytocin, and the intranasal delivery of these peptides to the brain. Intracerebroventricularly administered GLP-1, NmU, and oxytocin improved impairment of learning and memory in mice treated with lipopolysaccharide or β-amyloid protein. GLP-1 also improved impairment of learning and memory in juvenile diabetes model rats. On the other hand, GLP-2 exhibited antidepressant-like effects in mice during the forced-swim test, which were associated wi...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 8, 2019 Category: Drugs & Pharmacology Authors: Oka JI Tags: Yakugaku Zasshi Source Type: research

[Angiotensin II Regulates Excitability and Contractile Functions of Myocardium and Smooth Muscles through Autonomic Nervous Transmission].
Abstract Angiotensin II (Ang II) is an intrinsic peptide having strong vasopressor effects, and thus, it plays an important role in the physiological regulation of blood pressure. The vasopressor effects of Ang II include direct contraction of myocardium and vascular smooth muscles (SMs) along with aldosterone-mediated sodium retention. In addition, indirect vascular contractions induced by noradrenaline (NA), the release of which is mediated through Ang II receptor type 1 (AT1) existing at the sympathetic nerve terminals (SNTs), also contribute to the vasopressor effects of Ang II. Stimulation of NA release from ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - May 8, 2019 Category: Drugs & Pharmacology Authors: Yamaki F, Obara K, Tanaka Y Tags: Yakugaku Zasshi Source Type: research