Analysis and Control of in Vivo Kinetics of Exosomes for the Development of Exosome-based DDS.
Abstract   Exosomes are secretory membrane vesicles containing lipids, proteins, and nucleic acids. They act as intercellular transporters by delivering their components to exosome recipient cells. Based on their endogenous delivery system properties, exosomes are expected to become drug delivery systems (DDS) for various molecules such as nucleic acid-based drugs. Important factors such as drug loading to exosomes, production, and pharmacokinetics of exosomes need to be considered for the development of exosome-based DDS. Of these, the pharmacokinetics of exosomes have rarely been studied, proba...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 13, 2016 Category: Drugs & Pharmacology Authors: Takahashi Y, Nishikawa M, Takakura Y Tags: Yakugaku Zasshi Source Type: research

Mitochondrial DDS Opens Innovative Pharmaceutics.
Abstract   A variety of human diseases, including neurodegenerative disorders, ischemic heart disease, diabetes, and cancer have been reported to be associated with mitochondrial dysfunction. Because of this, mitochondrial therapy is expected to be useful and productive in the treatment of such diseases. We previously reported on the development of a MITO-Porter, a liposome-based nanocarrier that permits macromolecular cargos to be delivered into mitochondria via membrane fusion. Intracellular observations using the green fluorescence protein as a model macromolecule provided confirmation that a ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 13, 2016 Category: Drugs & Pharmacology Authors: Yamada Y Tags: Yakugaku Zasshi Source Type: research

Understanding and Responding to the New Wave of Substance Abuse: Law-evading Drugs and Prescription Drug Abuse.
PMID: 26725669 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 13, 2016 Category: Drugs & Pharmacology Authors: Shimane T, Funada M Tags: Yakugaku Zasshi Source Type: research

Drug Dependence and Cytotoxicity of Law-evading Drugs: Their Identities Explored from Basic Research.
Abstract   Cases of people experiencing disturbed consciousness or dyspnea, causing traffic accidents, or requiring ambulance transport to hospital due to abuse of law-evading chemical substances have become a serious social problem in Japan. Most law-evading herbal products are marketed as incense or herbs and consist of finely chopped, dry vegetative matter mixed with chemical substances (drugs). Analysis of the chemical substances in these herbal products has demonstrated that they contain synthetic cannabinoids. Because there are many cannabinoid compounds, even if a particular drug is regula...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 13, 2016 Category: Drugs & Pharmacology Authors: Funada M Tags: Yakugaku Zasshi Source Type: research

Knowledge regarding Proper Use Guidelines for Benzodiazepines.
Abstract   Benzodiazepines (BZs) work by agonising gamma-aminobutyric acid (GABA)-BZ-receptor complex and thereby produce sedation and anti-anxiety effects. BZs are commonly used in several clinical areas as hypnotics or anti-anxiety drugs. However, these drugs once supplied by medical institutions often lead to abuse and dependence. Thus it is important for institutions to supply and manage BZs properly. At Tokyo Women's Medical University Hospital educational activities about proper use of BZs are performed by not only medical doctors but also pharmacists. We coordinate distribution of leaflets...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 13, 2016 Category: Drugs & Pharmacology Authors: Inada K Tags: Yakugaku Zasshi Source Type: research

The Pharmacist as Gatekeeper of Prescription Drug Abuse: Return to “Community Scientists&rdquo.
This article begins by reviewing the current situation of prescription drug abuse and dependence in Japan. The role of pharmacists as gatekeepers in preventing prescription drug abuse is then examined. Finally, this article discusses the effect of intervention in the form of gatekeeper training for community pharmacists. PMID: 26725672 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 13, 2016 Category: Drugs & Pharmacology Authors: Shimane T Tags: Yakugaku Zasshi Source Type: research

The Characteristics of Law-evading Drug Users and Effective Approaches.
Abstract   The increasing number of law-evading drug users in Japan is becoming a serious social problem. Previous studies have shown that law-evading drug users are younger, more educated, and less antisocial than methamphetamine users. They also tend to have some type of psychiatric disorder before starting drug use; therefore one of the reasons that they start using drugs may be to alleviate certain psychiatric symptoms. Furthermore, if drug users are successful in avoiding arrest, they often lack the motivation to stop, which makes treatment difficult. Therapists are required to be non-confro...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 13, 2016 Category: Drugs & Pharmacology Authors: Kondo A Tags: Yakugaku Zasshi Source Type: research

Practical Use of Compound-target Interactions in Chemistry and Drug Discovery~A Chemoinformatics Approach~.
Practical Use of Compound-target Interactions in Chemistry and Drug Discovery ~A Chemoinformatics Approach~. Yakugaku Zasshi. 2016;136(1):95-6 Authors: Kaneko H, Nakamura S, Kawahsita N PMID: 26725674 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 13, 2016 Category: Drugs & Pharmacology Authors: Kaneko H, Nakamura S, Kawahsita N Tags: Yakugaku Zasshi Source Type: research

Classification and Contribution Analysis of Aromatic Clusters in Protein-Ligand Complexes.
Abstract   Intermolecular interactions are key features in the stabilization or destabilization of complexes. In particular, interactions involving aromatic rings have been extensively studied both theoretically and experimentally. Studies have shown that aromatic-aromatic interactions can be categorized by ring-ring orientation into a variety of different types, such as stacking interactions and T-shaped interactions. Because these different orientations affect stabilization, analyses of such interactions, for example ab initio molecular orbital calculations, are applied to pairs of aromatic rin...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 13, 2016 Category: Drugs & Pharmacology Authors: Yamasaki H, Koseki J, Nishibata Y, Hirono S Tags: Yakugaku Zasshi Source Type: research

Ring-system-based Chemical Structure Enumeration for de Novo Design.
Abstract   De novo molecular design aims to propose molecules exhibiting desired properties and/or activities, as constructed from scratch. Although this approach opposes the widely used virtual screening (VS), the same criteria should be applied, such as ones based on substructure filters, and quantitative structure-property relationship (QSPR) and quantitative structure-activity relationship (QSAR) regression models. QSPR/QSAR, which enables us to predict properties/activities by making use of experimental data, are widely used in academia as well as in industry. Herewith, we present a novel ch...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 13, 2016 Category: Drugs & Pharmacology Authors: Miyao T, Kaneko H, Funatsu K Tags: Yakugaku Zasshi Source Type: research

In Silico Drug Design Using an Evolutionary Algorithm and Compound Database.
Abstract   Computational drug design plays an important role in the discovery of new drugs. Recently, we proposed an algorithm for designing new drug-like molecules utilizing the structure of a known active molecule. To design molecules, three types of fragments (ring, linker, and side-chain fragments) were defined as building blocks, and a fragment library was prepared from molecules listed in G protein-coupled receptor (GPCR)-SARfari database. An evolutionary algorithm which executes evolutionary operations, such as crossover, mutation, and selection, was implemented to evolve the molecules. As...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 13, 2016 Category: Drugs & Pharmacology Authors: Kawai K, Takahashi Y Tags: Yakugaku Zasshi Source Type: research

Molecular Simulations of Protein Systems toward Drug Discovery.
In this study, we propose a new conformational search method for proteins based on a genetic algorithm. We applied this method to an α-helical protein. We found that the conformations obtained from our simulations are in good agreement with the experimental results. PMID: 26725678 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 13, 2016 Category: Drugs & Pharmacology Authors: Sakae Y, Nishikawa N, Tsukamoto S, Suzuki T, Okamoto Y Tags: Yakugaku Zasshi Source Type: research

Applications of the Fragment Molecular Orbital Method in Drug Discovery.
This study demonstrates applications of the FMO method related to drug discovery. First, IFIE, according to FMO calculations, was used in the optimization of drug candidates for the development of anti-prion compounds. The second example involved interaction analysis of the human immunodeficiency virus type 1 (HIV-1) protease and a drug compound that used a novel analytical method for dispersion interaction, i.e., fragment interaction analysis based on LMP2 (FILM). PMID: 26725679 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 13, 2016 Category: Drugs & Pharmacology Authors: Ishikawa T Tags: Yakugaku Zasshi Source Type: research

Evaluation of Research Experience Based on the Type of Degree Completed for the Development of Pharmacist-Scientists.
Abstract   “Pharmacist-scientists” are needed in the clinical setting. However, research competency, including logical thinking, differs among pharmacists. This difference stems from the varying experience of research during university and graduate school. Thus, to ascertain the research experience within different educational systems, we evaluated pharmacists in Kobe City Medical Center General Hospital. In most instances, there was a direct correlation between the duration of research (in the laboratory at university or graduate school), and research experience gained, such ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 13, 2016 Category: Drugs & Pharmacology Authors: Ikemura M, Hashida T Tags: Yakugaku Zasshi Source Type: research

Pharmaceutical Service after the Fukushima Disaster: A Case Report of Soma General Hospital.
Abstract   Despite being damaged by the 2011 Tohoku earthquake, tsunami, and nuclear disaster, Soma General Hospital, located approximately 40 km north of Fukushima Daiichi nuclear power plant, was able to fulfill its role as a key regional hospital in northeast Fukushima. To elucidate the pharmaceutical service in response to the disaster, we investigated the hospital's operations in 2011 according to the medical records and prescriptions. One of the difficulties that the department of pharmaceutical service faced at that time was the increase in emergency healthcare requests by evacuated patien...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - January 13, 2016 Category: Drugs & Pharmacology Authors: Fukunaga H, Momonoi T, Kumakawa H Tags: Yakugaku Zasshi Source Type: research

Treatment of Cancer Pain and Medical Narcotics.
Abstract   The World Health Organization has reported that when morphine is used to control pain in cancer patients, psychological dependence is not a major concern. Our studies were undertaken to ascertain the modulation of psychological dependence on morphine under a chronic pain-like state in rats. Morphine induced a dose-dependent place preference. We found that inflammatory and neuropathic pain-like states significantly suppressed the morphine-induced rewarding effect. In an inflammatory pain-like state, the suppressive effect was significantly recovered by treatment with a κ-opioid receptor a...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 6, 2015 Category: Drugs & Pharmacology Authors: Suzuki T Tags: Yakugaku Zasshi Source Type: research

Hetero-oligomerization and Functional Interaction between Purinergic Receptors Expressed in Platelets to Regulate Platelet Shape Change.
We examined the hetero-oligomerization and functional interactions of A2AR, P2Y1R, and P2Y12R. In HEK293T cells triply expressing all three receptors, hetero-oligomerization was observed among the three receptors. Additionally, P2Y1R agonist-evoked Ca(2+) signaling was significantly inhibited by co-treatment with an A2AR antagonist in HEK293T cells. In human platelets, we identified endogenous A2AR/P2Y1R and A2AR/P2Y12R heterodimers. We also observed functional Ca(2+)-signaling-related cross-talk similar to those found in HEK293T cells, and found that they appeared to affect platelet shape. These results collectively sugge...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 6, 2015 Category: Drugs & Pharmacology Authors: Suzuki T Tags: Yakugaku Zasshi Source Type: research

Multidimensional Analysis of Hippocampal Excitatory Neurotransmission and Development of Analytical Tools for Glycans.
Abstract   Sialidase removes sialic acid residues from sialoglycoconjugates such as glycoproteins and glycolipids. Since sialic acid plays crucial roles in synaptic plasticity and memory in the hippocampus, the regulation of sialyl signaling by sialidase is also necessary for neural functions. However, since mammalian sialidase activity is remarkably weak, it has been difficult to detect sialidase activity in mammalian tissues. Determination of the distribution of sialidase activity in living mammalian tissues would provide much valuable information for understanding the roles of sialidase in physiologic...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 6, 2015 Category: Drugs & Pharmacology Authors: Minami A Tags: Yakugaku Zasshi Source Type: research

Development and Characterization of a Novel Adenovirus Vector Exhibiting MicroRNA-mediated Suppression of the Leaky Expression of Adenovirus Genes.
Abstract   Replication-incompetent adenovirus (Ad) vectors have gained attention as gene delivery vehicles. Theoretically, no Ad genes should be expressed following transduction; however, Ad genes are expressed from the vector genome, leading to induction of cellular immunity against Ad proteins and Ad protein-induced toxicity. To suppress the leaky expression of Ad genes, a microRNA (miRNA)-regulated gene expression system was utilized. We developed novel Ad vectors by incorporating targeted sequences of miR-122a or miR-142-3p, which exhibit liver- or spleen-specific expression, respectively, in the 3'-...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 6, 2015 Category: Drugs & Pharmacology Authors: Shimizu K Tags: Yakugaku Zasshi Source Type: research

A Method for Protein Photo-cross-linking in Living Cells Facilitating Analysis of Physiological Interactions of Proteins.
Abstract   In living cells, most proteins form complexes with other proteins to exert their functions. Since protein functions are regulated in response to changes in the cellular environment, the components of the complexes can vary; therefore, proteins often interact in a weak and transient manner. To capture such labile protein interactions, we have developed a method for photo-cross-linking of proteins directly interacting in mammalian cells; this method involves expansion of the genetic code and site-specific incorporation of photoreactive amino acids into proteins. Upon cross-linking, protein compl...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 6, 2015 Category: Drugs & Pharmacology Authors: Hino N Tags: Yakugaku Zasshi Source Type: research

Practical Use Evaluation of Aluminum Packaging for Medicinal Products Based on Universal Design.
Abstract   Many pharmacists have requested optimization of aluminum packaging of medicinal products in terms of usability. To improve operational efficiency of aluminum packaging, we used Universal Design (UD)-based approach, which enables products to be used properly and consistently regardless of users. The UD-pack used in this research is composed of a film that can be easily opened and torn linear. Here, we compared the UD-pack to conventional aluminum packaging by evaluating the practical use of each under the cooperation of 24 pharmacists. Following opening and removal of contents of one sample for...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 6, 2015 Category: Drugs & Pharmacology Authors: Ohtani K, Hidaka T, Marubashi K, Takagi H, Kamimura N Tags: Yakugaku Zasshi Source Type: research

Improvement of the Convenience of White Petrolatum.
In conclusion, the improved white petrolatum demonstrated better usability, and the moisturizing effect was equivalent to conventional product, suggesting that the use of this improved product may lead to improved adherence. PMID: 26632153 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 6, 2015 Category: Drugs & Pharmacology Authors: Takaya K, Ohtani M, Nozawa A, Manabe H, Yamamura Y, Ohno Y, Akabane Y, Ishii H Tags: Yakugaku Zasshi Source Type: research

Necessity of Disaster Medical Instructions in Pharmaceutical Education, and a Discussion of the Details of These Instructions.
Discussion of the Details of These Instructions. Yakugaku Zasshi. 2015;135(12):1377-86 Authors: Yamaguchi T, Tanaka M, Tanaka A, Miyauchi Y, Araki H, Namba H Abstract   Since the Great East Japan Earthquake, the Ministry of Health, Labour, and Welfare, municipalities, and medical organizations have made various revisions to medical systems employed at the time of a disaster. To educate pharmacists who can contribute to medical teams conducting healthcare activities at the time of disasters, there is a need to develop disaster medical instructions in pharmaceutical education. However, the &qu...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 6, 2015 Category: Drugs & Pharmacology Authors: Yamaguchi T, Tanaka M, Tanaka A, Miyauchi Y, Araki H, Namba H Tags: Yakugaku Zasshi Source Type: research

Qualitative Research to Investigate the Needs of Pharmacists and Drug Therapy of Cancer Patients.
Abstract   We performed a survey of cancer patients' needs for drug treatment and support from pharmacists during treatment and evaluated the support that cancer patients can expect from community pharmacists in the future. The patients consisted of 16 members of the Cancer Patient Association in Aichi prefecture who underwent chemotherapy. The results of a semistructured group interview were qualitatively analyzed using the grounded theory method. Patients undergoing chemotherapy had high hopes for its effectiveness but were worried about side effects and medical costs. To overcome these problems, they ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 6, 2015 Category: Drugs & Pharmacology Authors: Takano Y, Hanya M, Tatematsu M, Nakamura C, Abe K, Fujisaki K, Kamei H Tags: Yakugaku Zasshi Source Type: research

Basic Studies on the Stability of Flavored Oral Solutions of Rebamipide.
Abstract   Stomatitis frequently occurs during chemotherapy and radiotherapy for cancer. Because of its pharmacological properties including anti-inflammatory activity and stimulatory effects on endogenous prostaglandin synthesis, rebamipide has been suggested as a potentially effective treatment against stomatitis. In the present study we tested the stability of oral rebamipide solutions prepared in our hospital pharmacy using sodium alginate as a thickener to increase retention of this agent in the oral cavity, and the addition of different flavoring mixtures intended for use in enteral diets to reduce...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 6, 2015 Category: Drugs & Pharmacology Authors: Yajima R, Imaoka F, Wako T, Kuroda Y, Matsumoto K, Kizu J, Katayama S Tags: Yakugaku Zasshi Source Type: research

Analysis of Factors Influencing the Development of Hypomagnesemia in Patients Receiving Cetuximab Therapy for Head and Neck Cancer.
In conclusion, the T group was more likely to develop hypomagnesemia than the NT group, and therefore the serum magnesium level in the T group requires careful monitoring so that magnesium supplementation can be provided to patients when the level decreases. PMID: 26632157 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 6, 2015 Category: Drugs & Pharmacology Authors: Inose R, Takahashi K, Nishikawa T, Nagayama K Tags: Yakugaku Zasshi Source Type: research

Tremendous Human, Social, and Economic Losses Caused by Obstinate Application of the Failed Linear No-threshold Model.
Abstract   The linear no-threshold model (LNT) was recommended in 1956, with abandonment of the traditional threshold dose-response for genetic risk assessment. Adoption of LNT by the International Commission on Radiological Protection (ICRP) became the standard for radiation regulation worldwide. The ICRP recommends a dose limit of 1 mSv/year for the public, which is too low and which terrorizes innocent people. Indeed, LNT arose mainly from the lifespan survivor study (LSS) of atomic bomb survivors. The LSS, which asserts linear dose-response and no threshold, is challenged mainly on three points. 1) R...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 5, 2015 Category: Drugs & Pharmacology Authors: Sutou S Tags: Yakugaku Zasshi Source Type: research

Basic Research on Neurotrophic Factors and Its Application to Medical Uses.
Abstract   The author has studied nerve growth factor (NGF) and its family of neurotrophic factors (neurotrophins) for over 40 years. During the first 20 years, my laboratory established a highly sensitive enzyme immunoassay for NGF and analyzed the regulatory mechanism of NGF synthesis in cultured primary cells. Fibroblast cells cultured from peripheral organs such as the heart and astrocytes from the brain produced a substantial amount of NGF in a growth-dependent manner. Furthermore, synthesis of NGF in these cells could be upregulated by catechol compounds including catecholamines. This observation m...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 5, 2015 Category: Drugs & Pharmacology Authors: Furukawa S Tags: Yakugaku Zasshi Source Type: research

Role of Monocarboxylate Transporter in Statin-induced Cytotoxicity.
Abstract   Although exercise and drug therapy are important to prevent progression of arteriosclerotic disease, exercise leads to an increase in muscular disorder induced by HMG-CoA reductase inhibitors (statins). Elucidation of this mechanism is needed to prevent the occurrence of muscular disorders. Since exercise induces expression of monocarboxylate transporter (MCT) 4, we focused on the association between MCT4 function and statin-induced muscle injury. First, we examined the transport of L-lactate via MCT4 using MCT4 cRNA-injected Xenopus laevis oocytes. L-lactate uptake by MCT4-expressing oocytes ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 5, 2015 Category: Drugs & Pharmacology Authors: Kobayashi M Tags: Yakugaku Zasshi Source Type: research

Role of Human Orphan Esterases in Drug-induced Toxicity.
Abstract   Esterases hydrolyze compounds containing ester, amide, and thioester bonds, causing prodrug activation or detoxification. Among esterases, carboxylesterases have been studied in depth due to their ability to hydrolyze a variety of drugs. However, there are several drugs for which the involved esterase(s) is unknown. We found that flutamide, phenacetin, rifamycins (rifampicin, rifabutin, and rifapentine), and indiplon are hydrolyzed by arylacetamide deacetylase (AADAC), which is highly expressed in human liver and gastrointestinal tissues. Flutamide hydrolysis is considered associated with hepa...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 5, 2015 Category: Drugs & Pharmacology Authors: Fukami T Tags: Yakugaku Zasshi Source Type: research

Stereoselective Synthesis of Multi-substituted Fluoro-β-lactams and Their Conversion to Fluorinated β-Amino Acid Core.
Stereoselective Synthesis of Multi-substituted Fluoro-β-lactams and Their Conversion to Fluorinated β-Amino Acid Core. Yakugaku Zasshi. 2015;135(11):1245-53 Authors: Tarui A Abstract   Multi-substituted β-lactam compounds have not only attracted considerable interest as core structures of pharmaceutical compounds such as antibiotics but also have been used as building blocks for the construction of β-amino acids. Electrophilic β-lactams can be used to enhance essential biological activities. Furthermore, the ring-opening reactions of electrophilic β-lactams can ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 5, 2015 Category: Drugs & Pharmacology Authors: Tarui A Tags: Yakugaku Zasshi Source Type: research

Multi-component Reactions Based on Formal [2+2] Reaction of Benzyne with Formamide.
Abstract   Arynes, such as benzyne, are highly strained and kinetically unstable intermediates that have been widely employed in organic synthesis. In particular, since the initial report regarding the in situ generation of arynes under neutral conditions from ortho-(trimethylsilyl)aryl triflates and fluoride ions in 1983, numerous nucleophilic additions to arynes have been utilized in the synthesis of carbocycles, heterocycles, and multi-substituted arenes. Recently, we reported the insertion of arynes into the π-bond in formamides, as well as related cascade reactions. First, we synthesized salicyla...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 5, 2015 Category: Drugs & Pharmacology Authors: Yoshioka E Tags: Yakugaku Zasshi Source Type: research

Molecular and Neural Mechanisms for the Robustness of the Circadian Clock.
Abstract   The endogenous circadian clock drives robust oscillations in physiology and behavior, such as hormone secretions and sleep/wake cycles, with a period of about 24 h. We are rarely aware of this internal clock system because it is usually synchronized with environmental light-dark cycles. However, travelling rapidly across multiple time zones in a jet airplane suddenly makes us aware of the desynchrony between the body clock and external time, causing sleep disturbances and gastrointestinal problems. Although jet lag is recognized as a chronobiological problem, its specific molecular and neural ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 5, 2015 Category: Drugs & Pharmacology Authors: Yamaguchi Y Tags: Yakugaku Zasshi Source Type: research

In Vitro and in Vivo Assessments of Drug-induced Hepatotoxicity and Drug Metabolism in Humans.
Abstract   Drug-induced hepatotoxicity is of concern in drug discovery and development. Reactive metabolites generated by drug metabolizing enzymes in the liver contribute to the induction of hepatotoxicity. Therefore, drug-induced hepatotoxicity, drug metabolism, and pharmacokinetics were evaluated in vitro and in vivo in this pre-clinical study. First, hepatotoxicity was tested in vitro using three-dimensional hepatocyte cultures. Hepatocyte spheroids formed in the three-dimensional culture systems maintain various liver functions such as the expression of drug metabolizing enzymes. High dose exposure ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 5, 2015 Category: Drugs & Pharmacology Authors: Sanoh S Tags: Yakugaku Zasshi Source Type: research

Structure and Function of a Novel Class of High Mannose-binding Proteins with Anti-viral or Anti-tumor Activity.
Abstract   The recently discovered high mannose (HM)-binding lectin family in lower organisms such as bacteria, cyanobacteria, and marine algae represents a novel class of anti-viral or anti-tumor compounds. This lectin family shows unique carbohydrate binding properties with exclusive high specificity for HM glycans with core trisaccharide comprising Manα(1-3)Manα(1-6)Man at the D2 arm. At low nanomolar levels, these lectins exhibit potent antiviral activity against HIV and influenza viruses through the recognition of HM glycans on virus spike glycoproteins. In addition, some of these lectin...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 5, 2015 Category: Drugs & Pharmacology Authors: Sato Y Tags: Yakugaku Zasshi Source Type: research

Development of Cyclodextrin-based Cancer Treatment.
In conclusion, FA-M-β-CyD has potential as a novel tumor-selective anticancer agent due to FR-α-mediated cellular uptake. The present results provide useful information for the design and development of novel antitumor drug carriers and antitumor drugs based on CyDs. PMID: 26521878 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 5, 2015 Category: Drugs & Pharmacology Authors: Motoyama K Tags: Yakugaku Zasshi Source Type: research

Structure-Function Analysis and Development of Inhibitors of Metallo-β-lactamases Conferring Drug Resistance in Bacteria.
Structure-Function Analysis and Development of Inhibitors of Metallo-β-lactamases Conferring Drug Resistance in Bacteria. Yakugaku Zasshi. 2015;135(11):1299-305 Authors: Yamaguchi Y Abstract   Metallo-β-lactamases (MBLs) are di-Zn(II) metalloenzymes that efficiently hydrolyze most β-lactam antibiotics used in clinical settings. Bacteria producing MBLs have been isolated from clinical settings and from natural environments such as rivers and soils, and are now recognized as a new potential threat to human health. No effective inhibitors are available for clinical use, making th...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 5, 2015 Category: Drugs & Pharmacology Authors: Yamaguchi Y Tags: Yakugaku Zasshi Source Type: research

Evaluation of Detachment and Clinical Usability of Transdermal Fentanyl Patches in Healthy Volunteers.
Abstract   The dose of a transdermal fentanyl patch is proportional to its application site area. Therefore, the absorption of fentanyl may decrease if the patch detaches, leading to insufficient analgesia. Sixteen healthy volunteers were enrolled in a study to investigate the appropriate application sites and clinical utility of three transdermal fentanyl patches available in Japan. Three placebos, Fentanyl 1-day (Fentos; Fen), Fentanyl 3-day (Durotep; Dur), and Generic Fentanyl 3-day (HMT) were administered using a crossover study design. The placebos were applied to 11 different sites, including both ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 5, 2015 Category: Drugs & Pharmacology Authors: Kurita K, Mochizuki Y, Kokubun H, Atsuta K Tags: Yakugaku Zasshi Source Type: research

Discussion on Partial Validation in Small Molecule Regulated Bioanalysis: Change in Analytical Instruments.
Abstract   In recent years, the necessity of a bioanalytical method validation has been discussed and guidance/guidelines have been released from regulatory agencies. However, none of these provides any details for partial validation (PV) in case of a partial change in the validated analytical method. Therefore eleven scientists have launched a discussion group (DG) with the approval of Japan Bioanalysis Forum (JBF), and have been discussing PV for chromatographic methods based on survey results of Japanese bioanalysts. This document reports the results of discussion on PV for a change of analytical inst...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 5, 2015 Category: Drugs & Pharmacology Authors: Nakai K, Kamimori H, Nagao A, Nakayama A Tags: Yakugaku Zasshi Source Type: research

Lessons Learned after 25 Years of Studies on the Physiological Roles of the Peroxisome Proliferator-activated Receptor.
Abstract   The peroxisome proliferator-activated receptor (PPAR) was discovered a quarter of a century ago. PPAR was soon recognized as a general transcriptional regulator of lipid homeostasis, and several hypolipidemic and antidiabetic agents were shown to be effective ligands for it. Since then, many attempts to develop more potent drugs have been made worldwide, but most were unsuccessful due to serious side effects. It appears that the PPAR boom has ended. This review summarizes the short history of PPAR studies, including our own results, and discusses the lessons learned from the rise and fall of s...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - October 4, 2015 Category: Drugs & Pharmacology Authors: Motojima K Tags: Yakugaku Zasshi Source Type: research

Search for Structurally Unique Bioactive Natural Products.
Abstract   In our continuing search for structurally and biologically interesting metabolites from marine organisms and plants, we investigated the constituents of Okinawan marine sponges and Hypericum plants, resulting in the isolation of several new and unique natural products. Their structures were elucidated on the basis of spectroscopic analyses and chemical conversions. Novel bromopyrrole alkaloids, nagelamides X-Z, were isolated from a sponge Agelas sp. Heteroaromatic alkaloids, hyrtimomines A and B, were isolated from a sponge Hyrtios sp. together with bisindole alkaloids, hyrtimomines C-E. An ox...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - October 4, 2015 Category: Drugs & Pharmacology Authors: Tanaka N Tags: Yakugaku Zasshi Source Type: research

Total Synthesis of Biologically Active Natural Products toward Elucidation of the Mode of Action.
Abstract   Total synthesis of biologically active cyclodepsipeptide destruxin E using solid- and solution-phase synthesis is described. The solid-phase synthesis of destruxin E was initially investigated for the efficient synthesis of destruxin analogues. Peptide elongation from polymer-supported β-alanine was efficiently performed using DIC/HOBt or PyBroP/DIEA, and subsequent cleavage from the polymer-support under weakly acidic conditions furnished a cyclization precursor in moderate yield. Macrolactonization of the cyclization precursor was smoothly performed using 2-methyl-6-nitrobenzoic anhydri...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - October 4, 2015 Category: Drugs & Pharmacology Authors: Yoshida M Tags: Yakugaku Zasshi Source Type: research

Discovery of Novel Biologically Active Compounds of Natural Origin, with a Focus on Anti-tumor Activity.
Abstract   Numerous clinically valuable medicines, including anticancer drugs, have been developed from biologically active natural compounds and their structurally related derivatives. This review discusses novel natural compounds with promising biological activities and those with novel chemical structures. Glaziovianin A, an isoflavone isolated from the leaves of Ateleia glazioviana (Legminosae), inhibited cell cycle progression at the M-phase with an abnormal spindle structure. AU-1 and YG-1, 5β-steroidal glycosides isolated from the whole plants of Agave utahensis and the underground parts of Y...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - October 4, 2015 Category: Drugs & Pharmacology Authors: Yokosuka A Tags: Yakugaku Zasshi Source Type: research

Effects of Xenobiotics on Drug Pharmacokinetics and Safety.
Abstract   The use of nanotechnology has increased over the past 10 years, and various nanomaterials with a wide range of applications have been developed. Carbon nanotubes (CNTs), which are cylindrical molecules consisting of hexagonally arranged carbon atoms, are nanomaterials with high utility. Recently, applications of single-walled CNT (SWCNT) in the medical field for drug-delivery and as gene-delivery agents have been proposed. Due to its structural characteristics and physicochemical properties, the inhalation of SWCNT could be considered as one route for targeted drug delivery into the lungs. The...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - October 4, 2015 Category: Drugs & Pharmacology Authors: Katoh M Tags: Yakugaku Zasshi Source Type: research

Optimization of Immunosuppression and the Prevention of Fungal Infection in Autoimmune Diseases.
Abstract   Mycophenolate mofetil (MMF) has recently been reported to be effective in the treatment of systemic lupus erythematosus (SLE). The therapeutic range of mycophenolic acid (MPA) and its 7-O-glucuronide (MPAG), and factors affecting their pharmacokinetics, remain to be clarified. The influence of the pharmacokinetics of MPA and MPAG on the activity of inosine 5'-monophosphate dehydrogenase (IMPDH), a target of the MPA, also remains to be revealed. The pharmacokinetic variability of hydroxy-itraconazole (OH-ITZ), an active metabolite of itraconazole frequently co-administered with immunosuppressan...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - October 4, 2015 Category: Drugs & Pharmacology Authors: Mino Y Tags: Yakugaku Zasshi Source Type: research

Efficient Pharmaceutical Formulation Designs and Their Development Using Mathematical and Statistical Analysis.
Abstract   With the aim of directly predicting the functionality and mechanism of pharmaceutical excipients, we investigated an analysis method based on available surface area (S(t)), which is the surface area of a drug in direct contact with the external solvent during dissolution. First, to study the effect of lubricant concentration on the dissolution rate of acetaminophen (APAP), the dissolution behaviors as well as the change over time in S(t) of APAP tablets were examined. In the dissolution tests, a retarded dissolution of APAP was not observed with new lubricant triglycerin full behenate (TR-FB),...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - October 4, 2015 Category: Drugs & Pharmacology Authors: Iwao Y Tags: Yakugaku Zasshi Source Type: research

Carrier-mediated Transport of Cationic Drugs across the Blood-Tissue Barrier.
Abstract   Studies of neurological dysfunction have revealed the neuroprotective effect of several cationic drugs, suggesting their usefulness in the treatment of neurological diseases. In the brain and retina, blood-tissue barriers such as blood-brain barrier (BBB) and blood-retinal barrier (BRB) are formed to restrict nonspecific solute transport between the circulating blood and neural tissues. Therefore study of cationic drug transport at these barriers is essential to achieve systemic delivery of neuroprotective agents into the neural tissues. In the retina, severe diseases such as diabetic retinopa...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - October 4, 2015 Category: Drugs & Pharmacology Authors: Kubo Y Tags: Yakugaku Zasshi Source Type: research

Establishment of a Method of Hepatocyte Differentiation from Human Pluripotent Stem Cells for Innovative Drug Development.
Abstract   Hepatocyte-like cells differentiated from human pluripotent stem cells (such as human embryonic stem (ES) cells and induced pluripotent stem (iPS) cells) are expected to be utilized in drug screening. However, the hepatocyte differentiation efficiency and hepatic functions of hepatocyte-like cells were not sufficient to perform ES/iPS cell-based drug discovery. Therefore, we decided to improve the method of hepatocyte differentiation from human ES/iPS cells. To enhance this hepatocyte differentiation efficiency, hepatocyte-related transcription factors, such as forkhead box protein A2 (FOXA2) ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - October 4, 2015 Category: Drugs & Pharmacology Authors: Takayama K Tags: Yakugaku Zasshi Source Type: research

Search of Neurotrophin-mimic Natural Products for Prevention and Treatment of Neurodegenerative Disease.
Abstract   As part of our continuing studies on neurotrophin-mimic active compounds in natural products, we investigated the chemical constituents of the pericarps of Illicium jiadifengpi and the roots of Indonesian ginger Zingiber purpureum, resulting in the isolation of new seco-prezizaane-type sesquiterpenoid 1 and phenylbutenoid dimer 3-4 and two new curcuminoids 5-6. The MeOH extract of I. jiadifengpi was fractionated, leading to the isolation of compound 1. Compound 1 significantly enhanced neurite outgrowth in primary cell cultures of fetal rat cortical neurons. It is noteworthy that compound 1 ha...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - October 4, 2015 Category: Drugs & Pharmacology Authors: Kubo M Tags: Yakugaku Zasshi Source Type: research

Effects of Bioactive Substances from Citrus on the Central Nervous System and Utilization as Food Material.
Abstract   We have recently shown that 3,5,6,7,8,3',4'-heptamethoxyflavone (HMF) and auraptene (AUR) have neuroprotective effects on the central nervous system. HMF, a citrus flavonoid, altered NMDA-type glutamate receptor antagonist MK-801-induced memory dysfunction and schizophrenia-positive symptom-like behavior. HMF also showed a protective effect against ischemia-induced short-term memory dysfunction. In the ischemic brain, HMF induced the following protective effects against brain dysfunction: 1) rescue of neuronal cell death in the hippocampus; 2) increased production of brain-derived neurotrophic...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - October 4, 2015 Category: Drugs & Pharmacology Authors: Okuyama S Tags: Yakugaku Zasshi Source Type: research