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Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan

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Easing human pain: challenges to a novel therapeutic drug in neuropathic pain.
Abstract   Pain control is very important since, even today, 20 million people suffer from neuropathic pain. Although many basic science and clinical researchers have made efforts to control pain, the mechanism of neuropathic pain is unfortunately still not fully understood. Morphine, a prototypical opioid, is a useful medicine to relieve severe pain. However, repeated or continuous use of morphine and other opioids are associated with a potential risk of analgesic tolerance, which requires an increase in dosage to maintain the same efficacy. In addition, morphine is not always effective in neuropathic pain. In t...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - October 5, 2014 Category: Drugs & Pharmacology Authors: Takano Y Tags: Yakugaku Zasshi Source Type: research

Development of New Therapeutic Strategy for Transporter-related Diseases.
Abstract   Significant technological advances in gene sequence analysis and construction of genetically-modified animals during the last two decades made it possible to reveal that many transporters are associated with diseases. The bile salt export pump (BSEP/ABCB11), a member of the family of ATP-binding cassette transporters, is localized on the canalicular membrane of hepatocytes and predominantly mediates the biliary excretion of bile salts. A hereditary defect of BSEP results in severe cholestasis called progressive familial intrahepatic cholestasis type 2 (PFIC2). Without liver transplantation, this diseas...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - October 5, 2014 Category: Drugs & Pharmacology Authors: Hayashi H Tags: Yakugaku Zasshi Source Type: research

Structure Analysis of Disease-related Proteins Using Vibrational Spectroscopy.
This article includes examples of structural analysis of disease-related proteins using vibrational spectroscopy in combination with additional techniques that facilitate data acquisition and analysis. Residue-specific conformation analysis of an amyloid fibril was conducted using IR absorption spectroscopy in combination with (13)C-isotope labeling, linear dichroism measurement, and analysis of amide I band features. We reveal a pH-dependent property of the interacting segment of an amyloidogenic protein, β2-microglobulin, which causes dialysis-related amyloidosis. We also reveal the molecular mechanisms underlying pH-de...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - October 5, 2014 Category: Drugs & Pharmacology Authors: Hiramatsu H Tags: Yakugaku Zasshi Source Type: research

Extracellular Adenosine Is a Therapeutic Target for Limiting Graft-versus-Host Disease and Enhancing the Graft-versus-Tumor Effect against Hematopoietic Malignancy.
Abstract   Allogeneic hematopoietic stem cell transplantation is performed in patients with hematologic malignancies refractory to chemotherapy. However, its efficacy is often limited by the development of graft-versus-host disease (GVHD) secondary to the allogeneic interaction of donor T cells with host dendritic cells. On the other hand, the antihost cytotoxicity of donor T cells enhances the graft-versus-tumor (GVT) effect. Extracellular adenosine generated by CD73/ecto-5'-nucleotidase from ATP via AMP plays pleiotropic roles under physiological and pathological conditions by engaging four adenosine receptors....
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - October 5, 2014 Category: Drugs & Pharmacology Authors: Tsukamoto H Tags: Yakugaku Zasshi Source Type: research

Effects of genetic and environmental factors on neuropsychological development.
Abstract   Abnormalities in early brain development contribute to the etiology of many neurological disorders in later life. Recent advances in genome analysis indicate that large numbers of common gene variants shape any individual's disease risk, including that for major mental illnesses. Polyriboinosinic-polyribocytidilic acid (polyI:C) is known to induce strong innate immune responses that mimic immune activation by viral infections. Our previous findings suggest that activation of the innate immune system in astrocytes results in impairments of neurite outgrowth and spine formation, which lead to behavioral ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - October 5, 2014 Category: Drugs & Pharmacology Authors: Nagai T Tags: Yakugaku Zasshi Source Type: research

Host Energy Regulation via SCFAs Receptors, as Dietary Nutrition Sensors, by Gut Microbiota.
We report that these SCFA receptors are involved in energy homeostasis: GPR41 regulates sympathetic activity, and GPR43 regulates adipose-insulin signaling by sensing SCFAs produced by gut microbiota. We believe that these results will provide valuable insight into therapeutic targets for treating metabolic disorders and diabetes, as well as in the use of probiotics to control gut microbiota. PMID: 25274213 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - October 5, 2014 Category: Drugs & Pharmacology Authors: Kimura I Tags: Yakugaku Zasshi Source Type: research

Adverse effects of nanomaterials on biological defense mechanisms.
Abstract   Nanomaterials are defined as substances that have at least one dimension <100 nm. They have unique physicochemical properties and innovative functions compared with conventional materials of submicron size. As such, they have many applications in nanomedicine, such as in drug delivery or diagnostic and imaging systems. However, there are a number of safety concerns regarding the use of nanomaterials. Therefore it is essential not only to obtain more information about nanomaterials to ensure their safety, but also to identify novel biomarkers that may predict adverse biological effects induced by nan...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - October 5, 2014 Category: Drugs & Pharmacology Authors: Higashisaka K Tags: Yakugaku Zasshi Source Type: research

Development of a Novel Nanocarrier Focusing on the Physicochemical Properties of an Anti-cancer Therapy Drug-Development of Anti-cancer Nanoparticles Containing Vitamin E Derivative with Mulitifaceted Anti-cancer Effect-.
Abstract   Successful cancer gene therapy is dependent upon the development of nanocarriers that exhibit anti-cancer effects via delivery of nucleic acids to the target site in tumor tissue. The effectiveness of such systems has typically relied on the potency of the anti-cancer nucleic acids, as conventional carriers do not exhibit inherent anti-cancer activity, serving only as vehicles for delivery. Ideal nanocarriers for effective cancer gene therapy should not only serve as delivery systems for transporting anti-cancer nucleic acids to the target tumor tissue, but should also exhibit their own inherent anti-c...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - October 5, 2014 Category: Drugs & Pharmacology Authors: Hama S Tags: Yakugaku Zasshi Source Type: research

Role of Orexin-A-mediated Communication System between Brain and Peripheral Tissues on the Development of Post-ischemic Glucose Intolerance-induced Neuronal Damage.
Abstract   I recently found that cerebral ischemic stress per se causes hyperglycemia (i.e., post-ischemic glucose intolerance) and suppression of post-ischemic glucose intolerance might be important to improve prognosis. Here, I analyzed the efficacy of suppression of post-ischemic glucose intolerance using orexin-A (OXA) endogenous neuropeptide as a novel therapeutic strategy against cerebral ischemic neuronal damage. OXA in hypothalamus plays a role in many physiological functions including regulation of glucose metabolism. I previously found that the development of post-ischemic glucose intolerance is suppres...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - October 5, 2014 Category: Drugs & Pharmacology Authors: Harada S Tags: Yakugaku Zasshi Source Type: research

Functional Analysis of Bioactive Natural Compounds Using Monoclonal Antibodies against Natural Compounds.
Abstract   Herbal medicines have recently attracted much importance owing to the rising interest in their health benefits. Hence, further elucidation of the functions and mechanisms of these natural compounds is necessary. Our laboratory has established more than 30 kinds of monoclonal antibodies (MAbs) against bioactive natural compounds. Moreover, we have developed highly sensitive measurement systems for natural compounds, such as enzyme-linked immunosorbent assay (ELISA) and eastern blotting using MAbs. To expand the application of these MAbs to the functional analysis of natural compounds, we established a n...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - October 5, 2014 Category: Drugs & Pharmacology Authors: Uto T Tags: Yakugaku Zasshi Source Type: research

Visualization and Analysis of Adverse Reactions of Molecularly Targeted Anticancer Agents Using the Self-organizing Map (SOM).
In this study we used the self-organizing map (SOM) technique to visualize the adverse reactions indicated on PIs of 23 molecularly targeted anticancer agents as of March 2013. In both the presence/absence version and the frequency version, SOM was divided into domains according to mechanism of action, antibody drug or low-molecular weight drug, and molecular target. The component planes of the 753 adverse reaction items in the frequency version enabled us to grasp all available information and differences among the drugs. In some component planes in the presence/absence version, an adverse reaction that had not been repor...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - October 5, 2014 Category: Drugs & Pharmacology Authors: Hamamoto T, Serizawa A, Ohtsuki K, Kawakami J, Sato K Tags: Yakugaku Zasshi Source Type: research

Establishment of Background Color to Discriminate among Tablets: Sharper and More Feasible with Color-weak Simulation as Access to Safe Medication.
Abstract   Color-weak persons, who in Japan represent approximately 5% of male and 0.2% of female population, may not be able to discriminate among colors of tablets. Thus using color-weak simulation by Variantor(TM) we evaluated the effects of background colors (light, medium, and dark gray, purple, blue, and blue green) on discrimination among yellow, yellow red, red, and mixed group tablets by our established method. In addition, the influence of white 10-mm ruled squares on background sheets was examined, and the change in color of the tablets and background sheets through the simulation measured. Variance an...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - October 5, 2014 Category: Drugs & Pharmacology Authors: Ishizaki M, Maeda H, Okamoto I Tags: Yakugaku Zasshi Source Type: research

Stereocontrolled synthesis of phosphinyl dipeptide isosteres using an asymmetric center at the phosphorus atom.
Abstract   Phosphinyl dipeptide isosteres (PDIs) are important compounds for the development of potent and selective inhibitors of various aspartic proteases and Zn metalloproteases. The stereochemistry of PDIs affects their biological activity. PDIs were prepared successfully using the concept of asymmetric induction from the chiral phosphorus atom of the phosphinate moiety to the neighboring carbon atom. This methodology involves diastereoselective α-alkylation and β'-alkylation of P-chiral phosphinate derivatives, prepared through lipase-catalyzed kinetic resolution, which produces Phe-Ala type and Pro-Phe t...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - September 4, 2014 Category: Drugs & Pharmacology Authors: Yamagishi T Tags: Yakugaku Zasshi Source Type: research

Alterations in Expression and Function of ABC Transporters and ERM Proteins in Inflammation.
We examined the effects of acute (on day 7) and chronic (on day 21) inflammation on the expression of ABC transporters in some major tissues in rats. Adjuvant-induced arthritis (AA) in rats was used as an animal model of inflammation. The mRNA levels of mdr1a and mdr1b encoding P-glycoprotein (P-gp) decreased significantly in the liver of AA rats on day 21. Hepatic protein levels of P-gp, Mrp2, and Bcrp decreased significantly in the membrane but not in the homogenate of AA rats after 7 days and after 21 days of treatment with adjuvant. Recently, ezrin/radixin/moesin (ERM) proteins have been found to show linker activity f...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - September 4, 2014 Category: Drugs & Pharmacology Authors: Kawase A Tags: Yakugaku Zasshi Source Type: research

Stoichiometric Analysis of Oligomerization of Membrane Proteins Using Coiled-coil Labeling and in-Cell Spectroscopy.
Abstract   Many membrane proteins are responsible for signaling and ionic transport necessary to maintain biological functions in vivo. Recently, not only conformational changes but also oligomerization have been proposed to regulate protein activation. Thus, the study of membrane protein oligomerization is crucial for new drug development. The existing destructive methodologies such as immunoprecipitation, however, are not suitable to determine oligomeric states precisely because of the artificial aggregation of proteins after detergent solubilization. In the present study, the coiled-coil tag-probe labeling met...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - September 4, 2014 Category: Drugs & Pharmacology Authors: Kawano K Tags: Yakugaku Zasshi Source Type: research

Synthesis and Structure of Silver(I) Coordination Polymers with Bis(pyridyl) Ligands Linked by an Aromatic Sulfonamide.
Abstract   Aromatic sulfonamides exist in a synclinal conformation with the twisted structure arising from rotation around the S-N bond in both the solid state and in solution. Simple bidentate ligands containing the sulfonamide moiety can be extended to form elongated ligands, and optically active components can be added to form a versatile building block for the construction of coordination polymers with many structures. Mixing the simple ligands 1 and 2 and the elongated ligands 3 and 4 with different Ag(I) salts yielded the corresponding complexes [Ag(1)OTf]n (1a), [Ag(2)]n•nOTf(2a), [Ag(3)OTf]n (3a), [Ag(3...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - September 4, 2014 Category: Drugs & Pharmacology Authors: Katagiri K Tags: Yakugaku Zasshi Source Type: research

Development of hospital pharmacy practice using therapeutic drug monitoring.
In conclusion, TDM can determine drug concentration and indicate optimal pharmaceutical approach for treatment. PMID: 25174365 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - September 4, 2014 Category: Drugs & Pharmacology Authors: Watanabe S Tags: Yakugaku Zasshi Source Type: research

Structure elucidation of antioxidative polyphenols and their biological properties.
Abstract   Tannins and related polyphenols have been reported to produce diverse biological effects that indicate their therapeutic potential, including antioxidative, antibacterial, and antiviral activities. In an exploratory study of natural antioxidants with biological effects, we investigated the tannin constituents of myrtaceous plants reported to be rich in polyphenols. We isolated 16 new compounds from five species of the Melaleuca, Eucalyptus, Syzygium, Pimenta, and Myrtus genera. Among the new polyphenols, nine were isolated from Melaleuca squarrosa and characterized as C-glucosidic ellagitannin monomers...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - September 4, 2014 Category: Drugs & Pharmacology Authors: Yoshimura M Tags: Yakugaku Zasshi Source Type: research

Synthesis and evaluation of novel nucleic Acid derivatives as bioactive substances.
Abstract   This review describes the synthesis and evaluation of novel nucleic acid derivatives performed by our research group to date. We developed a new method for the synthesis of 2-alkoxyadenosine analogs via nonaqueous diazotization-dediazoniation reactions. By applying these reactions, we effectively synthesized four types of carbocyclic oxetanocin analogs (2-alkoxy-C.OXT-A). The angiogenic activities of these compounds were evaluated using human umbilical vein endothelial cells. This resulted in increased activities of the analogs, especially of 2-methoxy-C.OXT-A and 2-isopropoxy-C.OXT-A, at a concentrati...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - September 4, 2014 Category: Drugs & Pharmacology Authors: Sakakibara N Tags: Yakugaku Zasshi Source Type: research

Elucidation of the Mechanism Responsible for the Oxidation of Serum Albumin and Its Application in Treating Oxidative Stress-related Diseases.
Abstract   Oxidative damage results in protein modification and is observed in numerous diseases. Human serum albumin (HSA), the most abundant protein in the plasma, exerts important antioxidant activities to prevent oxidative damage. This paper focuses on the characterization of chemical changes in HSA that are induced by oxidative damage, their relevance to human pathology, and the most recent advances in clinical applications. The antioxidant properties of HSA are largely dependent on Cys-34 and its contribution to the maintenance of intravascular homeostasis, including protecting the vascular endothelium unde...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - September 4, 2014 Category: Drugs & Pharmacology Authors: Anraku M Tags: Yakugaku Zasshi Source Type: research

Methods for reducing dacarbazine photodegradation and its accompanying venous pain.
In this study we evaluated the effectiveness of colored shields (orange and red) to protect against photodegradation of DTIC as determined by ascertaining the concentration of diazo-IC. Samples were prepared and stored under four conditions: (1) no shield; (2) covered with an aluminum (opaque) shield; (3) covered with an orange shield; and (4) covered with a red shield. The samples were exposed to natural light for a specified time (0, 30, 60, 120, and 180 min) prior to measuring the concentration of diazo-IC by HPLC. We found that after 180 min, the diazo-IC concentration was 5.7±0.6 (S.D.) μg/mL with no shield and 1.9...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - September 4, 2014 Category: Drugs & Pharmacology Authors: Tsuji T, Ohtsubo T, Umeyama T, Sudou M, Komesu K, Matsumoto M, Yoshida Y, Banno R, Mikami T, Kohno T Tags: Yakugaku Zasshi Source Type: research

Liposome Modified with VIP-Lipopeptide as a New Drug Delivery System.
Abstract   We have designed a novel lipid analog (lipopeptide) that mimics the structural features of modified phospholipids. This lipopeptide is easily synthesized using a peptide synthesizer and has been shown to be useful for the modification of liposomes, which are used as an active targeted drug delivery system (DDS). Vasoactive intestinal peptide (VIP) has high homology with pituitary adenylate cyclase activating peptide (PACAP). There are three major PACAP receptors: PAC1R, VPAC1R, and VPAC2R. PAC1R has affinity only for PACAP, whereas VPAC1R and VPAC2R have the same affinity for both VIP and PACAP. In the...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - September 4, 2014 Category: Drugs & Pharmacology Authors: Masaka T, Li Y, Kawatobi S, Koide Y, Takami A, Yano K, Imai R, Yagi N, Suzuki H, Hikawa H, Tatsuno I, Terada K, Yokoyama Y Tags: Yakugaku Zasshi Source Type: research

My research life: from synaptic transmission to behavior.
Abstract   I have studied signal transmission at synapses and the effects of drugs on it at the molecular and cellular levels. Specific areas of research interest are outlined here. 1) Electrophysiological experiments in cats and rabbits suggested that a new type of analgesic, the phenothiazine derivative levomepromazine, exerts analgesic effects by depressing emotional responses accompanying the sensation of pain. 2) It was hypothesized that motoneurons had long-term effects on muscle cell membrane properties, in addition to controlling moment-to-moment activities. The substance to recover the post-denervation c...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - August 9, 2014 Category: Drugs & Pharmacology Authors: Kuromi H Tags: Yakugaku Zasshi Source Type: research

Quality evaluation for pharmaceutical products and medical supplies: proper use.
Abstract   In the proper use of medicine, the quality of medical supplies is an important factor. Use of generic products not only reduces drug costs for the patient, but also offers substantial advantages for governments in reducing medical expenses. When evaluation of the quality of generic products is centered on tablets, products with qualities that are unstable over time may be encountered. Some dosage forms require suitable pharmaceutical tests, processes, and apparatuses, such as those for evaluating orally disintegrating tablets or cutaneous preparations. For example, although simple test equipment has be...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - August 9, 2014 Category: Drugs & Pharmacology Authors: Miyamoto E Tags: Yakugaku Zasshi Source Type: research

Universality of Amino Acid Signaling between Diverse Plasma Cells.
Abstract   Both glutamic (Glu) and gamma-aminobutyric (GABA) acids are believed to play roles as neurotransmitters released from particular neurons into synaptic clefts in the mammalian central nervous system. Although GABA has been shown to act as an extracellular signal outside the brain, little attention has been paid to the possible expression of machineries required for neuronal glutamatergic signaling in cells other than central neurons. We first demonstrated the presence of Glu receptors in peripheral tissues such as the adrenal and pituitary glands three decades ago. In this review, I will outline our exp...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - August 9, 2014 Category: Drugs & Pharmacology Authors: Yoneda Y Tags: Yakugaku Zasshi Source Type: research

Function of glycochains in virus infection.
Abstract   Influenza A virus (IAV) has two envelope glycoproteins, hemagglutinin (HA) and neuraminidase (NA). HA binds to sialic acids at the terminals of glycochains on the host cell surface as virus receptors. NA shows sialidase activity, which cleaves sialic acids from the terminals of glycochains. A new subtype (antigenicities of HA and NA) of IAV for humans has pandemic potential. We investigated the functions of HA and NA in IAV replication and pandemic potential in terms of glycoscience. We found that the sialidase activity of pandemic IAV had low pH stability, which enhanced IAV replication. It is thought...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - August 9, 2014 Category: Drugs & Pharmacology Authors: Takahashi T Tags: Yakugaku Zasshi Source Type: research

The Effect of BGM on Patients' Mood Change while Staying in a Pharmacy's Lounge.
In conclusion, BGM alleviates uncomfortable moods caused by illness, particularly among females in poor health. PMID: 25088321 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - August 9, 2014 Category: Drugs & Pharmacology Authors: Yoshida T, Yoshinaga M Tags: Yakugaku Zasshi Source Type: research

Degrading Anticancer Drugs in the Medical Environment Using a Visible Light-driven Photocatalyst.
In this study, we evaluated anticancer drug degradation using a visible light-driven photocatalyst (Cu/WO3). Anticancer drugs [cyclophosphamide (CPA), paclitaxel (PTX), methotrexate (MTX), irinotecan (CPT-11), cytarabine (Ara-C), and 5-fluorouracil (5-FU)], were experimentally deposited on a stainless steel plate. The visible light-driven photocatalytic agent (0.075% Cu/WO3 solution) was sprayed onto the plate, and the plate was then left under a fluorescent lamp for 12 h. The anticancer drugs remaining on the plate were assayed by high-performance liquid chromatography (HPLC). CPA, PTX, MTX, CPT-11, Ara-C, and 5-FU were f...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - August 9, 2014 Category: Drugs & Pharmacology Authors: Sato J, Kikuchi S, Kudo K Tags: Yakugaku Zasshi Source Type: research

Let's Discuss Metals and Metal Compounds across the Research Fields.
PMID: 24989464 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 7, 2014 Category: Drugs & Pharmacology Authors: Fujie T, Kanazawa J Tags: Yakugaku Zasshi Source Type: research

The Development of C-C Cross-Coupling Reaction of Monocarba-closo-dodecaborate Anion for the Synthesis of Functional Molecules.
Abstract   A cross-coupling reaction at the carbon vertex of a monocarba-closo-dodecaborate has been developed to allow introduction of various aryl groups and other sp(2)/sp-hybridized carbon centers. A copper(I) complex facilitated the coupling process with a wide range of electrophiles at room temperature. The reaction was successfully used to prepare a series of C-arylated caborane anion derivatives, some of which showed potent androgen-receptor binding activity and excellent mesogenic properties. PMID: 24989465 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 7, 2014 Category: Drugs & Pharmacology Authors: Kanazawa J, Takita R, Uchiyama M Tags: Yakugaku Zasshi Source Type: research

Design, Synthesis, and Structure-activity Relationship Study of Organoantimony Compounds That Induce the Expression of Perlecan in Vascular Endothelial Cells.
Abstract   Organometallic compounds and complexes possibly show novel bioactivities unprecedented with organic molecules that consist of C, H, O, and N atoms. We have already reported that an organoantimony compound selectively induces the expression of perlecan, a large heparin sulfate proteoglycan, in cultured vascular endothelial cells. Perlecan consists of a core protein with Mr of approximately 400 kDa and three anticoagulant heparan sulfate glycosaminoglycan chains. However, little is known about the molecular mechanisms of perlecan expression in endothelial cells. Since an organoantimony compound induces t...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 7, 2014 Category: Drugs & Pharmacology Authors: Naka H, Takita R, Kaji T, Uchiyama M Tags: Yakugaku Zasshi Source Type: research

Neural Differentiation of Pluripotent Stem Cells and Application for Metal-induced Neural Toxicity Study.
In this study, we investigated an impact of Mn together with Fe and dopamine (DA) on neural differentiation of mouse embryonic stem cells (mESCs). The differentiation of mESCs was initiated by embryoid bodies (EBs) formation in the presence of all-trans retinoic acid, and then EBs were treated with Mn, Fe and/or DA. Then, the mRNA levels of neural differentiation marker genes (Nestin, Emx2, Mtap2, Th, Olig2 and Gfap) were examined using realtime RT-PCR analysis. Mn or DA alone reduced Mtap2, Th and Olig2 expression levels and increased Nestin. Moreover, combined treatment of Mn and DA also increased Nestin expression level...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 7, 2014 Category: Drugs & Pharmacology Authors: Taniguchi Y, Tobe T, Hayami H, Okamoto Y, Ueda K, Takada T, Kojima N Tags: Yakugaku Zasshi Source Type: research

Development of New Peptide-based Chelating Agents for Site-specific Radiolabeling with (64)Cu.
In this study, we synthesized new peptide derivatives possessing an N-terminal tripeptide sequence (Xaa-Yaa-His) called the amino terminal Cu(2+)- and Ni(2+)-binding (ATCUN) motif as (64)Cu binding peptides for the proposed labeling method. Moreover, we studied the stability constants of Cu(2+)-ATCUN peptide complexes by pH titration. From these studies, we found that a low basicity of the N-terminal amine in the peptide resulted in a high stability constant of the complex. This finding may provide valuable guidelines in designing the ATCUN peptide with high-binding affinity toward (64)Cu. PMID: 24989468 [PubMed - in ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 7, 2014 Category: Drugs & Pharmacology Authors: Miyamoto T, Kamino S, Odani A, Hiromura M, Enomoto S Tags: Yakugaku Zasshi Source Type: research

The role of metallothionein and metal transporter on cadmium transport from mother to fetus.
In this study, female Wistar rats were given Cd (as CdCl2) at a dose of 0, 1, 2 and 5 mg Cd/kg/d. Animals were sacrificed on the pregnant 19-21 d. The concentrations of Cd and MT, and gene expression of MT and metal transporters were determined in the placenta and in the fetuses. In mother rats, the concentration of Cd in the placenta increased dose-dependently, significantly. The Cd of MT-Cd form and the Cd of non-MT-Cd form increased also dose-dependently. In pathological examination of placenta tissue, syncytial trophoblast cells were damaged dose-dependently, particularly in 5 mg Cd/kg group. In fetuses, the Cd concent...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 7, 2014 Category: Drugs & Pharmacology Authors: Fukase Y, Tsugami H, Nakamura Y, Ohba K, Ohta H Tags: Yakugaku Zasshi Source Type: research

Expression of ZIP8 in Vascular Endothelial Cells after Exposure to Cadmium.
In this report, we have described how cadmium is one of the inducers of ZIP8 expression in vascular endothelial cells, and that cadmium cytotoxicity partly depends on the ZIP8 expression levels. PMID: 24989470 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 7, 2014 Category: Drugs & Pharmacology Authors: Takahashi S, Yamamoto C, Kaji T Tags: Yakugaku Zasshi Source Type: research

The Regulation of the Activation in BCR Signaling by ZIP9 Transporter.
Abstract   Zinc is the essential trace element and important for all living organisms. Zinc functions not only as a nutritional factor, but also as a second messenger. However, the effects of intracellular zinc on the B cell-receptor (BCR) signaling pathway are not poorly understood. Here, we indicate that the ZIP9 induces increase in intracellular zinc level and plays an important role in the phosphorylation of Akt and Erk in response to BCR activation. In DT40 cells, the enhancement of Akt and Erk phosphorylation requires intracellular zinc. To clarify this event, we used chicken Zip9-knockout DT40 (cZip9KO) ce...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 7, 2014 Category: Drugs & Pharmacology Authors: Taniguchi M, Enomoto S, Hiromura M Tags: Yakugaku Zasshi Source Type: research

Activation of cellular defense mechanism by organic-inorganic hybrid molecules.
Abstract   Organic-inorganic hybrid molecules can exhibit biological activities by controlling the activities of their individual components. These molecules can be applied as seed/lead compounds in drug development, and can be used as molecular probes in chemical biology for the elucidation of the molecular mechanisms of biological systems. In this review, we introduce copper diethyldithiocarbamate (Cu10), a copper complex, as a compound that activates nuclear factor erythroid 2-related factor 2 (Nrf2) and induces metallothionein, which are the key cellular defense factors against toxic metals and oxidative stre...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 7, 2014 Category: Drugs & Pharmacology Authors: Fujie T, Naka H, Yamamoto C, Shinkai Y, Kumagai Y, Kaji T Tags: Yakugaku Zasshi Source Type: research

Regulation of Endothelial Cell-specific Robo4 Gene Expression by DNA Methylation and Non-lineage Specific Transcription Factors.
Abstract   Studies of tissue-specific gene expression have suggested that tissue-specific transcription factors or tissue-specific combinations of non-cell-type-specific transcription factors regulate tissue-specific gene expression. Although the studies of endothelial cell (EC)-specific gene expression has identified several transcriptional activators such as SP1, ETS family proteins, and GATA proteins, their expression and combinations are not likely to be EC-specific. To investigate the mechanism of EC-specific gene expression, we analyzed the regulation mechanism of an EC-specific gene, Roundabout4 (Robo4). W...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 7, 2014 Category: Drugs & Pharmacology Authors: Okada Y Tags: Yakugaku Zasshi Source Type: research

Pathological Changes in Hepatocytes of Mice with Obesity-induced Type 2 Diabetes by Monosodium Glutamate.
Abstract   Type 2 diabetes caused by chronic obesity is a major lifestyle-related disease. The present study aimed to determine the pathological changes in hepatocytes in chronic obesity. To develop our type 2 diabetes mouse model, we induced chronic obesity to mice by monosodium glutamate. By overeating, the mice significantly increased their body weight compared with age-matched healthy animals. To analyze the pathological changes in hepatocytes of chronic obesity before preclinical stage of type 2 diabetes, the mice were analyzed by hematoxylin-eosin staining of tissue sections at 15 w of age. In these mice, w...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 7, 2014 Category: Drugs & Pharmacology Authors: Nakadate K, Motojima K, Kamata S, Yoshida T, Hikita M, Wakamatsu H Tags: Yakugaku Zasshi Source Type: research

A Study on Comparison of Learning Effects between a Board Game and a Lecture about Infection Control.
Abstract   In order to provide an opportunity for community pharmacists to actively learn about infection control, this study created learning materials through a board game format and verified characteristics of learning by determining and comparing evaluation according to viewpoint and motivational effects between a lecture and the game. To create the board game, we collected cases of infection from 30 community pharmacists. The game was created using collected and created case studies, and we held a workshop on infection control. Participants were assigned to a lecture (n=32) or game group (n=27) and completed...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - July 7, 2014 Category: Drugs & Pharmacology Authors: Kawamura H, Kishimoto K, Matsuda T, Fukushima N Tags: Yakugaku Zasshi Source Type: research

New development of drug discovery research-novel molecular target and novel strategy-.
PMID: 24882642 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 8, 2014 Category: Drugs & Pharmacology Authors: Kawahara R, Hiruma W Tags: Yakugaku Zasshi Source Type: research

Effect of Repeated Oral Treatment with Etoposide on the Expression of Intestinal P-glycoprotein and Oral Morphine Analgesia.
Abstract   Currently, the World Health Organization recommends oral administration of opioid analgesics for patients with cancer to treat cancer-related pain from the initial stage of treatment. Furthermore, many anticancer drugs have been newly-developed and approved as oral form. Because of this trend, the chances of drug-drug interactions between anticancer drugs and opioid analgesics during absorption process from the intestine are likely to increase. To investigate these possible drug-drug interactions, we have focused on intestinal P-glycoprotein (P-gp) which regulates the absorption of various substrate dr...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 8, 2014 Category: Drugs & Pharmacology Authors: Kobori T, Harada S, Nakamoto K, Tokuyama S Tags: Yakugaku Zasshi Source Type: research

Anti-high Mobility Group Box-1 Antibody Therapy for Traumatic Brain Injury.
We presented the involvement of HMGB-1 in TBI and evaluated the ability of intravenously administered neutralizing anti-HMGB-1 monoclonal antibody (mAb) to attenuate brain injury. Anti-HMGB-1 mAb may provide a novel and effective therapy for TBI by protecting against blood brain barrier disruption and reducing the inflammatory responses induced by HMGB-1. PMID: 24882644 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 8, 2014 Category: Drugs & Pharmacology Authors: Okuma Y, Date I, Nishibori M Tags: Yakugaku Zasshi Source Type: research

Cardioprotective Effect of the Selective Sigma-1 Receptor Agonist, SA4503.
Abstract   We previously reported that the sigma-1 receptor is down-regulated in cardiomyocytes following heart failure in transverse aortic constriction (TAC) mice. In this review, we summarized the anti-hypertrophic action of selective sigma-1 receptor agonist, SA4503 in the hypertrophied cultured cardiomyocytes and discussed its possible mechanism of cardioprotection. Treatment with SA4503 (0.1-1 μM) dose-dependently inhibited hypertrophy in cultured cardiomyocytes induced by angiotensin II (Ang II). We also found that α1 receptor stimulation by phenylephrine (PE) promotes ATP production through IP3 receptor...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 8, 2014 Category: Drugs & Pharmacology Authors: Hirano K, Tagashira H, Fukunaga K Tags: Yakugaku Zasshi Source Type: research

Drug development for cardiorenal disease based on oxidative stress control.
Abstract   Oxidative stress is a key factor involved in the pathogenesis and progression of cardiovascular disease (CVD) and chronic kidney disease (CKD). Reactive oxygen species (ROS), produced as a result of redox reactions in various cells, have been recognized as key chemical mediators causing cellular damage and organ dysfunction in CVD and CKD. Nifedipine, a well-known calcium channel blocker, is extremely sensitive to light which gets converted to its nitroso analog, nitrosonifedipine (NO-NIF) in the presence of ultraviolet and visible light. The so formed NO-NIF blocks calcium channel quite weakly compare...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 8, 2014 Category: Drugs & Pharmacology Authors: Imanishi M, Ishizawa K, Sakurada T, Ishizawa Y, Yamano N, Kihira Y, Ikeda Y, Tsuchiya K, Tamaki T Tags: Yakugaku Zasshi Source Type: research

Recent topics on development of nanomaterials and nano-safety science.
PMID: 24882647 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 8, 2014 Category: Drugs & Pharmacology Authors: Yoshioka Y, Tsutsumi Y Tags: Yakugaku Zasshi Source Type: research

Cellular distribution and behavior of metallothionein in Mammalian cells following exposure to silver nanoparticles and silver ions.
Abstract   Silver nanoparticles (AgNPs) are commercially used mainly as antibacterial reagents in wound dressing and deodorant powders. However, the mechanisms underlying Ag toxicity in mammals are not fully understood. In the present study, we assessed cellular distribution and toxicity of AgNPs and AgNO3 in mouse macrophage cell line (J774.1) and those of AgNO3 in human bronchial epithelial cell line (BEAS-2B) focusing on behavior of metallothionein (MT). J774.1 cells were exposed to 0-100 μg Ag/mL AgNPs or AgNO3 and BEAS-2B cells were exposed to 0-100 μM AgNO3 for 24 h. The cytotoxicity was assayed by a modi...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 8, 2014 Category: Drugs & Pharmacology Authors: Miyayama T, Arai Y, Suzuki N, Hirano S Tags: Yakugaku Zasshi Source Type: research

In vitro safety evaluation of nanomaterials-cellular response to metal oxide nanoparticles-.
In this study, the effects of copper oxide nanoparticles on the global gene expression of human lung epithelial A549 cells were analyzed, and the molecular responses of A549 cells to the toxicity of the copper oxide (CuO) nanoparticles were inferred. Furthermore, the cytotoxic effects of silicon dioxide (SiO2) nanoparticles and titanium dioxide (TiO2) nanoparticles coexisting with some metal salts in Chinese hamster lung fibroblast V79 cells were also examined, and SiO2 nanoparticles increased the cytotoxicity of some of the coexisting metal salts as a result. Finally, the importance of in vitro studies in the safety evalu...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 8, 2014 Category: Drugs & Pharmacology Authors: Isama K Tags: Yakugaku Zasshi Source Type: research

Nano-safety Science for Sustainable Nanotechnology.
Abstract   Recently, it is concerned that nanomaterials induce undesirable biological responses (NanoTox) which is different from conventional materials attributed to their unique physicochemical properties in the world. However, for our enjoying the benefits of nanomateirals, it is most important not to regulate nanomaterials in the blind way but to assure the security of nanomaterials and support the development of nanomaterial industries. These are duty of our country to be advanced country, technology-oriented nation and intellectual property nation. From these viewpoints, we are engaged on not NanoTox study ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 8, 2014 Category: Drugs & Pharmacology Authors: Yoshioka Y, Tsutsumi Y Tags: Yakugaku Zasshi Source Type: research

Involvement of ATP in Radiation-induced Bystander Effect as a Signaling Molecule.
Abstract   We previously reported that low doses (0.25-0.5 Gy) of γ-rays induce intracellular antioxidant, radioresistant, DNA damage repair, and so on. Meanwhile, we have recently reported that ATP is released from the cells exposed to low-dose γ-rays. Here, it was investigated whether or not γ-radiation-induced release of extracellular ATP contributes to various radiation effects, in paricular, focusing on the inductions of intracellular antioxidant and DNA damage repair. Irradiation with γ-rays or exogenously added ATP increased expression of intracellular antioxidants such as thioredoxin and the increases...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - June 8, 2014 Category: Drugs & Pharmacology Authors: Kojima S Tags: Yakugaku Zasshi Source Type: research