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Next stages of drug discovery and evolution for intractable diseases created by young pharmacologists.
PMID: 25452232 [PubMed - in process] (Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan)
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 7, 2014 Category: Drugs & Pharmacology Authors: Morioka N, Takata K Tags: Yakugaku Zasshi Source Type: research

Establishment of a novel therapeutic strategy for heart failure based on the mechanism underlying maintenance of redox homeostasis by reactive sulfur species.
Abstract   Cardiac redox homeostasis is precisely regulated by reactive oxygen species (ROS) or electrophilic molecules that are formed by ROS reacting with intracellular substrates, and their eliminating systems. We have focused on the role of nitric oxide (NO) generated from inducible NO synthase (iNOS) that is continuously upregulated from early stage of heart failure, and revealed that iNOS-derived NO acts as a protective factor in the early stage of heart failure, whereas it contributes to induction of cardiac early senescence in later stages. The switching mechanism of NO-mediated signaling includes formati...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 7, 2014 Category: Drugs & Pharmacology Authors: Nishida M, Toyama T, Kumagai Y, Numaga-Tomita T Tags: Yakugaku Zasshi Source Type: research

Role of hydrogen sulfide, a gasotransmitter, in colonic pain and inflammation.
Abstract   Hydrogen sulfide (H2S), the third known gaseous transmitter following nitric oxide and carbon monoxide, is generated by multiple enzymes including cystathionine-γ-lyase (CSE) in vivo. We previously demonstrated that H2S activates Cav3.2 T-type Ca(2+) channels expressed on sensory neurons, leading to hyperalgesia and facilitation of inflammation. Here, we describe the role of H2S in processing of colonic pain and inflammation. Intracolonic (i.col.) administration of NaHS, an H2S donor, to mice evoked colonic pain-like nociceptive behavior and referred hyperalgesia accompanied by phosphorylation of ERK ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 7, 2014 Category: Drugs & Pharmacology Authors: Tsubota M, Kawabata A Tags: Yakugaku Zasshi Source Type: research

The causative gene of parkinsonism and its medical treatment strategy.
Abstract   Parkinsonism is a neurological syndrome characterized by tremor, hypokinesia, rigidity, and postural instability. The neurodegenerative condition of Parkinson's disease (PD) is the most common cause of parkinsonism. PD is classified as sporadic PD and familial PD. Whereas idiopathic PD is caused by a number of complex factors, familial PD is a result of mutations in PD-associated genes. Unraveling the mechanisms surrounding familial PD will offer pivotal clues in understanding etiology of not only familial PD but also sporadic PD. We have demonstrated neuroprotective effects with particular focus on DJ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 7, 2014 Category: Drugs & Pharmacology Authors: Inden M Tags: Yakugaku Zasshi Source Type: research

Regulation of Osteoclastogenesis by Osteocytes through Growth Differentiation Factor-15.
In this study, osteoclast differentiation was significantly enhanced by conditioned media derived from cultures of osteocytic MLO-Y4 cells that were cultured under hypoxic conditions. Using microarray analysis, we identified growth differentiation factor-15 (GDF15) as a pivotal factor secreted from osteocytes under hypoxia. Indeed, treatment with recombinant GDF15 markedly increased osteoclast differentiation in vitro. Further to investigate the importance of GDF15 in vivo, we used a hypoxic murine model that involved ligation of the right femoral artery. The volume of cancellous bone in the proximal tibia of the ligated l...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 7, 2014 Category: Drugs & Pharmacology Authors: Hinoi E Tags: Yakugaku Zasshi Source Type: research

A New Taxonomic System of the Genus Murraya (Rutaceae) Based on Integration of Morphology-based Taxonomy and Chemotaxonomy; and a Philological Survey on M. exotica in View of the Relationship between Okinawa and China.
Abstract   This review concerns the taxonomic status of the genus Murraya in tribe Clausenae, subfamily Aurantioideae, family Rutaceae, and presents a new system integrating both morphology-based taxonomy and chemotaxonomy. This genus has been morphologically divided into the sects Murraya and Bergera. This dichotomy is justified by the noticeable difference of secondary metabolites with 3-prenylindoles in Murraya and carbazoles in Bergera. As for other metabolites of genus Murraya, coumarins are found in both sects, but differ clearly in types; 8-prenylcoumarins occur throughout the sect Murraya whereas geranyla...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 7, 2014 Category: Drugs & Pharmacology Authors: Kinoshita T Tags: Yakugaku Zasshi Source Type: research

Synthesis of Hypervalent Organo-λ(3)-bromanes and Their Reactions by Using Leaving Group Ability of λ(3)-Bromanyl Group.
Abstract   Hypervalent organo-λ(3)-iodanes have attracted great interest in organic synthesis; however, the chemistry of hypervalent organo-λ(3)-bromanes remains largely unexplored, mainly because of synthetic difficulties. Iodobenzene is readily oxidized by common oxidants such as peracids under mild conditions, whereas bromobenzene is inert. Since the ionization potential of bromobenzene (8.98 eV) is higher than that of iodobenzene (8.69 eV), hypervalent-λ(3)-bromane would show much higher reactivity. We overcame this problem by using difluoro(aryl)-λ(3)-bromane (Frohn's reagent), which serves as a pivotal ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 7, 2014 Category: Drugs & Pharmacology Authors: Miyamoto K Tags: Yakugaku Zasshi Source Type: research

Mechanism of spinal pain transmission and its regulation.
Abstract   Morphine has been widely used for the treatment of acute, chronic, and cancer pain and is considered the strongest analgesic in clinical care. Conversely, morphine-induced analgesia may be accompanied by several side effects. Animal studies have demonstrated that low doses of morphine administered intrathecally can produce reliable analgesia for thermal, mechanical, and chemical nociceptive stimulation. On the other hand, high doses of morphine administered intrathecally may induce spontaneous nociceptive responses such as scratching, biting, and licking in mice as well as agitation and vocalization in...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 7, 2014 Category: Drugs & Pharmacology Authors: Watanabe C Tags: Yakugaku Zasshi Source Type: research

Efficient synthesis of multisubstituted aromatic compounds from phenol derivatives.
Abstract   Phenols are abundant in nature and diverse phenols are readily available commercially at low cost. Thus, phenols can be used as the raw materials for the synthesis of valuable multisubstituted aromatic compounds by the direct activation of phenolic hydroxyl groups (C-O bond activation), followed by substitutions with other substituents. Although the derivatization of phenolic hydroxyl groups to sulfonates, such as triflates, nonaflates, tosylates and mesylates, followed by the transition-metal-catalyzed coupling reactions has been extensively investigated for this purpose, the direct C-O bond activatio...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 7, 2014 Category: Drugs & Pharmacology Authors: Ikawa T Tags: Yakugaku Zasshi Source Type: research

Development of artificial nucleic acids functionalized for damaged gene diagnosis, gene inhibition and delivery system.
Abstract   Artificial nucleic acids have recently been widely used with their properties optimized for various technologies such as the inhibition of gene expression (antisense/antigene strategies, RNA interference) and genetic diagnosis (single nucleotide polymorphism (SNP), damaged nucleobase). For practical application of nucleic acid therapeutics, establishment of an effective delivery system for oligonucleotides is also required because of their poor permeability into cells. Various useful delivery technologies including lipoplexes formed using cationic lipids and polyplexes made with cationic polymers have ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 7, 2014 Category: Drugs & Pharmacology Authors: Nakagawa O Tags: Yakugaku Zasshi Source Type: research

Investigation of the educational effectiveness of including small group discussion as part of a drug abuse prevention program for junior high school students.
Abstract   We evaluated the effectiveness of small group discussion (SGD) in association with a drug abuse prevention program for junior high school students. The students first received a lecture about drug abuse prevention, then participated in SGD. The discussion focused on how to take action when tempted to abuse drugs. We gave a questionnaire 3 times; before and after the lecture (before SGD), and after SGD. Seventy-seven students replied to these questionnaires. After the lecture, knowledge about drug abuse was improved and all students answered that they had never abused drugs. However, in answer to a diff...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 7, 2014 Category: Drugs & Pharmacology Authors: Yamada J, Takayanagi R, Yokoyama H, Suzuki Y, Sinohara S, Yamada Y Tags: Yakugaku Zasshi Source Type: research

A Survey of Self-medication Practices and Related Factors in the General Population: the Ohasama Study.
Abstract   Encouraging self-medication is expected to reduce healthcare costs. To assess the current situation of self-medication practices in the general population, we conducted a questionnaire survey regarding the use of over-the-counter (OTC) medications or dietary supplements in 1008 participants (37% men; mean age, 64±13 years) from Ohasama, a rural Japanese community. A total of 519 (52%) participants used OTC medications or dietary supplements, with common cold medication (36%) and supplements (28%) such as shark cartilage products representing the most common choices. Stepwise logistic regression showed...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 7, 2014 Category: Drugs & Pharmacology Authors: Satoh M, Matsumoto A, Hara A, Iwamori S, Obara T, Kikuya M, Metoki H, Hosaka M, Asayama K, Takahashi N, Sato H, Mano N, Imai Y, Ohkubo T Tags: Yakugaku Zasshi Source Type: research

Trial and evaluation of a remedial education program at kobe pharmaceutical university.
Abstract   Pharmaceutical education is suffering from the decentralization of students due to the establishment of new pharmaceutical universities, the shift to a six-year program from a four-year program in the colleges of pharmacy in 2006, and a decrease in the number of students. Combined, these have lead to academic failings, even at high-ranking universities. However, abundant knowledge and ability are necessary to pass the national examination for pharmacists. At Kobe Pharmaceutical University, a Basic Education Center for Pharmacy was instituted in 2006 for the purpose of supporting the scholastic abilitie...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 7, 2014 Category: Drugs & Pharmacology Authors: Koyama J, Kodama N Tags: Yakugaku Zasshi Source Type: research

Necessity of personalized initial loading dose calculation of teicoplanin by clinical pharmacist-examination of the utility of using systemic inflammatory response syndrome score-.
Abstract   When teicoplanin (TEIC) is injected at the maintenance dose, a long period is required for achievement of the target plasma trough concentration because of its long elimination half-life. An initial loading dose is necessary for rapid achievement of an effective plasma trough concentration. Thus, we proposed that it is necessary for a pharmacist determine the initial loading dose of TEIC to reach an effective plasma trough concentration rapidly after its administration to a patient. In the present study, we evaluated the effectiveness of initial loading dose determination by pharmacists and physicians ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - December 7, 2014 Category: Drugs & Pharmacology Authors: Nakano T, Nakamura Y, Togawa A, Takata T, Ishikura H, Mishima K, Futagami K Tags: Yakugaku Zasshi Source Type: research

Expression and function of the histamine receptors in dermal and articular tissues.
Abstract   Histamine was first identified in 1910 as a physiologically active amine. It is now recognized for its multiple regulatory activities in the digestive, neuronal, and immune systems, and new roles are still being elucidated. Histamine exerts its effects through four distinct receptor subtypes. The histamine H4 receptor was identified in 2000 and is the most recently identified of the four histamine receptors. It is expressed primarily in immune cells and is involved in physiologic functions related to inflammation and allergy. Recently, the H4 receptor was highlighted as a promising therapeutic target i...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 10, 2014 Category: Drugs & Pharmacology Authors: Ueno K Tags: Yakugaku Zasshi Source Type: research

Coordination chemical studies on the zinc enzymes.
Abstract   The metal dissociation constants of bovine carbonic anhydrase II, bovine carboxypeptidase A, rat aminopeptidase B, and rat dipeptidyl peptidase III were measured using metal buffer solutions. The zinc dissociation constants of bovine carbonic anhydrase II, bovine carboxypeptidase A, rat aminopeptidase B, and rat dipeptidyl peptidase III were 5.8×10(-14), 3.5×10(-12), 3.7×10(-13), and 1.9×10(-13) M, respectively. The ternary complex between metal derivatives of bovine carbonic anhydrase and various chelating agents were characterized using the kinetic method and visible and magnetic circular dichroi...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 10, 2014 Category: Drugs & Pharmacology Authors: Hirose J Tags: Yakugaku Zasshi Source Type: research

A memoir of my research on pain and analgesia for 39 years.
Abstract   This review describes my research for the past 39 years regarding the pharmacology of pain and analgesia. We have demonstrated that the descending noradrenergic system is involved in the analgesic effect of morphine injected into the nucleus reticularis gigantocellularis, and that noradrenaline exerts antinociception mediated by α-adrenoceptors. We have found that noxious mechanical and thermal stimuli to the skin increase the release of substance P and somatostatin, respectively, from the dorsal horn in situ, and that noradrenaline inhibits the release of substance P and glutamate from primary affere...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 10, 2014 Category: Drugs & Pharmacology Authors: Kuraishi Y Tags: Yakugaku Zasshi Source Type: research

Development of the MITO-Porter, a Nano Device for Mitochondrial Drug Delivery via Membrane Fusion.
Abstract   Many human diseases have been reported to be associated with mitochondrial dysfunction. Therefore, mitochondrial therapy would be expected to be useful and productive in the treatment of various diseases. To achieve such an innovative therapy, it will be necessary to deliver therapeutic agents into mitochondria. However, only a limited number of methods are available for accomplishing this. We previously developed the MITO-Porter, a liposome-based carrier that permits macromolecular cargos to be transported into mitochondria via membrane fusion. Intracellular observations using the green fluorescence p...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 10, 2014 Category: Drugs & Pharmacology Authors: Yamada Y Tags: Yakugaku Zasshi Source Type: research

Role of intracellular degradation system in regulation of innate immune response.
Abstract   Innate immunity is induced after sensing microbial components by pattern-recognition receptors and functions as a first line of host defense against microbes. However, innate immunity is also induced after sensing host-derived stimulatory substances such as monosodium urate crystals and causes the development of inflammatory diseases, such as gout. Therefore, a better understanding of innate immunity is required for the development of effective therapeutic treatments for infectious and inflammatory diseases. This paper summarizes recent findings on regulation of the innate immune response. Accumulating...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 10, 2014 Category: Drugs & Pharmacology Authors: Saitoh T Tags: Yakugaku Zasshi Source Type: research

Immunohistochemical analysis of altered serotonin signaling and transient receptor potential vanilloid 1 channels in experimental colitis mice.
Abstract   Primary afferent nerve fibers are highly associated with visceral hypersensitivity state of inflammatory bowel disease. Hypersensitivity of afferent fibers occurs during inflammation, and therefore to gain insight into the alteration of receptors and channels, we examined receptors such as 5-HT receptors and transient receptor potential vanilloid type 1 (TRPV1), which are expressed in primary afferent neurons. The current study was designed to investigate the time-dependent dynamic changes of 5-HT3 receptors, 5-HT4 receptors, TRPV1 channels, and 5-HT regulatory factors in DSS-induced colitis model mice...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 10, 2014 Category: Drugs & Pharmacology Authors: Matsumoto K Tags: Yakugaku Zasshi Source Type: research

Cellular and molecular mechanisms underlying aberrant network reorganization in the epileptic brain.
Abstract   Well-refined wiring of neural circuits is fundamental to proper brain function. Aberrantly formed neural circuits may induce epileptiform discharges of neurons. Therefore, elucidating the cellular and molecular mechanisms that underlie the development of aberrant neural circuitry will advance the understanding and prevention of epilepsy. The dentate gyrus has been suggested to serve as a gate that prevents the propagation of epileptiform activity from the entorhinal cortex to the hippocampus. Within the dentate gyrus is the dentate granule cell layer, which consists of densely packed granule cells that...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 10, 2014 Category: Drugs & Pharmacology Authors: Koyama R Tags: Yakugaku Zasshi Source Type: research

Emerging roles of phospholipase a2s in mast cell biology.
Abstract   Tissue-resident mast cells are derived from circulating committed progenitors, which are originated from pluripotent hematopoietic stem cells in bone marrow. These progenitors migrate into extravascular tissues, where they undergo differentiation and maturation into tissue-specific mast cell phenotypes. When activated by antigen or microenvironmental factors, mast cells release various biologically active products, including pre-formed mediators stored in secretory granules, de novo synthesized lipid mediators, and newly transcribed cytokines and chemokines, thereby promoting anaphylactic inflammation ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 10, 2014 Category: Drugs & Pharmacology Authors: Taketomi Y Tags: Yakugaku Zasshi Source Type: research

Development of a highly sensitive separation method for the analysis of metabolites in human nails and applications in the diagnosis of chronic disease.
Abstract   We have recently developed target-specific derivatization methods for determining the metabolites in human nails. The nails can be used to obtain physiologic information and may serve as noninvasive biosamples for the diagnosis of chronic disease. Certain endogenous biogenic D,L-amino acids, polyamines, and advanced glycation end-products (AGEs) have been detected in human nails. By identifying biological trace components in human samples, we tested the possibility of using these new methods to diagnose chronic disease, i.e., diabetes and lung cancer. When comparing the index from diabetic patients to ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 10, 2014 Category: Drugs & Pharmacology Authors: Zhe Min J Tags: Yakugaku Zasshi Source Type: research

A Self-improvement and Participatory Career Development Education Program Involving Internships and Volunteer Training Experience for Pharmacy Students: Results Verified in a Follow-up Survey Three Years after Participation.
Abstract   The Faculty of Pharmaceutical Sciences, Setsunan University, offers the Self-improvement and Participatory Career Development Education Program: Internship and Volunteer Training Experience for Pharmacy Students to third-year students. We previously reported that the training experience was effective in cultivating important attributes among students, such as a willingness to learn the aims of pharmacists, an awareness of their own role as healthcare workers, and a desire to reflect on their future careers and lives. A follow-up survey of the participants was carried out three years after the training ...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 10, 2014 Category: Drugs & Pharmacology Authors: Kurio W, Konishi M, Okuno T, Nakao T, Kimura T, Tsuji T, Yamamuro A, Yamamoto Y, Nishikawa T, Yanada K, Yasuhara T, Kohno T, Ogita K, Sone T Tags: Yakugaku Zasshi Source Type: research

Structural analysis of carboxymethyl cellulose used as an antiadhesive material for surgical wound healing.
Abstract   Carboxymethyl cellulose (CMC) is one of the most important cellulose derivatives and used in the fields of food, pharmaceuticals, cosmetics, and paint. Fibrous CMC is used an antiadhesive material to prevent postoperative wound adhesions. The degree of substitution and distribution of the substituent (i.e., the carboxymethyl group) are the most important parameters for the function of CMC. Thus, CMC used for antiadhesive material must be carefully evaluated, because the CMC product is retained in patients' bodies over the long term. Although identification tests of CMC are defined in the Japanese Pharm...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 10, 2014 Category: Drugs & Pharmacology Authors: Yamada K, Kinoshita M, Jo Y, Inoue T, Aoshima M, Hasegawa K, Sei K, Kita S, Kakehi K Tags: Yakugaku Zasshi Source Type: research

Disinfection Efficacy of Hand Hygiene Based on Chlorhexidine Gluconate Content and Usage of Alcohol-based Hand-rubbing Solution.
Abstract   Recently, the procedure for surgical hand hygiene has been switching to a two-stage method and hand-rubbing method from the traditional hand-scrubbing method. Both the two-stage and hand-rubbing methods use alcohol-based hand-rubbing after hand washing. The former requires 5 min of antiseptic hand washing, and the latter 1 min of nonantiseptic hand washing. For a prolonged bactericidal effect in terms of surgical hand hygiene, chlorhexidine gluconate (CHG) has been noted due to its residual activity. However, no detailed study comparing the disinfection efficacy and prolonged effects according to diffe...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 10, 2014 Category: Drugs & Pharmacology Authors: Tanaka I, Watanabe K, Nakaminami H, Azuma C, Noguchi N Tags: Yakugaku Zasshi Source Type: research

Effects of practical training to increase motivation for learning and related factors.
Abstract   Under the six-year pharmaceutical education system that was initiated in April 2006, students who had completed the course in March 2012 became the first graduates. The six-year system encourages students to develop a well-rounded personality, a deep sense of ethics, knowledge required for health care professionals, abilities to identify and solve problems, and practical skills required in clinical settings, as well as basic knowledge and skills. Under the new education system based on the "pharmaceutical education model core curriculums" and "practical training model core curriculums", general pharmac...
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - November 10, 2014 Category: Drugs & Pharmacology Authors: Yamaguchi T, Akiyama S, Sagara H, Tanaka A, Miyauchi Y, Araki H, Shibata K, Izushi F, Namba H Tags: Yakugaku Zasshi Source Type: research

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