YAKUGAKU ZASSHI
Online ISSN : 1347-5231
Print ISSN : 0031-6903
ISSN-L : 0031-6903
134 巻, 8 号
選択された号の論文の6件中1~6を表示しています
総説
  • 黒見 坦
    2014 年 134 巻 8 号 p. 851-866
    発行日: 2014/08/01
    公開日: 2014/08/01
    ジャーナル フリー
      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 changes in muscle properties in culture was partially purified from mouse nerve extract, which suggested that trophic influences were exerted by substances released from motoneurons. 3) Muscles innervated by adrenergic fibers had sites responsive to acetylcholine as well as to adrenaline in early life in chicks, but only the adrenaline-responsive sites remained during development. Acetylcholine receptor clusters on Xenopus muscles were concentrated at the cholinergic neuromuscular junctions by the movement of receptors from outside the junctions during development. The passive diffusion-trap mechanism explained the accumulation of synaptic receptors at synapses. 4) We found two endocytic pathways and pools of synaptic vesicles contributing to low- and high-frequency synaptic transmission at Drosophila nerve terminals. We then identified two Ca2+ channels designated for the low- and high-frequency endocytosis of synaptic vesicles, straightjacket Ca2+ channels in the active zone and La3+-sensitive Ca2+ channels in the inactive zone at the terminals, respectively. Recently, Drosophila melanogaster has been used as a model for studying the social brain, and the heat avoidance response of the flies was found to be socially enhanced. Future studies are expected to reveal mechanisms underlying social brain functions at the gene level.
  • 宮本 悦子
    2014 年 134 巻 8 号 p. 867-877
    発行日: 2014/08/01
    公開日: 2014/08/01
    ジャーナル フリー
      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 been proposed for patches, a unified method is required. The pharmacist plays an important role in choosing high-quality generic products; however, a substantial amount of information needs to be made available to the public in order to achieve that goal.
  • 米田 幸雄
    2014 年 134 巻 8 号 p. 879-887
    発行日: 2014/08/01
    公開日: 2014/08/01
    ジャーナル フリー
      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 experimental findings accumulated since then on the physiological and pathological significance of neuronal amino acids as an extracellular signal for the maintenance of homeostasis in a variety of plasma cells. For example, Glu is released upon stimulation in a Ca2+-dependent manner for signal output in osteoblasts, where Glu is essential for the expression of the master regulator of osteoblastogenesis through a particular inotropic receptor subtype. In contrast, GABA plays a role in mechanisms underlying the suppression of cellular differentiation and maturation through a particular metabotropic receptor subtype in osteoblasts. Taken together, osteoblastic maturation proceeds as a delicate balancing between excitatory glutamatergic and inhibitory GABAergic signals, as seen in the brain. Re-evaluation of drugs currently used could be beneficial for the efficient discovery and development of innovative drugs useful for the prophylaxis and/or therapy of a variety of diseases relevant to the disturbance of glutamatergic and GABAergic signaling in diverse plasma cells.
  • 高橋 忠伸
    2014 年 134 巻 8 号 p. 889-899
    発行日: 2014/08/01
    公開日: 2014/08/01
    ジャーナル フリー
      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 that the low pH stability contributed to the pandemics in 1968 and 2009. HA also binds to sulfatide not containing sialic acid, and we found that sulfatide enhanced IAV replication. Binding of HA to sulfatide on the host cell surface enhanced progeny IAV formation in infected cells through the induction of the nuclear export of viral ribonucleoproteins by apoptosis. Sialic acid species are divided into N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc). The HAs of some human IAVs bind not only to Neu5Ac but also to Neu5Gc, which may facilitate the occurrence of a human IAV-based pandemic by genetic reassortment among IAV genomes in pig tracheas expressing Neu5Gc. We identified the amino acid residues of human IAV HA responsible for Neu5Gc binding and developed new techniques for the sensitive detection of IAV receptor specificities and infected cells. Our “glycovirology” research will provide new insights into the mechanisms of IAV replication and pandemic potential.
ノート
  • 吉田 智大, 吉永 真理
    2014 年 134 巻 8 号 p. 901-908
    発行日: 2014/08/01
    公開日: 2014/08/01
    ジャーナル フリー
      In order to examine the effects of music on mood, we administered a survey to patients awaiting the preparation of their prescription medicines in pharmacy lounges. Two pharmacies took part in this study, both of which are in a metropolitan area treating fewer than 100 prescription sheets per day. Two hundred and fifty-two patients were divided into two groups: one group listened to background music (BGM) while waiting (n=111) and the other did not listen to BGM (n=119). The questionnaire included items assessing mood, present state of health, and demographic information like gender and age. After excluding incomplete questionnaires, 230 patients were included in our final sample for further statistical analysis. BGM was involved in decreasing feelings of fatigue and increasing feelings of vigor in patients with poorer health. This trend was more evident in female patients than in male patients. Using multiple regression analysis, we found that, in addition to BGM, environmental factors such as light level and noise level significantly affected mood. In conclusion, BGM alleviates uncomfortable moods caused by illness, particularly among females in poor health.
  • 佐藤 淳也, 菊地 聡美, 工藤 賢三
    2014 年 134 巻 8 号 p. 909-914
    発行日: 2014/08/01
    公開日: 2014/08/01
    ジャーナル フリー
      Occupational exposure to anticancer drugs is recognized as a risk for healthcare workers. Reducing anticancer drugs in the environment is important to prevent the exposure of individuals to anticancer drugs. However, there are currently no effective degrading agents for all anticancer drugs used in clinical settings. We previously reported the resolution of an anticancer drug with the use of a photocatalyst (TiO2), which acts by absorbing ultraviolet light to degrade organic compounds. 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 found to be degraded by up to 37.7%, >99.0%, 57.1%, 54.6%, 69.5%, and 36.3%, respectively. The visible light-driven photocatalyst was therefore confirmed to degrade anticancer drugs under a fluorescent lamp. The ability of the visible light-driven photocatalyst to degrade multiple chemotherapeutic agents without the need for altering the light source could make it a useful tool for reducing anticancer drug pollution in clinical settings.
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