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Kyoto, Japan

京都薬科大学 Kyoto Pharmaceutical University is a private university in Kyoto, Kyoto, Japan. The predecessor of the school was founded in 1884. It was chartered as a university in 1949. As a university that trains Pharmacist-Scientists -- pharmacists that also possess research skills -- Kyoto Pharmaceutical University has laboratories in a wide range of fields. Each laboratory offers the optimal environment for enhancing skills, with about 10 members that each focus on their own research.Students devote themselves to around-the-clock research in order to master their own specialization and develop reformed medical care and a new vitality in the field of pharmaceuticals. Wikipedia.

Takeuchi K.,Kyoto Pharmaceutical University
World journal of gastroenterology : WJG | Year: 2012

This article reviews the pathogenic mechanism of non-steroidal anti-inflammatory drug (NSAID)-induced gastric damage, focusing on the relation between cyclooxygenase (COX) inhibition and various functional events. NSAIDs, such as indomethacin, at a dose that inhibits prostaglandin (PG) production, enhance gastric motility, resulting in an increase in mucosal permeability, neutrophil infiltration and oxyradical production, and eventually producing gastric lesions. These lesions are prevented by pretreatment with PGE 2 and antisecretory drugs, and also via an atropine-sensitive mechanism, not related to antisecretory action. Although neither rofecoxib (a selective COX-2 inhibitor) nor SC-560 (a selective COX-1 inhibitor) alone damages the stomach, the combined administration of these drugs provokes gastric lesions. SC-560, but not rofecoxib, decreases prostaglandin E 2 (PGE 2) production and causes gastric hypermotility and an increase in mucosal permeability. COX-2 mRNA is expressed in the stomach after administration of indomethacin and SC-560 but not rofecoxib. The up-regulation of indomethacin-induced COX-2 expression is prevented by atropine at a dose that inhibits gastric hypermotility. In addition, selective COX-2 inhibitors have deleterious influences on the stomach when COX-2 is overexpressed under various conditions, including adrenalectomy, arthritis, and Helicobacter pylori-infection. In summary, gastric hypermotility plays a primary role in the pathogenesis of NSAID-induced gastric damage, and the response, causally related with PG deficiency due to COX-1 inhibition, occurs prior to other pathogenic events such as increased mucosal permeability; and the ulcerogenic properties of NSAIDs require the inhibition of both COX-1 and COX-2, the inhibition of COX-1 upregulates COX-2 expression in association with gastric hypermotility, and PGs produced by COX-2 counteract the deleterious effect of COX-1 inhibition. Source

Fukushima K.,Kyoto Pharmaceutical University
Diabetes technology & therapeutics | Year: 2010

BACKGROUND: This study tested the hypothesis that dissolving microneedles are a useful transdermal drug delivery system (TDDS) for insulin. METHODS: Insulin was loaded on a patch (1.0 cm2) that had 100 dissolving microneedles with chondroitin sulfate by microfabrication technology. Pharmacodynamic evaluation was performed by applying two or four patches to the shaved abdominal skin of dogs, and blood samples were collected for 360 min to measure plasma glucose and insulin levels. In diffusion experiment, microneedles containing fluorescein isothiocyanate-insulin and/or Evans blue were administered to the rat skin, and the diffusion rates of tracers were recorded. RESULTS: The mean length, diameter of basement, and drug-loaded space from the top of the microneedles were 492.6 +/- 2.4, 290.0 +/- 3.6, and 316.0 +/- 7.3 microm, respectively. The insulin content was 1.67 +/- 0.17 IU per patch. The time when the minimum plasma glucose level was obtained was 50.0 +/- 8.7 min for two-patch and 82.5 +/- 14.4 min for four-patch studies. A dose-dependent hypoglycemic effect was observed. By comparing the cumulative percentage change in the plasma glucose level between insulin microneedles and solution, the relative physiological availabilities were calculated to be 71.1 +/- 17.8% (for two patches) and 59.3 +/- 4.4% (for four patches). Bioavailabilities of insulin from microneedles were 72.1 +/- 11.6% (for two patches) and 72.4 +/- 8.3% (for four patches). High diffusion rates of fluorescein isothiocyanate-insulin and Evans blue were observed at the administered skin site and correlated well with the high absorption rate of insulin into the systemic circulation. Insulin was stable in dissolving microneedles for 1 month at 4 degrees C; the recovered percentage was 99.2 +/- 13.9%. CONCLUSIONS: Dissolving microneedles were demonstrated to be a useful TDDS as an immediate-acting insulin preparation. Source

Mizutani N.,Kobe Pharmaceutical University | Nabe T.,Kyoto Pharmaceutical University | Yoshino S.,Kobe Pharmaceutical University
Immunology | Year: 2013

Allergen-specific IgE has long been regarded as a major molecular component of allergic asthma. Additionally, there is increasing evidence of the important roles of interleukin-33 (IL-33) in the disease. Here, we show that IL-33 and alveolar macrophages play essential roles in the exacerbation of IgE-mediated airway inflammation and remodelling. BALB/c mice passively sensitized with ovalbumin (OVA)-specific IgE monoclonal antibody (mAb) were challenged with OVA seven times intratracheally. The seventh challenge exacerbated airway inflammation and remodelling compared with the fourth challenge; furthermore, markedly increased expression of IL-33 in the lungs was observed at the fourth and seventh challenges. When anti-IL-33 or anti-ST2 antibody was administered during the fourth to seventh challenge, airway inflammation and remodelling were significantly inhibited at the seventh challenge. Because increases of IL-33+ and ST2+ alveolar macrophages and ST2+ CD4+ T cells in the lungs were observed at the fourth challenge, the roles of macrophages and CD4+ cells were investigated. Depletion of macrophages by 2-chloroadenosine during the fourth to seventh challenge suppressed airway inflammation and remodelling, and IL-33 production in the lung at the seventh challenge; additionally, anti-CD4 mAb inhibited airway inflammation, but not airway remodelling and IL-33 production. Meanwhile, treatment with 2-chloroadenosine or anti-CD4 mAb decreased IL-33-induced airway inflammation in normal mice; airway remodelling was repressed only by 2-chloroadenosine. These results illustrate that macrophage-derived IL-33 contributes to the exacerbation of IgE-mediated airway inflammation by mechanisms associated with macrophages and CD4+ cells, and airway remodelling through the activation of macrophages. © 2013 Blackwell Publishing Ltd. Source

Nakase I.,Kyoto University | Akita H.,Hokkaido University | Kogure K.,Kyoto Pharmaceutical University | Graslund A.,University of Stockholm | And 3 more authors.
Accounts of Chemical Research | Year: 2012

Over the last 20 years, researchers have designed or discovered peptides that can permeate membranes and deliver exogenous molecules inside a cell. These peptides, known as cell-penetrating peptides (CPPs), typically consist of 6-30 residues, including HIV TAT peptide, penetratin, oligoarginine, transportan, and TP10. Through chemical conjugation or noncovalent complex formation, these structures successfully deliver bioactive and membrane-impermeable molecules into cells. CPPs have also gained attention as an attractive vehicle for the delivery of nucleic acid pharmaceuticals (NAPs), including genes/plasmids, short oligonucleotides, and small interference RNAs and their analogues, due to their high internalization efficacy, low cytotoxicity, and flexible structural design.In this Account, we survey the potential of CPPs for the design and optimization of NAP delivery systems. First, we describe the impact of the N-terminal stearylation of CPPs. Endocytic pathways make a major contribution to the cellular uptake of NAPs. Stearylation at the N-terminus of CPPs with stearyl-octaarginine (R8), stearyl-(RxR) 4, and stearyl-TP10 prompts the formation of a self-assembled core-shell nanoparticle with NAPs, a compact structure that promotes cellular uptake. Researchers have designed modifications such as the addition of trifluoromethylquinoline moieties to lysine residues to destabilize endosomes, as exemplified by PepFect 6, and these changes further improve biological responsiveness. Alternatively, stearylation also allows implantation of CPPs onto the surface of liposomes. This feature facilitates "programmed packaging" to establish multifunctional envelope-type nanodevices (MEND). The R8-MEND showed high transfection efficiency comparable to that of adenovirus in non-dividing cells.Understanding the cellular uptake mechanisms of CPPs will further improve CPP-mediated NAP delivery. The cellular uptake of CPPs and their NAP complex involves various types of endocytosis. Macropinocytosis, a mechanism which is also activated in response to stimuli such as growth factors or viruses, is a primary pathway for arginine-rich CPPs because high cationic charge density promotes this endocytic pathway. The use of larger endosomes (known as macropinosomes) rather than clathrin- or caveolae-mediated endocytosis has been reported in macropinocytosis which would also facilitate the endocytosis of NAP nanoparticles into cells. © 2011 American Chemical Society. Source

Yonezawa A.,Kyoto University | Inui K.-I.,Kyoto University | Inui K.-I.,Kyoto Pharmaceutical University
Molecular Aspects of Medicine | Year: 2013

Riboflavin, a water-soluble vitamin also known as vitamin B2, is essential for normal cellular functions. Riboflavin transporters play important roles in its homeostasis. Recently, three novel riboflavin transporters were identified, and designated as RFT1, RFT2 and RFT3. Because the RFTs did not show similarity to other SLC transporters, and RFT1 and RFT3 are similar in sequence and function, they were assigned into a new SLC family, SLC52. Subsequently, RFT1/GPR172B, RFT3/GPR172A and RFT2/C20orf54 were renamed as RFVT1/SLC52A1, RFVT2/SLC52A2 and RFVT3/SLC52A3, respectively. In this review, we summarize recent findings on the cloning, nomenclature, functional characterization and genetic diseases of RFVT1/SLC52A1, RFVT2/SLC52A2 and RFVT3/SLC52A3. © 2012 Elsevier Ltd. All rights reserved. Source

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