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Volume 129, Issue 9
Displaying 1-15 of 15 articles from this issue
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Reviews
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Tsuyoshi SATOHArticle type: Review
2009 Volume 129 Issue 9 Pages 1013-1023
Published: September 01, 2009
Released on J-STAGE: September 01, 2009
JOURNAL FREE ACCESSSynthetic organic chemistry is a base of medicinal chemistry and the exploitation of new methods for carbon-carbon bond formation is of most importance in synthetic organic chemistry. Carbenes and carbenoids have long been known to be highly reactive carbon species that show a variety of unique reactivity. However, those reactive species are not fully used in organic synthesis. The reasons are as follows: one is the precursors for the generation of carbenes and carbenoids are quite limited and the other is that the reactivity of the species is too high to control. In order to solve the problem mentioned above, we used α-haloalkyl (or alkenyl) aryl sulfoxides as the precursors and used sulfoxide-magnesium exchange reaction for generation of much mild magnesium carbenoids. α-Haloalkyl (or alkenyl) aryl sulfoxides are quite easily synthesized in high overall yields. Magnesium carbenoids, cyclopropylmagnesium carbenoids, cyclobutylmagnesium carbenoids, magnesium β-oxido carbenoids, and magnesium alkylidene carbenoids are generated at low temperature from the corresponding sulfoxides with a Grignard reagent in quantitative yields. They were found to be stable usually at below -60°C for at least 30 min. The each magnesium carbenoids have their own unique reactivities and we could find many unprecedented reactions from these reactive species. Recent results for the developments of new synthetic methods based on the chemistry of magnesium carbenoids are described.
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Akira IKARIArticle type: Review
2009 Volume 129 Issue 9 Pages 1025-1031
Published: September 01, 2009
Released on J-STAGE: September 01, 2009
JOURNAL FREE ACCESSPatients with lifestyle-related diseases such as hypertension, diabetes, and hyperlipidemia are at high risk for the pathogenesis of a life-threatening atherosclerotic disease. The elucidation of the mechanism responsible for the pathogenesis can bring about the prevention and the cure of lifestyle-related diseases. We think that abnormal transport of electrolytes in renal tubule is involved in lifestyle-related diseases and renal failure. This review focuses on the regulatory mechanisms of Mg2+ transport pathways in renal tubular cells. Mg2+ filtrated by glomeruli is reabsorbed by transcellular and paracellular pathways in renal epithelial cells. Transient receptor potential melastatin 6 (TRPM6) channel is expressed in the apical membrane and involved in the reabsorption of Mg2+. Cyclosporine A decreased TRPM6 expression and Mg2+ influx, suggesting that the decrease in TRPM6 expression may cause hypomagnesemia. Claudin-16 is expressed in the tight junction (TJ) of the thick ascending limb of Henle and may be involved in the paracellular Mg2+ transport. We found that the phosphorylation of claudin-16 is necessary for its localization on the TJ and claudin-16 is de-phosphorylated in Dahl salt-sensitive (DS) hypertensive rats. In epidemiologic studies, magnesium is the correlate of both systolic and diastolic blood pressure. Dysfunction of claudin-16 may be involved in the salt-sensitive hypertension. Dysfunction of Mg2+ reabsorption in renal tubule may be involved in renal failure and lifestyle-related diseases.
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Minoru NAKANOArticle type: Review
2009 Volume 129 Issue 9 Pages 1033-1039
Published: September 01, 2009
Released on J-STAGE: September 01, 2009
JOURNAL FREE ACCESSBiomembrane is a place for signal transduction, where protein-membrane interactions are controlled by the membrane environment. This environment could be modified by lipid dynamics, such as interbilayer transport and transbilayer movement, which are governed by lipid transfer proteins and translocase enzymes, respectively. Thus, static and dynamic structural evaluations of the membranes are important to understand the links among function, structure, and dynamics of lipid membranes. This review describes our recent studies for 1) the production of lipid nanoparticles with nonlamellar liquid crystalline phases, 2) membrane-protein interaction that relates to the biogenesis of high-density lipoproteins, and 3) the characterization of lipid transfer dynamics by small-angle neutron scattering (SANS). It was demonstrated that different phospholipids have individual effect on membrane-apolipoprotein A-I (apoA-I) interactions that bring about a discoidal lipid-protein complex formation: Phosphatidylethanolamine, possessing the negative spontaneous curvature, increases both the degree of hydration at the membrane interface and the acyl chain order, and enhances the binding of amphipathic helices. A gel phase-forming lipid, sphingomyelin, forms heterogeneous interface of the mixed membranes and facilitates the discoidal particle formation with apoA-I. Phosphatidylserine partly contributes to a reduction in pH at membrane surface, which induces the conformational change of apoA-I and accelerates the discoidal complex formation. It was also demonstrated that SANS is available as a novel method to determine the dynamics of membrane lipids. This technique is perfectly suited to evaluate the activity of proteins relevant to lipid migrations.
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Yoichi KAWASAKIArticle type: Review
2009 Volume 129 Issue 9 Pages 1041-1047
Published: September 01, 2009
Released on J-STAGE: September 01, 2009
JOURNAL FREE ACCESSThe hazardous effects due to the insoluble microparticles generated in the injections have been pointed out. To our knowledge, however, there have been no reports about insoluble microparticulate contamination at ampoule opening. Therefore, we performed this study to evaluate the relationship between time and glass particulate sedimentation to examine the effect of swabbing the ampoule neck on particle generation to clarify the relationship between the inner-diameter size of an ampoule and the amount of glass particulate sedimentation to find out the effect of methods for ampule opening, and compare particle contamination in glass ampoule and that of plastic, after ampoule opening and assessed the contribution of material of ampoule to the particle generation. We observed that the glass particulate contamination of accumulation value at a size over 2 μm increased significantly after 60 seconds, the swabbing the neck of the ampoule prior to opening had a negative effect on prevention of glass particulate contamination, the glass particulate contamination was positively influenced by the inner-diameter size of the ampoule, but not by the thickness of the ampoule walls, the particulate contamination derived from glass significantly increased by general method as well as using ampoule open adaptor compared with our method, and the insoluble microparticulate contamination in plastic ampoule was significantly lower than that in glass ampoule. The present findings might provide an useful information to reduce glass particules after ampoule opening performed in clinical practice.
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Naoko TANAKAArticle type: Review
2009 Volume 129 Issue 9 Pages 1049-1053
Published: September 01, 2009
Released on J-STAGE: September 01, 2009
JOURNAL FREE ACCESSIn ischemic heart diseases, the use of the internal thoracic artery (ITA) as an arterial graft has been associated with longer survival and better quality of life. However, it has been reported that vasospasm of the ITA graft frequently occurs and increases perioperative and postoperative morbidity. Serotonin (5-HT) plays an important role in the occurrence of vasospasm. We examined 5-HT receptor subtypes responsible for the 5-HT-induced vasocontraction in the human ITA. The contractile response caused by 5-HT was mediated by activation of not only 5-HT2A receptors but also 5-HT1B receptors. We also examined the relationship between 5-HT-induced vasocontraction of the rabbit femoral artery and arteriosclerosis using the arteriosclerosis model of repeated balloon-injury. The contractile response caused by 5-HT in the femoral artery with arteriosclerosis was significantly greater than that in the normal artery. Additionally, we demonstrated that insulin induced internalization of 5-HT2A receptors from the plasma membrane in HEK293 cells. Diabetes mellitus (DM) is a risk factor for ischemic heart diseases. We evaluated the 5-HT-induced vasocontraction, mediated by activation of 5-HT2A and 5-HT1B receptors, in the ITA obtained from patients with DM or without DM undergoing coronary bypass surgery. The contractile response caused by 5-HT in the ITA from patients with DM was significantly greater than that from patients without DM. Our findings suggest that when the ITA is used as an arterial graft, simultaneous treatment with 5-HT2A and 5-HT1B receptor antagonists is useful to prevent 5-HT-induced vasospasm, especially in patients with DM.
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Shintaro FUMOTOArticle type: Review
2009 Volume 129 Issue 9 Pages 1055-1061
Published: September 01, 2009
Released on J-STAGE: September 01, 2009
JOURNAL FREE ACCESSSafety in gene therapy is an important issue since both viral and non-viral vectors have toxic side effects. Not only vectors themselves, but also distributions of produced proteins affect safety in gene therapy; thus, development of target-selective gene transfer methods is rational. We have developed organ-, region- and cell-selective gene transfer methods using non-viral vectors. To deliver foreign gene to liver parenchymal cells (hepatocytes), galactosylation of cationic liposome/plasmid DNA complex is useful strategy. Based on analyses for intrahepatic disposition characteristics and interaction with blood components, we formulated novel galactosylated lipoplex with regulated salt concentration to reduce particle size of lipoplex and to stabilize lipoplex simultaneously; as a consequence, we succeeded in improvement of hepatocyte-selective gene transfer after intraportal injection of the lipoplex in mice. On the other hand, administration routes are important for target-selective gene transfer. We discovered that simple instillation of naked plasmid DNA onto organ surface (the liver, kidney, spleen, stomach and lung) in mice and rats could result in effective and region-selective transgene expression. Neither physical force nor carriers are necessary for gene transfer onto organ surface mesothelial cells. To rationally improve transfection efficiency, mechanism of gene transfer should be elucidated. We clarified that Rac-mediated macropinocytosis was required for naked plasmid DNA transfer in gastric mesothelial cells.
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Regular Articles
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Takashi USAMI, Masayuki HASHIGUCHI, Tsuyoshi KOUHARA, Akira ISHII, Tai ...Article type: Regular Article
2009 Volume 129 Issue 9 Pages 1063-1068
Published: September 01, 2009
Released on J-STAGE: September 01, 2009
JOURNAL FREE ACCESSThis study was carried out to investigate whether the personal advocacy of influenza vaccination by community pharmacists to people aged 65 years and above affected the vaccination rate and number of influenza patients. A cluster randomized controlled trial was conducted with the cooperation of 84 community pharmacies in the wards of Suginami and Nerima, Tokyo. Participants were aged 65 years and above living in Suginami and Nerima wards, Tokyo, receiving dispensing services in their community pharmacies. The intervention was that pharmacists in the intervention pharmacy group provided information on the risk of influenza and benefits of influenza vaccination. Main outcome measures were the self-reported influenza vaccination rate in January 2004, and the number of participants with influenza, as confirmed by inspection of their prescriptions from January to May 2004. The vaccination rate in the intervention pharmacy group (81.6%) was significantly higher than that in the control pharmacy group (64.9%). The number of participants with influenza among the intervention group (2/881) was significantly lower than that among the control group (11/895). The personal advocacy of influenza vaccination by community pharmacists among people aged 65 years and above increases the vaccination rate and decreases the number of influenza patients.
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Tapan Kumar GIRI, Biswanath SAArticle type: Regular Article
2009 Volume 129 Issue 9 Pages 1069-1075
Published: September 01, 2009
Released on J-STAGE: September 01, 2009
JOURNAL FREE ACCESSThis study describes the formulation of rapidly disintegrating, fast dissolving diazepam tablets intended for use in the oral cavity. The tablets were prepared by the conventional wet granulation method using solid dispersion of the drug with PEG-4000 and/or PEG-6000. A 32 factorial design was used to reduce the number of experimental runs and to obtain several formulations by which tablets disintegrated within 3 min and released 85% of the drug in less than 30 min. Several tablet formulations prepared with different amounts of PEGs in solid dispersion met the above two criteria. However, tablets which were prepared with PEG-4000 alone at the lowest concentration disintegrated in the shortest time (32.12 sec) and released 85% of the drug most rapidly (11.03 min).
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Syuzo MASUDA, Ryusho OKA, Koji UWAI, Yumi MATSUDA, Tadashi SHIRAISHI, ...Article type: Regular Article
2009 Volume 129 Issue 9 Pages 1077-1086
Published: September 01, 2009
Released on J-STAGE: September 01, 2009
JOURNAL FREE ACCESSOne of the important roles of pharmacists as members of a nutrition support team is nutritional prescription support. We developed a nutritional prescription support system (NPSS) that facilitates prescription support and analysis and evaluated its usefulness in nutritional therapy. An NPSS for prescription support and the management of patient information was created. With this NPSS, the nutritional status was assessed, and, on the basis of the results, such variables as the total energy expenditure were calculated. This system allows prescription support for parenteral nutrition (PN) therapy, enteral nutrition (EN) therapy, and the transition period between them. This system was used for 2 representative patients and evaluated. In a malnourished patient receiving oral warfarin, EN solutions were compared by means of the NPSS, and an appropriate EN solution was selected. In addition, the prothrombin time-international normalized ratio was monitored, and favorable results were obtained regarding the adjustment of the warfarin dose and nutritional management. In a patient with aspiration pneumonia, continuous nutritional management to EN from PN therapy was straightforwardly performed with the NPSS. This NPSS allows rapid, comprehensive nutritional management during the transition period to EN from PN therapy, despite these therapies being considered separately in conventional nutritional management. The NPSS is useful for simplifying prescription support and facilitating information sharing among members of a nutrition support team.
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Tomohiro MIZUNO, Tadao TAGUCHI, Hiroshi KATO, Akira YOSHIMI, Shinnosuk ...Article type: Regular Article
2009 Volume 129 Issue 9 Pages 1087-1101
Published: September 01, 2009
Released on J-STAGE: September 01, 2009
JOURNAL FREE ACCESSIn 2006 the Faculty of Pharmacy, Meijo University has introduced an early exposure learning into the first-year curriculum of the 6-year pharmacy education system, with the aim of “understanding of patients,” “enhancing motivation to learn pharmacy,” and “understanding of the roles of pharmacists in the clinical setting”. This program has three approaches: “active learning”, “hybrid small group learning (SGL)” and “age-mixing”. The 2006 questionnaire survey on this program revealed some disadvantages, including the inability of student facilitators to get the program in perspective, due to their lack of numbers and time assigned to each group. In response to the survey results, steps were taken to rectify these defects. Accordingly, in the 2007 questionnaire survey, the first-year undergraduates, student facilitators and faculty facilitators responded that the program was achieving its aims. In particular, they acknowledged the usefulness of “age-mixing” and “hybrid SGL” as educational approaches fundamental to the 6-year education system. Thus, in 2007 the program became more useful through our efforts to remedy the issues pointed out in 2006, including the low degree of understanding of “age-mixing” among the first-year undergraduates, and poor assignment of student facilitators to each group. The challenges for 2008 include further enhancing motivation of first-year undergraduates regarding SGL and establishment of a method for student facilitator intervention in SGL. Focusing on these challenges, we will continue our efforts to enhance the quality of pharmaceutical education through such approaches as early exposure learning.
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Shin-ichiro SUZUKI, Masayoshi KOINUMA, Yukari HIDAKA, Katsuya KOIKE, H ...2009 Volume 129 Issue 9 Pages 1103-1112
Published: 2009
Released on J-STAGE: September 01, 2009
JOURNAL FREE ACCESSFor the purpose of providing a pre-education prior to clinical practice which can be reflected in clinical practices, we researched and analyzed the consciousness, requests, and etc, for pre-education prior to clinical practice of the directive pharmacists who work in a community hospital or pharmacy. We conducted questionnaire-survey which targeted for the directive pharmacists of the on-the-job trainees in the participating institutions (including 45 community hospitals and 179 community pharmacies) of the College of Pharmacy Nihon University. The average collection rate from each institution group was 55.9% (62.2% in community hospitals and 54.2% in community pharmacies). The answers for the degrees of expectations to the pre-education showed those responding as “promising” at 50.2%, “not-promising” at 6.3%, and “neither” at 43.5%, respectively. With the presence or absence of expectation as objective variable, we analyzed the relationship between the objective variable and respondent's attributes using the logistic regression analysis. The result demonstrated that those who worked in a community pharmacy and that had shorter teaching term and more superior post tended to have greater expectation. Also, when we performed a correspondence analysis for the images of the pre-education using the text-mining approach, we could confirm that each group member who had the manager posts in hospitals and in pharmacies had the same structure of consciousness. If we reflect the study results on the pre-education, we could establish the practical education system of the pre-education, which enable trainees to successfully advance into the on-the-job training.
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Sanae MATSUDA, Masayoshi HISAMA, Hiroharu SHIBAYAMA, Norihiko ITOU, Ma ...Article type: Regular Article
2009 Volume 129 Issue 9 Pages 1113-1120
Published: September 01, 2009
Released on J-STAGE: September 01, 2009
JOURNAL FREE ACCESSThe rabbit corneal epithelium model (RCE model) was developed as a three-dimensional in vitro model to replace animal testing for the assessment of eye irritation. In the model, a stratified culture of rabbit corneal epithelial cells is grown at the air-liquid interface on collagen gel that acts as a parabasal membrane. Histological cross-sections show that the structure of the RCE model closely parallels that of the rabbit corneal epithelium. The eye irritation potency of test samples is estimated from the measurement of viability using the MTT assay in conjunction with the RCE model. A set of 30 chemicals belonging to different families with known in vivo Draize score was investigated with the in vitro eye irritation test using the RCE model in order to internally validate the protocol. Use of the RCE model at concentrations of 0.05%, 0.50%, and 1.00% and the calculation of the IC50 and percentage of viability allowed the irritants to be divided into four classes. The performance of the in vitro eye irritation test at a concentration of 0.50% using the RCE model was characterized by good sensitivity (92.3%), good specificity (100%), and good accuracy (93.3%) compared with the irritation classification predicted by in vivo Draize score at concentrations of 10% and 100%. These results indicate that the RCE model may provide a useful and sensitive in vitro eye irritation test as an alternative method to the Draize test.
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Masuhiro NISHIMURA, Kazuhisa DOI, Riyo ENOMOTO, Eibai LEE, Shinsaku NA ...Article type: Regular Article
2009 Volume 129 Issue 9 Pages 1121-1126
Published: September 01, 2009
Released on J-STAGE: September 01, 2009
JOURNAL FREE ACCESSARTCEREB® irrigation and perfusion solution (Artcereb) is a preparation intended for the irrigation and perfusion of the cerebral ventricles, and it is therefore important to evaluate the effects of Artcereb on brain cells. In vitro assessment of the effects of Artcereb in cell cultures of human fetal astrocytes was conducted in comparison with normal saline and lactated Ringer's solution. The effects of exposure to Artcereb were evaluated based on microscopic images of the mitochondria stained with rhodamine 123. The effects of exposure to Artcereb on cell function were also evaluated by quantitative analysis of mitochondrial activity based on rhodamine 123 and 3H-thymidine incorporation. Morphological changes in nuclear structure were also evaluated. The results of the present study showed that cell function in cell cultures of human astrocytes was relatively unaffected by exposure to Artcereb as compared with normal saline or lactated Ringer's solution, suggesting that Artcereb has less effect on brain cells than normal saline or lactated Ringer's solution when used for the irrigation or perfusion of the cerebral ventricles.
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Keiko KISHIMOTO, Takeshi YOSHIDA, Noriko FUKUSHIMAArticle type: Regular Article
2009 Volume 129 Issue 9 Pages 1127-1136
Published: September 01, 2009
Released on J-STAGE: September 01, 2009
JOURNAL FREE ACCESSWe conducted a Web-based survey of approximately 40 000 Internet users on the purchase of over-the-counter (OTC) medications online in March 2009. The valid response rate was 97.8% and the number of responses was 39 208. The number of people who had purchased OTC medications online was 4 653 (11.9%), prescription medicines 792 (2.0%), and medical contact lenses 1 993 (5.1%). As a result of the multiple logistic regression analysis, independent variables with odds ratios (ORs) >1.5 were experience of purchasing prescription-only medicine online (OR=4.997, 95%CI=4.288-5.824), regular supplement use (OR=2.384, 95%CI=2.233-2.548), experience of purchasing colored contact lenses online (OR=2.206, 95%CI=1.632-2.983), no time to visit drugstores (OR=2.092, 95%CI=1.928-2.270), usage of Web sites of uncertain reliability (OR=1.992, 95%CI=1.857-2.137), and experience of purchasing therapeutic contact lenses online (OR=1.796, 95%CI=1.597-2.020). As some people have purchased prescription-only medicine or medical devices and had problems with drug information sources, the development of awareness of medical and pharmaceutical supplies and health and medical information literacy are key priorities to ensure safe OTC medication sales systems.
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Notes
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Fumihiro SOMEYA, Hiroki TAKUMA, Megumi IZUMISAWA, Makoto SHIRAGAMIArticle type: Note
2009 Volume 129 Issue 9 Pages 1137-1140
Published: September 01, 2009
Released on J-STAGE: September 01, 2009
JOURNAL FREE ACCESSMore prescription drugs are dispensed by pharmacists rather than doctors in response to government healthcare reform. However, the results of our preliminary survey suggested a hypothesis that patients were not always satisfied with explanations provided by pharmacists upon dispensing, and therefore patient satisfaction might be enhanced if pharmacists spent more time on consultation services. The survey was conducted in 1,800 people. 321 people (17.8%) answered that pharmacist explanations were not sufficient or that they expected further consultation with pharmacists. The most common reason why they did not ask for consultation was that other patients were waiting (41.7%). If up to 30-minute consultation service was available at a pharmacy where patient privacy was ensured, 898 people (49.9%) answered that they wanted to use the service. The average willingness-to-pay (WTP) for the service was 338 yen and the mean WTP was 400 yen. When those who answered 0 yen were excluded, the average was 386 yen and the mean was 400 yen. The online survey revealed that some patients were not satisfied with pharmacist explanations upon dispensing, and that there was a need for consultation services at pharmacies. Many of the reasons why patients did not ask for consultation although they wanted to were attributable to pharmacies, and the survey results suggested a need for improvement in their services. In view of the WTP for the service, it is considered worthwhile to discuss the introduction of such a system for consultation services into dispensing fee.
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