{"title":"[Cytogenetic study on safety evaluation of human mesenchymal stem cells cultured in vitro].","authors":"Atsuko Matsuoka","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Human mesenchymal stem cells (hMSCs) are one of the promising sources for regenerative medicine. In general, hMSCs are supposed to grow indefinitely and differentiate to various kinds of cells. The indefinite growth is concerned due to its misleading to carcinogenesis in the practical use of hMSCs in regenerative medicine. In the present study, we investigated unexpected changes, especially in genetic aspect, in hMSCs during culture utilizing fluorescence in situ hybridization (FISH) with chromosome specific DNA probes for chromosomes 1 and 4, or a locus specific identifier for c-myc. Three lots of hMSCs and three human cancer cell lines (HeLa S3, HOS and OUMS-27) were analyzed. The results of this study suggest that both observation of cell morphology and FISH analysis of c-myc aberrant cells in interphase cells are useful for evaluating safety of hMSCs expanded in vitro.</p>","PeriodicalId":35462,"journal":{"name":"Bulletin of National Institute of Health Sciences","volume":" 128","pages":"50-7"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29721977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Analysis of preservatives used in cosmetic products: salicylic acid, sodium benzoate, sodium dehydroacetate, potassium sorbate, phenoxyethanol, and parabens].","authors":"Yoshiaki Ikarashi, Tadashi Uchino, Tetsuji Nishimura","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Preservatives are used to inhibit the growth of microorganisms in cosmetic products. The Japanese standards for cosmetics set restrictions on the maximum amount of each preservative added to cosmetics as per the purpose of use of cosmetics. For the investigation into the actual conditions of commonly used preservatives in commercial cosmetics, we analyzed parabens, phenoxyethanol, sodium benzoate, sodium dehydroacetate, salicylic acid, and potassium sorbate by high-performance liquid chromatography (HPLC). Twenty-one samples were obtained from cosmetic product manufacturers located in 14 prefectures in Japan. Among different acid- and salt-based preservatives, sodium benzoate was observed to have been used in many products. These acid- and salt-based preservatives were used with parabens in personal washing products, such as shampoo and soap. The labels of two of the cosmetic product samples displayed inaccurate ingredient information, that is, a preservative other than the one used in the corresponding product was listed on them. The amount of preservatives used did not exceed regulatory limits in any of the analyzed samples.</p>","PeriodicalId":35462,"journal":{"name":"Bulletin of National Institute of Health Sciences","volume":" 128","pages":"85-90"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29721963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Needle fibers of an azo-dye mixture induce polyploidy in a Chinese hamster cell line CHL.","authors":"Atsuko Matsuoka, Yoshie Matsuda, Masa-aki Kaniwa","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In a routine Safety evaluation of chemicals included in household products, we found a mixture of azo dyes (CMBA, main component: N-[5-[(2-cyanoethyl)ethylamino]-4-methoxy-2-[(5-nitro-2,1-benzisothiazol-3-yl)azo]phenyl] acetamide) that precipitated in the culture medium in a characteristic fiber form (around 2 - 33 microm in length) similar to that of asbestos. We compared CMBA with an asbestos, chrysotile B, in a cytotoxicity, chromosome aberration (CA), and micronucleus (MN) test in a Chinese hamster lung cell line (CHL). In the cytotoxicity test, the 50% growth inhibition concentration was 11.0 microg/ml for CMBA and 0.398 microg/ml for chrysotile B asbestos. CMBA and chrysotile B both induced polyploidy in the CA test and equal-sized binucleated and polynuclear cells in the MN test. CMBA differs from chrysotile B chemically. The former is an organic chemical and the latter is a mineral. Although CMBA is soluble in methanol and can be safely disposed by burning, it should be handled carefully when manufactured in a factory.</p>","PeriodicalId":35462,"journal":{"name":"Bulletin of National Institute of Health Sciences","volume":" 128","pages":"65-70"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29717116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Study on the effects of HTST pasteurization temperatures on Mycobacterium avium subsp. paratuberculosis in an industrial fluid milk-processing system].","authors":"Shizunobu Igimi, Shoichi Iriguchi, Shuko Monden, Yumiko Okada, Shigeki Yamamoto, Yasuyuki Mori","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Johne disease is ruminant chronic granulomatous enteritis caused by Mycobacterium avium subsp. paratuberculosis (MAP). The domestic animals infected with this pathogen present severe weight loss due to chronic diarrhea and a reduction in lactation yield. These result in enormous economic loss since the affected animals are subsequently subject to artificial selections and disinfection of the environment are absolutely necessary. Furthermore, MAP has been suspected to have pathological relationship to Crohn's disease, human chronic granulomatous enteritis. The bacterium grows slower on solid culture and its colony becomes visible after two months of culture. In Japan, there has been almost no investigation on pasteurization temperature of commercial milk using MAP. It comes from the fact that the growth rate of MAP is very slow and that MAP is a related species to Mycobacterium tuberculosis, which pasteurization condition has been well defined. The studies on the pasteurization conditions of commercial milk have been mainly targeted to reduce the risk of infection to Coxiella and Mycobacterium tuberculosis. However, there has been a concern about the possibility that MAP is remained in pasteurized milk because MAPs form an aggregate and the bacterium at its center may not receive enough heat to get pasteurized. From these reasons, the present study aims to investigate validity of the current pasteurization conditions of commercial milk by implementing experimental pasteurization at various pasteurization temperatures using milk experimentally infected with MAP, and to clarify if MAP is eliminated at these temperatures in order to achieve smooth enforcement of the current ministry order. We conducted plant pasteurization experiment at four pasteurization conditions (high temperature, short time (HTST); 82, 77, 72 degrees C for 15 seconds and low temperature, long time (LTLT); 63 degrees C for 30 minutes) using two MAP strains, ATCC19698 and OKY-20. In conclusion, there appeared no colony of the two MAP strains formed from the milk pasteurized at the four pasteurization conditions examined.</p>","PeriodicalId":35462,"journal":{"name":"Bulletin of National Institute of Health Sciences","volume":" 128","pages":"81-4"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29721962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Pharmaceutical product quality control and good manufacturing practices].","authors":"Yukio Hiyama","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>This report describes the roles of Good Manufacturing Practices (GMP) in pharmaceutical product quality control. There are three keys to pharmaceutical product quality control. They are specifications, thorough product characterization during development, and adherence to GMP as the ICH Q6A guideline on specifications provides the most important principles in its background section. Impacts of the revised Pharmaceutical Affairs Law (rPAL) which became effective in 2005 on product quality control are discussed. Progress of ICH discussion for Pharmaceutical Development (Q8), Quality Risk Management (Q9) and Pharmaceutical Quality System (Q10) are reviewed. In order to reconstruct GMP guidelines and GMP inspection system in the regulatory agencies under the new paradigm by rPAL and the ICH, a series of Health Science studies were conducted. For GMP guidelines, product GMP guideline, technology transfer guideline, laboratory control guideline and change control system guideline were written. For the GMP inspection system, inspection check list, inspection memo and inspection scenario were proposed also by the Health Science study groups. Because pharmaceutical products and their raw materials are manufactured and distributed internationally, collaborations with other national authorities are highly desired. In order to enhance the international collaborations, consistent establishment of GMP inspection quality system throughout Japan will be essential.</p>","PeriodicalId":35462,"journal":{"name":"Bulletin of National Institute of Health Sciences","volume":" 128","pages":"1-16"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29722520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Researches on the in silico prediction of structure-activity relationship in the regulatory science sectors].","authors":"Akihiko Hirose","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Requirements of in silico toxicity prediction system are increasing in the chemical risk assessment fields, as well as in toxicity prediction at the early stage of the new drug development process. Recent amended chemical registration rules require internationally the risk assessment of huge amounts of existing chemicals. The (quantitative) structure-activity relationship ((Q)SAR) models are considered to be most effective tools for the acceleration of toxicity evaluation. In Europe or the United State, several research projects for the development of the (Q)SAR models are ongoing. Following this introduction, four researches on development of in silico prediction systems for (Q)SAR in the NIHS are reviewed. These activities must internationally contribute to the integrated chemical risk assessment approaches and/or could assist in the new drug development work.</p>","PeriodicalId":35462,"journal":{"name":"Bulletin of National Institute of Health Sciences","volume":" 128","pages":"27-8"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29722523","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Computational study on drug design and prediction of bioactivity for regulation of non-controlled psychotropic substances].","authors":"Masaaki Kurihara","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>We demonstrated design and synthesis of rescue ligands for agonists of the mutant vitamin D receptor (Arg274Leu), and performed QSAR study of non-controlled psychotropic substances and docking study of non-approved or unauthorized pharmaceuticals, inhibitors of human phosphodiesterase 5 (PDE5) using computer simulation.</p>","PeriodicalId":35462,"journal":{"name":"Bulletin of National Institute of Health Sciences","volume":" 128","pages":"29-33"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29721973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Endocrine disruptors in food contact articles and baby toys with their transition].","authors":"Yoko Kawamura","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A number of endocrine disruptors have been reported in food contact articles and baby toys mainly during the second half of the 1990s. Bisphenol A, nonylphenol, phthalates, styrene dimers and trimers, and their transision are described in this article. Bisphenol A was found in polycarbonate tableware, nursing bottles and the epoxy resin coating of cans, therefore, it was also found in the canned foods and drinks. Polycarbonate is now only slightly used for tableware or nursing bottles in Japan because consumers refused them. The can manufacturers changed their coating material to the low bisphenol A resin or PET films and voluntarily regulate its migration limit to under 5 or 10 ng/ml. Nonylphenol was found in most PVC wrapping films and gloves. It was generated from an oxidant, tris (nonylphenyl) phosphite. PVC wrapping film was extensively used in markets, thus many kinds of foods were contaminated. Among them, fillet or minced fish and meat contained it at high levels. In 2000, manufacturers voluntarily changed their composition and all wrapping films in Japan no longer contain nonylphenol. Di(2-ethylhexyl) phthalate (DEHP) was found in PVC gloves, which contaminated packed lunches and hospital meals at high levels. The government prohibited these gloves for all food contact use in 2000, moreover, other PVC food contact articles containing DEHP were prohibited for contact use with fatty foods in 2002. DEHP was also found in PVC toys which was prohibited in 2002. Styrene dimers and trimers were found in PS products, which migrated into cupped noodles after cooking. No changes have been made in them. In Japan, the exposure to bisphenol A, nonylphenol and DEHP have been significantly reduced and people also have more concerns with the safety of food contact articles.</p>","PeriodicalId":35462,"journal":{"name":"Bulletin of National Institute of Health Sciences","volume":" 128","pages":"17-26"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29722521","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Application of fragment molecular orbital (FMO) method to biomacromolecules].","authors":"Tatsuya Nakano","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Kitaura et al. (Chem. Phys. Lett. 312, 319-324 (1999)) have proposed an ab initio fragment molecular orbital (FMO) method by which large molecules such as proteins can be easily treated with chemical accuracy. In the ab initio FMO method, a molecule or a molecular cluster is divided into fragments, and the MO calculations on the fragments (monomers) and the fragment pairs (dimers) are performed to obtain the total energy that is expressed as a summation of the fragment energies and inter-fragment interaction energies (IFIEs). In this paper, we provide a brief description of the ab initio FMO method and demonstrate recent applications to the biomacromolecules.</p>","PeriodicalId":35462,"journal":{"name":"Bulletin of National Institute of Health Sciences","volume":" 128","pages":"34-8"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29721974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"[Effects of perinatal exposure to the brominated flame-retardant hexabromocyclododecane (HBCD) on the developing immune system in rats].","authors":"Akiko Hachisuka, Ryosuke Nakamura, Yuji Sato, Rika Nakamura, Makoto Shibutani, Reiko Teshima","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>To evaluate the developmental immunotoxicity of brominated flame retardant, hexabromocyclododecane (HBCD) , maternal Sprague-Dawley rats were given HBCD at dietary concentrations of 0, 100, 1000, 10000 ppm from gestational day 10 to postnatal day 21 (postnatal week 3, PNW3). At PNW3 and PNW11, lymphocytes in the spleen, thymus, and peripheral blood of male pups were subjected to flow cytometric analyses for expression of surface markers (CD3, CD4, CD8a, CD25, CD45RA, CD71, and CD161 (NKRP1A)). The spleen and thymus weights, and number of white blood cells of two organs did not change between HBCD-exposed and control groups at PNW3 and PNW11. A significant decrease in thyroid hormone T3 and increase in serum albumin concentration were observed at PNW3 and lasted until PNW11. By flow cytometric analysis, the dramatic change was not observed in the population of the splenic and thymic T/B lymphocyte between the HBCD treated groups and control group. In the peripheral blood of BNW3 rats, the population of activated T cells was decreased and that of inactivated B cells was increased. And the population of NK cells in the spleen was decreased. All of these changes were mild in degree, and returned to the normal levels by PNW11. Production of anti-KLH IgG antibody after KLH immunization was reduced by the 10000 ppm HBCD treatment. These results suggest that developmental exposure to the highest dose of HBCD had a weak immunomodulatory effect at PNW3, and most of the immunomodulatory effect had recovered to normal levels by PNW11.</p>","PeriodicalId":35462,"journal":{"name":"Bulletin of National Institute of Health Sciences","volume":" 128","pages":"58-64"},"PeriodicalIF":0.0,"publicationDate":"2010-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29721978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}