Responses to the Standard for Exchange of Nonclinical Data (SEND) in non-US countries     

Takayuki Anzai  Masamichi Kaminishi  Keizo Sato  Laura Kaufman  Hijiri Iwata  Dai Nakae 《Journal of toxicologic pathology》2015,28(2):57-64

The Standard for the Exchange of Nonclinical Data (SEND), adopted by the US FDA, is part of a set of regulations and guidances requiring the submission of standardized electronic study data for nonclinical and clinical data submissions. SEND is the nonclinical implementation of SDTM (Study Data Tabulation Model), the standard electronic format for clinical regulatory submissions to FDA. SEND, SDTM, and the associated Controlled Terminology have been developed by CDISC (Clinical Data Interchange Standards Consortium). In order to successfully implement SEND, interdisciplinary contributions between sponsors and CROs, need a model for task allocation. This is being undertaken by the Pharmaceutical Users Software Exchange (PhUSE). Because SEND is currently the preferred submission format of the US FDA only and will become required by it starting in December 2016, only American academic societies and companies are actively involved. An exception to this is the INHAND initiative, which leads the way in standardizing terminology for toxicological pathology. On the other hand, international globalization of other clinical and nonclinical practices is not feasible because there are substantial differences between the US and non-US countries in CRO involvement in drug development. Thus, non-US countries must consider and develop approaches to SEND that meet their needs. This paper summarizes the activities of the major organizations involved in SEND development and implementation, discusses the effective use of SEND, and details a compliance scheme (research material of the Showa University School of Medicine) illustrating how pharmaceutical companies can complete a large amount of work up to an FDA application with the effective utilization of CROs and solution providers.  相似文献   

Nutrient starvation affects expression of LC3 family at the feto-maternal interface during murine placentation     

Masato HIYAMA  Ken Takeshi KUSAKABE  Ai TAKESHITA  Sinji SUGI  Nobue KUNIYOSHI  Hiroyuki IMAI  Kiyoshi KANO  Yasuo KISO 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2015,77(3):305-311

LC3 − the mammalian homolog of Atg8 − was found as autophagosome membrane binding protein in mammals and widely used as an autophagosomal marker. LC3A, B and C show different expression patterns in each tissue. The aim of this study was to reveal the differences of expression patterns among LC3 families in mouse placenta under normal condition and nutrient starving condition. LC3A and B were highly expressed in decidual cells. LC3A and B were increased in D14 compared with D12 and D16 in mouse placenta, while LC3C was decreased. Starvation induced increase in LC3B expression specifically. Immunohistochemistry showed different expression patterns among LC3A, B and C. LC3A expression in syncytiotrophoblast was vanished by starvation. The results of real time RT-PCR suggested differences between D12 and D16 in autophagic cascade induced by starvation. Taken together, this study suggests that autophagy could play a role in placental invasion system and that nutrient starvation affects LC3B expression.  相似文献   

Expression of matrix metalloproteinases in bovine luteal cells induced by prostaglandin F2α, interferon γ and tumor necrosis factor α     

Hironori ABE  Ryosuke SAKUMOTO  Kiyoshi OKUDA 《The Journal of reproduction and development》2015,61(4):277-286

We recently demonstrated that luteal cells flow out from the ovary via lymphatic vessels during luteolysis. However, the regulatory mechanisms of the outflow of luteal cells are not known. Matrix metalloproteinases (MMPs) can degrade the extracellular matrix and basal membrane, and tissue inhibitors of matrix metalloproteinases (TIMPs) inhibit the activity of MMPs. To test the hypothesis that MMP expression in luteal cells is regulated by luteolytic factors, we investigated the effects of prostaglandin F2α (PGF), interferon γ (IFNG) and tumor necrosis factor α (TNF) on the mRNA expression of MMPs and TIMPs in cultured luteal cells. Luteal cells obtained from the CL at the mid-luteal stage (days 8–12 after ovulation) were cultured with PGF (0.01, 0.1, 1 μM), IFNG (0.05, 0.5, 5 nM) and TNF (0.05, 0.5, 0.5 nM) alone or in combination for 24 h. PGF and IFNG significantly increased the expression of MMP-1 mRNA. In addition, 1 μM PGF in combination with 5 nM IFNG stimulated MMP-1 and MMP-9 mRNA expression significantly more than either treatment alone. In contrast, IFNG significantly decreased the level of MMP-14 mRNA. The mRNA expression of TIMP-1, which preferentially inhibits MMP-1, was suppressed by 5 nM INFG. One μM PGF and 5 nM IFNG suppressed TIMP-2 mRNA expression. These results suggest a new role of MMPs: luteal MMPs stimulated by PGF and IFNG break down the extracellular matrix surrounding luteal cells, which accelerates detachment from the CL during luteolysis, providing an essential prerequisite for outflow of luteal cells from the CL to lymphatic vessels.  相似文献   

Preparation, characterization, and antioxidative effects of oligomeric proanthocyanidin-L-cysteine complexes     

Fujii H  Nakagawa T  Nishioka H  Sato E  Hirose A  Ueno Y  Sun B  Yokozawa T  Nonaka G 《Journal of agricultural and food chemistry》2007,55(4):1525-1531

Controlled acid-catalyzed degradation of proanthocyanidin polymers in grape seeds together with L-cysteine led to oligomeric proanthocyanidin-L-cysteine complexes along with monomeric flavan-3-ol derivatives being isolated, and their structures were confirmed on the basis of spectroscopic data and by chemical means. In addition, comparative studies on the antioxidative and survival effects of oligomeric proanthocyanidin-L-cysteine complexes and proanthocyanidin polymers were performed. The oligomeric proanthocyanidin-L-cysteine complexes showed higher bioavailability and antioxidant capacity and enhanced survival time in the animal test groups. In addition, it is suggested that the oligomeric complexes may help to prevent oxidative stress and may reduce free radical production.  相似文献   

Enantioseparation of isoxanthohumol in beer by hydroxypropyl-gamma-cyclodextrin-modified micellar electrokinetic chromatography     

Kodama S  Yamamoto A  Sato A  Suzuki K  Yamashita T  Kemmei T  Taga A  Hayakawa K 《Journal of agricultural and food chemistry》2007,55(16):6547-6552

Chiral resolution of isoxanthohumol (IX) in beer samples was performed by hydroxypropyl-gamma-cyclodextrin-modified micellar electrokinetic chromatography. The optimum running conditions were found to be 20 mM phosphate buffer (pH 7.0) containing 45 mM hydroxypropyl-gamma-cyclodextrin and 100 mM sodium dodecyl sulfate with an effective voltage of +20 kV at 20 degrees C using direct detection at 210, 295, and 370 nm. IX was detected in 12 beer samples and the total levels of (+)- and (-)-IX ranged from 0.15 to 1.4 mg/L. But the amount of xanthohumol (XN) was below the detection limit (0.017 mg/L). Each level of (-)-IX was almost the same as that of (+)-IX, suggesting that IX was a racemic mixture in these beer samples. The racemization of IX in beer could be attributed to the production of a racemic mixture from XN during boiling and to the fact that IX enantiomers were easily interconverted.  相似文献   

Estimation of Glomerular Filtration Rate in Cynomolgus Monkeys (Macaca fascicularis)     

Ryosuke IWAMA  Tsubasa SATO  Ken SAKURAI  Kiyoshi TAKASUNA  Toshihiro ICHIJO  Kazuhisa FURUHAMA  Hiroshi SATOH 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2014,76(10):1423-1426

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Purified Culture Systems for Bovine Oviductal Stromal Cells     

Yuki YAMAMOTO  Yoshihiko KOBAYASHI  Kiyoshi OKUDA 《The Journal of reproduction and development》2014,60(1):73-77

Isolated stromal cells from the ampullary and isthmic parts of bovine oviductal tissues were cultured in monolayer and spheroid (cell aggregate) systems. Prostaglandin F2α (PGF) plays a crucial role in oviductal contraction and is produced by oviductal epithelial cells in cattle. Since stromal cells of many organs produce PGF, PGF production by bovine oviductal stromal cells was investigated. After PGF synthesis was confirmed, the utility of isolation and culture methods for oviductal stromal cells was evaluated by PGF production in the present study. The homogeneity of the cells was > 99%. PGF production of the cells was increased by tumor necrosis factor-α. The stromal cells aggregated and formed a spheroid by the treatments with several reagents. PGF production was higher in the spheroid culture than in the monolayer culture. The isolation and culture methods described here will facilitate studies of the physiological function of bovine oviductal stromal cells.  相似文献   

Improvement of Preimplantation Development of In Vitro-Fertilized Bovine Zygotes by Glucose Supplementation to a Chemically Defined Medium     

Nobutada SAKAGAMI  Osamu NISHINO  Satoshi ADACHI  Hidenobu UMEKI  Hiroko UCHIYAMA  Kyoko ICHIKAWA  Kazuhisa TAKESHITA  Etsushi KANEKO  Kiyoshi AKIYAMA  Shuji KOBAYASHI  Hiromichi TAMADA 《The Journal of veterinary medical science / the Japanese Society of Veterinary Science》2014,76(10):1403-1405

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Effect of improvement cutting on the community structure of aphyllophoraceous fungi on Okinawa Island     

Satoshi Yamashita  Tsutomu Hattori  Shin Abe  Hideaki Goto  Hiroki Sato 《Journal of Forest Research》2014,19(1):143-153

Improvement cutting, which decreases tree density by cutting and thinning while leaving logging residues, has been practiced on Okinawa Island since the 1970s and changes not only the vegetation composition but also the amount and composition of woody debris on the forest floor. To quantitatively compare the effect of improvement cutting with the effects of woody debris and vegetation on the community structure of aphyllophoraceous fungi, we conducted a field survey of vegetation composition, the amount and composition of woody debris, and the aphyllophoraceous fungi flora on Okinawa Island in December 2006. We established 3 plots in forest stands without logging and 13 plots in a forest that had undergone improvement cutting from 1 to 22 years before our field survey. The number and volume of woody debris tended to be highest soon after improvement cutting. We recorded 1,172 fungal samples belonging to 81 species in four orders. Fungal species richness was correlated with the composition of the woody debris. Fungal species composition in forest plots 1 year after improvement cutting differed from most of the other logged forests. Variation partitioning revealed that the effects of improvement cutting explained 14.1 % of the total variation in fungal species composition, and that differences in woody debris and vegetation not related to improvement cutting explained 40.4 %. Changes in the composition of woody debris caused by improvement cutting explained at most 2.7 % of the variation. This suggests that improvement cutting does not have a strong effect on fungal community structure, but woody debris does.  相似文献   

Carbon source and trophic position of pelagic fish in coastal waters of south-eastern Izu Peninsula,Japan, identified by stable isotope analysis     

Noriyuki Takai  Noriyuki Hirose  Takuya Osawa  Kazuyuki Hagiwara  Takahito Kojima  Yuji Okazaki  Tomohiro Kuwae  Toru Taniuchi  Kiyoshi Yoshihara 《Fisheries Science》2007,73(3):593-608

ABSTRACT:   It is important to clarify trophic dynamics in marine ecosystems for management of the fishing ground. Organic carbon sources and trophic position of pelagic fishes in the coastal waters of the south-eastern Izu Peninsula, Japan, were examined on the basis of carbon and nitrogen stable isotope distributions. The δ¹³C of the fishes was mostly distributed from −19 to −16‰ for nektonic fishes (13 species of adults and immatures) and planktonic fishes (10 species of larvae and juveniles), close to the δ¹³C values of particulate organic matter and planktonic decapods. These δ¹³C signatures for the inhabitants of the water column were in contrast with the high δ¹³C values (mainly −16 to −13‰) for demersal fishes of Scorpaeniformes and benthic polychaetes collected in the surf zone. These results indicate that nektonic and planktonic fishes depend on phytoplankton for carbon supply. The δ¹⁵N signatures suggest that the trophic position ranged 3.1–4.5 for the nektonic fishes and 2.9–3.7 for the planktonic fishes, premised on trophic level 3 for larval Japanese anchovy Engraulis japonicus . Thus, planktivorous fishes should be mainly assigned to trophic levels 3 and 4 in this area.  相似文献