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Articles by Fujiko Sunaga
Total Records ( 4 ) for Fujiko Sunaga
  Gabriel O. Aboge , Honglin Jia , Mohamad A. Terkawi , Youn-Kyoung Goo , Yoshifumi Nishikawa , Fujiko Sunaga , Kuzuhiko Namikawa , Naotoshi Tsuji , Ikuo Igarashi , Hiroshi Suzuki , Kozo Fujisaki and Xuenan Xuan
  Dihydrofolate reductase-thymidylate synthase (DHFR-TS) is a well-validated antifolate drug target in certain pathogenic apicomplexans, but not in the genus Babesia, including Babesia gibsoni. Therefore, we isolated, cloned, and expressed the wild-type B. gibsoni dhfr-ts gene in Escherichia coli and evaluated the inhibitory effect of antifolates on its enzyme activity, as well as on in vitro parasite growth. The full-length gene consists of a 1,548-bp open reading frame encoding a 58.8-kDa translated peptide containing DHFR and TS domains linked together in a single polypeptide chain. Each domain contained active-site amino acid residues responsible for the enzymatic activity. The expressed soluble recombinant DHFR-TS protein was approximately 57 kDa after glutathione S-transferase (GST) cleavage, similar to an approximately 58-kDa native enzyme identified from the parasite merozoite. The non-GST fusion recombinant DHFR enzyme revealed Km values of 4.70 ± 0.059 (mean ± standard error of the mean) and 9.75 ± 1.64 µM for dihydrofolic acid (DHF) and NADPH, respectively. Methotrexate was a more-potent inhibitor of the enzymatic activity (50% inhibition concentration [IC50] = 68.6 ± 5.20 nM) than pyrimethamine (IC50 = 55.0 ± 2.08 µM) and trimethoprim (IC50 = 50 ± 12.5 µM). Moreover, the antifolates' inhibitory effects on DHFR enzyme activity paralleled their inhibition of the parasite growth in vitro, indicating that the B. gibsoni DHFR could be a model for studying antifolate compounds as potential drug candidates. Therefore, the B. gibsoni DHFR-TS is a molecular antifolate drug target.
  Ken Onda , Chikako Noda , Kazue Nakamura , Reiichiro Sato , Hideharu Ochiai , Sachiko Arai , Hiroo Madarame , Kazuhiro Kawai and Fujiko Sunaga
  Background: This study investigated changes in the blood acid-base balance to determine the effects of Lactated Ringer’s Solution (LRS) administration in a steer with liver damage caused by carbon tetrachloride (CCl4) administration and in a cow with a fatty liver caused by a parturient negative energy balance. Materials and Methods: The LRS was administered to the CCl4 steer before CCl4 administration and 2, 7 and 11 days after CCl4 administration. The fatty liver cow and a group of control cows were administered LRS once. The initiation of LRS infusion was designated time-point 0. Venous blood samples were collected periodically from time-point 0-360 min thereafter and parameters related to the acid-base balance were measured. Results: On day 2, blood pH of the CCl4 steer before LRS administration was 7.26 but it gradually increased after the initiation of LRS administration, before ultimately recovering to within the normal reference range. The HCO3– levels decreased transiently just after the administration of LRS on day 7, then rapidly returned normal. Despite the fatty liver cow having severe fat infiltration, there were no substantial differences in parameters related to the blood acid-base balance between the fatty liver cow and the control cows, after LRS administration. Conclusion: Even in a steer suffering from liver damage caused by CCl4 administration, lactate was metabolised in the liver and worked as an alkaliser. Therefore, LRS may be a safe extracellular replacement solution when administered at the recommended flow rate and dose (20 mL kg–1 h–1 and 30 mL kg–1, respectively) to dairy cows in clinics.
  Sachiko Arai , Keiji Takahashi , Fujiko Sunaga and Seigo Itoh
  Leg weakness is a regressive locomotory disease associated with osteochondrosis and osteoarthritis. However, there are no marked clinical symptoms and it is difficult to evaluate the prognosis or make a diagnosis before death. In humans joint markers to measure cartilage substances in blood are utilized. In particular, keratan sulfate specifically exists in cartilage. This parameter has been measured in dogs and horses. However, no study has reported measurement in pigs. Furthermore, age-/breed-related or gender differences are unclear. In this study, reserachers clarified the hemodynamics of keratan sulfate in pigs and confirmed that the keratan sulfate level decreased when leg weakness was clinically observed in the sow and growing pigs for breeding. In sows the blood level of keratan sulfate decreased to about 1/10 of that in piglets. This was possibly because a pig-specific breeding form with the stall was employed in sows affecting articular movement and reducing cartilage metabolism.
  Seigo Itoh , Maiko Watabnabe , Sachiko Arai , Fujiko Sunaga and Sugita- Konishi
  The emetic toxicities of deoxynivalenol and its acetyl derivatives were examined using house musk shrews (Suncus murinus). Emesis was observed after the oral administration of these toxins at doses ranging from 0-40 mg kg-1 B.W. The Effective Dose (ED) causing emesis was calculated using the Probit Method. The ED 50 of deoxynivalenol, 3-acetylnivalenol and 15-acetylnivalenol was 3.85, 0.87 and 8.85 mg kg-1 B.W., respectively. The results show that the emetic toxicity of 3-acetylnivalenol is 10 times higher than that of deoxynivalenol or 15-acetyl deoxynivalenol. Even though, acetyl deoxynivalenol has been determined to exhibit equivalent toxicity to deoxynivalenol by the FAO/WHO Joint Food Additives Committee, the different responses of acute emetic toxicity should, therefore be taken into account.
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