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81.
Naoki Ishiguro Takashi Nozawa Akiko Tsujihata Asami Saito Wataru Kishimoto Kazutoshi Yokoyama Takafumi Yotsumoto Kenji Sakai Takashi Igarashi Ikumi Tamai 《Drug metabolism and disposition》2004,32(5):519-524
We investigated influx and efflux transporters involved in blood-brain barrier transport of the nonsedative H1-antagonist epinastine. The basal-to-apical transport of [14C]epinastine was markedly higher than that in the opposite direction in LLC-GA5-COL150 cells stably transfected with human multidrug resistance (MDR)1 gene. The brain-to-plasma concentration ratio of [14C]epinastine in mdr1a/b(-/-) mice was 3.2 times higher than that in wild-type mice. The uptake of both [3H]mepyramine and [14C]epinastine into immortalized rat brain capillary endothelial cells (RBEC)1 showed temperature and concentration dependence. The kinetic parameters, K(m), V(max), and uptake clearance (V(max)/K(m)), of the initial uptake of [3H]mepyramine and [14C]epinastine by RBEC1 were 150 microM, 41.8 nmol/min/mg protein, and 279 microl/min/mg protein for mepyramine and 10.0 mM, 339 nmol/min/mg protein, and 33.9 microl/min/mg protein for epinastine, respectively. The uptake of [3H]mepyramine and [14C]epinastine by RBEC1 was inhibited by organic cations such as quinidine, amantadine, and verapamil, but not by other organic cations, tetraethyl ammonium, guanidine, and carnitine. Organic anions such as benzoic acid, estrone-3-sulfate, taurocholate, and neutral digoxin were not inhibitory. Furthermore, some cationic H1 antagonists (chlorpheniramine, cyproheptadine, ketotifen, and desloratadine) inhibited the [3H]mepyramine and [14C]epinastine uptake into RBEC1. In conclusion, the present study demonstrated that the combination of efficient efflux transport by P-glycoprotein and poor uptake by the influx transporter, which is identical with that responsible for the uptake of mepyramine, account for the low brain distribution of epinastine. 相似文献
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Akiko Tonosaki 《European Journal of Oncology Nursing》2012,16(5):475-482
PurposeThe purpose of this study was to analyze the effects of leg muscle strength and fatigue on step-count as a measure of physical activity for people staying at home after hematopoietic stem cell transplantation (HSCT).MethodNineteen persons receiving HSCT were assessed from hospitalization until about 2 months after discharge. Mean daily step-count was taken as a measure of physical activity. Leg muscle strength was measured in three ways (knee extension, ankle plantar flexion, and ankle dorsiflexion strength) at two points in time (time of hospital discharge and after 2 months). Fatigue and anxiety were assessed using the Japanese Cancer Fatigue Scale and State-Trait Anxiety Inventory. Correlations between the above and factors affecting physical activity were also investigated by multiple regression analysis.ResultsClinical follow-up measurements in subjects were made an average of 81.0 days after discharge. Subjects with higher mean step-count during hospitalization (β = 0.647, p = 0.000) and greater ankle plantar flexion strength/kg (β = 0.361, p = 0.021) reported higher mean step-count at home (adjusted R2 = 0.701, p = 0.021). Subjects with body mass index <22.0 kg/m2 also showed higher step-counts at home compared to other subjects. Mean fatigue score at home was 16.8 (SD = 8.75), a level not associated with clinical problems, and the proportion of physical fatigue was significantly lower than during hospitalization.ConclusionMean step-count at home was most strongly affected by ankle plantar flexion strength/kg, and increasing ankle plantar flexion strength/kg was shown to promote recovery of normal physical activities. 相似文献
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Katsuyoshi Horibata Akiko Ukai Takafumi Kimoto Tetsuya Suzuki Nagisa Kamoshita Kenichi Masumura Takehiko Nohmi Masamitsu Honma 《Environmental and molecular mutagenesis》2013,54(9):747-754
The recently developed Pig‐a mutation assay is based on flow cytometric enumeration of glycosylphosphatidylinositol (GPI) anchor‐deficient red blood cells caused by a forward mutation in the Pig‐a gene. Because the assay can be conducted in nontransgenic animals and the mutations accumulate with repeat dosing, we believe that the Pig‐a assay could be integrated into repeat‐dose toxicology studies and provides an alternative to transgenic rodent (TGR) mutation assays. The capacity and characteristics of the Pig‐a assay relative to TGR mutation assays, however, are unclear. Here, using transgenic gpt delta mice, we compared the in vivo genotoxicity of single oral doses of N‐ethyl‐N‐nitrosourea (ENU, 40 mg/kg), benzo[a]pyrene (BP, 100 and 200 mg/kg), and 4‐nitroquinoline‐1‐oxide (4NQO, 50 mg/kg) in the Pig‐a (peripheral blood) and gpt (bone marrow and liver) gene mutation assays. Pig‐a assays were conducted at 2, 4, and 7 weeks after the treatment, while gpt assays were conducted on tissues collected at the 7‐week terminal sacrifice. ENU increased both Pig‐a and gpt mutant frequencies (MFs) at all sampling times, and BP increased MFs in both assays but the Pig‐a MFs peaked at 2 weeks and then decreased. Although 4NQO increased gpt MFs in the liver, only weak, nonsignificant increases (two‐ or threefold above control) were detected in the bone marrow in both the Pig‐a and the gpt assay. These findings suggest that further studies are needed to elucidate the kinetics of the Pig‐a mutation assay in order to use it as an alternative to the TGR mutation assay. Environ. Mol. Mutagen. 54:747–754, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
88.
Clinical value of capsule endoscopy for detecting small bowel lesions in patients with intestinal Behçet's disease
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89.
Nogawa T Takahashi S Okano A Kawatani M Uramoto M Saito T Osada H 《The Journal of antibiotics》2012,65(3):123-128
Two new 6,6-spiroacetal polyketides, spirotoamides A (1) and B (2), were isolated from a microbial metabolite fraction library of Streptomyces griseochromogenes JC82-1223 by screening of structurally unique compounds based on a search of spectral database. The fraction library was constructed using a systematic separation method to efficiently discover new metabolites from microbial sources such as actinomycetes and fungi. The structures of 1 and 2 were elucidated by 2D-NMR and mass spectrometric measurements. They belong to a class of polyketides, and contain a 6,6-spiroacetal core structure and a carboxamide group. The biosynthetic pathway of 1 and 2 is discussed in the text. 相似文献