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No nonsynonymous single-nucleotide polymorphism (SNP) in PER1 has been reported with respect to diurnal preference. We aimed to determine whether a functional polymorphism in PER1 is involved in diurnal preference. Forty-seven morning-type (MT, age: 44.57 ± 12.33 years), 59 neither-type (NT, age: 35.20 ± 9.53 years), and 50 evening-type (ET, age: 28.96 ± 8.03 years) subjects were included in the final analysis. A synonymous (PER1 2485 C/T, rs2735611) and nonsynonymous (PER1 2495 G/T, rs138577469) polymorphism at 10-bp away from the PER1 2485 C/T were investigated as candidate SNPs. For the PER1 2485C/T SNP, no significant genotype distribution was observed among the three groups. For the PER1 2495G/T, the MT group showed significantly higher genotype distribution, T allele frequency, and proportion of T allele-positive subjects when compared to the combined group of NT and ET. Our findings suggest that a nonsynonymous polymorphism in PER1, which has only been found in Korean adults, is associated with morning preference. 相似文献
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Rezende KR Mundim IM Teixeira LS Souza WC Ramos DR Cardoso CR Souza IC Gratão MZ Bellório KB 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2007,850(1-2):59-67
A specific high performance liquid chromatography-mass spectrometric (LC-MS/MS) assay was developed for the determination of captopryl in plasma. The retention time was 1.45 and 1.37 min for captopril and enalapril, respectively. The overall mean recovery, using SPE extraction with OASIS HLB cartridges, was found to be 107.2+/-9.5 and 100.04+/-2%, respectively. Calibration curves were linear in the concentration range of 10.00-2000.00 ng/ml, and the lower limit of quantification (LLOQ) was 10.00 ng/ml. The LLOQ was sensitive enough for detecting terminal phase concentrations of the drug. Inter-batch precision of the method ranged from 0.88 to 1.95%. Intra-batch accuracy ranged from 97.15 to 105.77%, while intra-batch precision ranged from 2.49 to 5.66% at concentrations of 30.00, 760.00 and 1500.00 ng/ml. The developed method was applied to study bioequivalence of captopril in a group of 25 human subjects at a single oral dose of a 50mg tablet. 相似文献
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Astrup A Greenway FL Ling W Pedicone L Lachowicz J Strader CD Kwan R;for the Ecopipam Obesity Study Group 《Obesity (Silver Spring, Md.)》2007,15(7):1717-1731
Objective: To evaluate the efficacy and safety of the selective dopamine D1/D5 antagonist ecopipam for the treatment of obesity. Research Methods and Procedures: Four randomized, double‐blind, multicenter trials compared ecopipam (n = 1667) and placebo (n = 1118) in obese subjects including type 2 diabetic subjects. Subjects received oral ecopipam 10, 30, or 100 mg daily for 12 weeks (Phase 2) or 50 or 100 mg daily for 52 weeks (Phase 3) combined with a weight loss program. Primary efficacy variables were the proportion of subjects with ≥5% weight loss from baseline at 12 weeks (Phase 2) or the distribution of percentage weight loss from baseline at 52 weeks (Phase 3). Results: In the Phase 2 study, 26% of subjects administered ecopipam 100 mg vs. 6% of placebo subjects achieved ≥5% weight loss after 12 weeks (p < 0.01). In the Phase 3 studies, ecopipam 100 mg produced a 3.1% to 4.3% greater weight loss than placebo at 52 weeks. More subjects administered ecopipam vs. placebo achieved a 5% to 10% or >10% weight loss in two non‐diabetic phase 3 trials. Ecopipam‐treated subjects also maintained more weight loss compared with placebo subjects at 52 weeks. Phase 3 studies were discontinued because of unexpected psychiatric adverse events (ecopipam 31% vs. placebo 15%), including depression, anxiety, and suicidal ideation. Discussion: Ecopipam was effective for achieving and maintaining weight loss in obese subjects, including type 2 diabetic subjects; however, the adverse effects on mood observed in the Phase 3 studies exclude its projected use in weight management. 相似文献
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Kim IY Jeong SJ Kim ES Kim SH Moon A 《Journal of biochemistry and molecular biology》2007,40(5):825-831
Tumor cell invasion and metastasis are often associated with matrix metalloproteinases (MMPs), among which MMP-2 and MMP-9 are of central importance. We previously showed that H-Ras, but not N-Ras, induced invasion of MCF10A human breast epithelial cells in which the enhanced expression of MMP-2 was involved. MMP-2 is produced as a latent pro-MMP-2 (72 kDa) to be activated resulting the 62 kDa active MMP-2. The present study investigated if H-Ras and/or N-Ras induces pro-MMP-2 activation of MCF10A cells when cultured in two-dimensional gel of type I collagen. Type I collagen induced activation of pro-MMP-2 only in H-Ras MCF10A cells but not in N-Ras MCF10A cells. Induction of active MMP-2 by type I collagen was suppressed by blocking integrin alpha2, indicating the involvement of integrin signaling in pro-MMP-2 activation. Membrane-type (MT)1-MMP and tissue inhibitor of metalloproteinase (TIMP)-2 were up-regulated by H-Ras but not by N-Ras in the type I collagen-coated gel, suggesting that H-Ras-specific up-regulation of MT1-MMP and TIMP-2 may lead to the activation of pro-MMP-2. Since acquisition of pro-MMP-2 activation can be associated with increased malignant progression, these results may help understanding the mechanisms for the cell surface matrix-degrading potential which will be crucial to the prognosis and therapy of breast cancer metastasis. 相似文献