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- Becker, Richard C., et al.
(författare)
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Effect of apixaban, an oral and direct factor Xa inhibitor, on coagulation activity biomarkers following acute coronary syndrome
- 2010
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 104:5, s. 976-983
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Tidskriftsartikel (refereegranskat)abstract
- Apixaban is an oral, direct factor Xa inhibitor under development for secondary prevention in acute coronary syndrome (ACS) Apixaban's effect on D dimer and prothrombin fragment 12 (F1 2) (coagulation activity biomarkers) was determined in a randomised, double blinded, placebo controlled phase 2 study Patients (n=1,715) with either ST segment elevation or non ST segment elevation ACS received either placebo or apixaban 2 5 mg twice daily 10 mg once daily, 10 mg twice daily or 20 mg once daily for six months Samples were obtained at baseline (before study drug administration), week 3 and week 26 Apixaban plasma concentrations were measured directly by liquid chromatography/mass spectometry and anti Xa activity was determined using apixaban as a reference standard D dimer and F 1 2 were measured using ELISA based methods Most patients had elevated D dimer and Fl 2 levels at baseline Both coagulation activity biomarkers decreased by week 3 in all treatment groups but to a greater degree with apixaban than placebo (p<0 001) In a multivariable analysis, apixaban was independently associated with a change in biomarkers over time (p<0 0001) While the overall decrease did not differ significantly among the three highest apixaban doses, Fl 2 was suppressed more rapidly by the 10 mg once daily than the 2 5 mg twice daily dose (p<0 05) There was a strong and direct relationship between apixaban plasma concentrations and anti Xa apixaban levels, and an inverse relationship for both measures with coagulation activity biomarkers In conclusion the oral direct factor Xa inhibitor apixaban significantly reduced coagulation activity biomarkers among patients with ACS The 10 mg once daily dose reduced thrombin generation (F 1 2) and fibrin formation (D dimer) more rapidly and robustly than the 25 mg twice daily dose The effect on both D dimer and F 12 was apixaban concentration and factor Xa inhibition dependent durable and provided general guidance for dose selection in phase 3 investigation.
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| 2. |
- Börjesson, Anna E, et al.
(författare)
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The role of estrogen receptor-alpha in growth plate cartilage for longitudinal bone growth.
- 2010
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Ingår i: Journal of bone and mineral research. - : Wiley. - 1523-4681 .- 0884-0431. ; 25:12, s. 2414-24
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Tidskriftsartikel (refereegranskat)abstract
- Estrogens enhance skeletal growth during early sexual maturation while high estradiol levels during late puberty result in growth plate fusion in humans. Although the growth plates do not fuse directly after sexual maturation in rodents, a reduction in growth plate height is seen by treatment with a high dose of estradiol. It is unknown whether the effects of estrogens on skeletal growth are mediated directly via estrogen receptors (ERs) in growth plate cartilage and/or indirectly via other mechanisms such as the GH/IGF-I axis. To determine the role of ERalpha in growth plate cartilage for skeletal growth, we developed a mouse model with cartilage-specific inactivation of ERalpha. Although mice with total ERalpha inactivation displayed affected longitudinal bone growth associated with alterations in the GH/IGF-I axis, the skeletal growth was normal during sexual maturation in mice with cartilage-specific ERalpha inactivation. High dose estradiol treatment of adult mice reduced the growth plate height as a consequence of attenuated proliferation of growth plate chondrocytes in control mice but not in cartilage-specific ERalpha(-/-) mice. Adult cartilage-specific ERalpha(-/-) mice continued to grow after four months of age while growth was limited in control mice, resulting in increased femur length in one-year-old cartilage-specific ERalpha(-/-) mice compared with control mice. We conclude that during early sexual maturation ERalpha in growth plate cartilage is not important for skeletal growth. In contrast, it is essential for high dose estradiol to reduce the growth plate height in adult mice and for reduction of longitudinal bone growth in elderly mice. (c) 2010 American Society for Bone and Mineral Research.
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| 3. |
- Ning, F., et al.
(författare)
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Does abnormal insulin action or insulin secretion explain the increase in prevalence of impaired glucose metabolism with age in populations of different ethnicities?
- 2010
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Ingår i: DIABETES-METABOLISM RESEARCH AND REVIEWS. - 1520-7552. ; 26:4, s. 245-253
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Tidskriftsartikel (refereegranskat)abstract
- Background Age is associated with both impaired glucose and insulin metabolism. To what extent the age-related changes in insulin resistance (IR) and β-cell function contribute to the increase in prevalence of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) is less known, and this is investigated in this study. Methods This study included 6610 men and 7664 women of different ethnic groups aged 30-69 years. IR and β-cell function were examined by the homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-B). Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using logistic regression analysis adjusting for body mass index and study. Results In Chinese men, the ORs (95% CIs) for IFG were 2.69 (1.70, 4.26), 2.51 (1.49, 4.21) and 2.89 (1.68, 4.97), respectively, in age groups of 40–49, 50–59 and 60–69 years compared with 30–39 years (p < 0.001 for trend); the corresponding figures for IGT were 1.73 (1.25, 2.38), 2.54 (1.78, 3.63) and 3.57 (2.46, 5.19) (p < 0.001 for trend). Similar trends for IGT were observed also in Chinese women and other ethnic groups, but not for IFG in Mauritius Indian and Creole men. Adjustment for HOMA-IR and HOMA-B reduced the ORs in all age groups of all ethnicities for both IFG and IGT, but the risk gradient between age groups remained particularly for the IGT. Conclusions The age-related increase in glucose intolerance may not be fully explained by the defect in HOMA-IR and HOMA-B. As HOMA-IR and HOMA-B are only surrogate measures of insulin sensitivity and insulin secretion, the results need to be further investigated
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| 4. |
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| 5. |
- Nyamdorj, R, et al.
(författare)
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Ethnic comparison of the association of undiagnosed diabetes with obesity.
- 2010
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Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 34:2, s. 332-339
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of the study was to investigate the crude prevalence and estimated probability of undiagnosed diabetes in different ethnic groups, given the same level of obesity. DESIGN AND SUBJECTS: Cross-sectional data from 24 515 men and 29 952 women, aged >or=30 years, and free of previously diagnosed diabetes were included. Baseline body mass index (BMI) and waist circumference were measured. Diabetes was defined according to both fasting and 2-h 75-g glucose criteria. RESULTS: Prevalence of undiagnosed diabetes was the highest in Asian Indians, the lowest in Europeans and intermediate in others, given the same BMI or waist circumference category across the BMI or waist circumference ranges (P<0.001 for all BMI or waist categories). beta-Coefficients corresponding to a 1 s.d. increase in BMI were 0.34/0.28, 0.41/0.43, 0.42/0.61, 0.36/0.59 and 0.33/0.49 for the Asian Indians, Chinese, Japanese, Mauritian Indians and European men/women (homogeneity test: P>0.05 in men and P<0.001 in women), and in waist: 0.31/0.31, 0.30/0.46, 0.22/0.57 and 0.38/0.58 for the Asian Indians, Chinese, Mauritian Indians and Europeans, respectively (homogeneity test: P>0.05 in men and P<0.001 in women). CONCLUSION: Prevalence of undiagnosed diabetes increased with an increasing BMI or waist circumference to a similar degree in men in all ethnic groups but to a lesser degree in Asian Indian women than in others, regardless of the higher prevalence in Asian Indians than in others at the same BMI (or) waist circumference levels.
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