Compared with standard statin monotherapy, the combination of statin plus ezetimibe showed greater coronary plaque regression, which might be attributed to cholesterol absorption inhibition-induced aggressive lipid lowering. (Plaque Regression With Cholesterol Absorption Inhibitor or Synthesis Inhibitor Evaluated by Intravascular Ultrasound [PRECISE-IVUS]; NCT01043380).

CaSO,: Tm and CaSO,: Dy were found to be free from the serious disadvantage of rapid fading in CaS04:Mn and yet retain the outstanding property of high sensitivity of CaSO, : Mn, the most sensitive thermoluminescence dosimeter available at present. Glow curves of both CaS0,:Dy and CaS0,:Tm are rather simple showing a main peak at 22OoC and shoulders at 8OoC and 12OoC. Emission spectrum of CaS0,:Tm consists of a main sharp peak at 450 mp with minor ones at 360,470 and 520 mp and CaS0,:Dy has two main peaks at 480 and 570 mp without any minor one. The dosimetric characteristics of CaS0,:Tm and CaSO, : Dli are excellent exceDt for their non-tissue eauivalence: 1. 2.3. 4. 6.LitFle fading (1-2% per mbnth).Minimal detectable exposure is lower than 200 pR with standard deviation of f20%, by a commercial readout instrument.Dose response of CaS0,:Dy is linear up to 3000 R and supralinear over 3000 R, and that of CaS04:Tm is linear up to 300 R and supralinear over 300 R. Energy dependence is large for photon energies below 200 keV but a compensation shield made of tin and lead alters the response until it is within 40% down to 30 keV. Tribothermoluminescence is very low (about 25th of that in LiF). The thermoluminescence efficiency remains constant for more than 100 readout cycles sufficient to erase the previous dose.

Abstract-Dietary obesity is associated with type 2 diabetes and cardiovascular diseases, although the underlying mechanism is unknown. This study was undertaken to elucidate the role of angiotensin II and apoptosis signal regulating kinase-1 (ASK1) in obesity/diabetes-associated cardiovascular complications and hepatic steatosis. Mice fed a high-fat diet were treated with olmesartan, an angiotensin II type 1 receptor blocker, to elucidate the role of angiotensin II in diabetic mice. Treatment of mice fed a high-fat diet with olmesartan markedly suppressed cardiac inflammation and fibrosis, as well as vascular endothelial dysfunction and remodeling, induced by obesity/diabetes. Moreover, olmesartan suppressed the disruption of the vascular endothelial NO synthase dimer in diabetic mice. Olmesartan also significantly prevented hepatic steatosis and fibrosis in diabetic mice. These beneficial effects of olmesartan on diabetic mice were associated with the attenuation of ASK1 activation in these mice. ASK1-deficient mice and wild-type mice were compared, regarding the effects of a high-fat diet. A comparison between ASK1-deficient and wild-type mice showed that ASK1 deficiency attenuated cardiac inflammation and fibrosis, as well as vascular endothelial dysfunction and remodeling induced by obesity/diabetes. The amelioration of vascular endothelial impairment by ASK1 deficiency was attributed to the prevention of endothelial NO synthase dimer disruption. ASK1 deficiency also significantly lessened hepatic steatosis in diabetic mice. In conclusion, our work provided the evidence that ASK1 is significantly activated in diet-induced diabetic mice and contributes to cardiovascular diseases and hepatic steatosis in diabetic mice. Moreover, the beneficial effects of angiotensin II inhibition on dietary diabetic mice seem to be mediated by the inhibition of ASK1 activation. Key Words: diabetes Ⅲ obesity Ⅲ angiotensin Ⅲ ASK1 Ⅲ reactive oxygen species Ⅲ vascular endothelial function Ⅲ cardiac injury O besity, particularly dietary obesity, is associated with type 2 diabetes 1 and an increased risk of cardiovascular diseases. 2-5 However, the underlying mechanism is poorly understood. Accumulating experimental and clinical evidence indicate that the renin-angiotensin system is involved not only in hypertension but also in various cardiovascular diseases. 6 Furthermore, emerging experimental and clinical data support the notion that the renin-angiotensin system participates in the pathophysiology of obesity and type 2 diabetes, 7-13 although the underlying mechanism remains to be elucidated.Reactive oxygen species (ROS) are supposed to be involved in obesity, 14 -17 insulin resistance, diabetes, 1,18 and cardiovascular diseases. 19,20 Apoptosis signal regulating kinase-1 (ASK1), one of the mitogen-activated protein kinase kinase kinases, is markedly activated by ROS and plays a critical role in a variety of cellular responses induced by ROS, including cell apoptosis, growth, differentiation, gene expression, etc. 21-23 Previous...

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