OBJECTIVE -Serum triglyceride levels are important in the development of atherosclerosis. Although triglyceride levels are generally increased in the postprandial periods, the association between postprandial triglyceride (pTG) levels and atherosclerosis has not been investigated in diabetic patients. To investigate the role of pTG levels in atherosclerosis, we examined the correlation between pTG levels and carotid intimal-medial thickness (IMT).RESEARCH DESIGN AND METHODS -Carotid IMT was measured by ultrasonography in 61 patients with type 2 diabetes. Plasma glucose (PG), insulin, total cholesterol, triglycerides, and HDL cholesterol levels were measured after overnight fasting and 4 h after a meal.RESULTS -Carotid IMT of the patients with fasting hypertriglyceridemia was greater than that of the patients with normal fasting triglyceride (fTG) levels (0.85 ± 0.12 vs. 0.76 ± 0.14 mm; P = 0.02). The carotid IMT was increased in the patients with pTG levels Ͼ2.27 mmol/l. The normo-normo (NN) and normo-hyper (NH) groups consisted of patients with normal fTG levels but with pTG levels Ͻ2.27 and Ͼ2.27 mmol/l, respectively. Patients with both hypertriglyceridemia and pTG levels Ͼ2.27 mmol/l formed the hyper-hyper (HH) group. Carotid IMT was significantly increased in the NH (0.86 ± 0.13 mm) and HH (0.85 ± 0.12 mm) groups compared with the NN group (0.73 ± 0.13 mm; P Ͻ 0.01). Although postprandial PG, pTG, and fasting LDL cholesterol levels were all independently correlated with carotid IMT, pTG levels had the strongest statistical influence (P = 0.002).CONCLUSIONS -Postprandial hypertriglyceridemia despite normal fTG levels may be an independent risk factor for early atherosclerosis in type 2 diabetes.

These results suggest that cerivastatin can directly modulate the biology of the AAA wall and suppress MMP-9 production in the AAA wall by inhibiting the activation of neutrophils and macrophages, indicating that statin therapy could be useful for the prevention or treatment of AAA.

Our results from both the Xenopus oocyte and HEK293 cell expression systems and green fluorescent protein tagging and Western blot analyses support the conclusion that the G601S mutant is a hypomorphic mutation, resulting in a reduced current amplitude. Thus, it represents a novel mechanism underlying LQT2.

Tanezumab was safe and generally well tolerated and may improve pain symptoms in Japanese patients with moderate to severe osteoarthritis of the knee. CLINICALTRIALS.GOV IDENTIFIER: NCT00669409.

Cyclin-dependent kinase 2 (cdk2) plays a critical role in the G1- to S-phase checkpoint of the cell cycle. Adult cardiomyocytes are believed to withdraw from the cell cycle. To determine whether forced overexpression of cdk2 results in altered cell-cycle regulation in the adult heart, we generated transgenic mice specifically overexpressing cdk2 in hearts. Transgenic hearts expressed high levels of both cdk2 mRNA and catalytically active cdk2 proteins. Cdk2 overexpression significantly increased the levels of cdk4 and cyclins A, D3, and E. There was an increase in both DNA synthesis and proliferating cell nuclear antigen levels in the adult transgenic hearts. The ratio of heart weight to body weight in cdk2 transgenic mice was significantly increased in neonatal day 2 but not in adults compared with that of wild-type mice. Analysis of dispersed individual adult cardiomyocytes showed a 5.6-fold increase in the proportion of smaller mononuclear cardiomyocytes in the transgenic mice. Echocardiography revealed that transgenic heart was functionally normal. However, adult transgenic ventricles expressed beta-myosin heavy chain and atrial natriuretic factor. Surgically induced pressure overload caused an exaggerated maladaptive hypertrophic response in transgenic mice but did not change the proportion of mononuclear cardiomyocytes. The data suggest that overexpression of cdk2 promotes smaller, less-differentiated mononuclear cardiomyocytes in adult hearts that respond in an exaggerated manner to pressure overload.

Background-Cystic medial degeneration (CMD) is a histological abnormality that is common in the aortic diseases associated with Marfan's syndrome (MFS). Although little known about the mechanism underlying CMD, several recent reports have demonstrated that vascular smooth muscle cell (VSMC) apoptosis could play a substantial role in CMD.On the other hand, angiotensin II (Ang II) has been reported to play an important role in the regulation of VSMC growth and apoptosis via the Ang II type 1 receptor (AT1R) and type 2 receptor (AT2R). Methods and Results-To elucidate the role of Ang II signaling via the Ang II receptors in CMD, we investigated AT1R and AT2R mRNA expression and tissue concentration of Ang II in MFS aortas (nϭ10) and control aortas (nϭ12). Furthermore, we examined the effects of an ACE inhibitor, an AT1R blocker, and an AT2R blocker on serum deprivation-induced VSMC apoptosis by organ culture system. AT1R expression was significantly decreased (PϽ0.01) and AT2R expression was significantly increased (PϽ0.001) in MFS aortas compared with control aortas, and tissue Ang II concentration was significantly higher in CMD than in the control condition (PϽ0.01). Both the ACE inhibitor and AT2R blocker significantly inhibited serum deprivation-induced VSMC apoptosis (PϽ0.05), although the AT1R blocker did not inhibit apoptosis in cultured aortic media from MFS patients. Conclusions-Accelerated ACE-dependent Ang II formation and signaling via upregulated AT2R play a pivotal role in VSMC apoptosis in CMD, and the ACE inhibitor could have clinical value in the prevention and treatment of CMD. (Circulation. 2001;104[suppl I]:I-282-I-287.)

Aims HMG-CoA reductase inhibitors (statins) have been demonstrated to have in vitro vascular effects. The aim of this study was to determine whether statins actually have in vivo vascular effects independent of their cholesterol-lowering effect. Methods We investigated the effect of a single dose of cerivastatin on vascular endothelial function by measuring flow-mediated dilatation of the brachial artery on ultrasound in 30 healthy volunteers with normal serum cholesterol concentrations. They were randomized to either placebo group ( n = 15) or cerivastatin group ( n = 15), and flow-mediated dilatation and endothelium-dependent dilatation were evaluated at before and 1 h, 3 h, 6 h, and 12 h after administration of placebo or cerivastatin. Results There were no differences in total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, malondialdehyde-LDL, and high-sensitivity C-reactive protein before and after administration of placebo or cerivastatin. Cerivastatin significantly increased flow-mediated dilatation at 3 h ( P < 0.001), and this increase rapidly returned to the baseline level 6 h after administration. Endotheliumindependent dilatation of brachial artery was not altered. Conclusions A single dose of cerivastatin increased vascular endothelial responsiveness. Our data suggest that cerivastatin has a direct effect on the blood vessels that is independent of its lipid-lowering effect, and thus can be considered as a vascular statin.

TAS-114 has shown both a favorable safety and pharmacokinetic profile after single and repeated doses. TAS-114 was considered to possess a moderate DPD inhibitory effect. These findings will facilitate clinical studies of the combination chemotherapies in cancer patients and may reduce the safety risk in the frail cancer patients.