The ability of statins to protect low density lipoprotein from oxidation in hypercholesterolemic patients

Objective: It is unclear at the present time whether hydroxy-methylglutaryl coenzyme A reductase inhibitors (HMG-CoA reductase inhibitors; statins) exert a protective effect on low-density lipoproteins (LDL) oxidation in vivo. In addition, it is speculated that pharmacological differences between statins may account for differences in their antioxidative capacities. This is of clinical relevance, because there is strong evidence that oxidized LDL initiates the atherosclerosis process. Material and methods: In a controlled, randomized, double-blind study we compared the effects of three different statins (simvastatin, pravastatin and atorvastatin) on the ability to protect LDL from oxidation in 70 hypercholesterolemic but otherwise healthy subjects. Statins were adininistered in doses which were nearly equi-effective in lowering LDL-cholesterol. Changes in LDL oxidation were measured using diene conjugation (DIENES) and thiobarbituric acid reactive substances (TBARS) at entry and three months after beginning therapy with the statins. Results: Levels of DIENES, usually generated during the early phases of lipid peroxidation, were significantly reduced by 10.2 +/- 5.5% (mean +/- SEM; p 0.23). Levels of TBARS, reflecting late phases of LDL oxidation, showed no significant changes against baseline (p > 0.34). Pooled data (n = 70) indicated that statins reduce DIENES levels by 90% versus baseline (p 0.29) after three months of therapy. Conclusion: This study showed that atorvastatin and pravastatin were capable of protecting LDL from oxidation in vivo in the early treatment phase. Pooled data levels of DIENES were significantly affected by statin therapy over a period of 3 months. No protective effect appeared to be present in the late phases of oxidation evaluated using measurement of TBARS but it should be noted that the clinical impact of such observations are currently discussed controversially in the literature

A new shear strength model incorporating influence of infill materials for rock joints

Overall mechanical behaviour of jointed rock masses is predominantly controlled by the shear strength of rock joints which contain infill materials. Barton’s empirical model has been shown to be one of the most successful model in predicting joint shear strength (Barton and Choubey in Rock Mech 10:1–54, 1977). However, the Barton model does not express the effect of infill material explicitly, but only incorporates influence of infill into the factors of joint-wall compressive strength (JCS) and residual friction angle. Although there are a large number of studies carried out on the effects of infill materials on the shear strength of rock joints, none of them incorporated infill influence directly into the Barton’s formulation. This paper investigates the effect of infill thickness on JCS and the overall joint shear strength. The interface between wall rock and infill material thicknesses ranging from 1 to 5 mm is simulated by using smooth-joint model. A natural joint is digitally scanned and the roughness geometry is used in all PFC3D models. The results showed that JCS does not show a significant variation at high infill thickness up to a threshold limit of 2 mm. However, JCS decreases drastically at low infill thickness. As expected the shear strength of filled joints reduces from fresh joints to the infill materials, as the infill thickness increases. The reduction is inversely related to the infill thickness. The reduction factor k has a negative exponential relation with the normal stress, indicating that the effect of infill material is stronger at lower normal stress while effect of joint roughness is stronger at higher normal stress.Murat Karakus, Yi Liu, Guangcheng Zhang, Huiming Tan