Hyperthyroidism is associated with increased aortic oxidative DNA damage in a rat model

BACKGROUND: Hyperthyroidism is associated with increased oxidative stress and oxygen free radical production. Oxygen free radicals are implicated in several signalling pathways leading to vascular pathology. The present study evaluates the extent of aortic oxidative stress in experimental hyperthyroidism. MATERIALS AND METHODS: Chronic hyperthyroidism was induced in 20 male Wistar rats; another 20 animals served as controls. Oxidative damage to lipids and genomic DNA was assessed by measuring serum and aortic wall 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) levels (a mutagenic marker of oxidative DNA damage), as well as serum ceruloplasmin, malondialdehyde (MDA) and lipids. RESULTS: Hyperthyroid animals had significantly higher values of serum ceruloplasmin (11.27+/-1.16 vs. 9.58+/-1.17 mg/dl), MDA (5.34+/-1.32 vs. 0.64+/-0.53 nmol/ml) and 8-oxo-dG (33.91+/-9.63 vs. 17.56+/-4.44 ng/ml) compared with controls (p<0.001 for all associations). Aortic 8-oxo-dG levels were elevated in the thyrotoxic compared with the control group (13.01+/-2.38 vs. 4.09+/-1.27 ng/ml, respectively; p<0.001). 8-Oxo-dG measurements in aortic rings and in serum were positively correlated in the hyperthyroid rats (Pearson's correlation coefficient =0.66; p=0.007). CONCLUSION: Hyperthyroidism is associated with increased oxidative stress in the aortic wall. The animal model we describe has provided some preliminary data regarding the effect of hyperthyroidism on the vascular system. Verification of our results and further exploration of our animal model may help determine the association between oxidative DNA damage with functional changes of the vascular wall, such as endothelial function and vascular nitric oxide signalling.     

Fenofibrate plus simvastatin (fixed-dose combination) for the treatment of dyslipidaemia

INTRODUCTION: Statin use results in a significant reduction of cardiovascular disease (CVD) risk. However, patients still have residual CVD risk, even if they are receiving optimal statin treatment. AREAS COVERED: This review, based on a Pubmed/Scopus search, discusses the available evidence regarding the use of a fixed-dose fenofibrate plus simvastatin combination. This combination is useful for patients with mixed dyslipidaemia because it improves the overall lipoprotein profile. Although in clinical trials the rate of adverse events was not significantly greater than monotherapy, patients who receive combination treatment should be monitored carefully. Furthermore, in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Study, this combination did not result in a significant reduction of CVD events compared with simvastatin monotherapy. However, a possible benefit in this trial was observed in the subgroup of patients with high triglyceride and low high-density lipoprotein cholesterol levels. EXPERT OPINION: The fixed-dose fenofibrate plus simvastatin combination treatment produces additive results and is safe when patients are properly monitored. Existing evidence appears to support the addition of fenofibrate to simvastatin treatment for the reduction of residual CVD risk in patients with atherogenic dyslipidaemia. However, this combination did not lead to better clinical outcomes in the absence of dyslipidaemia.     

Combination drug treatment in patients with non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) includes simple steatosis, a benign condition, and non-alcoholic steatohepatitis, a condition that beyond TG accumulation also includes necroinflammation and fibrosis. An association between NAFLD and cardiovascular disease (CVD) has been recently suggested. NAFLD patients usually have an increased CVD risk profile. NAFLD is also associated with metabolic syndrome (MetS) and is considered as the hepatic component of MetS by some authors. Currently, the only established treatment of NAFLD is gradual weight loss. However, multifactorial treatment of NAFLD risk factors may be needed to reduce the increased CVD risk of NALFD patients. Drug combinations that include antiobesity drugs (such as orlistat and sibutramine) and target CVD risk factors may be a good approach to NAFLD patients. Our group has investigated the orlistat-fenofibrate combination treatment in obese patients with MetS and the orlistat-ezetimibe and sibutramine-antihypertensive combination treatment in obese patients with hyperlipidaemia with promising results in CVD risk factor reduction and improvement of liver function tests. Small studies give promising results but double-blind, randomized trials examining the effects of such multifactorial treatment in hard CVD endpoints in NAFLD patients are missing.     

Ovine blood: establishment of a list of reference values relevant for blood coagulation in sheep

Ovine animal models are widely used to conduct preclinical studies, e.g., to evaluate cardiovascular prostheses intended to be applied in man. However, although analyzed in many of those studies, information about ovine blood reference values is scanty. The aim of this study is to establish a reference list of ovine blood parameters relevant for blood coagulation. A cohort of 47 mature ewes was evaluated. Parameters comprised the following: cells and cellular components-platelet, red, and white cell counts (including subsets), hemoglobin (Hb), hematocrit (HCT), mean corpuscular hemoglobin (MCH) and mean corpuscular volume (MCV), and MCH concentration (MCHC); global tests of coagulation-prothrombin time (Quick's time) and activated partial thromboplastin time (aPTT); and parameters relevant for blood coagulation-fibrinogen, antithrombin (AT), and von Willebrand Factor. After explorative data analysis, a list of ovine reference values was established. Interestingly, a comparison with human reference values revealed some interspecies differences between sheep and man, i.e., much higher ovine ranges for some cell counts (neutrophils, lymphocytes, basophils, eosinophils, and platelets) but lower values for some other parameters (Hb, HCT, MCV, MCH, AT, and Quick's test). We established a reference list of ovine blood count and blood coagulation parameters. Because of some peculiarities of the ovine blood, this list may have implications for the interpretation of experimental data.     

HRCT findings in the lungs of non-smokers with neurofibromatosis

Purpose

Interstitial lung disease in neurofibromatosis (NF) has been disputed and attributed to smoking-related changes. The aim of this study was to describe HRCT findings in the lungs of non-smokers with NF.

Materials and methods

Six never-smokers with NF underwent lung HRCT. Two radiologists evaluated the HRCT scans and a final decision was reached by consensus. The HRCT scans were analyzed with regard to the number, size, location (upper, middle or lower lung zone) and distribution (peripheral and central) of lung cysts and the presence of ground-glass density centrilobular micronodules.

Results

All patients with NF had small (2–18 mm) thin wall cysts and upper-lobe predominant patchy areas of ground-glass density centrilobular micronodules. In five cases, there were 3–17 cysts and in one there were numerous (>100). Lung cysts were central (1), subpleural (1) and in both locations (4).

Conclusion

Interstitial lung disease in NF is not associated with smoking and may be entirely asymptomatic. HRCT may reveal small cysts, with barely perceptible walls therefore not representing emphysema and occasionally a minimal micronodular pattern of ground glass opacity. There was no radiologic evidence of lung fibrosis, honeycombing or severe bullous disease.