In Vitro and Computational Thrombosis on Artificial Surfaces With Shear Stress

Implantable devices in direct contact with flowing blood are associated with the risk of thromboembolic events. This study addresses the need to improve our understanding of the thrombosis mechanism and to identify areas on artificial surfaces susceptible to thrombus deposition. Thrombus deposits on artificial blood step transitions are quantified experimentally and compared with shear stress and shear rate distributions using computational fluid dynamics (CFD) models. Larger steps, and negative (expanding) steps result in larger thrombus deposits. Fitting CFD results to experimental deposit locations reveals a specific shear stress threshold of 0.41 Pa or a shear rate threshold of 54 s^?1 using a shear thinning blood viscosity model. Thrombosis will occur below this threshold, which is specific to solvent‐polished polycarbonate surfaces under in vitro coagulation conditions with activated clotting time levels of 200–220 s. The experimental and computational models are valuable tools for thrombosis prediction and assessment that may be used before proceeding to clinical trials and to better understand existing clinical problems with thrombosis.     

Cholestasis induces apoptosis in mice cardiac cells: the possible role of nitric oxide and oxidative stress

Background/Aims: Acute cholestasis is associated with cardiovascular complications. The purpose of the present study was to investigate the effect of cholestasis on heart apoptosis and the involvement of nitric oxide (NO) and oxidative stress in the possible altered apoptosis of cholestatic hearts. Methods: Cholestasis was induced by bile duct–ligation, and sham‐operated mice served as controls. Three days after the surgery, heart tissues were evaluated for apoptosis and the level of malondialdehyde (MDA), and the activities of catalase (CAT), glutathione peroxidase (GSHPx) and superoxide dismutase (SOD) have been studied in cardiac tissues. The role of treatment with l ‐NAME, a non‐selective inhibitor of NO synthase, or with d ‐NAME, an inactive isomer of l ‐NAME, on cholestatic and sham cardiac apoptosis, level of MDA and CAT, SOD and GSHPx activities was also investigated. The content of NO in cardiac tissue was also determined. Results: Cholestatic hearts showed structural abnormalities and increased apoptosis compared with sham hearts. Treatment with l ‐NAME, but not d ‐NAME, improved both structural abnormalities and enhanced apoptosis of cholestatic hearts. Cholestatic hearts also had an increased level of MDA and decreased activities of CAT and GSHPx, which were not modified by d ‐NAME treatment. By l ‐NAME treatment, the level of MDA decreased and activities of CAT, GSHPx and SOD increased in BDL mice. The content of NO was higher in cholestatic cardiac tissue, which was decreased by l ‐NAME treatment. Conclusion: In conclusion, apoptosis in cholestatic heart might have occurred because of NO overproduction, which could induce oxidative stress in the heart of cholestatic mice.     

Treatment gaps in the management of cardiovascular risk factors in patients with type 2 diabetes in Canada

OBJECTIVES:

To evaluate vascular protection treatment patterns and attainment of the 2003 Canadian Diabetes Association’s recommended targets in ambulatory patients with type 2 diabetes.

METHODS:

Between 2005 and 2006, 3002 outpatients with type 2 diabetes were enrolled by 229 primary health care settings across Canada. Baseline characteristics, therapeutic regimens and treatment success – defined as the achievement of a blood pressure (BP) of 130/80 mmHg or lower, glycosylated hemoglobin (A1C) of 7% or lower, low-density lipoprotein cholesterol (LDL-C) lower than 2.5 mmol/L and total cholesterol/high-density lipoprotein cholesterol ratio lower than 4.0 – are reported.

RESULTS:

Overall, 46% of individuals had a BP that was above the Canadian Diabetes Association’s recommended target. Of these, 11% were untreated, 28% were receiving monotherapy, 38% were not receiving an angiotensin-converting enzyme inhibitor and 16% were not receiving either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Optimal A1C levels were achieved in 53% of patients. Of those who did not attain A1C targets, 3% were not on glucose-lowering pharmacotherapy and 27% were receiving monotherapy. A total of 74% of patients were treated with statins. Overall, 64% and 62%, respectively, met the target LDL-C and the target total cholesterol/high-density lipoprotein cholesterol ratio. Statins were not prescribed to 43% of patients with LDL-C above target. Antiplatelet therapy was implemented in 81% of patients. In total, 21% achieved the combined targets for BP, A1C and LDL-C.

INTERPRETATION:

A substantial proportion of patients did not achieve guideline-recommended targets and were not receiving evidence-based therapy for vascular protection two years after publication of the Canadian guidelines. More research is warranted, and novel and effective strategies must be tested and implemented to correct this ongoing treatment gap.     

Fc gamma receptor IIa polymorphism in patients with brucellosis

Recent evidence suggests that certain Fc gamma receptor alleles are genetic risk factors for infectious diseases. In this study, we evaluated Fc gamma RIIa polymorphism in patients with brucellosis. In a case-control study, the frequency of two alleles and three genotypes for Fc gamma RIIa were measured by PCR in 150 patients with brucellosis and 125 healthy controls. The H131 and R131 alleles were found in 133 (44.3%) and 167 patients (47.6%), respectively. The frequencies for the three genotypes (a/a, a/r, r/r) were 10 (6.7%), 113 (75.3%) and 27 (18%), respectively. There was no significant difference in the distribution of Fc gamma RIIa genotypes and the two allelic forms between the patients and controls. Our study indicates that Fc gamma RIIa polymorphism is not decisive for the acquisition of brucellosis.     

A decision tree-based approach for determining low bone mineral density in inflammatory bowel disease using WEKA software

BACKGROUND: Decision tree classification is a standard machine learning technique that has been used for a wide range of applications. Patients with inflammatory bowel disease (IBD) are at increased risk of developing low bone mineral density (BMD). This study aimed at developing a new approach to select truly affected IBD patients who are indicated for densitometry, hence, subjecting fewer patients for bone densitometry and reducing expenses. MATERIALS AND METHODS: Simple decision trees have been developed by means of WEKA (Waikato Environment for Knowledge Analysis) package of machine learning algorithms to predict factors influencing the bone density among IBD patients. The BMD status was the outcome variable whereas age, sex, duration of disease, smoking status, corticosteroid use, oral contraceptive use, calcium or vitamin D supplementation, menstruation, milk abstinence, BMI, and levels of calcium, phosphorous, alkaline phosphatase, and 25-OH vitamin D were all attributes. RESULTS: Testing showed the decision trees to have sensitivities of 65.7-82.8%, specificities of 95.2-96.3%, accuracies of 86.2-89.8%, and Matthews correlation coefficients of 0.68-0.79. Smoking status was the most significant node (root) for ulcerative colitis and IBD-associated trees whereas calcium status was the root of Crohn's disease patients' decision tree. CONCLUSION: BD specialists could use such decision trees to reduce substantially the number of patients referred for bone densitometry and potentially save resources.     

Association of changes in oxidative and proinflammatory states with changes in vascular function after a lifestyle modification trial among obese children

BACKGROUND: The association of changes in oxidative and proinflammatory states with vascular function after diet and exercise intervention among obese children has not been previously explored. METHODS: In this 6-week diet and exercise intervention study in 35 obese children, age 12 to 18 years, we evaluated the relationship between changes in anthropometric indices, measures of insulin resistance, C-reactive protein (CRP), oxidized LDL (ox-LDL), and oxidative stress markers with changes in carotid intima-media thickness (C-IMT) and flow mediated dilation (FMD) of the brachial artery. RESULTS: At the end of the study, body mass index (BMI), waist circumference, and percentage body fat were decreased (P <0.05), but participants remained overweight (BMI > or = 95th percentile). Although FMD improved (P <0.05), the improvement in C-IMT did not reach statistical significance. The changes in BMI, waist circumference, fat mass, ox-LDL, malondialdehyde (MDA), CRP, insulin, and homeostasis model assessment for insulin resistance (HOMA-IR) had an inverse correlation with the changes in mean FMD after adjustment for age and sex, with the highest correlations documented for ox-LDL, CRP, and WC. The age- and sex-adjusted changes in ox-LDL, waist circumference, CRP, MDA, and body fat mass had the highest correlations with changes in C-IMT. CONCLUSIONS: Our findings suggest that a common inflammatory stress condition associated with childhood obesity, notably with abdominal fat deposition, may play a role in the development of the earliest stages of proatherosclerotic inflammatory processes and subsequent vascular dysfunction. These changes might be partially reversible by short-term diet and exercise intervention, even if patients do not reach ideal body weight.