E-Selectin is Elevated in Cord Blood of South Asian Neonates Compared with Caucasian Neonates

Diabetes mellitus: pathophysiological changes and therap

Characterization of anticoagulant heparinoids by immunoprofiling

Heparinoids are used in the clinic as anticoagulants. A specific pentasaccharide in heparinoids activates antithrombin III, resulting in inactivation of factor Xa and–when additional saccharides are present–inactivation of factor IIa. Structural and functional analysis of the heterogeneous heparinoids generally requires advanced equipment, is time consuming, and needs (extensive) sample preparation. In this study, a novel and fast method for the characterization of heparinoids is introduced based on reactivity with nine unique anti-heparin antibodies. Eight heparinoids were biochemically analyzed by electrophoresis and their reactivity with domain-specific anti-heparin antibodies was established by ELISA. Each heparinoid displayed a distinct immunoprofile matching its structural characteristics. The immunoprofile could also be linked to biological characteristics, such as the anti-Xa/anti-IIa ratio, which was reflected by reactivity of the heparinoids with antibodies HS4C3 (indicative for 3-O-sulfates) and HS4E4 (indicative for domains allowing anti-factor IIa activity). In addition, the immunoprofile could be indicative for heparinoid-induced side-effects, such as heparin-induced thrombocytopenia, as illustrated by reactivity with antibody NS4F5, which defines a very high sulfated domain. In conclusion, immunoprofiling provides a novel, fast, and simple methodology for the characterization of heparinoids, and allows high-throughput screening of (new) heparinoids for defined structural and biological characteristics

Inflammation increases plasma angiopoietin-like protein 4 in patients with the metabolic syndrome and type 2 diabetes

Contains fulltext : 138901.pdf (publisher's version ) (Open Access)BACKGROUND: Angiopoietin-like protein 4 (ANGPTL4) inhibits lipoprotein lipase and associates with dyslipidemia. The expression of ANGPTL4 is regulated by free fatty acids (FFA) that activate lipid-sensing peroxisome proliferator-activated receptors (PPARs), but FFA can also activate pattern recognition receptors including Toll-like receptor 4 (TLR4) in macrophages. OBJECTIVE: To assess whether systemic low-grade inflammation is a determinant for plasma ANGPTL4 levels in patients with the metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM). DESIGN: We studied 335 male participants: healthy controls (Controls), patients with the MetS without inflammation (MetS-I) and with low-grade inflammation (MetS+I), and patients with T2DM. All patients without diabetes included in the present study were initially matched for waist circumference. In plasma, ANGPTL4, C reactive protein (CRP) and metabolic parameters were determined. Underlying mechanisms were examined using human macrophages in vitro. RESULTS: As compared with Controls, plasma ANGPTL4 levels were increased in patients with MetS-I, MetS+I, and T2DM. Furthermore, ANGPTL4 was increased in T2DM compared with MetS-I. In fact, plasma CRP correlated positively with plasma ANGPTL4. In vitro studies showed that TLR 3/4 activation largely increased the expression and release of ANGPTL4 by macrophages. CONCLUSIONS: Plasma ANGPTL4 levels in humans are predicted by CRP, a marker of inflammation, and ANGPTL4 expression by macrophages is increased by inflammatory stimuli

Regulation of glomerular epithelial cell production of fibronectin and transforming growth factor-beta by high glucose,not by angiotensin II

Contains fulltext : 24785___.PDF (publisher's version ) (Open Access

A Systematic Review of Implementation of Established Recommended Secondary Prevention Measures in Patients with PAOD

AbstractObjectiveSince patients with peripheral arterial occlusive disease (PAOD) are at high-risk for cardiovascular morbidity and mortality, preventive measures aimed to reduce cardiovascular adverse events are advocated in the current guidelines. We conducted a systematic review to assess the implementation of secondary prevention (SP) measures in PAOD patients.MethodsPubMed, Cochrane Library, EMBASE and Web of Science databases were searched to perform a systematic review of the literature from 1999 till June 2008 on SP for PAOD patients. Assessment of study quality was done following the Cochrane Library review system. The record outcomes were antiplatelet agents, heart rate lowering agents, blood pressure lowering agents, lipid lowering agents, glucose lowering agents, smoking cessation and walking exercise.ResultsFrom a total of 2137 identified studies, 83 observational studies met the inclusion criteria, of which 24 were included in the systematic review comprising 34 157 patients. These patients suffered from coronary artery disease (n=3516, 41%), myocardial infraction (n=2647, 38%), angina pectoris (n=1790, 31%), congestive heart failure (n=2052, 14%), diabetes mellitus (n=10 690, 31%),hypertension (n=20 823, 73%) and hyperlipidaemia (n=15 067, 64%). Contrary to what the guidelines prescribe, antiplatelet agents, heart rate lowering agents, blood pressure lowering agents and lipid lowering agents were prescribed in 63%, 34%, 46% and 45% of the patients, respectively. Glucose lowering agents were prescribed in 81% and smoking cessation in 39% of the patients.ConclusionThe majority of patients suffering from PAOD do not receive the entire approach of SP measures as suggested by the current guidelines. To our knowledge, the cause of this undertreatment is multifactorial: patient, physician or health-care-related

Accuracy of carotid plaque detection and intima-media thickness measurement with ultrasonography in routine clinical practice

Background: Current guidelines in cardiovascular disease prevention advocate the use of carotid ultrasound measurements for risk stratification. Carotid abnormalities (plaques or increased intima-media thickness (IMT)) are associated with high risk of coronary and peripheral artery disease. An office-based measurement by clinicians would considerably broaden the clinical applicability of carotid ultrasound. In the present study we have assessed the accuracy of ultrasound detection of carotid plaques and intima-media thickness by trained internists in a routine outpatient setting. Methods and results: Carotid ultrasound was performed in 112 vascular outpatients by internists, after a six-week training period. The internists' results were independently compared to the reference standard, consisting of carotid ultrasound performed in a specialized vascular laboratory. Sensitivity and specificity were calculated for plaque detection and IMT determination. The mean time required to perform the scans on the outpatient department was 7.3 min (range 4.5 to 16.7 min). A high level of accuracy for detecting plaques (sensitivity 78.5%; specificity 93.6%) was achieved. Identifying abnormal IMT had lower sensitivity but adequate specificity of 46.7% and 87.6%, respectively. Conclusions: In conclusion, our findings demonstrate that clinicians can be trained well enough in six weeks to accurately and efficiently detect carotid plaques in an outpatient setting. IMT abnormalities were less accurately detected in the office-based approach and may require a specialized vascular laboratory. (C) 2009 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.The pathogenesis, clinical presentation and therapy of arterial and venous vascular disorder

The tolerability and efficacy of low-dose simvastatin in statin-intolerant patients

Background/aim: Statin intolerance is increasingly recognized as a therapy limiting factor in the primary and secondary prevention of cardiovascular disease. Since vulnerability to dose related adverse events differ between subjects treated with statins we hypothesized low-dose simvastatin would be tolerated and effective in statin-intolerant patients. Method: A single center open label prospective observational study was performed assessing tolerability and efficacy of low-dose simvastatin treatment in 35 statin-intolerant patients. Statin intolerance was defined as not being able to tolerate a registered dose statin due to myalgia-myopathy, myositis, or elevation of serum liver enzyme levels. These statin-intolerant patients were treated with simvastatin with an initial dose of 2.5 mg every other day. The dose was titrated upwards if possible. Tolerability was defined as remaining on treatment. Efficacy was defined as change of LDL-cholesterol compared to baseline. Results: The reached simvastatin dose ranged from 0.825 to 8.75 mg/day with a mean dose of 4 mg/day. Fifty-seven percent of the patients tolerated low-dose therapy and remained on treatment. Of these patients, 30% noted recurrent myalgia. Low-dose simvastatin significantly decreased mean(SD) LDL-cholesterol levels with 25.9(12.1)% (p<0.001). Eleven percent of the patients reached LDL-cholesterol target levels (<2.6 mmol/l) in an intention to treat analysis and in 20% of patients that tolerated low-dose simvastatin. Conclusion: Low-dose simvastatin therapy is tolerated in a considerable proportion of statin-intolerant patients with significant lipid lowering efficacy. Low-dose statin therapy can be considered in multidrug regimens in statin-intolerant patients. (C) 2010 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.Vascular Biology and Interventio

Accuracy of carotid plaque detection and intima-media thickness measurement with ultrasonography in routine clinical practice

Background: Current guidelines in cardiovascular disease prevention advocate the use of carotid ultrasound measurements for risk stratification. Carotid abnormalities (plaques or increased intima-media thickness (IMT)) are associated with high risk of coronary and peripheral artery disease. An office-based measurement by clinicians would considerably broaden the clinical applicability of carotid ultrasound. In the present study we have assessed the accuracy of ultrasound detection of carotid plaques and intima-media thickness by trained internists in a routine outpatient setting. Methods and results: Carotid ultrasound was performed in 112 vascular outpatients by internists, after a six-week training period. The internists' results were independently compared to the reference standard, consisting of carotid ultrasound performed in a specialized vascular laboratory. Sensitivity and specificity were calculated for plaque detection and IMT determination. The mean time required to perform the scans on the outpatient department was 7.3 min (range 4.5 to 16.7 min). A high level of accuracy for detecting plaques (sensitivity 78.5%; specificity 93.6%) was achieved. Identifying abnormal IMT had lower sensitivity but adequate specificity of 46.7% and 87.6%, respectively. Conclusions: In conclusion, our findings demonstrate that clinicians can be trained well enough in six weeks to accurately and efficiently detect carotid plaques in an outpatient setting. IMT abnormalities were less accurately detected in the office-based approach and may require a specialized vascular laboratory. (C) 2009 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved

ATHEROSCLEROTIC VARIATION IN A GROUP OF OBESE MALE PATIENTS WITH IDENTICAL FRAMINGHAM RISK SCORES

Thrombosis and Hemostasi

THE EFFECT OF CARDIOVASCULAR RISK FACTORS ON THE INTIMA MEDIA THICKNESS IN AN INDONESIAN POPULATION UNDERGOING THE SECONDARY EPIDEMIOLOGICAL TRANSITION: A COHORT STUDY

The pathogenesis, clinical presentation and therapy of arterial and venous vascular disorder