Biomedical subjects

J De Backer

Publications and source records attributed to J De Backer.

11 recordsLinked to original sources

PubMed2002

Parameters of inflammation and infection in a community based case-control study of coronary heart disease.

BACKGROUND: increased levels of systemic inflammatory markers appear to be related to coronary heart disease (CHD) both in asymptomatic individuals and in subjects with established CHD. Whether these associations are related to confounding coronary risk factors or are explicable through chronic infectious conditions is not clear. OBJECTIVES: (1) to determine whether subjects with stable CHD differ from normal controls in inflammatory markers (CRP, SAA and fibrinogen) and/or in serostatus of four infectious agents (Helicobacter pylori, Chlamydia pneumoniae, CMV and EBV), independent of classical coronary risk factors. (2) To determine whether these inflammatory markers are related to the serostatus against these four infectious agents either in patients with CHD or in normal subjects. METHODS: in a large epidemiologic survey, 446 out of 16307 men at work, aged 35-59 years, had antecedents of myocardial infarction, CABG or PTCA or had prominent Q/QS waves on their resting ECG. They were compared with double the number (n=892) of men, matched for age, educational level and industry. Inflammatory biomarkers (CRP, fibrinogen and SAA) and antibodies against H. pylori, C. pneumoniae, CMV and EBV were measured, besides classical coronary risk factors. RESULTS: in univariate analyses, cases had higher CRP, fibrinogen and SAA levels than controls, but no differences were observed in serumantibody levels to any of the infectious agents. Markers of previous infections were not related to inflammatory biomarkers. In multivariate analyses CRP was significantly different between cases and controls independent of differences in other coronary risk factors and in the use of lipid lowering drugs and antiplatelet aggregants. CONCLUSIONS: in men at work with CHD, CRP levels are significantly different from controls, independent of known risk factors. No association was found between inflammatory biomarkers and positive serostatus against four infectious agents, neither in the patients nor in the healthy controls.

Acute-Phase Proteins↗

PubMed2001

Tight binding of the angiotensin AT(1) receptor antagonist.

Angiotensin II induces angiotensin AT(1) receptor internalization via Clathrin coated pits formation. We investigated whether insurmountable inhibition by the non-peptide antagonist 2-ethoxy-1-[(2'-(1H-tetrazol-5-yl) biphenyl-4-yl) methyl]-1H-benzimidazoline-7-carboxylic acid (candesartan) was related to receptor internalization. Mild acid treatment can discriminate between internalized and cell surface bound [(3)H]angiotensin II. In contrast, it provides no information about the subcellular localization of bound [(3)H]candesartan since this binding is acid resistant. The internalization of [(3)H]angiotensin II is rapidly inhibited in the presence of 0.4 M sucrose. Yet, no such rapid effect was noticed for [(3)H]candesartan. [(3)H]candesartan displays insurmountable/long lasting binding to the vast majority of both wild type and L(314) truncated rat angiotensin AT(1A) receptors with impaired receptor internalization. In agreement with previously published AT(1) angiotensin receptor visualization experiments, the present data suggest that non-peptide antagonist-angiotensin AT(1) receptor complexes remain at the cell surface. Insurmountable antagonism of candesartan is therefore independent from receptor internalization via clathrin-coated pits.

Angiotensin II↗

PubMed2000

Reversible and syntopic interaction between angiotensin receptor antagonists on Chinese hamster ovary cells expressing human angiotensin II type 1 receptors.

Evidence for a competitive type of interaction between angiotensin II type 1 (AT(1)) antagonists on Chinese hamster ovary cells expressing the human AT(1) receptor (CHO-AT(1)) was obtained by analyzing the binding of [(3)H]-2-ethoxy-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-1H- ben zimidazoline-7-carboxylic acid ([(3)H]candesartan) and by measuring the AT-induced production of inositol phosphates. The AT(1) antagonists candesartan, 2-n-butyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]+ ++imid azole-5-carboxylic acid (EXP3174), or 2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2'-(1H-tetrazol-5-yl)bip hen yl- 4-yl)methyl]imidazole (losartan) produced a concentration-dependent increase in the apparent K(d) values of [(3)H]candesartan in saturation binding experiments, while the B(max) values were unchanged. Furthermore, the dissociation rate of the radioligand initiated by 1 microM unlabelled candesartan was not changed in the presence of 10 microM losartan, 10 microM EXP3174, or 10 microM irbesartan (2-n-butyl-4-spirocyclopentane-1-[(2'-(1H-tetrazol-5-yl)b iph enyl-4-yl) methyl]2-imidazolin-5-one)). Preincubation of the CHO-AT(1) cells with candesartan, EXP3174, and irbesartan caused a reduction in the maximal AT-induced inositol mono-, bis-, and trisphosphate production. This insurmountable effect was reversed in the presence of 1 microM losartan. In line with this finding, the insurmountable antagonist concentration-inhibition curves at 10 microM AT were shifted to the right in the presence of losartan. For candesartan this effect was concentration-dependent, yielding a pK(B) value for losartan of 7.7, which is similar to the pK(B) from previously obtained AT concentration-response curves. Finally, the dissociation rate of candesartan, EXP3174, irbesartan, and losartan was determined by measuring the recovery of AT responses after antagonist pretreatment and washing of the cells with medium containing 1 microM losartan to prevent re-association of the insurmountable antagonists. In addition, similar kinetic data were obtained from the slowing of the [(3)H]candesartan association rate to antagonist preincubated cells.

Angiotensin Receptor Antagonists↗

PubMed1999

QT dispersion is not related to infarct size or inducibility in patients with coronary artery disease and life threatening ventricular arrhythmias.

OBJECTIVE: To relate QT parameters to infarct size and inducibility during electrophysiological studies. DESIGN: Analysis of a prospective register. SETTING: University hospital. PATIENTS: 64 patients with coronary artery disease and documented life threatening ventricular arrhythmias. INTERVENTIONS: Measurements of QT-max, QTc-max, and QT dispersion (QT-d) on a simultaneous 12 lead ECG (50 mm/s). Estimation of myocardial infarct size with radionuclide left ventricular ejection fraction (LVEF), echocardiography (left ventricular end diastolic diameter, LVEDD), and a defect score based on a quantitative stress redistribution 201-thallium perfusion study. Electrophysiological study to assess inducibility. RESULTS: Mean (SD) QT parameters were: QT-max 440 (50) ms, QTc-max 475 (46) ms, and QT-d 47 (20) ms. Mean (SD) estimates of infarct size were: LVEF 34 (13)%, LVEDD 61 (9) mm, and defect score 18 (11). There was no significant correlation between any index of infarct size and QT parameters. QT parameters were not significantly different between patients with inducible (n = 57) and non-inducible arrhythmias (n = 7) (QT-max: 416 (30) v 443 (51) ms, p = 0.18; QTc-max 485 (34) v 473 (47) ms, p = 0.34; QT-d 47 (12) v 47 (21) ms, p = 0.73). Non-inducible patients had a significant lower defect score: 8 (9) v 19 (11), p = 0.02, but comparable LVEF: 38 (12)% v 34 (12)%, p = 0.58, and LVEDD: 54 (10) v 61 (8) mm, p = 0.13. CONCLUSIONS: QT parameters are not influenced by infarct size and do not predict inducibility during electrophysiological study in patients with coronary artery disease and malignant ventricular arrhythmias. In contrast, the amount of scar tissue determined by perfusion imaging is strongly correlated with inducibility.

Aged↗

PubMed1998