Jean-Paul Cheramy-Bien

Evaluation of autoantibodies against oxidized LDL and antioxidant status in top soccer and basketball players after 4 months of competition.

Antioxidant status and titers of autoantibodies against oxidized low-density lipoproteins (ox-LDL-Ab) were investigated in top soccer (S; n = 21, age 24.6 +/- 4.3 years) and basketball (B; n 3,000 mIU/ml) in ox-LDL-Ab were found in half the players (12S and 4B) with a maximum reaching 6000 mIU/ml (normal range: 200-600 mIU/ml), showing an in vivo LDL oxidation. There was no correlation between ox-LDL-Ab titers and chlolesterol, LDL cholesterol, or antioxidant levels. Nevertheless, plasma vitamin C concentration was lower in athletes having high levels of ox-LDL-Ab when compared with those with normal levels (8.49 +/- 3.14 mirogram/ml vs. 10.39 +/- 2.55 microgram/ml), but this difference was not statistically significant. In conclusion, our data suggest that potential atherogenic and cardiovascular risks as reflected by high titers in ox-LDL-Ab may exist in some top athletes despite a nonaltered antioxidant status.

Multifactorial Relationship Between 18F-Fluoro-Deoxy-Glucose Positron Emission Tomography Signaling and Biomechanical Properties in Unruptured Aortic Aneurysms

Background—The relationship between biomechanical properties and biological activities in aortic aneurysms was investigated with finite element simulations and 18F-fluoro-deoxy-glucose (18F-FDG) positron emission tomography. Methods and Results—The study included 53 patients (45 men) with aortic aneurysms, 47 infrarenal (abdominal aortic) and 6 thoracic (thoracic aortic), who had ≥1 18F-FDG positron emission tomography/computed tomography. During a 30-month period, more clinical events occurred in patients with increased 18F-FDG uptake on their last examination than in those without (5 of 18 [28%] versus 2 of 35 [6%]; P=0.03). Wall stress and stress/strength index computed by finite element simulations and 18F-FDG uptake were evaluated in a total of 68 examinations. Twenty-five (38%) examinations demonstrated ≥1 aneurysm wall area of increased 18F-FDG uptake. The mean number of these areas per examination was 1.6 (18 of 11) in thoracic aortic aneurysms versus 0.25 (14 of 57) in abdominal aortic aneurysms, whereas the mean number of increased uptake areas colocalizing with highest wall stress and stress/strength index areas was 0.55 (6 of 11) and 0.02 (1 of 57), respectively. Quantitatively, 18F-FDG positron emission tomographic uptake correlated positively with both wall stress and stress/strength index (P<0.05). 18F-FDG uptake was particularly high in subjects with personal history of angina pectoris and familial aneurysm. Conclusions—Increased 18F-FDG positron emission tomographic uptake in aortic aneurysms is strongly related to aneurysm location, wall stress as derived by finite element simulations, and patient risk factors such as acquired and inherited susceptibilities.

Family Members of Patients with Abdominal Aortic Aneurysms are at Increased Risk for Aneurysms: Analysis of 618 Probands and their Families from the Liege AAA Family Study.

BACKGROUND The objectives were to answer the following questions with the help of a well-characterized population in Liège, Belgium: 1) what percentage of patients with abdominal aortic aneurysm (AAA) have a positive family history for AAA? 2) what is the prevalence of AAAs among relatives of patients with AAA? and 3) do familial and sporadic AAA cases differ in clinical characteristics? METHODS Patients with unrelated AAA diagnosed at the Cardiovascular Surgery Department, University Hospital of Liège, Belgium, between 1999 and 2012 were invited to the study. A detailed family history was obtained in interviews and recorded using Progeny software. We divided the 618 patients into 2 study groups: group I, 296 patients with AAA (268; 91% men) were followed up with computerized tomography combined with positron emission tomography; and group II, 322 patients with AAA (295; 92% men) whose families were invited to ultrasonographic screening. RESULTS In the initial interview, 62 (10%) of the 618 patients with AAA reported a positive family history for AAA. Ultrasonographic screening identified 24 new AAAs among 186 relatives (≥50 years) of 144 families yielding a prevalence of 13%. The highest prevalence (25%) was found among brothers. By combining the number of AAAs found by ultrasonographic screening with those diagnosed previously the observed lifetime prevalence of AAA was estimated to be 32% in brothers. The familial AAA cases were more likely to have a ruptured AAA than the sporadic cases (8% vs. 2.4%; P < 0.0001). CONCLUSIONS The findings confirm previously found high prevalence of AAA among brothers, support genetic contribution to AAA pathogenesis, and provide rationale for targeted screening of relatives of patients with AAA.

Tissue PET) Vascular metabolic imaging and peripheral plasma biomarkers in the evolution of chronic aortic dissections

AIMS Despite adequate medical management, dissection of the descending aorta (type B) may develop complications, including aneurysmal progression and eventually rupture. Partial false lumen thrombosis has been identified as a marker of adverse evolution in chronic dissection. The aim of this study was to test the ability of complementary information, provided by (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computed tomography (PET/CT) and peripheral biomarkers, to add pathophysiological significance and a prognostic value to morphological data. METHODS AND RESULTS We explored serial aortic (18)F-FDG uptake by PET/CT imaging and plasma biomarkers in a series of 23 patients with type B dissection to predict complications from initial data and to investigate potential associations with aneurysmal expansion during follow-up. Complications occurred in 17 patients. Acute initial characteristics associated with complications were male gender (P = 0.021), arterial hypertension (P = 0.040), aortic dissection diameter (P = 0.0086), partial thrombosis of the false channel (P = 0.0046), and enhanced focal (18)F-FDG uptake (P = 0.045). During follow-up (mean 16.7 ± 8.0 months), aneurysmal expansion was associated with false lumen morphology (P< 0.0001), quantitative (18)F-FDG uptake, (P = 0.0029), elevated plasma concentrations of biomarkers of platelets (P-selectin, P = 0.0009) and thrombin activation (TAT complexes, P = 0.0075), and fibrinolysis (PAP complexes, P < 0.0001; D-dimers, P = 0.0006). Plasma markers of coagulation and fibrinolysis were related to false channel morphology, suggesting that thrombus biological dynamics may drive progressive expansion of type B dissections. CONCLUSION Enhanced FDG uptake may be considered as a complementary imaging marker associated with secondary complications in type B dissections. During follow-up, aneurysmal progression is related to PET/CT and biomarkers of thrombus renewal and lysis.

Lifestyle Behaviours and Plasma Vitamin C and β-Carotene Levels from the ELAN Population (Liège, Belgium)

Several factors, including fruit and vegetables intakes, have been shown to significantly influence the plasma concentrations of the two antioxidants vitamin C and β-carotene. Deficiency levels of 6 mg/L (34.2 μM) for vitamin C and of 0.22 mg/L (0.4 μM) for β-carotene have been suggested below which cardiovascular risk might be increased. The present study performed on 897 presumably healthy subjects aged 40–60 years aimed to examine how modifiable lifestyle factors may be related to vitamin C and/or β-carotene deficiency. Gender, smoking, lack of regular physical activity and of daily fruit consumption (≥2/day), and social status (in particular, unemployment) were found to be significant risk factors for vitamin C deficiency. For β-carotene deficiency, the same factors were identified except social status; moreover, overweight and OC use in women were also found to have a deleterious effect. For non exposed subjects, the probability of developing vitamin C deficiency was 4% in men and 2.4% in women. This probability increased to 66.3% for men and to 44.3% for women (and even to 50.4% under OC use), when all risk factors were present. For β-carotene deficiency, the corresponding probabilities were equal to 29.7% in men and 13.7% in women (no risk factor present), and to 86.1% for men and 69.9% (91.6% for OC use) for women (all factors present), respectively.

Effects of Large-Pore Hemofiltration in a Swine Model of Fulminant Hepatic Failure

Among the different potential mechanisms that could lead to brain edema and intracranial hypertension in fulminant hepatic failure (FHF), the inflammatory hypothesis implies that systemic inflammation might be in part responsible for an increase in cerebral blood flow (CBF) and brain water content. In this study, the authors used a validated ischemic FHF swine model to evaluate the effects of 80 kDa large-pore membrane hemofiltration (LPHF) on intracranial pressure (ICP) and CBF, in relation with the clearance of proinflammatory cytokines and blood liver tests, as primary end points. Fifteen pigs were randomized into one of three groups: SHAM, FHF, and FHF + LPHF. All experiments lasted 6 h. In the FHF groups, liver failure was induced by liver ischemia. After 2 h, the FHF + LPHF group underwent 4 h of a zero-balance continuous veno-venous hemofiltration using a 0.7-m(2), large-pore (78 Å) membrane with a cutoff of 80 kDa. ICP, CBF, mean arterial pressure, central venous pressure, and heart rate were continuously monitored and recorded. Arterial aspartate aminotransferase, total bilirubin, creatinine, international normalized ratio, glucose, lactate and serum cytokines interleukin (IL)-6, IL-10, and tumor necrosis factor-α were measured at T0, T120, and T360. Over the 6 h following liver ischemia, the FHF group developed a significant increase in ICP. This ICP rise was not observed in the SHAM group and was attenuated in the FHF + LDHF group. However, the ICP levels were not different at T360 in the FHF + LDHF group compared to the FHF group. No significant effect of LPHF on liver tests or levels of proinflammatory cytokines could be demonstrated. In this model, 80 kDa LPHF was not efficient to control FHF intracranial hypertension and to decrease serum cytokine levels.

Intracellular free iron content of rat liver tissue after cold ischemia

TRANSPLANTABLE ORGANS are usually stored in a preservation medium, such as University of Wisconsin (UW) solution, under hypothermic conditions due to the energy deficiency. During cold storage significant cellular alterations may occur. Rauen et al have described that the preservation injury to cultured liver endothelial cells and hepatocytes is mediated by the formation of reactive oxygen species (ROS) through energy-dependent mechanisms that occur independent of hypoxia and subsequent reoxygenation. Damage to cultured hepatocytes was prevented when the cells were preincubated with desferrioxamine, suggesting iron-dependent generation of ROS. Kozlov et al have provided evidence that intracellular free iron in the liver represents an intermediate step in the transport of iron from blood transferrin to the site of synthesis of iron-containing molecules such as ferritin. Detected by electron paramagnetic resonance (EPR) spectroscopy as paramagnetic complexes in presence of desferioxamine, this transit pool consists of low-molecular weight (LMW) iron compounds able to participate in ROS generation. In the present paper, we examine the effect of cold ischemia on the intracellular free iron content of rat liver tissue.

Abdominal Aortic Aneurysm (AAA): Is There a Role for the Prevention and Therapy Using Antioxidants?

BACKGROUND Abdominal aortic aneurysm (AAA) is a degenerative disease that causes mortality in people aged > 65 years. Increased reactive oxygen species (ROS) and oxidative stress seem to play a pivotal role in AAA pathogenesis. Several sources of ROS have been identified in aortic tissues using experimental models: inflammation, increased activity of NAD(P)H or NOX, over-expression of inducible nitric oxide synthase (iNOS), uncoupled endothelial nitric oxide synthase (eNOS), platelets activation and iron release from hemoglobin. OBJECTIVES Human studies confirmed that oxidative stress and endothelial dysfunction, an important source of ROS production, were well associated with AAA development. Reducing oxidative stress by antioxidants can therefore be a good strategy for limiting AAA development. The objective of the present study is to review literature data favoring or not such a hypothesis. There is currently no evidence showing that strategies using classical low molecular weight antioxidants (vitamins C and E, β- carotene) as target for ROS is effective to reduce human AAA progression. However, recent epidemiological data have highlighted the positive role of a diet enriched in fruits which contain high amounts of antioxidant polyphenols. By their ability to restore endothelial function and also their capacity to stimulate enzymatic antioxidants through activation of the Keap1/Nrf2/ARE pathway, polyphenols can represent a promising treatment target for reducing human AAA progression. CONCLUSION Clinical studies are therefore urgently necessary to confirm the potential beneficial effect of polyphenols in preventing or limiting AAA.

Efficacy of the RemoweLL cardiotomy reservoir for fat and leucocyte removal from shed mediastinal blood: a randomized controlled trial.

Introduction: Re-transfusion of lipid particles and activated leucocytes with shed mediastinal blood (SMB) can aggravate cardiopulmonary bypass-associated inflammation and increase the embolic load. This study evaluated the fat and leucocyte removal capacity of the RemoweLL cardiotomy reservoir. Methods: Forty-five patients undergoing elective on-pump cardiac surgery were randomly allocated to filtration of SMB using the RemoweLL or the Admiral cardiotomy reservoir. The primary outcome was a drop in leucocytes and lipid particles obtained with the two filters. The effect of the filters on other blood cells and inflammatory mediators, such as myeloperoxidase (MPO), was also assessed. Results: The RemoweLL cardiotomy filter removed 16.5% of the leucocytes (p<0.001) while no significant removal of leucocytes was observed with the Admiral (p=0.48). The percentage reductions in lipid particles were similar in the two groups (26% vs 23%, p=0.2). Both filters similarly affected the level of MPO (p=0.71). Conclusion: The RemoweLL filter more effectively removed leucocytes from SMB than the Admiral. It offered no advantage in terms of lipid particle clearance.

Therapeutic Applications of Prostaglandins and Thromboxane A2 Inhibitors in Abdominal Aortic Aneurysms

BACKGROUND Abdominal aortic aneurysm (AAA) is one of the leading causes of death in western countries. Surgery is still, at the present time, the sole treatment that has however a significant mortality and cost rate. Many pharmacological agents are under investigation aiming to reduce growth and prevent AAA rupture. These drugs target different pathological pathways and, notably, the excessive production of prostanoids by cyclooxygenases (COX). Intra-aneurysmal thrombus plays an adverse key role in the progression of AAA, platelets being a primary source of prostanoids as thromboxane A2. OBJECTIVE In this review, we summarize studies targeting prostanoids production and down-stream pathways in cardiovascular diseases, and more specifically in AAA. RESULTS AND CONCLUSION Various inhibitors of COX or antagonists of prostanoids receptors have been investigated in AAA animal models with conflicting results. In human AAA, only a few number of studies focused on anti-platelet therapy mostly using acetylsalicylic acid (aspirin, ASA), a COX1 inhibitor. Finally, we report preliminary promising results of a model of AAA in rats receiving a thromboxane A2 inhibitor, BM-573 that induced a reduction of aneurysmal growth.