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Biomedical subjects

Eric Perrier

Publications and source records attributed to Eric Perrier.

At least 19 recordsLinked to original sources
PubMed2006

Non-invasive detection of coronary artery disease in patients with left bundle branch block using 64-slice computed tomography.

OBJECTIVES: The goal of this study was to evaluate the diagnostic accuracy of 64-slice computed tomography (CT) to identify coronary artery disease (CAD) in patients with complete left bundle branch block (LBBB). BACKGROUND: Left bundle branch block increases risk of cardiac mortality, and prognosis is primarily determined by the underlying coronary disease. Non-invasive stress tests have limited performance, and conventional coronary angiography (CCA) is usually required. METHODS: Sixty-six consecutive patients with complete LBBB and sinus rhythm admitted for CCA were enrolled. Computed tomography was performed 3 +/- 3.9 days before CCA. The accuracy of 64-slice CT to detect significant stenosis (>50% lumen narrowing) was compared with quantitative coronary angiography. All segments were analyzed regardless of image quality from coronary calcification or motion artifacts. Results were analyzed by patient and by coronary segment (990) using the American Heart Association 15-segment model. RESULTS: Lower heart rates were associated with improved image quality. Computed tomography correctly identified 35 of 37 (95%) patients without significant stenosis and 28 of 29 (97%) patients with significant stenosis on CCA. Computed tomography correctly assessed 68 of 94 (72%) significant stenosis. Overall, accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of 64-slice CT for identifying CAD by patient was 95%, 97%, 95%, 93%, and 97%, respectively, and by segment was 97%, 72%, 99%, 91%, and 97%, respectively. CONCLUSIONS: In a routine clinical practice, 64-slice CT detects with excellent accuracy a significant CAD in patients with complete LBBB. A normal CT in this clinical setting is a robust tool to act as a filter and avoid invasive diagnostic procedures.

Aged↗
PubMed2006

Comparison of coronary minimal lumen area quantification by sixty-four-slice computed tomography versus intravascular ultrasound for intermediate stenosis.

The present study assessed 64-slice computed tomographic accuracy to quantify minimal lumen area (MLA) and determine lesion severity in intermediate stenosis by angiography compared with intravascular ultrasound (IVUS). Sixty-four-slice computed tomography (CT) has been shown to be effective in coronary stenotic assessment by visual estimation compared with angiography. However, angiography is not an accurate gold standard for intermediate stenotic quantification compared with IVUS. Forty patients (54 lesions) with 30% to 70% coronary stenosis by angiography in a major coronary branch were included. All patients underwent quantitative angiography, retrospective electrocardiographically gated 64-slice CT (Siemens), and IVUS (40-MHz Atlantis; Boston Scientific). MLA was manually traced by 2 blinded and independent operators on 64-slice computed tomographic cross-sectional reconstruction and compared with IVUS MLA. A lesion was considered significant if the MLA was <or=6 mm(2) for the left main coronary artery and <or=4 mm(2) for another epicardial vessel with CT and IVUS. The correlation between IVUS MLA and computed tomographic MLA was r = 0.88 (p <0.001). Interobserver variabilities (mean +/- SD) were 1.2 mm(2) for CT and 1.1 mm(2) for CT versus IVUS. Bland-Altman analysis showed a 95% confidence interval of -42% to +44% for computed tomographic measurement using IVUS as a reference. Sensitivity, specificity, accuracy, and Cohen's kappa coefficient for significant lesion classification using CT were 87%, 72%, 80%, and 0.6, respectively (p <0.0001). In conclusion, when using MLA, 64-slice CT was able to quantify coronary stenosis with good correlation compared with IVUS and determine lesion severity in patients with intermediate lesions by angiography.

Coronary Angiography↗
PubMed2006

Mixed Langerhans cell and interstitial/dermal dendritic cell subsets emanating from monocytes in Th2-mediated inflammatory conditions respond differently to proinflammatory stimuli.

The skin harbors two dendritic cell (DC) subsets, Langerhans cells (LC) and interstitial/dermal DC (IDDC), which traffic to lymph nodes after inflammation and ultraviolet stress. To demonstrate that monocytes may act as DC precursors for skin DC in postinflammatory recolonization, we generated LC and IDDC from monocytes by using cytokines related to the T helper cell type 2 environment [granulocyte macrophage-colony stimulating factor/transforming growth factor-beta/interleukin-13/tumor necrosis factor alpha (GM-CSF/TGF-beta/IL-13/TNF-alpha)]. In this study, skin DC [LC as Langerin/CD207(+) cells and IDDC as DC-specific intercellular adhesion molecule-grabbing nonintegrin (SIGN)/CD209(+) cells] displayed desynchronized programs along their differentiation, activation/maturation processes in response to stimuli characteristics of a proinflammatory context. First, we demonstrate that monocytes are able to diverge simultaneously along two distinct pathways toward Langerin(+)-LC-type DC and DC-SIGN(+)-IDDC. Second, as TGF-beta is known to antagonize the TNF-alpha-induced maturation process of DC, we showed that IDDC did not mature and acquired a low CC chemokine receptor 7 (CCR7) receptor expression even when stimulated with prolonged incubation with TNF-alpha. It is striking that the LC subset is able to express a high level of CCR7 expression and the maturation marker DC-lysosome-associated membrane protein (DC-LAMP). Third, mixed LC and IDDC subsets secrete IL-10 and IL-12 when stimulated by CD40 ligand and lipopolysaccharide (LPS) but not after prolonged incubation with TNF-alpha. In contrast, LPS was a better activator of IL-10 secretion than the CD40 ligand for GM-CSF/IL-4-generated DC and for GM-CSF/TGF-beta/IL-13-generated LC and IDDC populations. To summarize, the phenotypic/migratory maturation status of LC may be more easily enhanced by stimuli mimicking a proinflammatory situation, and IDDC are more resistant. Moreover, our culture system provided a means of studying cross-talk between two skin DC outside of their respective skin compartment.

Animals↗
PubMed2006

The lysyl oxidase LOX is absent in basal and squamous cell carcinomas and its knockdown induces an invading phenotype in a skin equivalent model.

Lysyl oxidase initiates the enzymatic stage of collagen and elastin cross-linking. Among five isoforms comprising the lysyl oxidase family, LOX is the better studied. LOX is associated to an antitumor activity in ras-transformed fibroblasts, and its expression is down-regulated in many carcinomas. The aim of this work was to shed light on LOX functions within the epidermis by studying its expression in human basal and squamous cell carcinomas and analyzing the effect of its enzymatic activity inhibition and protein absence on human keratinocytes behavior in a skin equivalent. In both carcinomas, LOX expression by epidermal tumor cells was lacking, while it was up-regulated around invading tumor cells in association with the stromal reaction. Lysyl oxidase activity inhibition using beta-aminoproprionitrile in a skin equivalent model prepared with both primary human keratinocytes and HaCaT cell line affected keratin 10 and filaggrin expression and disorganized the collagen network and the basement membrane. In spite of all these changes, no invasion phenotype was observed. Modelization of the invasive phenotype was only noticed in the skin equivalent developed with LOX antisense HaCaT cell line, where the protein LOX is specifically absent. Our results clearly indicate that lysyl oxidase enzymatic activity is essential not only for the integrity maintenance of the dermis but also for the homeostasis of the epidermis. Moreover, LOX protein plays a role in the skin carcinomas and invasion but not through its enzymatic activity.

Aminopropionitrile↗
PubMed2006

Analogues of N-hydroxycinnamoylphenalkylamides as inhibitors of human melanocyte-tyrosinase.

Melanin play a major role in human skin protection and their biosynthesis is vital. Due to their color, they contribute to the skin pigmentation. Tyrosinase is a key enzyme involved in the first stage of melanin synthesis, catalyzing the transformation of tyrosine to l-dopaquinone. The aim of the present study was to study molecules able to inhibit melanin synthesis through inhibition of tyrosinase and their potential use in treating pigmentation-related disorders. We targeted amides obtained from coupling p-hydroxycinnamic acid derivatives with phenylalkylamines. The biological activity was evaluated on human melanocytes by an assay which measures tyrosine-catalyzed L-Dopa oxidation. The most active amides were: trans-N-caffeoyltyramine, N-dihydrocaffeoyltyramine, and trans-N-dihydro-p-hydroxycinnamoyltyramine which induce complete inhibition at 0.1mM. At the latter concentration, kojic acid, which was used as the reference inhibitor, was inactive.

Amides↗
PubMed2006

Discovery of benzylidenebenzofuran-3(2H)-one (aurones) as inhibitors of tyrosinase derived from human melanocytes.

Tyrosinase is a copper-dependent enzyme which converts l- tyrosine to dopaquinone and is involved in different biological processes such as melanogenesis and skin hyperpigmentation. The purpose of this study was to investigate naturally occurring aurones (Z-benzylidenebenzofuran-3(2H)-one) and analogues as human tyrosinase inhibitors. Several aurones bearing hydroxyl groups on A-ring and different substituents on B-ring were synthesized and evaluated as inhibitors of human melanocyte-tyrosinase by an assay which measures tyrosinase-catalyzed l-Dopa oxidation. We found that unsubstituted aurones were weak inhibitors; however, derivatives with two or three hydroxyl groups preferably at 4,6 and 4' positions are able to induce significant tyrosinase inhibition. The most potent aurone was found to be the naturally occurring 4,6,4'-trihydroxyaurone which induces 75% inhibition at 0.1 mM concentration and is highly effective when compared to kojic acid, one of the best tyrosinase inhibitors known so far (the latter is completely inactive at such concentrations). Active aurones are devoid of toxic effects as shown by in vivo studies.

Administration, Oral↗
PubMed2006

LOXL as a target to increase the elastin content in adult skin: a dill extract induces the LOXL gene expression.

The lysyl oxidases lysyl oxidase (LOX) and lysyl oxidase-like (LOXL) are responsible for elastin cross-linking. It was shown recently that LOXL is essential for the elastic fibres homeostasis and for their maintenance at adult age. We first determined whether or not elastin, LOX and LOXL are less expressed during adulthood. The LOX and LOXL mRNA level, quantified by real-time reverse transcriptase-polymerase chain reaction decreased in adult skin fibroblasts compared with fibroblasts from children. In contrast, the elastin mRNA level remains stable at all ages. The goal of this study was to induce elastogenesis at the adult age. Therefore, both enzymes, and in particular LOXL, of which expression is the most affected by age, could be targeted to induce elastogenesis in adult skin. We screened a library of about 1000 active ingredients to find activators capable to stimulate specifically the LOXL gene expression in adult dermal fibroblasts. The positive effect of selected active ingredients was confirmed on fibroblasts grown on monolayers and on dermal and skin equivalent cultures. One extract, obtained from dill (LYS'LASTINE V, Engelhard, Lyon, France), stimulates the LOXL gene expression in dermal equivalents (+64% increase in the LOXL mRNA level when compared with control). At the same time, the elastin detection is increased in dermal equivalents and under the dermal-epidermal junction of skin equivalents, without increase of the elastin mRNA. In conclusion, LOXL can be considered as a new target to reinduce elastogenesis. Its stimulation by a dill extract is correlated with increased elastin detection, suggesting an increase in elastogenesis efficiency.

Adult↗
PubMed2006

Essential thrombocytosis and myocardial infarction in an aircrew member: aeromedical concerns.

Of essential thrombocytosis (ET) cases, 25% occur in patients younger than 40 yr of age, and are often discovered as an incidental laboratory abnormality. However, the risk for thrombosis remains of concern and needs to be closely evaluated, especially in the aerospace environment. We report on the case of a 40-yr-old, female French military air traffic controller (ATC) admitted for an ST-elevation myocardial infarction. She was a smoker and had no previous medical history of ET. The coronary angiogram showed a thrombus of the left anterior descending coronary artery. She was treated medically with angioplasty and stent. Laboratory data revealed an elevated platelet count (495,000 x mm(-3)), confirmed 6 mo later (645,000 x mm(-3)). The diagnosis of ET was then established. No platelet-lowering therapy was prescribed, aspirin was continued, and this ATC was considered unfit for operational duties. Arterial thrombosis is more frequent than venous in ET, and can affect the whole arterial tree from the microscopic to the main arteries. Thrombosis is unpredictable and, due to abnormalities of the platelet functions and associated cardiovascular risk cofactors, may occur even with an almost normal platelet count. Risk-adjusted therapy is needed, including lifestyle modification to address vascular risk factors, antiplatelet drugs (aspirin), and platelet-lowering agents with their risk of leukomutagenesis. Furthermore, there is no consensus for the prevention of venous thrombosis. The decision for the aeromedical expert is difficult and depends on the specialty of the aircrew member, the type and duration of the mission, the therapeutics used, and the benefit-risk ratio of platelet-lowering agents.

Adult↗
PubMed2006

LBBB in aircrew with low cardiac risk: diagnostic application of multislice CT.

INTRODUCTION: Because of its excellent negative predictive value for diagnosing coronary stenoses, multislice computed tomography (MSCT) may be a way to assess the absence of significant coronary stenosis. We discussed its place in aeromedical decision-making for aircrew members with a low level of cardiovascular risk factors and acquired left bundle branch block (LBBB). METHODS AND RESULTS: During the period 2002-2004, 12 male aircrew members (mean age: 42.9 yr) with acquired LBBB were admitted to our cardiovascular and aeronautical department. The exploration of LBBB was classical, including an electrophysiological study, the usual coronary angiography, and MSCT. All the morphological explorations of the coronary tree were normal. DISCUSSION: In addition to complex electrophysiological mechanisms, coronary artery disease (CAD) is suspected, but remains infrequent in some EKG findings such as acquired LBBB, especially for patients with low cardiovascular risk factors as demonstrated with our aircrew members. However, in aerospace medicine the expert needs to prove the absence of CAD. The use of standard examinations (exercise stress test, stress myocardial scintigraphy, etc.) is controversial because of artifacts and a conventional coronary angiography is necessary. According to previous studies, including using a validated technique in our department (with 16-slice computed tomography), the excellent negative predictive value of MSCT (97 to 99%) may be a way to avoid invasive exploration during the investigation of a newly acquired LBBB in aviators with low cardiovascular risk.

Adult↗
PubMed2006

Evolutive skin reconstructions: from the dermal collagen-glycosaminoglycan-chitosane substrate to an immunocompetent reconstructed skin.

The development of human skin models that have the same properties as genuine human skin is of particular significance. Very promising skin models are the three-dimensional artificial skin constructs, which, similar to genuine skin, consist of an epidermis of differentiated keratinocytes and a dermis. A skin equivalent based on a collagen-glycosaminoglycan-chitosan dermal substrate has been developed to meet the growing demand in tissue engineered skin equivalents. We used this model to investigate whether CD34-generated Langerhans/dendritic cell precursors could be integrated into this skin equivalent model and pursue their differentiation without addition of cytokine and growth factor. To address the issue of dendritic cell (DC) differentiation, an endothelialized skin equivalent coculture model was used to study the behaviour of haematopoietic progenitor cells (HPC) in epidermal and dermal environments. CD34(+) HPC were cultured for 6 days with GM-CSF, TGFbeta1 and TNFalpha and seeded in the endothelialized skin equivalent at different time points to favour dermal or epidermal integration. This integration (after keratinocyte seeding, only and in absence of exogenous GM-CSF, TNFalpha, TGFbeta1) gave rise both cutaneous DC, i.e. epidermal Langerhans cells (CD1a(+), HLA-DR(+)) and dermal DC (DC-SIGN(+), HLA-DR(+)) while endothelial cells are sufficiently activated to acquire HLA-DR expression. For the first time, the presence of a living dermal equivalent could provide a more complex environment integrating vascular components to study the differentiation of interstitial DC in a dermis equivalent. Such sophisticated skin equivalent may clarify some intriguing aspects of the numerous regulatory mechanisms controlling skin homeostasis.

Animals↗
PubMed2005

Comparison of lumens of intermediate coronary stenosis using 16-slice computed tomography versus intravascular ultrasound.

We aimed to quantify ambiguous coronary stenosis using the minimal lumen area with 16-slice computed tomography compared with intravascular ultrasound. The sensitivity, specificity, and accuracy for significant lesion classification was 68%, 86%, and 78%, respectively. The correlation between intravascular ultrasound and CT minimal lumen area was r = 0.73 (p <0.001), and the 95% confidence interval for CT measurement was -72% to +56%.

Aged↗
PubMed2003

Interactions of heparin with human skin cells: binding, location, and transdermal penetration.

The development of new materials for tissue engineering of skin substitutes requires an increasing knowledge of their interactions with human skin cells. Since carbohydrate recognition is involved in numerous biologic processes, including skin regeneration, the aim of this study was to identify sugar receptors expressed at the surface of human dermic and epidermic cells. Binding of fluorescent sugar-polyhydroxyethylacrylamide derivatives was analyzed by flow cytofluorimetry on cultured human skin fibroblasts, keratinocytes, and melanocytes. We observed that these three cell types express a membrane receptor specific for GlcNAc6S. Since the polysaccharide heparin contains this sugar moiety, we further investigated the interactions of heparin with skin cells. We analyzed the in vitro cell binding and ex vivo diffusion with the Franz cell of heparin and of two other polysaccharides of similar molecular weight, dextran and chondroitin sulfate. We found evidence of the preferential binding of heparin on keratinocytes and its high transcutaneous penetration of skin. Altogether, our results describe the affinity of heparin for human skin cells and suggest it may be an excellent candidate for use in the skin delivery of drugs or cosmetics and also as an active component in engineered skin.

Chondroitin Sulfates↗
PubMed2003

Quantitative analysis of vitamin A degradation by Raman spectroscopy.

Vitamin A is known to support cell growth promotion, maintenance, and differentiation of epithelial tissues. Retinol is currently used in cosmetic formulations and products to deliver these and other benefits to the skin. However, retinol is known to be unstable and, therefore, remains of great concern to the cosmetic industry. The decomposition pathways of the retinoids in general have been previously postulated and investigated mostly by high-performance liquid chromatography (HPLC) with UV/Vis spectroscopy. In our studies, we examined specific conditions at which retinol degrades and subsequently identified and quantified the products of retinol decomposition by Raman spectroscopy. We reveal which experimental settings and computational tools allow monitoring of in situ evolution of an all-trans retinol solution when submitted to UV light in the presence of oxygen.

2-Propanol↗
PubMedDate not supplied

Optimization and characterization of an engineered human skin equivalent.

Skin equivalents (SEs) have been designed to meet both basic and applied research needs. The successful application of tissue-engineered SEs requires that the reconstituted tissues be endowed with the correct organization and function. A large body of experimental evidence now supports the notion that the inducing effects of mesenchymal tissue on epithelial cell morphogenesis are mediated, at least in part, by extracellular matrix components in addition to cell-cell interactions. A coculture model including both fibroblasts and keratinocytes was used to study the effects of progressive serum reduction on epidermal differentiation, quality of dermal and dermal-epidermal junctions, and expression of extracellular matrix proteins. The cells were successively added to a dermal substrate composed of collagen, glycosaminoglycans, and chitosan. The main aim of this study was to optimize this model for pharmacotoxicological trials. Control skin equivalents were cultured with medium containing 10% serum throughout the production process. Serum content was reduced to 1 and 0% at the air-liquid interface and compared with control skin equivalents. First, we demonstrated that serum deprivation at the air-liquid interface improves keratinocyte terminal differentiation. Second, we showed that, in the absence of serum, the specific characteristics of the SE are maintained, including epidermal and dermal ultrastructure, the expression of major dermal extracellular matrix components (human collagen types I, III, and V, fibronectin, elastin, and fibrillin 1), and the dermal-epidermal junction (laminin, human type IV collagen, alpha6 integrin). Furthermore, our results indicate that coculture models using keratinocytes and fibroblasts have both morphological and functional properties required for biologically useful tissues.

Basement Membrane↗