References of "De Tullio, Pascal"
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See detailFrom Metabolomics Study of Age-Related Macular Degeneration (AMD) to the Development of New Pyruvate Dehydrogenase Kinase Inhibitors (PDK)
Arslan, Deniz ULg; Schoumacher, Matthieu ULg; Pirotte, Bernard ULg et al

Poster (2016, May)

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly population of industrialized countries. This blindness results from the deterioration of the macula, a small part of ... [more ▼]

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly population of industrialized countries. This blindness results from the deterioration of the macula, a small part of the retina specialized for the high-acuity vision. Exudative AMD, called “wet”, is characterized by the formation of new blood vessels growing under the retina according to a process named choroidal neovascularization (CNV). Currently, the aetiology and pathogenesis of AMD remain unclear. Nevertheless, a recent metabolomics study performed on the serum of “wet” AMD patients and on a CNV murine model, that mimics the effect of “wet” AMD, have demonstrated that lactate level is clearly involved in the severity of the pathology as well as the relationship between lactate, CNV and AMD. According to this result, we suggest a new therapeutic approach of AMD based on the normalization of blood lactate level. The modulation of the lactate plasma concentration by treatment of the animals with synthetic compounds and more specifically Pyruvate Dehydrogenase Kinase (PDK) inhibitors significantly decrease the CNV. PDK and its four isoforms (PDK1-4) regulate the activity of the pyruvate dehydrogenase complex (PDH), a mitochondrial enzyme that plays a major role in the metabolic pathway of glucose, by reversible phosphorylation. Starting from these results, development of new PDK inhibitors could open the way to innovative treatment opportunities in AMD disease. Different analogues of (R)-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide (fig.1) have been already synthetized and pharmacological evaluation is currently in progress. According to the results obtained, various pharmacomodulations will be investigated [less ▲]

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See detailFrom Metabolomics to Identification of a new therapeutic approach for Age-Related Macular Degeneration (AMD)
Schoumacher, Matthieu ULg; De Tullio, Pascal ULg; LAMBERT, Vincent ULg et al

Poster (2016, May)

Age-related macular degeneration (AMD) is the leading cause of vision loss in the western world among people aged 50 or older. 90% of all vision loss due to AMD result from the exudative form, which is ... [more ▼]

Age-related macular degeneration (AMD) is the leading cause of vision loss in the western world among people aged 50 or older. 90% of all vision loss due to AMD result from the exudative form, which is characterized by choroidal neovascularization (CNV). Age-related changes that induce pathologic CNV are incompletely understood and critical issues remain to be addressed. Metabolomics is defined as the comprehensive study of endogenous metabolites changes in various biological systems. This newly emerging “omic” science provides a unique opportunity to correlate variation of the metabolome with pathological occurrence or progression and/or to identify metabolites that are implicated in the disease. We apply a 1H NMR metabolomics approach on sera collected from AMD patient and healthy volunteers and form a mice model of laser-induced CNV which mimics the effect of exudative AMD. After post-processing treatments, the different spectra were analyzed by statistical discriminant methodologies (PCA, ICA, PLS-DA, O-PLS-DA). These approaches allow the differentiation between control and AMD patients and between laser-induced mice and the control mice group. Moreover, the same discriminating spectral zones have been identified in human and mice model, leading to the emergence of different putative biomarkers. Among these markers, lactate emerges as a key metabolite in both settings. Mechanistically, lactate produced locally and by inflammatory cells, plays a critical role in the onset of the inflammatory and angiogenic phases. In mice model of laser-induced CNV, normalization of circulating lactate by dichloroacetate a pyruvate dehydrogenase kinase (PDK) inhibitor, decreases CNV development. Our data support the innovative concept of lactate as a parainflammation- and angio-metabolite associated to AMD and CNV progression. Moreover, control of blood lactate level via inhibition of PDK provides new options for the treatment of exudative AMD. This study demonstrates the ability of metabolomics for drug target discovery and opens new perspectives for AMD treatment and patient follow-up. [less ▲]

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See detailSynthesis, characterization and biological evaluation of benzothiazoles and tetrahydrobenzothiazoles bearing urea or thiourea moieties as vasorelaxants and inhibitors of the insulin releasing process
Harrouche, K; Renard, JF; Bouider, N et al

in European Journal of Medicinal Chemistry (2016), 115

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See detailMetabolomics as a Challenging Approach for Medicinal Chemistry and Personalized Medicine.
Frederich, Michel ULg; Pirotte, Bernard ULg; Fillet, Marianne ULg et al

in Journal of Medicinal Chemistry (2016)

"Omics" sciences have been developed to provide a holistic point of view of biology and to better understand the complexity of an organism as a whole. These systems biology approaches can be examined at ... [more ▼]

"Omics" sciences have been developed to provide a holistic point of view of biology and to better understand the complexity of an organism as a whole. These systems biology approaches can be examined at different levels, starting from the most fundamental, i.e., the genome, and finishing with the most functional, i.e., the metabolome. Similar to how genomics is applied to the exploration of DNA, metabolomics is the qualitative and quantitative study of metabolites. This emerging field is clearly linked to genomics, transcriptomics, and proteomics. In addition, metabolomics provides a unique and direct vision of the functional outcome of an organism's activities that are required for it to survive, grow, and respond to internal and external stimuli or stress, e.g., pathologies and drugs. The links between metabolic changes, patient phenotype, physiological and/or pathological status, and treatment are now well established and have opened a new area for the application of metabolomics in the drug discovery process and in personalized medicine. [less ▲]

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See detailCompensatory Metabolism Promotes Cancer Cell Adaptation to HDAC5 Silencing
Hendrick, Elodie ULg; Peixoto, Paul; Polese, Catherine et al

Poster (2015, December 03)

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See detailAnalytical Tools and Strategic Approach to Detect Poor Quality Medicines, Identify Unknown Components, and Timely Alerts for Appropriate Measures: Case Study of Antimalarial Medicines
Habyalimana, Védaste ULg; Mbinze Kindenge, Jérémie; Kalenda Tshilombo, Nicodème ULg et al

in American Journal of Analytical Chemistry (2015), 6

Nowadays, the circulation of poor quality medicines is becoming an alarming worldwide phenomenon with serious public health and socio-economic concerns. The situation is particularly critical in ... [more ▼]

Nowadays, the circulation of poor quality medicines is becoming an alarming worldwide phenomenon with serious public health and socio-economic concerns. The situation is particularly critical in developing countries where drug quality assurance and regulatory systems for drug manufacturing, importation, distribution and sales are weak. A sustained vigilance on poor quality medicines that regroup counterfeit/falsified, substandard and degraded medicines is therefore required to ensure patient safety and genuine medicines integrity. A case situation is illustrated including a strategic approach and analytical tools that were found useful to detect poor quality medicines, identify unknown components, and timely alerts for appropriate measures against the spread of those harmful products. Several suspected medicines randomly sampled in several strategic Rwandan areas were firstly check-controlled by means of visual inspection and then applying several analytical techniques from simple to more complex ones. The following medicines were studied: quinine sulfate tablets, artemisinin-based combination tablets, and artesunate powders for injection. Taking into account the pharmaceutical forms and the chemical characteristics, the following tests were applied: uniformity of mass, friability, disintegration, fluorescence, identification and assay. They were followed by more complex analytical techniques that allowed more comprehension of abnormal findings among which the presence of a wrong active pharmaceutical ingredient in quinine sulfate tablets which is mainly discussed in this paper to illustrate a strategic approach and various analytical tools that can be used in detecting and identifying unknown component in poor quality medicines. [less ▲]

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See detailFROM METABOLOMICS STUDY OF AGE RELATED MACULAR DEGENERATION (AMD) TO THE DEVELOPMENT OF NEW PDK INHIBITORS
Arslan, Deniz ULg; Schoumacher, Matthieu ULg; Pirotte, Bernard ULg et al

Poster (2015, November 12)

Metabolomics is one of the most recent technologies in the Omics sciences defined as “the comprehensive characterization of small molecules (called metabolites) in different biological samples.” This ... [more ▼]

Metabolomics is one of the most recent technologies in the Omics sciences defined as “the comprehensive characterization of small molecules (called metabolites) in different biological samples.” This methodology can be applied in many areas, such as biomarker discovery, clinical studies, drug efficacy and toxicity evaluation, diagnostic tools, quality control or drug discovery. Its capability to extract biochemical information associated with a cellular or biological system makes this technique a powerful tool for Medicinal Chemistry. In this work, we present a 1H NMR metabolomics study applied to therapeutic target discovery. Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly population of industrialized countries. This blindness results from the deterioration of the macula, a small part of the retina specialized for the high-acuity vision. Exudative AMD, called “wet”, is characterized by the formation of new blood vessels growing under the retina according to a process named choroidal neovascularization (CNV). Currently, the aetiology and pathogenesis of AMD remain unclear. Nevertheless, a recent metabolomics study performed on the serum of “wet” AMD patients and on a CNV murine model, that mimics the effect of “wet” AMD, have demonstrated that lactate level is clearly involved in the severity of the pathology as well as the relationship between lactate, CNV and AMD. According to this result, we suggest a new therapeutic approach of AMD based on the normalization of blood lactate level. The modulation of the lactate plasma concentration by treatment of the animals with synthetic compounds and more specifically Pyruvate Dehydrogenase Kinase (PDK) inhibitors significantly decrease the CNV. Starting from these results, development of new PDK inhibitors could open the way to innovative treatment opportunities in AMD disease. [less ▲]

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See detailStatistical treatment of 2D NMR COSY spectra in metabolomics: data preparation, clustering-based evaluation of the Metabolomic Informative Content and comparison with 1H-NMR
Feraud, Baptiste; Govaerts, Bernadette; Verleysen, Michel et al

in Metabolomics : Official journal of the Metabolomic Society (2015), 11(6), 1756-1768

Compared with the widely used 1H-NMR spectroscopy, two-dimensional NMR experiments provide more sophisticated spectra which should facilitate the identification of relevant spectral zones or biomarkers in ... [more ▼]

Compared with the widely used 1H-NMR spectroscopy, two-dimensional NMR experiments provide more sophisticated spectra which should facilitate the identification of relevant spectral zones or biomarkers in metabolomics. This paper focuses on 1H-1H COrrelation SpectroscopY (COSY) spectral data. In spite of longer inherent acquisition times, it is commonly accepted by users (biologists, healthcare professionals) that the introduction of an additional dimension probably represents a huge qualitative step for investigations in terms of metabolites identification. Moreover, it seems natural that more information leads to more predictive power. But, until now, very few statistical studies clearly proved this assumption. Therefore a fundamental question is “Is this supplementary information relevant?”. In order to extend the statistical properties developed for 1D spectroscopy to the challenges raised by 2D spectra, a rigorous study of the performances of COSY spectra is needed as a prerequisite. Having introduced new pre-processing concepts, such as the Global Peak List or an ad hoc 2D “bucketing”, this paper presents an innovative methodology based on multivariate clustering algorithms to evaluate this question. Numerical clustering quality indexes and graphical results are proposed, based both on the spectral presence or absence of peaks (binary position vectors) and on peak intensities, and through different levels of spectral resolution. The second goal of this paper is to compare clustering performances obtained on COSY and on 1H-NMR spectra, with the aim of understanding to what extent the COSY spectra carry more Metabolomic Informative Content about the signal than 1D ones. The methodology is applied to two real experimental designs involving different groups of spectra (which define the signal): a 4-mixture cell culture media containing various supervised metabolites and a complex human serum based design. It is shown that COSY spectra appear to be statistically powerful and, in addition, provide better clustering results than corresponding 1H-NMR when using unlabeled information. Consequently, additional information appears to be relevant for metabolomics applications [less ▲]

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See detailMetabolomics analysis of Galium odoratum (L.) Scop.: impact of the plant population origin and growth conditions.
Ledoux, Allison ULg; Martin, Bertrand; De Tullio, Pascal ULg et al

Poster (2015, July 16)

Galium odoratum is a plant used in traditional medicine and to prepare beverages. This work aimed at studying the impact of plant origin and growth conditions on the metabolite content of the plant ... [more ▼]

Galium odoratum is a plant used in traditional medicine and to prepare beverages. This work aimed at studying the impact of plant origin and growth conditions on the metabolite content of the plant. Material and methods- Aerial biomass of Galium odoratum was collected from five natural populations (in situ conditions) and from controlled environment (ex situ conditions). Results- Quantitative analysis of selected phytochemicals including phenylpropranoids and iridoids showed clear differences between the plants from nature and those of controlled growth conditions as well as internal variation within the group. The metabolomic approach emphasized the decrease of the secondary metabolites pool paralleled by an increase of the carbohydrates in ex situ conditions. Conclusion- Metabolomics approaches using 1H-NMR and HPLC is worth to consider for studying the impact of climate factors on the regulation of the phytochemical profile in relation to the origin of the plant material. [less ▲]

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