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Geffard M.,Institute for Development of Research on Human Pathology and Therapeutics IDRPHT | Geffard M.,University of Bordeaux 1 | de Bisschop L.,Institute for Development of Research on Human Pathology and Therapeutics IDRPHT | Duleu S.,Institute for Development of Research on Human Pathology and Therapeutics IDRPHT | And 9 more authors.
Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry | Year: 2010

Endotherapia is a new therapeutic approach against chronic diseases such as multiple sclerosis, amyotrophic lateral sclerosis, and rheumatoid arthritis. It combines the evaluation of circulating antibodies directed against specific self antigens and self-antigens modified by free radicals. Here, we review the literature concerning this topic. In addition, our biological assays have allowed us to follow up the evolution of chronic diseases along time, checking remission phases. For more than 25 years, our scientific group has suggested that the chronicity of diseases may be due to nonpathological bacteria living in different biotopes. Endotherapia is the result of immunopathologic work addressing chronic incurable diseases with a multifactorial etiology. Several genes are susceptible to toxic environmental immunologic agents. Thus, the intestinal ecosystem plays an important role in these mechanisms. Therapy is a "tailor made" combination (MG1/RA, GEMSP) of the small molecules (e.g., vitamins.) linked to poly-Llysine (PLL). Each individual linkage to PLL offers great advantages owing to the chemical characteristics of PLL (e.g., non immunogenic), increasing the half-life of the active PLL derivatives. Clinical trials have enabled us to confirm very good safety. Our results confirm the efficacy of the approach and we believe that it could be very promising for chronic diseases. © 2010 Bentham Science Publishers Ltd. Source

Ladner Y.,Montpellier University | Coussot G.,Montpellier University | Ebner S.,Montpellier University | Ibrahim A.,Montpellier University | And 2 more authors.
Electrophoresis | Year: 2016

This work aims at studying the optimization of an on-line capillary electrophoresis (CE)-based tryptic digestion methodology for the analysis of therapeutic polypeptides (PP). With this methodology, a mixture of surrogate peptide fragments and amino acid were produced on-line by trypsin cleavage (enzymatic digestion) and subsequently analyzed using the same capillary. The resulting automation of all steps such as injection, mixing, incubation, separation and detection minimizes the possible errors and saves experimental time. In this paper, we first study the differents parameters influencing PP cleavage inside the capillary (plug length, reactant concentration, incubation time, diffusion and electrophoretic plugs mixing). In a second part, the optimization of the electrophoretic separation conditions of generated hydrolysis products (nature, pH and ionic strength (I) of the background electrolyte (BGE)) is described. Using the optimized conditions, excellent repeatability was obtained in terms of separation (migration times) and proteolysis (number of products from enzymatic hydrolysis and corresponding amounts) demonstrating the robustness of the proposed methodology. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Coussot G.,Montpellier University | Ladner Y.,Montpellier University | Bayart C.,Montpellier University | Faye C.,COLCOM | And 2 more authors.
Journal of Chromatography A | Year: 2015

This work aims at studying the potentialities of an on-line capillary electrophoresis (CE)-based digestion methodology for evaluating polymer-drug conjugates degradability in the presence of free trypsin (in-solution digestion). A sandwich plugs injection scheme with transverse diffusion of laminar profile (TDLFP) mode was used to achieve on-line digestions. Electrophoretic separation conditions were established using poly-. l-Lysine (PLL) as reference substrate. Comparison with off-line digestion was carried out to demonstrate the feasibility of the proposed methodology. The applicability of the on-line CE-based digestion methodology was evaluated for two PLL-drug conjugates and for the four first generations of dendrigraft of lysine (DGL). Different electrophoretic profiles presenting the formation of di, tri, and tetralysine were observed for PLL-drug and DGL. These findings are in good agreement with the nature of the linker used to link the drug to PLL structure and the predicted degradability of DGL. The present on-line methodology applicability was also successfully proven for protein conjugates hydrolysis. In summary, the described methodology provides a powerful tool for the rapid study of biodegradable polymers. © 2014 Elsevier B.V. Source

Ait-Aissa S.,Bordeaux University | Ait-Aissa S.,EPHE Paris | Billaudel B.,Bordeaux University | Poulletier de Gannes F.,Bordeaux University | And 15 more authors.
Bioelectromagnetics | Year: 2012

An experimental approach was used to assess immunological biomarkers in the sera of young rats exposed in utero and postnatal to non-ionizing radiofrequency fields. Pregnant rats were exposed free-running, 2h/day and 5 days/week to a 2.45GHz Wi-Fi signal in a reverberation chamber at whole-body specific absorption rates (SAR) of 0, 0.08, 0.4, and 4W/kg (with 10, 10, 12, and 9 rats, respectively), while cage control rats were kept in the animal facility (11 rats). Dams were exposed from days 6 to 21 of gestation and then three newborns per litter were further exposed from birth to day 35 postnatal. On day 35 after birth, all pups were sacrificed and sera collected. The screening of sera for antibodies directed against 15 different antigens related to damage and/or pathological markers was conducted using enzyme-linked immunosorbent assay (ELISA). No change in humoral response of young pups was observed, regardless of the types of biomarker and SAR levels. This study also provided some data on gestational outcome following in utero exposure to Wi-Fi signals. Mass evaluation of dams and pups and the number of pups per litter was monitored, and the genital tracts of young rats were observed for abnormalities by measuring anogenital distance. Under these experimental conditions, our observations suggest a lack of adverse effects of Wi-Fi exposure on delivery and general condition of the animals. © 2012 Wiley Periodicals, Inc. Source

Geffard M.,Institute for Development of Research on Human Pathology and Therapeutics IDRPHT | Geffard M.,University of Bordeaux 1 | Duleu S.,Institute for Development of Research on Human Pathology and Therapeutics IDRPHT | Bessede A.,Institute for Development of Research on Human Pathology and Therapeutics IDRPHT | And 5 more authors.
Central Nervous System Agents in Medicinal Chemistry | Year: 2012

A new therapeutic approach called Endotherapia (GEMSP) for the treatment of Multiple Sclerosis (MS) is suggested. Endotherapia is the result of an immunopathological strategy addressing chronic incurable diseases with a multifactorial etiology. This approach combines a biomedical evaluation of circulating immunoglobulins directed against specific self-antigens and self-antigens modified by free radicals. GEMSP is a "tailor-made" combination of small molecules (fatty acids, antioxidants, radical scavengers, amino acids) linked to a non-immunogenic linear chain of poly-L.lysine (PLL). Each individual linkage or PLL derivative offers great advantages, such as an increase in the half-life of the active small molecules. GEMSP inhibits brain leukocyte infiltration and abolishes episodes of experimental autoimmune encephalomyelitis. In a clinical trial with 102 MS patients treated with GEMSP Endotherapia, 28% of them showed a worsening of their state; 20% showed a decrease in the progression of the disease; 17% showed disease stabilization; and 35% showed a reversal of the evolution of disease; i.e., an improvement in their disease state. In 72% of the cases, a positive evolution of the state of the MS patients treated with Endotherapia was observed (a decrease or stabilization of disease evolution or an improvement). Endotherapia is very safe and no side-effects were reported for GEMSP. Moreover, GEMSP showed no toxicity either in experimental animals or in humans. It seems that Endotherapia is a promising therapy for MS, with no side-effects, which should be considered in the management of long-term pathologies. © 2012 Bentham Science Publishers. Source

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