Personne :
Calon, Frédéric

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Université Laval. Faculté de pharmacie
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  • Publication
    Accès libre
    Spray and freeze drying of human milk on the retention of immunoglobulins (IgA, IgG, IgM)
    (M. Dekker, 2016-03-07) Castro-Albarràn, Jorge; St-Amour, Isabelle; Aguilar-Uscanga, Blanca Rosa; Calon, Frédéric; Saucier, Linda; Solís-Pacheco, Josué; Ratti, Cristina
    Several freeze-drying and spray-drying methods were investigated in relation to the retention of immunoglobulins (Ig) A, IgG, and IgM. Spray drying produced human milk powders with 2% humidity and a good retention of IgG (>88%) and IgM (∼70%). However, only 38% of IgA remained after spray drying. For freeze drying, only the highest heating plate temperature used in this study (40°C) brought IgA content down to 55% in powder with 1.75% residual humidity, whereas milk samples undergoing lower temperatures had higher preservation rates (75% for IgA and 80% for IgG and IgM) and higher residual moisture contents. From these results, it can be concluded that IgA is the most sensitive Ig lost during drying processing of human milk. The best method to generate human milk powders without a significant loss of Ig was thus freeze drying at 30°C heating plate temperature, which accelerated the process compared to lower processing temperatures, but still had good overall Ig retention.
  • Publication
    Cystamine prevents MPTP-induced toxicity in young adult mice via the up-regulation of the brain-derived neurotrophic factor
    (Elsevier, 2009-11-11) Bousquet, Mélanie; Calon, Frédéric; Gibrat, Claire; Saint-Pierre, Martine; Lévesque, Daniel; Rouillard, Claude; Cicchetti, Francesca
    Preclinical data suggest that cystamine stands as a promising neuroprotective agent against Huntington's and Parkinson's diseases. To decipher the mechanisms of action of cystamine, we investigated the effects of various doses of cystamine (10, 50, and 200 mg/kg) on the regulation of the brain-derived neurotrophic factor (BDNF), its receptor tropomyosin-receptor-kinase B (TrkB) and on the heat shock protein 70 (Hsp70) brain mRNA expression in relation to the time after administration. We have determined that the lower cystamine dose is the most efficient to promote putative neuroprotective effects. Indeed, an acute administration of 10 mg/kg of cystamine increased the expression of BDNF mRNA in the substantia nigra compacta (SNc), although it did not significantly influence TrkB or Hsp70 mRNA. Higher cystamine doses resulted in the absence of activation of any of these markers or led to non-specific effects. We have also substantiated the neuroprotective effect of a 21-day treatment of 10 mg/kg/day of cystamine in young adult mice against MPTP-induced loss of tyrosine hydroxylase-striatal fiber density, nigral dopamine cells and nigral Nurr1 mRNA expression. The neuroprotective action of cystamine in the same animals was associated with an up-regulation of BDNF in the SNc. Taken together, these results strengthen the neuroprotective potential of cystamine in the treatment of Parkinson's disease and point towards the up-regulation of BDNF as an important mechanism of action.
  • Publication
    Cystamine metabolism and brain transport properties : clinical implications for neurodegenerative diseases
    (Wiley, 2010-06-20) Bousquet, Mélanie; Calon, Frédéric; Gibrat, Claire; Rouillard, Claude; Cicchetti, Francesca; Ouellet, Mélissa
    Cystamine has shown significant neuroprotective properties in preclinical studies of Parkinson’s disease (PD) and Huntington’s disease (HD). Cysteamine, its FDA-approved reduced form, is scheduled to be tested for clinical efficacy in HD patients. Here, we studied the key cystamine metabolites, namely cysteamine, hypotaurine and taurine, as well as cysteine, in order to identify which one is more distinctively responsible for the neuroprotective action of cystamine. After a single administration of cystamine (10, 50 or 200 mg/kg), naïve mice were perfused with phosphate-buffered saline (PBS) at 1, 3, 12, 24 or 48 h post-injection and brain and plasma samples were analyzed by two distinct HPLC methods. Although plasma levels remained under the detection threshold, significant increases in cysteamine brain levels were detected with the 50 and 200 mg/kg doses in mice perfused 1 and 3 h following cystamine injection. To further assess cysteamine as the candidate molecule for pre-clinical and clinical trials in PD, we evaluated its capacity to cross the blood brain barrier. Using an in situ cerebral perfusion technique, we determined that the brain transport coefficient (Clup) of cysteamine (259 μM) was 0.15 ± 0.02 μL/g/s and was increased up to 0.34 ± 0.07 μL/g/s when co-perfused in the presence of cysteine. Taken together, these results strongly suggest that cysteamine is the neuroactive metabolite of cystamine and may further support its therapeutic use in neurodegenerative diseases, particularly in HD and PD.