Monday, October 24, 2011
Saturday, October 22, 2011
Hidden Administration of Drugs
Clinical Pharmacology & Therapeutics 90, 651-661 (November 2011) | doi:10.1038/clpt.2011.206
F Benedetti, E Carlino and A Pollo
Keywords: placebo-controlled trials, dummy treatment (placebo), psychological component, psychology and pharmacodynamics.
F Benedetti, E Carlino and A Pollo
Keywords: placebo-controlled trials, dummy treatment (placebo), psychological component, psychology and pharmacodynamics.
An unusual atrial tachycardia in a patient with Friedreich ataxia
Europace (2011) 13 (11): 1660-1661. doi: 10.1093/europace/eur156
Justin M.S. Lee1,*, Ian Turner1, Ajit Agarwal2 and Simon P. Fynn1
1Department of Cardiology, Papworth Hospital, Cambridge CB23 3RE, UK
2Department of Cardiology, West Suffolk Hospital, Bury St Edmunds, IP33 2QZ, UK
Keywords: atrial tachycardia, Friedreich ataxia, arrhythmi, linear ablation.
Justin M.S. Lee1,*, Ian Turner1, Ajit Agarwal2 and Simon P. Fynn1
1Department of Cardiology, Papworth Hospital, Cambridge CB23 3RE, UK
2Department of Cardiology, West Suffolk Hospital, Bury St Edmunds, IP33 2QZ, UK
Keywords: atrial tachycardia, Friedreich ataxia, arrhythmi, linear ablation.
Anaesthesia for a patient with Friedreich's ataxia.
Indian J Anaesth. 2011 Jul;55(4):418-20.
Ganesan I.
Department of Anaesthesiology, SRM Medical College Hospital and Research Centre, Chennai, Tamil Nadu, India.
NO ABSTRAC
Ganesan I.
Department of Anaesthesiology, SRM Medical College Hospital and Research Centre, Chennai, Tamil Nadu, India.
NO ABSTRAC
Thursday, October 20, 2011
Inactivation of mitochondrial aspartate aminotransferase contributes to the respiratory deficit of yeast frataxin-deficient cells
Biochem. J. (2011) Immediate Publication, doi:10.1042/BJ20111574
Dominika Sliwa, Julien Dairou, Jean-Michel Camadro and Renata Santos
Institut Jacques Monod, Paris, France
Keywords: Friedreich ataxia, frataxin, iron homeostasis, hypersensitivity to oxidants, NAD+ and NADH, malate-aspartate NADH shuttle, mitochondrial aspartate aminotransferase (Aat1), mitochondrial acetylated proteins, post-translational modification.
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Dominika Sliwa, Julien Dairou, Jean-Michel Camadro and Renata Santos
Institut Jacques Monod, Paris, France
Keywords: Friedreich ataxia, frataxin, iron homeostasis, hypersensitivity to oxidants, NAD+ and NADH, malate-aspartate NADH shuttle, mitochondrial aspartate aminotransferase (Aat1), mitochondrial acetylated proteins, post-translational modification.
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Monday, October 17, 2011
Physiological oxygen level is critical for modeling neuronal metabolism in vitro
Zhu, J., Aja, S., Kim, E.-K., Park, M. J., Ramamurthy, S., Jia, J., Hu, X., Geng, P. and Ronnett, G. V. (2011), Journal of Neuroscience Research. doi: 10.1002/jnr.22765
KEYWORDS: In vitro models, nonphysiological conditions, ambient (21%) oxygen levels, physiological oxygen level (5% O2), glucose uptake, glycolysis, glucose oxidation , fatty acid oxidation, AMPK activity, intracellular ATP level,
"Oxygen level is an important parameter to consider when modeling neuronal responses to stress in vitro".
KEYWORDS: In vitro models, nonphysiological conditions, ambient (21%) oxygen levels, physiological oxygen level (5% O2), glucose uptake, glycolysis, glucose oxidation , fatty acid oxidation, AMPK activity, intracellular ATP level,
"Oxygen level is an important parameter to consider when modeling neuronal responses to stress in vitro".
Friday, October 14, 2011
Un score pour évaluer la stabilité au cours de la marche : méthodologie et validation chez le patient atteint d’ataxie de Friedreich
A. Gouelle a, ⁎, F. Mégrot b, A. Yelnik c, G.-F. Penneçot d
a Plate-forme d’analyse du mouvement, hôpital Robert-Debré, AP–HP, 48, boulevard Sérurier, 75019 Paris, France
b Unité clinique d’analyse de la marche et du mouvement, CMPRE Bois-Larris, Lamorlaye, France
c Service de médecine physique et de réadaptation, hôpital Fernand-Widal, Paris, France
d Service de chirurgie orthopédique, hôpital Robert-Debré, Paris, France
KEYWORDS : Score, Marche, Stabilité dynamique, Paramètres spatiotemporels
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a Plate-forme d’analyse du mouvement, hôpital Robert-Debré, AP–HP, 48, boulevard Sérurier, 75019 Paris, France
b Unité clinique d’analyse de la marche et du mouvement, CMPRE Bois-Larris, Lamorlaye, France
c Service de médecine physique et de réadaptation, hôpital Fernand-Widal, Paris, France
d Service de chirurgie orthopédique, hôpital Robert-Debré, Paris, France
KEYWORDS : Score, Marche, Stabilité dynamique, Paramètres spatiotemporels
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Tuesday, October 11, 2011
Friedreich ataxia: The vicious circle hypothesis revisited
BMC Medicine 2011, 9:112doi:10.1186/1741-7015-9-112, Published: 11 October 2011
Aurelien Bayot, Renata Santos, Jean-Michel Camadro and Pierre Rustin
OPEN ACCES
Abstract (provisional)
Friedreich ataxia, the most frequent progressive autosomal recessive disorder involving the central and peripheral nervous system, is mostly associated with an unstable expansion of GAA trinucleotide repeats in the first intron of the FXN gene which encodes the mitochondrial frataxin protein. Since FXN was shown to be involved in Friedreich ataxia in the late 1990s, the consequence of frataxin loss of function has been generating vigorous debate. Very early on, we suggested a unifying hypothesis according to which frataxin deficiency leads to a vicious circle of faulty iron handling, impaired iron-sulfur cluster synthesis, and increased oxygen radical production. However, data from cell and animal models now indicate that iron accumulation is an inconsistent and late event and that frataxin deficiency does not always impair the activity of iron-sulfur cluster-containing proteins. In contrast, frataxin deficiency appears consistently associated with increased sensitivity to reactive oxygen species, as opposed to increased oxygen radical production. Compiling findings from fundamental researches to clinical observations, we defend here the opinion that the very first consequence of frataxin depletion is indeed an abnormal oxidative status which initiates the pathogenic mechanism underlying Friedreich ataxia.
FULL TEXT PDF
Aurelien Bayot, Renata Santos, Jean-Michel Camadro and Pierre Rustin
OPEN ACCES
Abstract (provisional)
Friedreich ataxia, the most frequent progressive autosomal recessive disorder involving the central and peripheral nervous system, is mostly associated with an unstable expansion of GAA trinucleotide repeats in the first intron of the FXN gene which encodes the mitochondrial frataxin protein. Since FXN was shown to be involved in Friedreich ataxia in the late 1990s, the consequence of frataxin loss of function has been generating vigorous debate. Very early on, we suggested a unifying hypothesis according to which frataxin deficiency leads to a vicious circle of faulty iron handling, impaired iron-sulfur cluster synthesis, and increased oxygen radical production. However, data from cell and animal models now indicate that iron accumulation is an inconsistent and late event and that frataxin deficiency does not always impair the activity of iron-sulfur cluster-containing proteins. In contrast, frataxin deficiency appears consistently associated with increased sensitivity to reactive oxygen species, as opposed to increased oxygen radical production. Compiling findings from fundamental researches to clinical observations, we defend here the opinion that the very first consequence of frataxin depletion is indeed an abnormal oxidative status which initiates the pathogenic mechanism underlying Friedreich ataxia.
FULL TEXT PDF
Saturday, October 8, 2011
Mesenchymal Stem Cells Restore Frataxin Expression and Increase Hydrogen Peroxide Scavenging Enzymes in Friedreich Ataxia Fibroblasts
PLoS ONE 6(10): e26098. doi:10.1371/journal.pone.0026098 (2011)
Kemp K, Mallam E, Hares K, Witherick J, Scolding N, et al.
Multiple Sclerosis and Stem Cell Group, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom
OPEN ACCESS
Abstract Top
Dramatic advances in recent decades in understanding the genetics of Friedreich ataxia (FRDA)—a GAA triplet expansion causing greatly reduced expression of the mitochondrial protein frataxin—have thus far yielded no therapeutic dividend, since there remain no effective treatments that prevent or even slow the inevitable progressive disability in affected individuals. Clinical interventions that restore frataxin expression are attractive therapeutic approaches, as, in theory, it may be possible to re-establish normal function in frataxin deficient cells if frataxin levels are increased above a specific threshold. With this in mind several drugs and cytokines have been tested for their ability to increase frataxin levels. Cell transplantation strategies may provide an alternative approach to this therapeutic aim, and may also offer more widespread cellular protective roles in FRDA. Here we show a direct link between frataxin expression in fibroblasts derived from FRDA patients with both decreased expression of hydrogen peroxide scavenging enzymes and increased sensitivity to hydrogen peroxide-mediated toxicity. We demonstrate that normal human mesenchymal stem cells (MSCs) induce both an increase in frataxin gene and protein expression in FRDA fibroblasts via secretion of soluble factors. Finally, we show that exposure to factors produced by human MSCs increases resistance to hydrogen peroxide-mediated toxicity in FRDA fibroblasts through, at least in part, restoring the expression of the hydrogen peroxide scavenging enzymes catalase and glutathione peroxidase 1. These findings suggest, for the first time, that stem cells may increase frataxin levels in FRDA and transplantation of MSCs may offer an effective treatment for these patients.
Full text PDF
Kemp K, Mallam E, Hares K, Witherick J, Scolding N, et al.
Multiple Sclerosis and Stem Cell Group, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom
OPEN ACCESS
Abstract Top
Dramatic advances in recent decades in understanding the genetics of Friedreich ataxia (FRDA)—a GAA triplet expansion causing greatly reduced expression of the mitochondrial protein frataxin—have thus far yielded no therapeutic dividend, since there remain no effective treatments that prevent or even slow the inevitable progressive disability in affected individuals. Clinical interventions that restore frataxin expression are attractive therapeutic approaches, as, in theory, it may be possible to re-establish normal function in frataxin deficient cells if frataxin levels are increased above a specific threshold. With this in mind several drugs and cytokines have been tested for their ability to increase frataxin levels. Cell transplantation strategies may provide an alternative approach to this therapeutic aim, and may also offer more widespread cellular protective roles in FRDA. Here we show a direct link between frataxin expression in fibroblasts derived from FRDA patients with both decreased expression of hydrogen peroxide scavenging enzymes and increased sensitivity to hydrogen peroxide-mediated toxicity. We demonstrate that normal human mesenchymal stem cells (MSCs) induce both an increase in frataxin gene and protein expression in FRDA fibroblasts via secretion of soluble factors. Finally, we show that exposure to factors produced by human MSCs increases resistance to hydrogen peroxide-mediated toxicity in FRDA fibroblasts through, at least in part, restoring the expression of the hydrogen peroxide scavenging enzymes catalase and glutathione peroxidase 1. These findings suggest, for the first time, that stem cells may increase frataxin levels in FRDA and transplantation of MSCs may offer an effective treatment for these patients.
Full text PDF
Friday, October 7, 2011
Rare Diseases and Orphan Products: Accelerating Research and Development (2011)
THE NATIONAL ACADEMIES PRESS
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