Cannabinoid Receptor Type 2, but not Type 1, is Up-Regulated in Peripheral Blood Mononuclear Cells of Children Affected by Autistic Disorders / Dario SINISCALCO in Journal of Autism and Developmental Disorders, 43-11 (November 2013)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 43-11 (November 2013) . - p.2686-2695 Titre : Cannabinoid Receptor Type 2, but not Type 1, is Up-Regulated in Peripheral Blood Mononuclear Cells of Children Affected by Autistic Disorders Type de document : Texte imprimé et/ou numérique Auteurs : Dario SINISCALCO, Auteur ; Anna SAPONE, Auteur ; Catia GIORDANO, Auteur ; Alessandra CIRILLO, Auteur ; Laura MAGISTRIS, Auteur ; Francesco ROSSI, Auteur ; Alessio FASANO, Auteur ; James Jeffrey BRADSTREET, Auteur ; Sabatino MAIONE, Auteur ; Nicola ANTONUCCI, Auteur Article en page(s) : p.2686-2695 Langues : Anglais (eng) Mots-clés : Autistic disorders  Cannabinoid system  Gene expression  PBMCs Index. décimale : PER Périodiques Résumé : Autistic disorders (ADs) are heterogeneous neurodevelopmental disorders arised by the interaction of genes and environmental factors. Dysfunctions in social interaction and communication skills, repetitive and stereotypic verbal and non-verbal behaviours are common features of ADs. There are no defined mechanisms of pathogenesis, rendering curative therapy very difficult. Indeed, the treatments for autism presently available can be divided into behavioural, nutritional and medical approaches, although no defined standard approach exists. Autistic children display immune system dysregulation and show an altered immune response of peripheral blood mononuclear cells (PBMCs). In this study, we investigated the involvement of cannabinoid system in PBMCs from autistic children compared to age-matched normal healthy developing controls (age ranging 3–9 years; mean age: 6.06 ± 1.52 vs. 6.14 ± 1.39 in autistic children and healthy subjects, respectively). The mRNA level for cannabinoid receptor type 2 (CB2) was significantly increased in AD-PBMCs as compared to healthy subjects (mean ± SE of arbitrary units: 0.34 ± 0.03 vs. 0.23 ± 0.02 in autistic children and healthy subjects, respectively), whereas CB1 and fatty acid amide hydrolase mRNA levels were unchanged. mRNA levels of N-acylphosphatidylethanolamine-hydrolyzing phospholipase D gene were slightly decreased. Protein levels of CB-2 were also significantly increased in autistic children (mean ± SE of arbitrary units: 33.5 ± 1.32 vs. 6.70 ± 1.25 in autistic children and healthy subjects, respectively). Our data indicate CB2 receptor as potential therapeutic target for the pharmacological management of the autism care. En ligne : http://dx.doi.org/10.1007/s10803-013-1824-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=217 [article] Cannabinoid Receptor Type 2, but not Type 1, is Up-Regulated in Peripheral Blood Mononuclear Cells of Children Affected by Autistic Disorders [Texte imprimé et/ou numérique] / Dario SINISCALCO, Auteur ; Anna SAPONE, Auteur ; Catia GIORDANO, Auteur ; Alessandra CIRILLO, Auteur ; Laura MAGISTRIS, Auteur ; Francesco ROSSI, Auteur ; Alessio FASANO, Auteur ; James Jeffrey BRADSTREET, Auteur ; Sabatino MAIONE, Auteur ; Nicola ANTONUCCI, Auteur . - p.2686-2695. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 43-11 (November 2013) . - p.2686-2695 Mots-clés : Autistic disorders  Cannabinoid system  Gene expression  PBMCs Index. décimale : PER Périodiques Résumé : Autistic disorders (ADs) are heterogeneous neurodevelopmental disorders arised by the interaction of genes and environmental factors. Dysfunctions in social interaction and communication skills, repetitive and stereotypic verbal and non-verbal behaviours are common features of ADs. There are no defined mechanisms of pathogenesis, rendering curative therapy very difficult. Indeed, the treatments for autism presently available can be divided into behavioural, nutritional and medical approaches, although no defined standard approach exists. Autistic children display immune system dysregulation and show an altered immune response of peripheral blood mononuclear cells (PBMCs). In this study, we investigated the involvement of cannabinoid system in PBMCs from autistic children compared to age-matched normal healthy developing controls (age ranging 3–9 years; mean age: 6.06 ± 1.52 vs. 6.14 ± 1.39 in autistic children and healthy subjects, respectively). The mRNA level for cannabinoid receptor type 2 (CB2) was significantly increased in AD-PBMCs as compared to healthy subjects (mean ± SE of arbitrary units: 0.34 ± 0.03 vs. 0.23 ± 0.02 in autistic children and healthy subjects, respectively), whereas CB1 and fatty acid amide hydrolase mRNA levels were unchanged. mRNA levels of N-acylphosphatidylethanolamine-hydrolyzing phospholipase D gene were slightly decreased. Protein levels of CB-2 were also significantly increased in autistic children (mean ± SE of arbitrary units: 33.5 ± 1.32 vs. 6.70 ± 1.25 in autistic children and healthy subjects, respectively). Our data indicate CB2 receptor as potential therapeutic target for the pharmacological management of the autism care. En ligne : http://dx.doi.org/10.1007/s10803-013-1824-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=217

Initial Observations of Elevated Alpha-N-Acetylgalactosaminidase Activity Associated with Autism and Observed Reductions from GC Protein—Macrophage Activating Factor Injections / James Jeffrey BRADSTREET in Autism Insights, (December 2012)  

Public ISBD [article]  inAutism Insights > (December 2012) . - p.31-38 Titre : Initial Observations of Elevated Alpha-N-Acetylgalactosaminidase Activity Associated with Autism and Observed Reductions from GC Protein—Macrophage Activating Factor Injections Type de document : Texte imprimé et/ou numérique Auteurs : James Jeffrey BRADSTREET, Auteur ; Emar VOGELAAR, Auteur ; Lynda THYER, Auteur Année de publication : 2012 Article en page(s) : p.31-38 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorders (ASD) are developmental disorders affecting 1:88 children, and which appear to be associated with a variety of complex immune dysregulations including autoimmunity. The enzyme, alpha-N-acetylgalactosaminidase (Nagalase) deglycosylates serum Gc protein (vitamin D3 – binding protein) rendering it incapable of activating macrophage defenses. Increased Nagalase activity has been associated with a variety of malignancies, immune disorders and viral infections. Macrophage activating factor (GcMAF) has been repeatedly published as an intervention to lower serum Nagalase activity for a variety of cancer and HIV patients. GcMAF is a naturally occurring protein with well-established safety and therapeutic benefit(s) supported by numerous human studies. Methods: Initially, parents of 40 individuals with ASD sought testing for Nagalase serum activity as part of an evaluation of immune dysregulation. Nagalase enzyme activity measurement was performed by the European Laboratory of Nutrients (ELN), Bunnik, the Netherlands, using an end-point enzymatic assay of a chromogenic substrate. Some parents of patients with elevated Nagalase activity opted for weekly GcMAF injections provided by Immuno Biotech Ltd., Guernsey UK (www.gcmaf.eu). GcMAF is purified from human serum obtained from the American Red Cross using 25-hydroxyvitamin D3-Sepharose high affinity chromatography. The protein is then further diluted to obtain therapeutically appropriate levels for patients based on their clinical presentations. Results: Individuals with ASD (32 males and 8 females, n = 40, ages: 1 year 4 months - 21 years 2 months) had initial and post treatment assessment of Nagalase activity. Dosing of GcMAF was recommended based on previously reported response curves adjusted by the treating clinician for age, weight, and Nagalase levels. The average pre-treatment Nagalase activity of the autism group was 1.93 nmol/min/mg of substrate. This was well above the laboratory reported normal range of <0.95 nmol/min/mg. For the ASD group the average level at the time of second testing was 1.03 nmol/min/mg, reflecting an average reduction of 0.90 nmol/min/mg (P < 0.0001). Apart from the likely immunological benefits of lowering the Nagalase activity of these individuals, uncontrolled observations of GcMAF therapy indicated substantial improvements in language, socialization and cognition. No significant side-effects were reported during the course of injections. Conclusions: In this first report of Nagalase activity in patients with autism, it appears that most individuals have substantially higher levels than the expected healthy ranges. Although Nagalase is a nonspecific marker of immune dysregulation, its observed levels in autism may have both etiological and therapeutic significance. Importantly, this is also the first report of reduction of Nagalase activity in an autism population with GcMAF injections. En ligne : http://dx.doi.org/10.4137/AUI.S10485 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=211 [article] Initial Observations of Elevated Alpha-N-Acetylgalactosaminidase Activity Associated with Autism and Observed Reductions from GC Protein—Macrophage Activating Factor Injections [Texte imprimé et/ou numérique] / James Jeffrey BRADSTREET, Auteur ; Emar VOGELAAR, Auteur ; Lynda THYER, Auteur . - 2012 . - p.31-38. Langues : Anglais (eng) in Autism Insights > (December 2012) . - p.31-38 Index. décimale : PER Périodiques Résumé : Background: Autism spectrum disorders (ASD) are developmental disorders affecting 1:88 children, and which appear to be associated with a variety of complex immune dysregulations including autoimmunity. The enzyme, alpha-N-acetylgalactosaminidase (Nagalase) deglycosylates serum Gc protein (vitamin D3 – binding protein) rendering it incapable of activating macrophage defenses. Increased Nagalase activity has been associated with a variety of malignancies, immune disorders and viral infections. Macrophage activating factor (GcMAF) has been repeatedly published as an intervention to lower serum Nagalase activity for a variety of cancer and HIV patients. GcMAF is a naturally occurring protein with well-established safety and therapeutic benefit(s) supported by numerous human studies. Methods: Initially, parents of 40 individuals with ASD sought testing for Nagalase serum activity as part of an evaluation of immune dysregulation. Nagalase enzyme activity measurement was performed by the European Laboratory of Nutrients (ELN), Bunnik, the Netherlands, using an end-point enzymatic assay of a chromogenic substrate. Some parents of patients with elevated Nagalase activity opted for weekly GcMAF injections provided by Immuno Biotech Ltd., Guernsey UK (www.gcmaf.eu). GcMAF is purified from human serum obtained from the American Red Cross using 25-hydroxyvitamin D3-Sepharose high affinity chromatography. The protein is then further diluted to obtain therapeutically appropriate levels for patients based on their clinical presentations. Results: Individuals with ASD (32 males and 8 females, n = 40, ages: 1 year 4 months - 21 years 2 months) had initial and post treatment assessment of Nagalase activity. Dosing of GcMAF was recommended based on previously reported response curves adjusted by the treating clinician for age, weight, and Nagalase levels. The average pre-treatment Nagalase activity of the autism group was 1.93 nmol/min/mg of substrate. This was well above the laboratory reported normal range of <0.95 nmol/min/mg. For the ASD group the average level at the time of second testing was 1.03 nmol/min/mg, reflecting an average reduction of 0.90 nmol/min/mg (P < 0.0001). Apart from the likely immunological benefits of lowering the Nagalase activity of these individuals, uncontrolled observations of GcMAF therapy indicated substantial improvements in language, socialization and cognition. No significant side-effects were reported during the course of injections. Conclusions: In this first report of Nagalase activity in patients with autism, it appears that most individuals have substantially higher levels than the expected healthy ranges. Although Nagalase is a nonspecific marker of immune dysregulation, its observed levels in autism may have both etiological and therapeutic significance. Importantly, this is also the first report of reduction of Nagalase activity in an autism population with GcMAF injections. En ligne : http://dx.doi.org/10.4137/AUI.S10485 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=211

Randomized trial of hyperbaric oxygen therapy for children with autism / Doreen GRANPEESHEH in Research in Autism Spectrum Disorders, 4-2 (April-June 2010)  

Public ISBD [article]  inResearch in Autism Spectrum Disorders > 4-2 (April-June 2010) . - p.268-275 Titre : Randomized trial of hyperbaric oxygen therapy for children with autism Type de document : Texte imprimé et/ou numérique Auteurs : Doreen GRANPEESHEH, Auteur ; Dennis R. DIXON, Auteur ; Jonathan TARBOX, Auteur ; Arthur E. WILKE, Auteur ; Michael S. ALLEN, Auteur ; James Jeffrey BRADSTREET, Auteur Année de publication : 2010 Article en page(s) : p.268-275 Langues : Anglais (eng) Mots-clés : Autism-Spectrum-Disorders Autism-Treatment Hyperbaric-oxygen-therapy Applied-behavior-analysis Index. décimale : PER Périodiques Résumé : Autism Spectrum Disorders (ASDs) are characterized by the presence of impaired development in social interaction and communication and the presence of a restricted repertoire of activity and interests. While numerous treatments for ASDs have been proposed, very few have been subjected to rigorous scientific investigation. Hyperbaric oxygen therapy (HBOT) has been recently popularized as a treatment for the symptoms of ASDs. The purpose of this study was to test the hypothesis that HBOT would have a beneficial effect on ASD symptoms in the context of a double-blind placebo-controlled trial. This randomized double-blind placebo-controlled trial compared HBOT used to deliver 24% oxygen at 1.3 atmospheric pressure (n = 18) to placebo (n = 16) in children with Autistic Disorder. Both direct observational measures of behaviors symptomatic of autism and standardized psychological assessments were used to evaluate the effects of the treatment. No differences were detected between HBOT and placebo groups across any of the outcome measures. The present study demonstrates that HBOT delivered at 24% oxygen at 1.3 atmospheric pressure does not result in a clinically significant improvement of the symptoms of Autistic Disorder. En ligne : http://dx.doi.org/10.1016/j.rasd.2009.09.014 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=974 [article] Randomized trial of hyperbaric oxygen therapy for children with autism [Texte imprimé et/ou numérique] / Doreen GRANPEESHEH, Auteur ; Dennis R. DIXON, Auteur ; Jonathan TARBOX, Auteur ; Arthur E. WILKE, Auteur ; Michael S. ALLEN, Auteur ; James Jeffrey BRADSTREET, Auteur . - 2010 . - p.268-275. Langues : Anglais (eng) in Research in Autism Spectrum Disorders > 4-2 (April-June 2010) . - p.268-275 Mots-clés : Autism-Spectrum-Disorders Autism-Treatment Hyperbaric-oxygen-therapy Applied-behavior-analysis Index. décimale : PER Périodiques Résumé : Autism Spectrum Disorders (ASDs) are characterized by the presence of impaired development in social interaction and communication and the presence of a restricted repertoire of activity and interests. While numerous treatments for ASDs have been proposed, very few have been subjected to rigorous scientific investigation. Hyperbaric oxygen therapy (HBOT) has been recently popularized as a treatment for the symptoms of ASDs. The purpose of this study was to test the hypothesis that HBOT would have a beneficial effect on ASD symptoms in the context of a double-blind placebo-controlled trial. This randomized double-blind placebo-controlled trial compared HBOT used to deliver 24% oxygen at 1.3 atmospheric pressure (n = 18) to placebo (n = 16) in children with Autistic Disorder. Both direct observational measures of behaviors symptomatic of autism and standardized psychological assessments were used to evaluate the effects of the treatment. No differences were detected between HBOT and placebo groups across any of the outcome measures. The present study demonstrates that HBOT delivered at 24% oxygen at 1.3 atmospheric pressure does not result in a clinically significant improvement of the symptoms of Autistic Disorder. En ligne : http://dx.doi.org/10.1016/j.rasd.2009.09.014 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=974

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