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[article]
Titre : Gut Permeability in Autism Spectrum Disorders Type de document : Texte imprimé et/ou numérique Auteurs : Neil R. DALTON, Auteur ; Susie CHANDLER, Auteur ; Charles TURNER, Auteur ; Tony CHARMAN, Auteur ; Andrew PICKLES, Auteur ; Tom LOUCAS, Auteur ; Emily SIMONOFF, Auteur ; Peter SULLIVAN, Auteur ; Gillian BAIRD, Auteur Article en page(s) : p.305-313 Langues : Anglais (eng) Mots-clés : autism autism spectrum disorders gut permeability lactulose/mannitol ratio Index. décimale : PER Périodiques Résumé : Objective To test whether gut permeability is increased in autism spectrum disorders (ASD) by evaluating gut permeability in a population-derived cohort of children with ASD compared with age- and intelligence quotient-matched controls without ASD but with special educational needs (SEN). Patients and Methods One hundred thirty-three children aged 10–14 years, 103 with ASD and 30 with SEN, were given an oral test dose of mannitol and lactulose and urine collected for 6?hr. Gut permeability was assessed by measuring the urine lactulose/mannitol (L/M) recovery ratio by electrospray mass spectrometry-mass spectrometry. The ASD group was subcategorized for comparison into those without (n?=?83) and with (n?=?20) regression. Results There was no significant difference in L/M recovery ratio (mean (95% confidence interval)) between the groups with ASD: 0.015 (0.013–0.018), and SEN: 0.014 (0.009–0.019), nor in lactulose, mannitol, or creatinine recovery. No significant differences were observed in any parameter for the regressed versus non-regressed ASD groups. Results were consistent with previously published normal ranges. Eleven children (9/103?=?8.7% ASD and 2/30?=?6.7% SEN) had L/M recovery ratio ?0.03 (the accepted normal range cut-off), of whom two (one ASD and one SEN) had more definitely pathological L/M recovery ratios ?0.04. Conclusion There is no statistically significant group difference in small intestine permeability in a population cohort-derived group of children with ASD compared with a control group with SEN. Of the two children (one ASD and one SEN) with an L/M recovery ratio of ?0.04, one had undiagnosed asymptomatic celiac disease (ASD) and the other (SEN) past extensive surgery for gastroschisis. Autism Res 2014, 7: 305–313. © 2013 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1350 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=235
in Autism Research > 7-3 (June 2014) . - p.305-313[article] Gut Permeability in Autism Spectrum Disorders [Texte imprimé et/ou numérique] / Neil R. DALTON, Auteur ; Susie CHANDLER, Auteur ; Charles TURNER, Auteur ; Tony CHARMAN, Auteur ; Andrew PICKLES, Auteur ; Tom LOUCAS, Auteur ; Emily SIMONOFF, Auteur ; Peter SULLIVAN, Auteur ; Gillian BAIRD, Auteur . - p.305-313.
Langues : Anglais (eng)
in Autism Research > 7-3 (June 2014) . - p.305-313
Mots-clés : autism autism spectrum disorders gut permeability lactulose/mannitol ratio Index. décimale : PER Périodiques Résumé : Objective To test whether gut permeability is increased in autism spectrum disorders (ASD) by evaluating gut permeability in a population-derived cohort of children with ASD compared with age- and intelligence quotient-matched controls without ASD but with special educational needs (SEN). Patients and Methods One hundred thirty-three children aged 10–14 years, 103 with ASD and 30 with SEN, were given an oral test dose of mannitol and lactulose and urine collected for 6?hr. Gut permeability was assessed by measuring the urine lactulose/mannitol (L/M) recovery ratio by electrospray mass spectrometry-mass spectrometry. The ASD group was subcategorized for comparison into those without (n?=?83) and with (n?=?20) regression. Results There was no significant difference in L/M recovery ratio (mean (95% confidence interval)) between the groups with ASD: 0.015 (0.013–0.018), and SEN: 0.014 (0.009–0.019), nor in lactulose, mannitol, or creatinine recovery. No significant differences were observed in any parameter for the regressed versus non-regressed ASD groups. Results were consistent with previously published normal ranges. Eleven children (9/103?=?8.7% ASD and 2/30?=?6.7% SEN) had L/M recovery ratio ?0.03 (the accepted normal range cut-off), of whom two (one ASD and one SEN) had more definitely pathological L/M recovery ratios ?0.04. Conclusion There is no statistically significant group difference in small intestine permeability in a population cohort-derived group of children with ASD compared with a control group with SEN. Of the two children (one ASD and one SEN) with an L/M recovery ratio of ?0.04, one had undiagnosed asymptomatic celiac disease (ASD) and the other (SEN) past extensive surgery for gastroschisis. Autism Res 2014, 7: 305–313. © 2013 International Society for Autism Research, Wiley Periodicals, Inc. En ligne : http://dx.doi.org/10.1002/aur.1350 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=235 Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders / M. FIORENTINO in Molecular Autism, 7 (2016)
[article]
Titre : Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : M. FIORENTINO, Auteur ; A. SAPONE, Auteur ; S. SENGER, Auteur ; S. S. CAMHI, Auteur ; S. M. KADZIELSKI, Auteur ; Timothy M. BUIE, Auteur ; D. L. KELLY, Auteur ; N. CASCELLA, Auteur ; A. FASANO, Auteur Article en page(s) : 49p. Langues : Anglais (eng) Mots-clés : Adolescent Adult Autism Spectrum Disorder/genetics/immunology/metabolism/pathology Biopsy Blood-Brain Barrier/immunology/metabolism/pathology Case-Control Studies Cerebellum/immunology/metabolism/pathology Cerebral Cortex/immunology/metabolism/pathology Child Child, Preschool Claudin-3/genetics/immunology Claudin-5/genetics/immunology Claudins/genetics/immunology DNA-Binding Proteins/genetics/immunology Duodenum/immunology/metabolism/pathology Female Gene Expression Humans Interleukin-1beta/genetics/immunology Interleukin-8/genetics/immunology MARVEL Domain Containing 2 Protein/genetics/immunology Male Matrix Metalloproteinase 9/genetics/immunology Middle Aged Permeability Schizophrenia/genetics/immunology/metabolism/pathology Tight Junctions/immunology/metabolism/pathology Autism spectrum disorders Blood-brain barrier Duodenal biopsies Gut permeability Gut-brain axis Neuroinflammation Postmortem brain Schizophrenia Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASD) are complex conditions whose pathogenesis may be attributed to gene-environment interactions. There are no definitive mechanisms explaining how environmental triggers can lead to ASD although the involvement of inflammation and immunity has been suggested. Inappropriate antigen trafficking through an impaired intestinal barrier, followed by passage of these antigens or immune-activated complexes through a permissive blood-brain barrier (BBB), can be part of the chain of events leading to these disorders. Our goal was to investigate whether an altered BBB and gut permeability is part of the pathophysiology of ASD. METHODS: Postmortem cerebral cortex and cerebellum tissues from ASD, schizophrenia (SCZ), and healthy subjects (HC) and duodenal biopsies from ASD and HC were analyzed for gene and protein expression profiles. Tight junctions and other key molecules associated with the neurovascular unit integrity and function and neuroinflammation were investigated. RESULTS: Claudin (CLDN)-5 and -12 were increased in the ASD cortex and cerebellum. CLDN-3, tricellulin, and MMP-9 were higher in the ASD cortex. IL-8, tPA, and IBA-1 were downregulated in SCZ cortex; IL-1b was increased in the SCZ cerebellum. Differences between SCZ and ASD were observed for most of the genes analyzed in both brain areas. CLDN-5 protein was increased in ASD cortex and cerebellum, while CLDN-12 appeared reduced in both ASD and SCZ cortexes. In the intestine, 75% of the ASD samples analyzed had reduced expression of barrier-forming TJ components (CLDN-1, OCLN, TRIC), whereas 66% had increased pore-forming CLDNs (CLDN-2, -10, -15) compared to controls. CONCLUSIONS: In the ASD brain, there is an altered expression of genes associated with BBB integrity coupled with increased neuroinflammation and possibly impaired gut barrier integrity. While these findings seem to be specific for ASD, the possibility of more distinct SCZ subgroups should be explored with additional studies. En ligne : http://dx.doi.org/10.1186/s13229-016-0110-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328
in Molecular Autism > 7 (2016) . - 49p.[article] Blood-brain barrier and intestinal epithelial barrier alterations in autism spectrum disorders [Texte imprimé et/ou numérique] / M. FIORENTINO, Auteur ; A. SAPONE, Auteur ; S. SENGER, Auteur ; S. S. CAMHI, Auteur ; S. M. KADZIELSKI, Auteur ; Timothy M. BUIE, Auteur ; D. L. KELLY, Auteur ; N. CASCELLA, Auteur ; A. FASANO, Auteur . - 49p.
Langues : Anglais (eng)
in Molecular Autism > 7 (2016) . - 49p.
Mots-clés : Adolescent Adult Autism Spectrum Disorder/genetics/immunology/metabolism/pathology Biopsy Blood-Brain Barrier/immunology/metabolism/pathology Case-Control Studies Cerebellum/immunology/metabolism/pathology Cerebral Cortex/immunology/metabolism/pathology Child Child, Preschool Claudin-3/genetics/immunology Claudin-5/genetics/immunology Claudins/genetics/immunology DNA-Binding Proteins/genetics/immunology Duodenum/immunology/metabolism/pathology Female Gene Expression Humans Interleukin-1beta/genetics/immunology Interleukin-8/genetics/immunology MARVEL Domain Containing 2 Protein/genetics/immunology Male Matrix Metalloproteinase 9/genetics/immunology Middle Aged Permeability Schizophrenia/genetics/immunology/metabolism/pathology Tight Junctions/immunology/metabolism/pathology Autism spectrum disorders Blood-brain barrier Duodenal biopsies Gut permeability Gut-brain axis Neuroinflammation Postmortem brain Schizophrenia Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorders (ASD) are complex conditions whose pathogenesis may be attributed to gene-environment interactions. There are no definitive mechanisms explaining how environmental triggers can lead to ASD although the involvement of inflammation and immunity has been suggested. Inappropriate antigen trafficking through an impaired intestinal barrier, followed by passage of these antigens or immune-activated complexes through a permissive blood-brain barrier (BBB), can be part of the chain of events leading to these disorders. Our goal was to investigate whether an altered BBB and gut permeability is part of the pathophysiology of ASD. METHODS: Postmortem cerebral cortex and cerebellum tissues from ASD, schizophrenia (SCZ), and healthy subjects (HC) and duodenal biopsies from ASD and HC were analyzed for gene and protein expression profiles. Tight junctions and other key molecules associated with the neurovascular unit integrity and function and neuroinflammation were investigated. RESULTS: Claudin (CLDN)-5 and -12 were increased in the ASD cortex and cerebellum. CLDN-3, tricellulin, and MMP-9 were higher in the ASD cortex. IL-8, tPA, and IBA-1 were downregulated in SCZ cortex; IL-1b was increased in the SCZ cerebellum. Differences between SCZ and ASD were observed for most of the genes analyzed in both brain areas. CLDN-5 protein was increased in ASD cortex and cerebellum, while CLDN-12 appeared reduced in both ASD and SCZ cortexes. In the intestine, 75% of the ASD samples analyzed had reduced expression of barrier-forming TJ components (CLDN-1, OCLN, TRIC), whereas 66% had increased pore-forming CLDNs (CLDN-2, -10, -15) compared to controls. CONCLUSIONS: In the ASD brain, there is an altered expression of genes associated with BBB integrity coupled with increased neuroinflammation and possibly impaired gut barrier integrity. While these findings seem to be specific for ASD, the possibility of more distinct SCZ subgroups should be explored with additional studies. En ligne : http://dx.doi.org/10.1186/s13229-016-0110-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=328