290 research outputs found
Efficacy of epicutaneous immunotherapy (EPIT) in a new model of peanut-induced eosinophilic esophagitis (EoE) and allergic enterpathy (AE)
Background
Eosinophilia is often linked to allergic gastrointestinal
disorders linked to food allergy. EPIT using Viaskin®
device has been described as a therapeutic method in
food allergy. We developed a model of mice sensitized
to peanut, exhibiting EoE and AE after exclusive feeding
with peanut protein extracts (PPE). This study was conducted
in order to evaluate the efficacy of EPIT.
Methods
After oral sensitization with PPE and cholera toxin, 30
BALB/c mice were treated weekly during 8 weeks by
PPE skin applications (EPIT), 20 mice were not treated
(Sham) and 10 mice constituted the control group (C).
Mice were then exclusively fed with PPE. Specific IgE,
IgG1 and IgG2a were monitored during immunotherapy.
Esophageal and jejunal samples were taken for histological
analyses.
Results
sIgE increased after oral sensitization, respectively 0.207
±0.03 and 0.214±0.04 μg/ml, in EPIT and Sham, with
undetectable values in C. Following EPIT, sIgE
decreased and sIgG2a increased, respectively 0.139±0.01
vs 0.166±0.01 μg/ml (EPIT vs Sham, p<0.05) and 14.96
±0.60 vs 4.73±1.75 μg/ml (p<0.05). Esophageal eosinophilic
infiltration (measured in 6 high power fields) was
higher in Sham, 136±32, than in EPIT, 50±12 (p<0.05)
and C, 7±3 cells/mm2 (p<0.01). Esophagus mucosa
thickness was increased in Sham compared to EPIT and
C (p<0.001). Sham group exhibited higher mRNA levels
of cytokines than EPIT: eotaxin (p<0.05), IL-5 (p<0.05),
IL-13 (p<0.05). The mRNA levels of these cytokines in
EPIT were similar to C. The expression of Foxp3
mRNA increased significantky after EPIT compared
with Sham and C (p<0.05). The jejunal villus/crypt ratio
was lower in Sham than in EPIT and C, respectively 1.6
±0.1 vs 2.3±0.2 (p<0.01) and 2.4±0.1 (p<0.001). Eosinophilic
infiltration in jejunum was increased in Sham
compared to EPIT (p<0.01) and C (p<0.001).
Conclusion
EPIT is effective in preventing EoE and AE induced by
oral challenge in mice sensitized to peanut
Epicutaneous Immunotherapy (EPIT) Blocks the Allergic Esophago-Gastro-Enteropathy Induced by Sustained Oral Exposure to Peanuts in Sensitized Mice
Background: Food allergy may affect the gastrointestinal tract and eosinophilia is often associated with allergic gastrointestinal disorders. Allergy to peanuts is a life-threatening condition and effective and safe treatments still need to be developed. The present study aimed to evaluate the effects of sustained oral exposure to peanuts on the esophageal and jejunal mucosa in sensitized mice. We also evaluated the effects of desensitization with epicutaneous immunotherapy (EPIT) on these processes. Methods: Mice were sensitized by gavages with whole peanut protein extract (PPE) given with cholera toxin. Sensitized mice were subsequently exposed to peanuts via a specific regimen and were then analysed for eosinophilia in the esophagus and gut. We also assessed mRNA expression in the esophagus, antibody levels, and peripheral T-cell response. The effects of EPIT were tested when intercalated with sensitization and sustained oral peanut exposure. Results: Sustained oral exposure to peanuts in sensitized mice led to severe esophageal eosinophilia and intestinal villus sub-atrophia, i.e. significantly increased influx of eosinophils into the esophageal mucosa (136 eosinophils/mm2) and reduced villus/crypt ratios (1.660.15). In the sera, specific IgE levels significantly increased as did secretion of Th2 cytokines by peanut-reactivated splenocytes. EPIT of sensitized mice significantly reduced Th2 immunological response (IgE response and splenocyte secretion of Th2 cytokines) as well as esophageal eosinophilia (50 eosinophils/mm2, p,0.05), mRNA expression of Th2 cytokines in tissue - eotaxin (p,0.05), IL-5 (p,0.05), and IL-13 (p,0.05) -, GATA-3 (p,0.05), and intestinal villus sub-atrophia (2.360.15). EPIT also increased specific IgG2a (p,0.05) and mRNA expression of Foxp3 (p,0.05) in the esophageal mucosa. Conclusions: Gastro-intestinal lesions induced by sustained oral exposure in sensitized mice are efficaciously treated by allergen specific EPIT
FoxO3a overexpression prevents both glycogen overload and autophagic buildup in skeletal muscle of Pompe disease
FoxO3a overexpression prevents both glycogen overload and autophagic buildup in skeletal muscle of Pompe disease. 6eme congrès international de Myologi
Gene expression profiling in equine polysaccharide storage myopathy revealed inflammation, glycogenesis inhibition, hypoxia and mitochondrial dysfunctions
<p>Abstract</p> <p>Background</p> <p>Several cases of myopathies have been observed in the horse Norman Cob breed. Muscle histology examinations revealed that some families suffer from a polysaccharide storage myopathy (PSSM). It is assumed that a gene expression signature related to PSSM should be observed at the transcriptional level because the glycogen storage disease could also be linked to other dysfunctions in gene regulation. Thus, the functional genomic approach could be conducted in order to provide new knowledge about the metabolic disorders related to PSSM. We propose exploring the PSSM muscle fiber metabolic disorders by measuring gene expression in relationship with the histological phenotype.</p> <p>Results</p> <p>Genotypying analysis of GYS1 mutation revealed 2 homozygous (AA) and 5 heterozygous (GA) PSSM horses. In the PSSM muscles, histological data revealed PAS positive amylase resistant abnormal polysaccharides, inflammation, necrosis, and lipomatosis and active regeneration of fibers. Ultrastructural evaluation revealed a decrease of mitochondrial number and structural disorders. Extensive accumulation of an abnormal polysaccharide displaced and partially replaced mitochondria and myofibrils. The severity of the disease was higher in the two homozygous PSSM horses.</p> <p>Gene expression analysis revealed 129 genes significantly modulated (p < 0.05). The following genes were up-regulated over 2 fold: IL18, CTSS, LUM, CD44, FN1, GST01. The most down-regulated genes were the following: mitochondrial tRNA, SLC2A2, PRKCα, VEGFα. Data mining analysis showed that protein synthesis, apoptosis, cellular movement, growth and proliferation were the main cellular functions significantly associated with the modulated genes (p < 0.05). Several up-regulated genes, especially IL18, revealed a severe muscular inflammation in PSSM muscles. The up-regulation of glycogen synthase kinase-3 (GSK3β) under its active form could be responsible for glycogen synthase (GYS1) inhibition and hypoxia-inducible factor (HIF1α) destabilization.</p> <p>Conclusion</p> <p>The main disorders observed in PSSM muscles could be related to mitochondrial dysfunctions, glycogenesis inhibition and the chronic hypoxia of the PSSM muscles.</p
Satellite cells fail to contribute to muscle repair but are functional in Pompe disease (glycogenosis type II)
Satellite cells fail to contribute to muscle repair but are functional in Pompe disease (glycogenosis type II). 6eme congrés international de Myologi
Application of texture analysis to muscle MRI: 1-What kind of information should be expected from texture analysis?
Several previous clinical or preclinical studies using computerized texture analysis
of MR Images have demonstrated much more clinical discrimination than visual image analysis by the radiologist. In muscular dystrophy, a discriminating power has been already demonstrated with various methods of texture analysis of magnetic resonance images (MRI-TA). Unfortunately, a scale gap exists between the spatial resolutions of histological and MR images making a direct correlation impossible. Furthermore, the effect of the various histological modifications on the gray level
of each pixel is complex and cannot be easily analyzed. Consequently, clinicians will not accept the use of MRI-TA in routine practice if TA remains a “black box” without clinical correspondence at a tissue level. A goal therefore of the multicenter European COST action MYO-MRI is to optimize MRI-TA methods in muscular dystrophy and to elucidate the histological meaning of MRI textures.info:eu-repo/semantics/publishedVersio
Cell therapy of Duchenne muscular dystrophy: preclinical trial in GRMD dogs
Duchenne muscular dystrophy (DMD), a genetic progressive X-linked muscular dystrophy, is the most
common genetic disease in humans. Cell therapy based on the use of somatic stem cells is a very promising
approach. In a dog myopathy model, we isolated a muscle stem cell (MuStem) with the essential
requirements for therapeutic use: high amplification capacity, ability to fuse with muscle fibers,
renewal of the satellite cell population, dispersion in the whole body after vascular administration,
persistence of long-term effect, and dramatic clinical improvement of treated animals. These preclinical
results pave the way for a therapeutic trial in children with Duchenne muscular dystrophy.La dystrophie musculaire de
Duchenne (DMD) est une maladie génétique progressive du muscle liée au chromosome X. Elle
est la maladie génétique la plus fréquente chez l'homme. La thérapie cellulaire basée sur
l'utilisation de cellules souches somatiques est une voie thérapeutique riche d'intérêt.
Nous avons isolé, chez un modèle de chien myopathe, une cellule souche musculaire (MuStem)
qui présente les qualités indispensables à une utilisation thérapeutique: forte capacité
d'amplification, capacité à fusionner avec les fibres musculaires, renouvellement du
contingent de cellules satellites, dispersion dans l'organisme après administration
vasculaire, persistance de l'effet à long terme, spectaculaire amélioration clinique des
animaux traités. Ces résultats précliniques ouvrent la voie à un essai thérapeutique chez
l'enfant atteint de dystrophie musculaire de Duchenne
Cadeia produtiva do gengibre (Zingiber officinale ROSCOE) no estado do Paraná : análise e recomendações para melhoria da qualidade
Orientador : Raquel R.B.NegrelleCo-orientadores: Luiz Doni Filho, Neusa G.A. RuckerTese (doutorado) - Universidade Federal do Paraná. Setor de CiĂŞncias Agrárias. Curso de PĂłs-Graduação em Agronomia - área de concentração Produção Vegetal, Departamento de Fitotecnia e FitossanitarismoInclui bibliografia e glossárioResumo: O presente trabalho teve como objetivo o estudo prospectivo da cadeia produtiva do Zingiber officinale Roscoe no Estado do Paraná, identificando os principais agentes envolvidos e paralelamente proceder análise dos pontos de estrangulamentos, especificamente no que concerne Ă qualidade microbiolĂłgica deste produto em todos os nĂveis, desde a produção atĂ© a fase final da comercialização, visando identificar causas e propor soluções no sentido da melhoria do sistema como um todo. Este estudo foi desenvolvido no perĂodo de 2000 a 2002 englobando pesquisa de campo, entrevistas abertas com representantes de estabelecimentos de comercialização, produtores e demais atores da cadeia produtiva, alĂ©m de análises laboratoriais do produto "in natura" disponĂvel no mercado consumidor da RegiĂŁo Metropolitana de Curitiba - PR. Este documento está organizado em 9 capĂtulos, que apresentam vastas informações englobando aspectos botânicos, ecolĂłgicos, fisico-quĂmicos e farmacolĂłgicos do gengibre, e que estĂŁo incluĂdas nos capĂtulos 1 e 2. O capĂtulo 3 apresenta caracterĂsticas gerais da principal regiĂŁo produtora brasileira, Morretes - PR, englobando localização, aspectos sĂłcio-econĂ´micos, geolĂłgicos e geomorfolĂłgicos e caracterização climática. O capĂtulo 4 apresenta o estudo prospectivo da cadeia produtiva do gengibre no Estado do Paraná, que engloba panorama mundial, brasileiro e paranaense do volume de produção agrĂcola de gengibre. Inclui-se tambĂ©m caracterização da comunidade produtora agrĂcola do litoral paranaense, alĂ©m da identificação e caracterização dos outros diferentes nĂveis da cadeia produtiva do gengibre e a detecção dos principais pontos de estrangulamento nos diferentes nĂveis desta cadeia produtiva. A caracterização do cultivo e beneficiamento do gengibre no litoral paranaense Ă© apresentada no capĂtulo 5, evidenciando suas particularidades frente ao descrito na literatura especializada. No capĂtulo 6 avaliou-se as condições higiĂŞnico-sanitárias dos estabelecimentos produtores, do processo de beneficiamento pĂłs-colheita (lavagem, limpeza, secagem e embalagem) e das condições de manipulação do gengibre "in natura" no litoral paranaense. De maneira geral, as condições de higiene e limpeza observadas foram consideradas precárias, determinando alta potencialidade de contaminação do gengibre com agentes que poderiam colocar em risco a saĂşde do consumidor. No capĂtulo 7 sĂŁo apresentados os resultados dos estabelecimentos de comercialização da RegiĂŁo Metropolitana de Curitiba - PR, no que tange Ă qualidade e adequação Ă s normas vigentes. Dos aspectos observados, as condições dos vestuários e dos equipamentos de proteção individual (manipuladores) foram considerados precários, o que pode potencializar a contaminação do produto e colocar em risco a saĂşde do consumidor. O capĂtulo 8 teve como objetivo caracterizar o perfil microbiolĂłgico do gengibre "in natura" comercializado na RegiĂŁo Metropolitana de Curitiba - PR, tendo como base a Resolução - CNPPA n. 12 - Brasil, 1978 e a Resolução - RDC n. 12 - Brasil, 2001. Para tanto, foram realizadas a determinação do nĂşmero mais provável (NMP) de coliformes totais, coliformes a 45° C/g e Escherichia coli, e a presença de Salmonella sp em 25 gramas. Sintetizando, um conjunto de propostas e recomendações aos agentes econĂ´micos que atuam e processam a cadeia produtiva do gengibre no Estado do Paraná, em especial o municĂpio de Morretes - PR, Ă© apresentado no capĂtulo 9Abstract: Prospective studies of the productive chain of the Zingiber officinale Roscoe on Parana State identifying the main agents envolved and parallel procedure analysis of the strangulation points, in order to microbiology qualify this product in whole levels from the production until commercialization last phase, aiming identify causes and propose solutions to the improvement of the system in general. This survey developed from 2000 to 2002 involved field research, interviews with representative of the commercialization establishments, producers and others actors of the productive chain, besides made in laboratories of the quality of crude product available to the consumer market in Curitiba. This paper is organized in nine chapters that present information involving botanical, ecological, physique-chemical and pharmacological aspects of ginger that are included in chapters 1 and 2. The chapter 3 presents the characteristics of the main brazilian productive area, embody localization, social and economic aspects, geologycal, geomorphologycal and climate characterization. The chapter 4 the study of the productive chain of this product in Parana State, which includes the paranaense, the brazilian and the worldwide panoramic view of the production volume and commercialization of the ginger; characterization of the agricultural community; identification and characterization of others different levels of the productive chain and also, the main strangulation points on these different levels of the productive chain. In the chapter 5 the agricultural process of the ginger benefit and cultivation in Morretes Town, Paraná, Brazil was caracterized. In the chapter 6 the hygienic-sanitary conditions of the producers establishments, postharvest benefit system and manipulation conditions of crude ginger in the paranaense coastland, Brazil were evaluated with an aim to subsidy the ofert of the best quality product to consumer market. In general, the cleaning and hygienic conditions were precarious, determining a high potential of ginger contamination with agents that can put in risk the consumers' health. The chapter 7 presents the results of the commercialization establishments in the metropolitan area of Curitiba considering adequation to the current norm. Of the observed items, the manipulation conditions was considered precarious due to the inadequate conditions that contributes to contamination, bringing about serious problems to consumers' health. The chapter 8 aimed the microbiological quality of the ginger market in the metropolitan area of Curitiba based on the Brazilian legislation. The microbiological analysis found total coliforms, 45° C/g coliforms, Escherichia coli most probable number (MPN) and Salmonella sp presence. Synthetizing, a group of considerations and recommendations to economic agents that actuate and carry on the productive chain of the ginger in the Parana State, specially in Morretes Town, is presented in the chapter
Evaluation of the dystrophin carboxy-terminal domain for micro-dystrophin gene therapy in cardiac and skeletal muscles in the DMDmdx rat model
Duchenne muscular dystrophy (DMD) is a muscle wasting disorder caused by mutations in the gene encoding dystrophin. Gene therapy using micro-dystrophin (MD) transgenes and recombinant adeno-associated virus (rAAV) vectors hold great promise. To overcome the limited packaging capacity of rAAV vectors, most MD do not include dystrophin carboxy-terminal (CT) domain. Yet, the CT domain is known to recruit α1- and β1-syntrophins and α-dystrobrevin, a part of the dystrophin-associated protein complex (DAPC), which is a signaling and structural mediator of muscle cells. In this study, we explored the impact of inclusion of the dystrophin CT domain on ΔR4-23/ΔCT MD (MD1), in DMDmdx rats, which allows for relevant evaluations at muscular and cardiac levels. We showed by LC-MS/MS that MD1 expression is sufficient to restore the interactions at a physiological level of most DAPC partners in skeletal and cardiac muscles, and that inclusion of the CT domain increases the recruitment of some DAPC partners at supra-physiological levels. In parallel, we demonstrated that inclusion of the CT domain does not improve MD1 therapeutic efficacy on DMD muscle and cardiac pathologies. Our work highlights new evidences of the therapeutic potential of MD1 and strengthens the relevance of this candidate for gene therapy of DMD
The caecal microbiota promotes the acute inflammatory response and the loss of the intestinal barrier integrity during severe Eimeria tenella infection
IntroductionCoccidiosis, a disease caused by intestinal apicomplexan parasites Eimeria, is a threat to poultry production. Eimeria tenella is one of the most pathogenic species, frequently causing a high prevalence of opportunistic infections.ObjectiveThe objective of this study is to investigate the role of the microbiota in the pathogenesis of severe Eimeria tenella infection.MethodsWe have previously shown that microbiota can promote parasite development. To study the effect of the microbiota on the pathogenesis of this infection, we used an experimental condition (inoculum of 10 000 oocysts E. tenella INRAE) in which the parasite load is similar between germ-free and conventional broilers at 7 days post-infection (pi). Thirteen conventional and 24 germ-free chickens were infected. Among this latter group, 12 remained germ-free and 12 received a microbiota from conventional healthy chickens at 4 days pi. Caeca and spleens were collected at 7 days pi.ResultsOur results demonstrated caecal lesions and epithelium damage in conventional chickens at 7 days pi but not in germ-free infected chickens. Administration of conventional microbiota to germ-free chickens partially restored these deleterious effects. At day 7 pi, both infected conventional and germ-free chickens exhibited increased gene expression of inflammatory mediators, including IL15, IFNγ, TNFα and the anti-inflammatory mediator SOCS1, whereas the inflammatory mediators CXCLi2, CCL20, IL18, CSF1, NOS2, PTGS2, IL1β, IL6, the receptor CCR2, and the anti-inflammatory mediators TGFβ1 and IL10 were upregulated only in infected conventional chickens. Notably, the IL18, PTGS2 gene expression was significantly higher in the infected conventional group. Overall, the inflammatory response enhanced by the microbiota might be in part responsible for higher lesion scores. Epithelial tight junction protein gene expression analysis revealed a significant upregulation of CLDN1 with the infection and microbiota, indicating a potential loss of the intestinal barrier integrity.ConclusionThese observations imply that, during E. tenella infection, the caecal microbiota could trigger an acute inflammatory response, resulting in a loss of intestinal integrity. Increase in bacterial translocation can then lead to the likelihood of opportunistic infections. Hence, modulating the microbiota may offer a promising strategy for improving poultry gut health and limiting caecal coccidiosis
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