2,544 research outputs found

    Is it true coeliacs do not digest gliadin ?. Degradation pattern of gliadin in coeliac disease small intestinal mucosa

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    Prolyl-endopeptidase supplementation has been proposed to favour gliadin degradation as an alternative treatment for coeliac disease (CD), although the real usefulness of this therapy in vivo is still under discussion. 1 However, our data point to alternative treatments aiming to modify the intestinal microbiota in patients with CD by the use of probiotics and/or prebiotics. We propose that the induction of gliadin proteolysis in the human gut might not be the solution but the origin of CD

    Checklist for the Multidisciplinary Approach to United Airway in Patients with Chronic Rhinosinusitis with Nasal Polyps (CRSwNP) and asthma

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    Dear Editor, The united airways concept calls for a multidisciplinary approach to asthma and/or chronic rhinitis/rhinosinusitis (CRS), aimed at integral airway treatment1, 2 and better coordination among specialists.3 Failure to treat rhinitis/rhinosinusitis is associated with poor asthma control, especially of severe asthma.4, 5 Biological treatments targeting type 2 (T2) inflammatory mediators in severe respiratory diseases offer a new therapeutic option directed against the pathophysiological mechanism of these difficult-to-control united airways diseases (UAD)..

    Comparison of autologous bone marrow and adipose tissue derived mesenchymal stem cells, and platelet rich plasma, for treating surgically induced lesions of the equine superficial digital flexor tendon

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    Several therapies have been investigated for equine tendinopathies, but satisfactory long term results have not been achieved consistently and a better understanding of the healing mechanism elicited by regenerative therapies is needed. The aim of this study was to assess the separate effects of autologous bone marrow (BM) and adipose tissue (AT) derived mesenchymal stem cells (MSCs), and platelet rich plasma (PRP), for treating lesions induced in the superficial digital flexor tendon (SDFT) of horses. Lesions were created surgically in both SDFTs of the forelimbs of 12 horses and were treated with BM-MSCs (six tendons), AT-MSCs (six tendons) or PRP (six tendons). The remaining six tendons received lactated Ringer''s solution as control. Serial ultrasound assessment was performed prior to treatment and at 2, 6, 10, 20 and 45 weeks post-treatment. At 45 weeks, histopathology and gene expression analyses were performed. At week 6, the ultrasound echogenicity score in tendons treated with BM-MSCs suggested earlier improvement, whilst all treatment groups reached the same level at week 10, which was superior to the control group. Collagen orientation scores on histological examination suggested a better outcome in treated tendons. Gene expression was indicative of better tissue regeneration after all treatments, especially for BM-MSCs, as suggested by upregulation of collagen type I, decorin, tenascin and matrix metalloproteinase III mRNA. Considering all findings, a clear beneficial effect was elicited by all treatments compared with the control group. Although differences between treatments were relatively small, BM-MSCs resulted in a better outcome than PRP and AT-MSCs

    EXPLORING THE IMPACT OF APOE POLYMORPHISM ON THE MOLECULAR, MORPHOLOGICAL AND FUNCTIONAL PROFILE OF iPSC-DERIVED ASTROCYTES FROM ALZHEIMER'S PATIENTS

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    Comunicación presentada a FENS Forum 2022Alzheimer¿s disease (AD) is pathologically characterised by the presence of amyloid-beta plaques, neurofibrillary tangles containing hyperphosphorylated Tau protein, neuroinflammation and neuronal death leading to progressive cognitive impairment. The ¿4 allele of the gene encoding apolipoprotein E (APOE), which is mainly expressed in glial cells, is the strongest genetic risk factor for sporadic AD. Increasing evidence has shown that APOE4 may disrupt normal astrocyte activity, potentially contributing to AD pathology, but the impact of different APOE alleles on astrocyte differentiation, maturation and function is not yet fully understood. To go in depth on these questions, we obtained induced pluripotent stem cells (iPSCs) from fibroblasts of AD patients carrying ¿3 and ¿4 alleles (in homozygosis) and from healthy patients. We also used gene-edited iPSC lines homozygous for the main APOE variants and an APOE knock-out line. iPSC-derived human astrocytes were generated by establishing a differentiation protocol through the consecutive addition of small molecules and growth factors, and the expression of typical markers (GFAP, GLT1, AQP4 and S100beta) and APOE was analysed. In addition, astrocytes exhibited functional features like glutamate uptake capacity and calcium waves production. They also responded to an inflammatory stimulus (IL-1beta and TNF-alpha) or to the presence of amyloid-beta 1-42 peptide by changing their morphology and increasing the expression levels of pro-inflammatory factors and cytokines. Our results shed light on the potential dual role of APOE polymorphism and the individual¿s genetic background in favouring or perhaps preventing AD pathology

    ANALYSING THE MOLECULAR, MORPHOLOGICAL AND FUNCTIONAL PROFILE OF iPSC-DERIVED ASTROCYTES FROM ALZHEIMER'S DISEASE PATIENTS

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    Comunicación presentada en Global Summit on Neurodegenerative Diseases NEURO 2020/22The ε4 allele of the gene encoding apolipoprotein E (APOE), which is mainly expressed in glial cells, is the strongest genetic risk factor for sporadic AD. Increasing evidence has shown that APOE4 may disrupt normal astrocyte activity, potentially contributing to AD pathology, but the impact of different APOE alleles on astrocyte maturation and function as well as their inflammatory profile is not yet fully understood. To answer these questions, we obtained induced pluripotent stem cells (iPSCs) from fibroblasts of AD patients carrying ε3 and ε4 alleles (in homozygosis) and from healthy patients. We also used gene-edited iPSC lines homozygous for the main APOE variants and an APOE knock-out line. iPSC-derived human astrocytes were generated through the consecutive addition of small molecules and growth factors to the culture medium, and the expression of typical markers (GFAP, GLT1, AQP4 and S100beta) was analysed. In addition, astrocytes exhibited functional features like glutamate uptake capacity and calcium waves. They also responded to an inflammatory stimulus (IL-1beta and TNF-alpha) or to the presence of amyloid-beta 1-42 peptide by changing their morphology and increasing the expression levels of pro-inflammatory factors and cytokines. Our results shed light on the potential dual role of APOE polymorphism and the individual's genetic background in favouring or perhaps preventing AD pathology

    SERCA inhibition improves lifespan and healthspan in a chemical model of Parkinson disease in Caenorhabditis elegans

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    Introduction: The high prevalence of neurodegenerative diseases in our population and the lack of effective treatments encourage the search for new therapeutic targets for these pathologies. We have recently described that submaximal inhibition of the Sarco-Endoplasmic Reticulum Ca2+ ATPase (SERCA), the main responsible for ER calcium storage, is able to increase lifespan in Caenorhabditis elegans worms by mechanisms involving mitochondrial metabolism and nutrient-sensitive pathways.Methods: We have studied here the effects of submaximal SERCA inhibition in a chemical model of Parkinson’s disease (PD) induced in C. elegans worms by treatment with the mitochondrial complex I inhibitor rotenone. For specific SERCA inhibition, we treated worms with RNAi against sca-1, the sole orthologue of SERCA in C. elegans.Results and Discussion: Our results show that rotenone produces alterations in worms that include decreased lifespan, smaller size, reduced fertility, decreased motility, defecation and pumping rate, increased mitochondrial ROS production, reduced mitochondrial membrane potential and oxygen consumption rate, altered mitochondrial structure, and altered ethanol preference in behavioral studies. Most of these alterations were either fully or partially reversed in worms treated with sca-1 RNAi, suggesting that SERCA inhibition could be a novel pharmacological target in the prevention or treatment of neurodegeneration

    HIV/STI co-infection among men who have sex with men in Spain

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    In Spain, neither the HIV nor the STI national surveillance systems collect information on HIV/STI co-infection. However, there are two networks based on HIV/STI clinics which gather this data. We describe HIV prevalence in men who have sex with men (MSM) diagnosed with infectious syphilis and/or gonorrhoea in 15 STI clinics; and concurrent diagnoses of STI in MSM newly diagnosed with HIV in 19 HIV/STI clinics. In total, 572 MSM were diagnosed with infectious syphilis and 580 with gonorrhoea during 2005-2007. HIV prevalence among syphilis and gonorrhoea cases was 29.8% and 15.2% respectively. In the multivariate analysis, HIV/syphilis co-infection was associated with being Latin American; having a history of STI; reporting exclusively anal intercourse; and having sex with casual or several types of partners. HIV and gonorrhoea co-infection was associated with age older than 45 years; having no education or only primary education completed; and having a history of STI. In total, 1,462 HIV infections were newly diagnosed among MSM during 2003-2007. Of these, 31.0% were diagnosed with other STI at the same time. Factors associated with STI co-infection among new HIV cases in MSM were being Latin American; and having sex with casual partners or with both steady and casual partners. In Spain, a considerable proportion of MSM are co-infected with HIV and STI.This work was funded by two grants (36646/07; 36794/08) from the Foundation for Research and Prevention of AIDS in Spain (Fundación para la Investigación y la Prevención del SIDA en España–FIPSE).S
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