178 research outputs found

    Guias multidisciplinarias de mucopolosacaridosis tipo I

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    Seroreactivity against specific L5P antigen from <i>Mycobacterium avium</i> subsp. <i>paratuberculosis</i> in children at risk for T1D

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    Aims/Hypothesis: Although numerous environmental agents have been investigated over the years as possible triggers of type 1 diabetes (T1D), its causes remain unclear. We have already demonstrated an increased prevalence of antibodies against peptides derived from Mycobacterium avuim subsp. paratuberculosis (MAP) homologous to human zinc transporter 8 protein (ZnT8) and proinsulin in Italian subjects at risk for or affected by T1D. In this study, we compared titers of the previously detected antibodies with seroreactivity to MAP lipopentapetide (L5P) that recently emerged as a strong immunogenic component able to specifically distinguish MAP from other mycobacteria. Methods: Plasma of 32 children and youth at risk for T1D including follow-up samples and 42 age-matched healthy controls (HC) recruited at the Tor Vergata University Hospital in Rome was analyzed by indirect ELISA for the presence of antibodies against MAP-derived epitopes MAP3865c133–141, MAP3865c125-133, MAP2404c70-85 and MAP1,4αgbp157-173 along with their ZnT8 and proinsulin homologs. The data were analyzed through two-tailed Mann-Whitney U test and relation between variables was determined by principal component analysis. Results: Responses to L5P were not detectable in subjects whose initial seroreactivity to MAP peptides and their human homologs was lost in follow-up samples, whereas anti-L5P antibodies appeared constantly in individuals with a stable immunity against MAP antigens. The overall coincidence in positivity to L5P and the four MAP epitopes both in children at risk for T1D and HC exceeded 90%. Conclusions: MAP-derived homologs may cross-react with ZnT8 and proinsulin peptides inducing immune responses at a young age in subjects predisposed for T1D. Thus, L5P may have a diagnostic value to immediately indicate the presence of anti-MAP seroreactivity when evaluation of a more complex antibody status is not required. Almost complete coincidence in responses to both types of antigens lends support to the involvement of MAP in T1D

    The Immunoregulatory Actions of DHEA in Tuberculosis, A Tool for Therapeutic Intervention?

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    Dehydroepiandrosterone (DHEA) is an androgen synthesized by the adrenal cortex, which is an intermediary in the biosynthesis of sex hormones, such as testosterone and estradiol. DHEA mostly circulates as a conjugated ester, in the form of sulfate (DHEA-S). There exist several endogenous factors able to influence its synthesis, the most common ones being the corticotrophin-releasing hormone (CRH), adrenocorticotrophin (ACTH), growth factors, and proinflammatory cytokines, among others. Like other steroid hormones, DHEA, can alter the functioning of immune cells and therefore the course of diseases exhibiting an immune-inflammatory component, mostly from autoimmune or infectious nature. We herein review the role played by DHEA during a major infectious disease like tuberculosis (TB). Data recorded from TB patients, mouse models, or in vitro studies show that DHEA is likely to be implied in better disease control. This provides a stimulating background for carrying out clinical studies aimed at assessing the usefulness of DHEA as an adjuvant in TB patients.Fil: Bongiovanni, Bettina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentina. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas; ArgentinaFil: Díaz, Ariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Santucci, Natalia Estefanía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: D'attilio, Luciano David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Bottasso, Oscar Adelmo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Hernández Pando, Rogelio. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; MéxicoFil: Bay, Maria Luisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentin

    Using DNA metabarcoding for simultaneous inference of common vampire bat diet and population structure

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    Metabarcoding diet analysis has become a valuable tool in animal ecology; however, co-amplified predator sequences are not generally used for anything other than to validate predator identity. Exemplified by the common vampire bat, we demonstrate the use of metabarcoding to infer predator population structure alongside diet assessments. Growing populations of common vampire bats impact human, livestock and wildlife health in Latin America through transmission of pathogens, such as lethal rabies viruses. Techniques to determine large scale variation in vampire bat diet and bat population structure would empower locality- and species-specific projections of disease transmission risks. However, previously used methods are not cost-effective and efficient for large scale applications. Using blood meal and faecal samples from common vampire bats from coastal, Andean and Amazonian regions of Peru, we showcase metabarcoding as a scalable tool to assess vampire bat population structure and feeding preferences. Dietary metabarcoding was highly effective, detecting vertebrate prey in 93.2% of the samples. Bats predominantly preyed on domestic animals, but fed on tapirs at one Amazonian site. In addition, we identified arthropods in 9.3% of samples, likely reflecting consumption of ectoparasites. Using the same data, we document mitochondrial geographic population structure in the common vampire bat in Peru. Such simultaneous inference of vampire bat diet and population structure can enable new insights into the interplay between vampire bat ecology and disease transmission risks. Importantly, the methodology can be incorporated into metabarcoding diet studies of other animals to couple information on diet and population structure

    Liver disease and dyslipidemia as a manifestation of lysosomal acid lipase deficiency (LAL-D). Clinical and diagnostic aspects, and a new treatment. An update

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    Lysosomal acid lipase deficiency (LAL-D) is still a little recognized genetic disease with significant morbidity and mortality in children and adults. This document provides guidance on when to suspect LAL-D and how to diagnose it. It is recommended to add lysosomal acid lipase deficiency to the list of differential diagnoses of sepsis, oncological diseases, storage diseases, persistent diarrhea, chronic malnutrition, and hemophagocytic lymphohistiocytosis. It should also be considered in young patients with dyslipidemia and atherosclerosis as well as diseases associated with fatty liver and/or hepatomegaly. LAL-D should be suspected in patients with hepatomegaly, hyperlipidemia and/or elevated transaminases found during routine checks or testing for other conditions, and in patients with cryptogenic cirrhosis. At present, there is the option of a specific enzyme replacement treatment.Instituto de Estudios Inmunológicos y FisiopatológicosFacultad de Ciencias Exacta

    Increased frequency of CD4+ CD25+ FoxP3+ T regulatory cells in pulmonary Tuberculosis patients undergoing specific treatment and its relationship with their immune-endocrine profile

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    Tuberculosis (TB) is a major health problem requiring an appropriate cell immune response (IR) to be controlled. Since regulatory T cells (Tregs) are relevant in IR regulation, we analyzed Tregs variations throughout the course of TB treatment and its relationship with changes in immune-endocrine mediators dealing with disease immunopathology. The cohort was composed of 41 adult patients, 20 of them completing treatment and follow-up. Patients were bled at diagnosis (T0) and at 2 (T2), 4 (T4), 6 (T6), and 9 months following treatment initiation. Twenty-four age- and sex-matched healthy controls (HCo) were also included. Tregs (flow cytometry) from TB patients were increased at T0 (versus HCo < 0.05), showing even higher values at T2 (versus T0 < 0.01) and T4 (versus T0 < 0.001). While IL-6, IFN-, TGF- (ELISA), and Cortisol (electrochemiluminescence, EQ) were augmented, DHEA-S (EQ) levels were diminished at T0 with respect to HCo, with cytokines and Cortisol returning to normal values at T9. Tregs correlated positively with IFN- ( = 0.868, < 0.05) at T2 and negatively at T4 ( = −0.795, < 0.05). Lowered levels of proinflammatory cytokines together with an increased frequency of Tregs of patients undergoing specific treatment might reflect a downmodulatory effect of these cells on the accompanying inflammation.Fil: Díaz, Ariana. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico Rosario; ArgentinaFil: Santucci, Natalia Estefanía. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico Rosario; ArgentinaFil: Bongiovanni, Bettina. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico Rosario; ArgentinaFil: D'attilio, Luciano David. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico Rosario; ArgentinaFil: Massoni, Claudia. Provincia de Santa Fe. Ministerio de Salud y Medio Ambiente - Rosario. Hospital Provincial del Centenario; ArgentinaFil: Lioi, Susana. Provincia de Santa Fe. Ministerio de Salud y Medio Ambiente - Rosario. Hospital Provincial del Centenario; ArgentinaFil: Radcliffe, Stella. Provincia de Santa Fe. Ministerio de Salud y Medio Ambiente - Rosario. Hospital Provincial del Centenario; ArgentinaFil: Didoli, Griselda. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología; ArgentinaFil: Bottasso, Oscar Adelmo. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico Rosario; ArgentinaFil: Bay, Maria Luisa. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología; Argentin

    Evidence for a More Disrupted Immune-Endocrine Relation and Cortisol Immunologic Influences in the Context of Tuberculosis and Type 2 Diabetes Comorbidity

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    Pulmonary tuberculosis (PTB), caused by Mycobacterium tuberculosis (Mtb), is a major health problem worldwide, further aggravated by the convergence of type 2 diabetes mellitus (DM) which constitutes an important risk factor for TB development. The worse scenario of patients with PTB and DM may be partly related to a more unbalanced defensive response. As such, newly diagnosed PTB patients with DM (TB+DM, n = 11) or not (TB, n = 21), as well as DM (n = 18) patients and pair matched controls (Co, n = 22), were investigated for the circulating immuno-endocrine-metabolic profile (ELISA), along with studies in peripheral blood mononuclear cells (PBMC) analyzing transcript expression (RT-qPCR) of mediators involved in glucocorticoid functionality. Given the hyperglycemic/hypercortisolemic scenario of TB+DM patients, PBMC were also exposed to stress-related cortisol concentrations (0.1 and 1 μM) and supraphysiologic glucose doses (10, 20, and 40 mM) and assessed for the specific response against Mtb stimulation (lymphoproliferation, -thymidine incorporation-, and cytokine production -bead-cytometry). All TB patients displayed increased plasma amounts of cortisol, growth hormone -hGH-, and proinflammatory mediators. In turn, TB+DM showed even higher levels of interferon gamma -IFN-γ- and hGH (vs. TB), or IL-6, C reactive protein, cortisol and hGH (vs. DM). Both DM groups had equally augmented values of IL-10. All TB patients showed decreased dehydroepiandrosterone- sulfate concentrations, even more in TB+DM cases. Leptin was also decreased in both TB cases, particularly in the TB group, revealing a lower body mass index, as well. Unlike PBMC from TB cases showing a decreased relationship between the glucocorticoids receptor (GR) isoforms (GRα/GRβ; functional isoform/negative isoform), cells from TB+DM patients had no changes in this regard, along with an increased expression of 11-beta hydroxysteroid dehydrogenase type-1, the enzyme facilitating intracellular cortisone to cortisol conversion. TB+DM patients also showed an increased Mtb antigen-driven lymphoproliferation. Compared to TB, DM and HCo counterparts, PBMC from TB+DM patients had a biased Th1 response to Mtb stimulation (increased IL-2 and IFN-γ production), even when exposed to inhibitory cortisol doses. TB+DM patients show a more unbalanced immuno-endocrine relationship, respect the non-diabetic counterparts, with a relative deficiency of cortisol immunomodulatory influences, despite their more favorable microenvironment for cortisol-mediated immune effects.Fil: Fernández, Rocío del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Díaz, Ariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Bongiovanni, Bettina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Gallucci, Georgina Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Bértola, Diego. Universidad Nacional de Rosario; ArgentinaFil: Gardeñez, Walter. Universidad Nacional de Rosario; ArgentinaFil: Lioi, Susana. Hospital Provincial del Centenario; ArgentinaFil: Bertolin, Yésica. Hospital Provincial del Centenario; ArgentinaFil: Galliano, Romina. Hospital Provincial del Centenario; ArgentinaFil: Bay, Maria Luisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: Bottasso, Oscar Adelmo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; ArgentinaFil: D'attilio, Luciano David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Inmunología Clinica y Experimental de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Médicas. Instituto de Inmunología Clinica y Experimental de Rosario; Argentin

    Liver disease and dyslipidemia as a manifestation of lysosomal acid lipase deficiency (LAL-D). Clinical and diagnostic aspects, and a new treatment. An update

    Get PDF
    Lysosomal acid lipase deficiency (LAL-D) is still a little recognized genetic disease with significant morbidity and mortality in children and adults. This document provides guidance on when to suspect LAL-D and how to diagnose it. It is recommended to add lysosomal acid lipase deficiency to the list of differential diagnoses of sepsis, oncological diseases, storage diseases, persistent diarrhea, chronic malnutrition, and hemophagocytic lymphohistiocytosis. It should also be considered in young patients with dyslipidemia and atherosclerosis as well as diseases associated with fatty liver and/or hepatomegaly. LAL-D should be suspected in patients with hepatomegaly, hyperlipidemia and/or elevated transaminases found during routine checks or testing for other conditions, and in patients with cryptogenic cirrhosis. At present, there is the option of a specific enzyme replacement treatment.Instituto de Estudios Inmunológicos y FisiopatológicosFacultad de Ciencias Exacta
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