52 research outputs found
Reestructurados de pollo saludables, evaluaciĂłn del efecto de varias estrategias tecnolĂłgicas combinadas
La innovaciĂłn juega un rol clave en el desarrollo de nuevos productos y extensiones de lĂnea. La reformulaciĂłn de productos cárnicos es una estrategia, que aplica la industria actual, basada en el conocimiento de las necesidades y expectativas de los consumidores. Siguiendo estas tendencias se desarrolla un reestructurado de pollo con fibra soluble y omega 3, sin el agregado de grasa y sal. Para proteger los omega 3 de la autoxidaciĂłn se emplean mĂ©todos de cocciĂłn a calor moderado y vacĂo en la precoccion del producto, que luego se va conservar en refrigeraciĂłn. Además se evaluará la acciĂłn del nitrito en la estabilidad oxidativa, aunque se agrega por motivos de seguridad alimentaria. La fibra soluble se incorpora por aspectos tecnolĂłgicos como la retenciĂłn de agua pero además por su reconocido efecto saluble. Y los omega tres vienen a paliar deficit nutricionales considerados crĂticos para la salud humana, en recientes avances de estudios de desnutriciĂłn.Boari De Greissing, VM. (2014). Reestructurados de pollo saludables, evaluaciĂłn del efecto de varias estrategias tecnolĂłgicas combinadas [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/37192TESI
Tumor-induced senescent T cells promote the secretion of pro-inflammatory cytokines and angiogenic factors by human monocytes/macrophages through a mechanism that involves Tim-3 and CD40L
Solid tumors are infiltrated by immune cells where macrophages and senescent T cells are highly represented. Within the tumor microenvironment, a cross-talk between the infiltrating cells may occur conditioning the characteristic of the in situ immune response. Our previous work showed that tumors induce senescence of T cells, which are powerful suppressors of lympho-proliferation. In this study, we report that Tumor-Induced Senescent (TIS)-T cells may also modulate monocyte activation. To gain insight into this interaction, CD4+ or CD8+TIS-T or control-T cells were co-incubated with autologous monocytes under inflammatory conditions. After co-culture with CD4+ or CD8+TIS-T cells, CD14+ monocytes/macrophages (Mo/Ma) exhibit a higher expression of CD16+ cells and a reduced expression of CD206. These Mo/Ma produce nitric oxide and reactive oxygen species; however, TIS-T cells do not modify phagocyte capacity of Mo/Ma. TIS-T modulated-Mo/Ma show a higher production of pro-inflammatory cytokines (TNF, IL-1β and IL-6) and angiogenic factors (MMP-9, VEGF-A and IL-8) and a lower IL-10 and IP-10 secretion than monocytes co-cultured with controls. The mediator(s) present in the supernatant of TIS-T cell/monocyte-macrophage co-cultures promote(s) tubulogenesis and tumor-cell survival. Monocyte-modulation induced by TIS-T cells requires cell-to-cell contact. Although CD4+ shows different behavior from CD8+TIS-T cells, blocking mAbs against T-cell immunoglobulin and mucin protein 3 and CD40 ligand reduce pro-inflammatory cytokines and angiogenic factors production, indicating that these molecules are involved in monocyte/macrophage modulation by TIS-T cells. Our results revealed a novel role for TIS-T cells in human monocyte/macrophage modulation, which may have deleterious consequences for tumor progression. This modulation should be considered to best tailor the immunotherapy against cancer.Fil: Ramello, MarĂa Cecilia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; ArgentinaFil: Tosello Boari, Jimena. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; ArgentinaFil: Canale, Fernando Pablo. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; ArgentinaFil: Mena, Hebe Agustina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Negrotto, Soledad. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Gastman, B. Cleveland Clinic; Estados UnidosFil: Gruppi, Adriana. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; ArgentinaFil: Acosta Rodriguez, Eva Virginia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; ArgentinaFil: Montes, Carolina Lucia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; Argentin
Inhibitory Receptor Expression on T Cells as a Marker of Disease Activity and Target to Regulate Effector Cellular Responses in Rheumatoid Arthritis
Objective: Inhibitory receptors are essential for the regulation of effector immune responses and may play critical roles in autoimmune diseases. We evaluated whether inhibitory receptor expression on T cells from patients with rheumatoid arthritis (RA) were correlated with immune activation, disease activity, and response to treatment, as well as whether inhibitory receptor–mediated pathways were functional. Methods: Using flow cytometry, we performed extensive phenotypic and functional evaluation of CD4+ and CD8+ T cells from the blood and synovial fluid (SF) of RA patients ex vivo and after culture. The relationship of each parameter with the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR) and response to treatment was examined. Results: In RA patients with low levels of T cell activation, inhibitory receptor expression showed an inverse relationship with the DAS28-ESR. The frequency of T cells expressing multiple inhibitory receptors was reduced in untreated RA patients but returned to normal levels in treated patients. RA patients who responded to treatment showed an augmented frequency of inhibitory receptor–expressing T cells that correlated with reduced inflammatory cytokine production in comparison to nonresponders. Higher frequencies of effector and memory T cells that expressed multiple inhibitory receptors were seen in SF than in peripheral blood. Notably, inhibitory pathways were operative in blood and synovial T cells from all RA patients, although cells from nonresponder patients were less sensitive to inhibition. Conclusion: Inhibitory receptor expression on T cells from RA patients is inversely correlated with effector T cell function and disease activity and may predict response to treatment. Furthermore, different inhibitory pathways are functional and cooperatively suppress synovial T cells, providing a rationale for new treatment strategies to regulate acute local inflammation.Fil: Onofrio, Luisina InĂ©s. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; Argentina. Universidad Nacional de CĂłrdoba. Facultad de Medicina. Hospital Nacional de ClĂnicas; ArgentinaFil: Zacca, EstefanĂa. Universidad Nacional de CĂłrdoba. Facultad de Medicina. Hospital Nacional de ClĂnicas; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; ArgentinaFil: Ferrero, Paola Virginia. Universidad Nacional de CĂłrdoba. Facultad de Medicina. Hospital Nacional de ClĂnicas; ArgentinaFil: Acosta, Cristina. Universidad Nacional de CĂłrdoba. Facultad de Medicina. Hospital Nacional de ClĂnicas; ArgentinaFil: Mussano, Eduardo. Universidad Nacional de CĂłrdoba. Facultad de Medicina. Hospital Nacional de ClĂnicas; ArgentinaFil: Onetti, Laura. Universidad Nacional de CĂłrdoba. Facultad de Medicina. Hospital Nacional de ClĂnicas; ArgentinaFil: Cadile, Isaac. Universidad Nacional de CĂłrdoba. Facultad de Medicina. Hospital Nacional de ClĂnicas; ArgentinaFil: Gazzoni, M. Victoria. Universidad Nacional de CĂłrdoba. Facultad de Medicina. Hospital Nacional de ClĂnicas; ArgentinaFil: Jurado, RaĂşl. Universidad Nacional de CĂłrdoba. Facultad de Medicina. Hospital Nacional de ClĂnicas; ArgentinaFil: Tosello Boari, Jimena. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; ArgentinaFil: Ramello, MarĂa Cecilia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; ArgentinaFil: Montes, Carolina Lucia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; ArgentinaFil: Gruppi, Adriana. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; ArgentinaFil: Acosta Rodriguez, Eva Virginia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; Argentin
IL-17RA-signaling modulates CD8+ T Cell survival and exhaustion during trypanosoma cruzi infection
The IL-17 family contributes to host defense against many intracellular pathogens by mechanisms that are not fully understood. CD8+ T lymphocytes are key elements against intracellular microbes, and their survival and ability to mount cytotoxic responses are orchestrated by several cytokines. Here, we demonstrated that IL-17RA-signaling cytokines sustain pathogen-specific CD8+ T cell immunity. The absence of IL-17RA and IL-17A/F during Trypanosoma cruzi infection resulted in increased tissue parasitism and reduced frequency of parasite-specific CD8+ T cells. Impaired IL-17RA-signaling in vivo increased apoptosis of parasite-specific CD8+ T cells, while in vitro recombinant IL-17 down-regulated the pro-Apoptotic protein BAD and promoted the survival of activated CD8+ T cells. Phenotypic, functional, and transcriptomic profiling showed that T. cruzi-specific CD8+ T cells derived from IL-17RA-deficient mice presented features of cell dysfunction. PD-L1 blockade partially restored the magnitude of CD8+ T cell responses and parasite control in these mice. Adoptive transfer experiments established that IL-17RA-signaling is intrinsically required for the proper maintenance of functional effector CD8+ T cells. Altogether, our results identify IL-17RA and IL-17A as critical factors for sustaining CD8+ T cell immunity to T. cruzi.Fil: Tosello Boari, Jimena. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; Argentina. Universidad Nacional de CĂłrdoba. Facultad de Ciencias QuĂmicas. Departamento de BioquĂmica ClĂnica; ArgentinaFil: Araujo Furlan, Cintia Liliana. Universidad Nacional de CĂłrdoba. Facultad de Ciencias QuĂmicas. Departamento de BioquĂmica ClĂnica; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; ArgentinaFil: Fiocca Vernengo, Facundo. Universidad Nacional de CĂłrdoba. Facultad de Ciencias QuĂmicas. Departamento de BioquĂmica ClĂnica; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; ArgentinaFil: Rodriguez, Constanza. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; Argentina. Universidad Nacional de CĂłrdoba. Facultad de Ciencias QuĂmicas. Departamento de BioquĂmica ClĂnica; ArgentinaFil: Ramello, MarĂa Cecilia. Universidad Nacional de CĂłrdoba. Facultad de Ciencias QuĂmicas. Departamento de BioquĂmica ClĂnica; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; ArgentinaFil: Amezcua Vesely, Maria Carolina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; Argentina. Universidad Nacional de CĂłrdoba. Facultad de Ciencias QuĂmicas. Departamento de BioquĂmica ClĂnica; ArgentinaFil: Gorosito Serran, Melisa. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; Argentina. Universidad Nacional de CĂłrdoba. Facultad de Ciencias QuĂmicas. Departamento de BioquĂmica ClĂnica; ArgentinaFil: Nuñez, Nicolás G.. Institute Curie; Francia. Institut National de la SantĂ© et de la Recherche MĂ©dicale; FranciaFil: Richer, Wilfrid. Institut National de la SantĂ© et de la Recherche MĂ©dicale; Francia. Institute Curie; FranciaFil: Piaggio, Eliane. Institut National de la SantĂ© et de la Recherche MĂ©dicale; Francia. Institute Curie; FranciaFil: Montes, Carolina Lucia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; Argentina. Universidad Nacional de CĂłrdoba. Facultad de Ciencias QuĂmicas. Departamento de BioquĂmica ClĂnica; ArgentinaFil: Gruppi, Adriana. Universidad Nacional de CĂłrdoba. Facultad de Ciencias QuĂmicas. Departamento de BioquĂmica ClĂnica; Argentina. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; ArgentinaFil: Acosta Rodriguez, Eva Virginia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; Argentina. Universidad Nacional de CĂłrdoba. Facultad de Ciencias QuĂmicas. Departamento de BioquĂmica ClĂnica; Argentin
Calidad sensorial de productos cárnicos funcionales. Percepción por los consumidores e influencia de su composición
A medallion of chicken meat supplemented ω3 fatty acids, oat bran, low sodium content, by cooking "sous-vide" and was formulated vacuum packaging. The design used a mixture of spices to achieve a reduced sodium product and acceptable taste. Each medallion was packaged and sealed in a vacuum packaging (VACUUM PACKING 80060/80080), in polyethylene bags (O2 permeability of 25 to 30 cm3 / m2; water vapor permeability of 5 g / m2). The cooking method "sous-vide" was conducted in bath with temperature control and time constant circulation of water (RONER COMPACT 80060/80080), the combination of time / temperature was 80 °C and 10 minutes. Subsequently it cooled to 0 °C. The formulation was analyzed using sensory affective tests: preference and satisfaction, by a panel of 35 persons. In the study of consumer perception, projective type surveys were used. Sensory characterization of samples was performed by CATA questions (check-all-that-apply). Thus an accessible functional product with input ω3 fatty acid, soluble fiber and reduced sodium respect to traditional chicken medallion, microbiologically stable and sensorially accepted was obtained.Se formulĂł un medallĂłn de carne de pollo suplementada en ácidos grasos ω3, con salvado de avena, de bajo contenido de sodio, mediante cocciĂłn “sous-vide” y envasado al vacĂo. El diseño utilizĂł una mezcla de especias para lograr un producto reducido en sodio y de sabor aceptable. Cada medallĂłn fue empaquetado y sellado en una envasadora a vacĂo (VACUUM PACKING 80060/80080), en bolsas de polietileno (permeabilidad al O2 de 25 a 30 cm3 /m2; permeabilidad del vapor de agua de 5 g/m2). El mĂ©todo de cocciĂłn “sous-vide” fue efectuado en baño con control de temperatura y tiempo de circulaciĂłn constante de agua (RONER COMPACT 80060/80080), cuya combinaciĂłn temperatura/tiempo fue de 80°C y 10 minutos. Posteriormente se refrigerĂł a 0ÂşC. La formulaciĂłn fue analizada sensorialmente mediante pruebas afectivas: de preferencia y grado de satisfacciĂłn, por un panel de 35 personas. En el estudio de la percepciĂłn de los consumidores, se emplearon encuestas de tipo proyectivas. La caracterizaciĂłn sensorial de las muestras se realizĂł mediante las preguntas CATA (check-all-that-apply). De esta manera se obtuvo un producto funcional accesible con aporte de ácidos grasos ω3, fibra soluble y reducido en sodio respecto al medallĂłn de pollo tradicional, microbiolĂłgicamente estable y sensorialmente aceptado.Foi formulado um medalhĂŁo de carne de frango suplementado w3 ácidos graxos, farelo de aveia, baixo teor de sĂłdio, por cozimento "sous-vide" e embalados a vácuo. O projeto usou uma mistura de especiarias para conseguir um produto de sĂłdio reduzido e sabor aceitável. Cada medalhĂŁo foi embalado e selado numa embalagem de vácuo (vácuo EMBALAGEM 80060/80080), em sacos de polietileno (O2 permeabilidade de 25 a 30 cm3 / m2; a permeabilidade ao vapor de água de 5 g / m2). O mĂ©todo de cozimento "sous-vide" foi realizada em banho com controlo de temperatura e tempo de circulação constante de água (Roner COMPACTO 80060/80080), a combinação de tempo / temperatura foi de 80 ° C e 10 minutos. Posteriormente ele esfriou a 0 ° C. A formulação foi analisada utilizando testes afetivos sensoriais: preferĂŞncia e satisfação, por um painel de 35 pessoas. No estudo da percepção do consumidor, foram utilizados levantamentos tipo projetivas. Acaracterização das amostras foi realizada por meio de perguntas CATA (check-tudo-que-extra). Assim, um produto funcional acessĂvel Ă© obtido com a entrada de w3 ácidos graxos, fibras solĂşveis e redução de sĂłdio em comparação com medalhĂŁo de frango tradicional, microbiologicamente estável e sensorialmente aceitos
Extrafollicular plasmablast present in the acute phase of infections express high levels of PD-L1 and are able to limit T cell respose
During infections with protozoan parasites or some viruses, T cell immunosuppression is generated simultaneously with a high B cell activation. It has been described that, as well as producing antibodies, plasmablasts, the differentiation product of activated B cells, can condition the development of protective immunity in infections. Here, we show that, in T. cruzi infection, all the plasmablasts detected during the acute phase of the infection had higher surface expression of PD-L1 than other mononuclear cells. PD-L1hi plasmablasts were induced in vivo in a BCR-specific manner and required help from Bcl-6+CD4+T cells. PD-L1hi expression was not a characteristic of all antibody-secreting cells since plasma cells found during the chronic phase of infection expressed PD-L1 but at lower levels. PD-L1hi plasmablasts were also present in mice infected with Plasmodium or with lymphocytic choriomeningitis virus, but not in mice with autoimmune disorders or immunized with T cell-dependent antigens. In vitro experiments showed that PD-L1hi plasmablasts suppressed the T cell response, partially via PD-L1. Thus, this study reveals that extrafollicular PD-L1hi plasmablasts, whose peaks of response precede the peak of germinal center response, may have a modulatory function in infections, thus influencing T cell response.Fil: Gorosito Serran, Melisa. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; ArgentinaFil: Fiocca Vernengo, Facundo. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; ArgentinaFil: Almada, Laura. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; ArgentinaFil: Beccaria, Cristian Gabriel. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; ArgentinaFil: Gazzoni, Yamila Natali. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; ArgentinaFil: Canete, Pablo F.. Australian National University; ArubaFil: Roco, Jonathan A.. Australian National University; ArubaFil: Tosello Boari, Jimena. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; ArgentinaFil: Ramello, MarĂa Cecilia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; ArgentinaFil: Wehrens, Ellen. University of California; Estados UnidosFil: Cai, Yeping. Australian National University; ArubaFil: Zuniga, Elina Isabel. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas; ArgentinaFil: Montes, Carolina Lucia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; ArgentinaFil: Cockburn, Ian A.. Australian National University; ArubaFil: Acosta Rodriguez, Eva Virginia. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; ArgentinaFil: Vinuesa, Carola G.. Australian National University; ArubaFil: Gruppi, Adriana. Consejo Nacional de Investigaciones CientĂficas y TĂ©cnicas. Centro CientĂfico TecnolĂłgico CĂłrdoba. Centro de Investigaciones en BioquĂmica ClĂnica e InmunologĂa; Argentin
IL-17RA Signaling Reduces Inflammation and Mortality during Trypanosoma cruzi Infection by Recruiting Suppressive IL-10-Producing Neutrophils
Members of the IL-17 cytokine family play an important role in protection against pathogens through the induction of different effector mechanisms. We determined that IL-17A, IL-17E and IL-17F are produced during the acute phase of T. cruzi infection. Using IL-17RA knockout (KO) mice, we demonstrate that IL-17RA, the common receptor subunit for many IL-17 family members, is required for host resistance during T. cruzi infection. Furthermore, infected IL-17RA KO mice that lack of response to several IL-17 cytokines showed amplified inflammatory responses with exuberant IFN-Îł and TNF production that promoted hepatic damage and mortality. Absence of IL-17RA during T. cruzi infection resulted in reduced CXCL1 and CXCL2 expression in spleen and liver and limited neutrophil recruitment. T. cruzi-stimulated neutrophils secreted IL-10 and showed an IL-10-dependent suppressive phenotype in vitro inhibiting T-cell proliferation and IFN-Îł production. Specific depletion of Ly-6G+ neutrophils in vivo during T. cruzi infection raised parasitemia and serum IFN-Îł concentration and resulted in increased liver pathology in WT mice and overwhelming wasting disease in IL-17RA KO mice. Adoptively transferred neutrophils were unable to migrate to tissues and to restore resistant phenotype in infected IL-17RA KO mice but migrated to spleen and liver of infected WT mice and downregulated IFN-Îł production and increased survival in an IL-10 dependent manner. Our results underscore the role of IL-17RA in the modulation of IFN-Îł-mediated inflammatory responses during infections and uncover a previously unrecognized regulatory mechanism that involves the IL-17RA-mediated recruitment of suppressive IL-10-producing neutrophils
Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register
Beta (β)-blockers (BB) are useful in reducing morbidity and mortality in patients with heart failure (HF) and concomitant chronic obstructive pulmonary disease (COPD). Nevertheless, the use of BBs could induce bronchoconstriction due to β2-blockade. For this reason, both the ESC and GOLD guidelines strongly suggest the use of selective β1-BB in patients with HF and COPD. However, low adherence to guidelines was observed in multiple clinical settings. The aim of the study was to investigate the BBs use in older patients affected by HF and COPD, recorded in the REPOSI register. Of 942 patients affected by HF, 47.1% were treated with BBs. The use of BBs was significantly lower in patients with HF and COPD than in patients affected by HF alone, both at admission and at discharge (admission, 36.9% vs. 51.3%; discharge, 38.0% vs. 51.7%). In addition, no further BB users were found at discharge. The probability to being treated with a BB was significantly lower in patients with HF also affected by COPD (adj. OR, 95% CI: 0.50, 0.37-0.67), while the diagnosis of COPD was not associated with the choice of selective β1-BB (adj. OR, 95% CI: 1.33, 0.76-2.34). Despite clear recommendations by clinical guidelines, a significant underuse of BBs was also observed after hospital discharge. In COPD affected patients, physicians unreasonably reject BBs use, rather than choosing a β1-BB. The expected improvement of the BB prescriptions after hospitalization was not observed. A multidisciplinary approach among hospital physicians, general practitioners, and pharmacologists should be carried out for better drug management and adherence to guideline recommendations
Prescription appropriateness of anti-diabetes drugs in elderly patients hospitalized in a clinical setting: evidence from the REPOSI Register
Diabetes is an increasing global health burden with the highest prevalence (24.0%) observed in elderly people. Older diabetic adults have a greater risk of hospitalization and several geriatric syndromes than older nondiabetic adults. For these conditions, special care is required in prescribing therapies including anti- diabetes drugs. Aim of this study was to evaluate the appropriateness and the adherence to safety recommendations in the prescriptions of glucose-lowering drugs in hospitalized elderly patients with diabetes. Data for this cross-sectional study were obtained from the REgistro POliterapie-Società Italiana Medicina Interna (REPOSI) that collected clinical information on patients aged ≥ 65 years acutely admitted to Italian internal medicine and geriatric non-intensive care units (ICU) from 2010 up to 2019. Prescription appropriateness was assessed according to the 2019 AGS Beers Criteria and anti-diabetes drug data sheets.Among 5349 patients, 1624 (30.3%) had diagnosis of type 2 diabetes. At admission, 37.7% of diabetic patients received treatment with metformin, 37.3% insulin therapy, 16.4% sulfonylureas, and 11.4% glinides. Surprisingly, only 3.1% of diabetic patients were treated with new classes of anti- diabetes drugs. According to prescription criteria, at admission 15.4% of patients treated with metformin and 2.6% with sulfonylureas received inappropriately these treatments. At discharge, the inappropriateness of metformin therapy decreased (10.2%, P < 0.0001). According to Beers criteria, the inappropriate prescriptions of sulfonylureas raised to 29% both at admission and at discharge. This study shows a poor adherence to current guidelines on diabetes management in hospitalized elderly people with a high prevalence of inappropriate use of sulfonylureas according to the Beers criteria
Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes
Objective: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. Methods: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI—Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. Results: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p < 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). Conclusion: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription
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