Inmunopatogenia de los granulomas producidos por micobacterias de interés veterinario en especies animales productoras de alimento

Tuberculosis (TB) and Paratuberculosis (PTB) in cattle, caused by Mycobacterium bovis and M. avium subsp paratuberculosis respectively, induce granulomatous inflammation in affected tissues. However, pathogenesis after natural infection remains unknown. The aim of this study was to evaluate the immune response profile developed after the infection by both agents. Samples from 5 cows with TB (2 from liver, 2 from lymph nodes and 1 from cerebellum) and 6 with PTB (ileum) were analysed. Tissues with TB lesions (except the cerebellum) were autolysed. Microscopic changes, presence of acid fast bacilli (AFB) and expression of IL10, βTGF, αTNF and γINF were evaluated by hematoxilin/eosin and Ziehl Nielsenn staining and by immunohistochemistry. The microscopic changes found were similar to those described for TB and PTB, and the autolysis grossly described was confirmed in the TB tissues. TB changes were multifocal granulomatous inflammation with necrosis. All animals with PTB showed diffuse granulomatous enteritis. Intracytoplasmic AFB were found in all tissues, scanty in TB cases and numerous in PTB animals. Immunostaining was negative for all cytokines in all TB samples, and strongly positive for all cytokines in the PTB cases. The lack of immunostaining in cases of TB could be originated by the low expression of the studied cytokines in this type of granuloma, or by the autolysis process which might affect the integrity of these molecules. The detection of high levels of cytokines with pro and anti-inflammatory effect in tissues with PTB changes confirm that pathogenesis of PTB development is hard to determine. The αTNF and γINF levels would explain the diffuse extension of lesions, and the levels of βTGF and IL10 could be related with the survival and proliferation of AFB within the macrophages. Further studies are necessary to determine the cytokine’s expression in TB and PTB affected tissues at different stages after infection.Mycobacterium bovis y M. avium subsp paratuberculosis son agentes causales de tuberculosis (TB) y paratuberculosis (PTB) en bovinos, las cuales afectan la producción animal y la salud pública. Aunque ambos producen inflamación granulomatosa, poco se conoce de su patogenia tras la infección natural debido al prolongado período de incubación. El objetivo del presente trabajo fue evaluar el perfil de respuesta inmune desarrollado tras la infección natural por ambas micobacterias. Se analizaron muestras de 5 bovinos con lesiones de TB (2 de hígado, 2 de ganglio linfático y 1 de cerebelo) y 6 de animales con PTB (íleon). Los tejidos con TB (excepto el cerebelo) mostraron autolisis. Se evaluó la presencia de lesiones microscópicas y micobacterias mediante las coloraciones con hematoxilina, eosina, y de Ziehl Nielsen, y se determinó la expresión de las citoquinas IL10, βTGF, αTNF y γINF mediante inmunohistoquímica (IHQ). Las lesiones microscópicas observadas fueron similares a las descriptas para ambas enfermedades, con lo cual se confirmó la autolisis descripta en 4 casos de TB. Las lesiones de TB fueron granulomas multifocales con necrosis de tamaño variable. Por su parte, en los casos de PTB se detectó enteritis granulomatosa difusa. Se encontraron bacilos ácido-alcohol resistente (BAAR) en el citoplasma de macrófagos de los 11 animales, escasos en aquellos con TB y abundantes en los que padecían PTB. No se observó inmunomarcación para ninguna citoquina en ningún animal con lesiones de TB. Por el contrario, se evidenció marcación intensa frente a todas las citoquinas en los casos con PTB. Los resultados obtenidos indican que la técnica de IHQ empleada permite la detección de las citoquinas de interés. La ausencia de inmunotinción en los casos de TB podría relacionarse con una baja expresión de las citoquinas analizadas en este tipo de lesiones, como también con el proceso de autolisis observado, el cual afectaría la integridad de estos mediadores. La detección de citoquinas de efecto pro y antiinflamatorio en los animales con PTB confirman el desarrollo de un proceso inflamatorio complejo. La abundante expresión de αTNF y γINF explicaría la extensión de la lesión, mientras que la presencia de βTGF e IL10 podría relacionarse con la sobrevida y proliferación de los BAAR observados. Futuros estudios serán necesarios para determinar la diferente expresión de citoquinas en tejidos con lesiones de TB y PTB en diferente estadío de desarrollo

HCT116 cells deficient in p21Waf1 are hypersensitive to tyrosine kinase inhibitors and adriamycin through a mechanism unrelated to p21 and dependent on p53

El pdf del artículo es la versión de autor.-- et al.p21Waf1 (p21) was described as a cyclin-dependent kinase inhibitor, but other p21 activities have subsequently been described, including its ability to inhibit apoptosis in some models. Comparative work on the human colon cancer isogenic cell lines HCT116 and HCT116p21-/- led to the proposal that p21 protects colon cancer cells against apoptosis by genotoxic drugs. We asked whether p21 also protected from cell death induced by non-genotoxic drugs, such as tyrosine kinase inhibitors. We found that p21-deficient cells were dramatically more sensitive towards imatinib and gefitinib than parental cells. Interestingly, HCT116p21-/- also showed higher basal activity of protein kinases as c-Abl, c-Src, and Akt. We generated HCT116p21-/- sublines with inducible p21 expression and found that p21 did not rescue the hypersensitivity to imatinib. Moreover, down-regulation of p21 by enforced c-Myc expression or by p21 siRNA did not sensitize parental HCT116 cells. We found that, in HCT116p21-/- cells, p53 showed higher stability, higher transcriptional activity and phosphorylation in serines associated with p53 activity. Furthermore, silencing of p53 with siRNA and inactivation of p53 with a dominant negative mutant rescued the hypersensitive response to kinases inhibitors, 5-fluorouracil and adriamycin in HCT116p21-/- cells. Consistently, HCT116p53-/- cells are more resistant to imatinib than parental cells, suggesting that imatinib activity is partly dependent on p53 in colon cancer cells. We conclude that high p53 activity, rather than p21 deficiency, is the mechanism responsible for hypersensitivity to drugs of HCT116p21-/- cells. Therefore the role of p21 on apoptosis of HCT116 colon cancer cells should be re-evaluated. © 2008 Elsevier B.V. All rights reserved.N.F. is funded by a predoctoral fellowship from the Spanish Ministry of Education and Science (MEC) and from the University of Cantabria. Work at the laboratory of J.L. is funded by MEC grants SAF2005-00461 and Spanish Ministry of Health and Consume (MSC) grant ISCIII-RETIC-RD06/0020. M.D.D. is funded by MSC grant FIS04-1083, and J.M.P. is funded by grants from Fundación de Investigación Médica Mutua Madrileña and MEC grant SAF2006-00371.Peer Reviewe

Ganadería ecológica de vacuno de carne: aspectos prácticos

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Destete precoz de los terneros en explotaciones de vacuno de carne: consecuencias sobre los rendimentos técnico-económicos del rebaño

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Tracking the optical constants of porous vanadium dioxide thin films during metal-insulator transition: Influence of processing conditions on their application in smart glasses

Vanadium dioxide (VO2) is widely recognized as a thermochromic material with great potential for application in smart glazing for energy-efficient buildings. The monoclinic (M1) VO2 phase undergoes a first-order reversible phase transition from the semiconductor to the rutile metallic state. In this study, an M1 VO2 porous film was synthesized via a polymer-assisted sol-gel route. Processing parameters, such as drying and reduction temperatures, were varied to evaluate their influence on the thermochromic behavior of VO2 and to determine the necessary trade-off between a significant thermochromic effect and high luminous transmittance. Film-silica glass-film systems with luminous transmittance close to 80% and IR solar modulation ability as large as 20% were prepared. By tracking the optical constants of the films during the thermochromic process, the changes produced at the microscopic level in the material could be correlated with its macroscopic behavior when used as an energy-saving material.Y J. Outon acknowledges the support by the Spanish Ministerio de Educacion y Cultura through grant FPU19-02638. M. Dominguez ac-knowledges the support by the Spanish Ministerio de Ciencia, Innovacion y Universidades under project EQC2018-004704-P. The authors thank the University of Cadiz and IMEYMAT for financing the mutual facilities available at the UCA R&D Central Services (SC-ICYT) and the IMEYMAT Institute project reference PLP2020335-1 respec-tively. The authors also acknowledge J. Gonzalez and F. Delgado for their assistance in the preparation of the STEM specimens

Myc Inhibits p27-Induced Erythroid Differentiation of Leukemia Cells by Repressing Erythroid Master Genes without Reversing p27-Mediated Cell Cycle Arrest

Inhibition of differentiation has been proposed as an important mechanism for Myc-induced tumorigenesis, but the mechanisms involved are unclear. We have established a genetically defined differentiation model in human leukemia K562 cells by conditional expression of the cyclin-dependent kinase (Cdk) inhibitor p27 (inducible by Zn2+) and Myc (activatable by 4-hydroxy-tamoxifen). Induction of p27 resulted in erythroid differentiation, accompanied by Cdk inhibition and G1 arrest. Interestingly, activation of Myc inhibited p27-mediated erythroid differentiation without affecting p27-mediated proliferation arrest. Microarray-based gene expression indicated that, in the presence of p27, Myc blocked the upregulation of several erythroid-cell-specific genes, including NFE2, JUNB, and GATA1 (transcription factors with a pivotal role in erythropoiesis). Moreover, Myc also blocked the upregulation of Mad1, a transcriptional antagonist of Myc that is able to induce erythroid differentiation. Cotransfection experiments demonstrated that Myc-mediated inhibition of differentiation is partly dependent on the repression of Mad1 and GATA1. In conclusion, this model demonstrates that Myc-mediated inhibition of differentiation depends on the regulation of a specific gene program, whereas it is independent of p27-mediated cell cycle arrest. Our results support the hypothesis that differentiation inhibition is an important Myc tumorigenic mechanism that is independent of cell proliferation. Copyright © 2008, American Society for Microbiology. All Rights Reserved.This study was supported by grants CICYT SAF05-00461 from the Spanish Ministerio de Educación y Ciencia (MEC), ISCIII-RETIC RD06/0020 from the Spanish Ministerio de Sanidad y Consumo, API-17-05 from the Fundación Marques de Valdecilla (to J.L), and FIS04/1083 (to M.D.D). J.C.A., G.B., and N.F. were supported by fellowships from the MEC, and V.T. was supported by a Lady Tata Memorial Trust award.Peer Reviewe

The ATLAS ASMA Study : Assessing the Impact of Asthma on Patients' Life - The Spanish Patients' Perspective

ATLAS ASMA described the psychosocial impact of asthma on patients' daily life from patients' perspectives (in terms of impaired personal and intimate relationships, sleep quality, leisure time, daily activities, and others) in Spain. Secondary objective includes description of time since diagnosis, expectations, and satisfaction of patients about disease, treatment and medical assistance received, adherence to treatment, perceived control of asthma, and health-related quality of life. This was a cross-sectional, observational study, based on a self-administered online survey for adult patients (≥18 years) with asthma. Patients with asthma diagnosis of any type and severity who voluntarily participated in the survey through a web link were included consecutively. In the present manuscript, only adult patients' data are included. A total of 132 adults with asthma were included. Moderate/severe asthma constituted 59.1% of the patients (females 71.2%). Overall, most relevant areas affected due to asthma were leisure activities (67.0%) and the quality/quantity of sleep (52.3%). Moderate/severe patients perceived some degree of impairment in work, school, or at home due asthma more frequently vs mild patients (55.2% vs 10.9%). Poorly controlled asthma (ACT≤19) was reported in 41 (70.7%) and 10 (21.7%) moderate/severe and mild patients (p<0.000), respectively. Mild patients obtained higher mean (SD) Mini-AQLQ score than moderate/severe asthma patients (5.6 [1.0] vs 4.3 [1.1], p<0.000), likewise higher significant results for every individual dimension. Most patients cited little limitation to intense efforts (20.5%). Half of the patients mentioned needing more information about asthma. Topics those patients like to have more information were difficulties that may can have and legal topics (78.6%), asthma evolution (78.6%), secondary effects or issues related to the treatment (61.9%) and legal topics (61.9%). The study reported important insights on psychosocial impact of asthma on patients' daily life from patients' perspectives along with health determinants in asthma-related health outcomes, sociodemographic and psychosocial factors

Recommendations by the Spanish Society of Epidemiology and Oral Public Health (SESPO) for the healthcare adaptation of public health dental clinics in Spain during the COVID-19 pandemic

In March 2020, the World Health Organization (WHO) declared the COVID-19 pandemic and, a few days later, the Spanish Government declared a State of Emergency and the population lockdown. This crisis situation crisis forced deep changes in health care. A