A Transmissible Gastroenteritis Coronavirus Nucleoprotein Epitope Elicits T Helper Cells That Collaborate in the in Vitro Antibody Synthesis to the Three Major Structural Viral Proteins

AbstractFour strong T cell epitopes have been identified studying the blastogenic response of lymphocytes from haplotype-defined transmissible gastroenteritis virus (TGEV) immune miniswine to sixty-one 15-mer synthetic peptides. Three of these epitopes are located on the nucleoprotein (N48 amino acids 46 to 60; N272, amino acids 272 to 286; and N321 amino acid 321 to 335), and one on the membrane protein (M196, amino acids 196 to 210). N321, peptide induced the highest T cell response and was recognized by immune miniswine lymphocytes with haplotypes dd, aa , and cc. T lymphocytes from peptide N321-immune miniswine reconstituted the in vitro synthesis of TGEV-specific antibodies by complementing CD4- TGEV-immune cells. This response was directed at least against the three major structural proteins. The synthesized antibodies specific for S protein preferentially recognized discontinous epitopes and neutralized TGEV infectivity. These results show that peptide N321 defines a functional T helper epitope eliciting T cells capable of collaborating with B cells specific for different proteins of TGEV

Blockade of TGF-β 1 Signalling Inhibits Cardiac NADPH Oxidase Overactivity in Hypertensive Rats

NADPH oxidases constitute a major source of superoxide anion (·O2 −) in hypertension. Several studies suggest an important role of NADPH oxidases in different effects mediated by TGF-β 1. In this study we show that chronic administration of P144, a peptide synthesized from type III TGF-β 1 receptor, significantly reduced the cardiac NADPH oxidase expression and activity as well as in the nitrotyrosine levels observed in control spontaneously hypertensive rats (V-SHR) to levels similar to control normotensive Wistar Kyoto rats. In addition, P144 was also able to reduce the significant increases in the expression of collagen type I protein and mRNA observed in hearts from V-SHR. In addition, positive correlations between collagen expression, NADPH oxidase activity, and nitrotyrosine levels were found in all animals. Finally, TGF-β 1-stimulated Rat-2 exhibited significant increases in NADPH oxidase activity that was inhibited in the presence of P144. It could be concluded that the blockade of TGF-β 1 with P144 inhibited cardiac NADPH oxidase in SHR, thus adding new data to elucidate the involvement of this enzyme in the profibrotic actions of TGF-β 1

Seguimiento de las guías españolas para el manejo del asma por el médico de atención primaria: un estudio observacional ambispectivo

Objetivo Evaluar el grado de seguimiento de las recomendaciones de las versiones de la Guía española para el manejo del asma (GEMA 2009 y 2015) y su repercusión en el control de la enfermedad. Material y métodos Estudio observacional y ambispectivo realizado entre septiembre del 2015 y abril del 2016, en el que participaron 314 médicos de atención primaria y 2.864 pacientes. Resultados Utilizando datos retrospectivos, 81 de los 314 médicos (25, 8% [IC del 95%, 21, 3 a 30, 9]) comunicaron seguir las recomendaciones de la GEMA 2009. Al inicio del estudio, 88 de los 314 médicos (28, 0% [IC del 95%, 23, 4 a 33, 2]) seguían las recomendaciones de la GEMA 2015. El tener un asma mal controlada (OR 0, 19, IC del 95%, 0, 13 a 0, 28) y presentar un asma persistente grave al inicio del estudio (OR 0, 20, IC del 95%, 0, 12 a 0, 34) se asociaron negativamente con tener un asma bien controlada al final del seguimiento. Por el contrario, el seguimiento de las recomendaciones de la GEMA 2015 se asoció de manera positiva con una mayor posibilidad de que el paciente tuviera un asma bien controlada al final del periodo de seguimiento (OR 1, 70, IC del 95%, 1, 40 a 2, 06). Conclusiones El escaso seguimiento de las guías clínicas para el manejo del asma constituye un problema común entre los médicos de atención primaria. Un seguimiento de estas guías se asocia con un control mejor del asma. Existe la necesidad de actuaciones que puedan mejorar el seguimiento por parte de los médicos de atención primaria de las guías para el manejo del asma. Objective: To assess the degree of compliance with the recommendations of the 2009 and 2015 versions of the Spanish guidelines for managing asthma (Guía Española para el Manejo del Asma [GEMA]) and the effect of this compliance on controlling the disease. Material and methods: We conducted an observational ambispective study between September 2015 and April 2016 in which 314 primary care physicians and 2864 patients participated. Results: Using retrospective data, we found that 81 of the 314 physicians (25.8%; 95% CI 21.3–30.9) stated that they complied with the GEMA2009 recommendations. At the start of the study, 88 of the 314 physicians (28.0%; 95% CI 23.4–33.2) complied with the GEMA2015 recommendations. Poorly controlled asthma (OR, 0.19; 95% CI 0.13–0.28) and persistent severe asthma at the start of the study (OR, 0.20; 95% CI 0.12–0.34) were negatively associated with having well-controlled asthma by the end of the follow-up. In contrast, compliance with the GEMA2015 recommendations was positively associated with a greater likelihood that the patient would have well-controlled asthma by the end of the follow-up (OR, 1.70; 95% CI 1.40–2.06). Conclusions: Low compliance with the clinical guidelines for managing asthma is a common problem among primary care physicians. Compliance with these guidelines is associated with better asthma control. Actions need to be taken to improve primary care physician compliance with the asthma management guidelines

Effect of Familial Longevity on Frailty and Sarcopenia: A Case–Control Study

Familial longevity confers advantages in terms of health, functionality, and longevity. We sought to assess potential differences in frailty and sarcopenia in older adults according to a parental history of extraordinary longevity. A total of 176 community-dwelling subjects aged 65–80 years were recruited in this observational case–control study, pair-matched 1:1 for gender, age, and place of birth and residence: 88 centenarians’ offspring (case group) and 88 non-centenarians’ offspring (control group). The main variables were frailty and sarcopenia based on Fried’s phenotype and the European Working Group on Sarcopenia in Older People (EWGSOP) definitions, respectively. Sociodemographics, comorbidities, clinical and functional variables, the presence of geriatric syndromes, and laboratory parameters were also collected. Related sample tests were applied, and conditional logistic regression was performed. Cases had a higher percentage of robust patients (31.8% vs. 15.9%), lower percentages of frailty (9.1% vs. 21.6%) and pre-frailty (59.1% vs. 62.5%) (p = 0.001), and lower levels of IL-6 (p = 0.044) than controls. The robust adjusted OR for cases was 3.00 (95% CI = 1.06–8.47, p = 0.038). No significant differences in muscle mass were found. Familial longevity was also associated with less obesity, insomnia, pain, and polypharmacy and a higher education level and total and low-density lipoprotein cholesterol. The results suggest an inherited genetic component in the frailty phenotype, while the sarcopenia association with familial longevity remains challenging

Abnormal Priming of CD4(+) T Cells by Dendritic Cells Expressing Hepatitis C Virus Core and E1 Proteins

Patients infected with hepatitis C virus (HCV) have an impaired response against HCV antigens while keeping immune competence for other antigens. We hypothesized that expression of HCV proteins in infected dendritic cells (DC) might impair their antigen-presenting function, leading to a defective anti-HCV T-cell immunity. To test this hypothesis, DC from normal donors were transduced with an adenovirus coding for HCV core and E1 proteins and these cells (DC-CE1) were used to stimulate T lymphocytes. DC-CE1 were poor stimulators of allogeneic reactions and of autologous primary and secondary proliferative responses. Autologous T cells stimulated with DC-CE1 exhibited a pattern of incomplete activation characterized by enhanced CD25 expression but reduced interleukin 2 production. The same pattern of incomplete lymphocyte activation was observed in CD4(+) T cells responding to HCV core in patients with chronic HCV infection. However, CD4(+) response to HCV core was normal in patients who cleared HCV after alpha interferon therapy. Moreover, a normal CD4(+) response to tetanus toxoid was found in both chronic HCV carriers and patients who had eliminated the infection. Our results suggest that expression of HCV structural antigens in infected DC disturbs their antigen-presenting function, leading to incomplete activation of anti-HCV-specific T cells and chronicity of infection. However, presentation of unrelated antigens by noninfected DC would allow normal T-cell immunity to other pathogens