Efecto de los Edulcorantes GE y Sucralosa en la respuesta inmunológica Pro-Inflamatoria

El sistema inmunológico es uno de los mecanismos biológicos más importantes que permite mantener la integridad estructural y funcional del organismo, conservando así la homeostasis. Las citocinas son proteínas fundamentales para la respuesta inmunológica, actúan comunicando a las células del sistema inmunitario entre sí. Estas proteínas son de gran interés, debido a que las Enfermedades Crónicas No Transmisibles (ECNT) se caracterizan por una respuesta inflamatoria crónica de bajo grado, causada por la producción anormal de este tipo de moléculas

Smoking cessation is associated with lower disease activity and predicts cardiovascular risk reduction in rheumatoid arthritis patients

Objectives: Smoking is a major risk factor for the development of both cardiovascular disease (CVD) and RA and may cause attenuated responses to anti-rheumatic treatments. Our aim was to compare disease activity, CVD risk factors and CVD event rates across smoking status in RA patients. Methods: Disease characteristics, CVD risk factors and relevant medications were recorded in RA patients without prior CVD from 10 countries (Norway, UK, Netherlands, USA, Sweden, Greece, South Africa, Spain, Canada and Mexico). Information on CVD events was collected. Adjusted analysis of variance, logistic regression and Cox models were applied to compare RA disease activity (DAS28), CVD risk factors and event rates across categories of smoking status. Results: Of the 3311 RA patients (1012 former, 887 current and 1412 never smokers), 235 experienced CVD events during a median follow-up of 3.5 years (interquartile range 2.5-6.1). At enrolment, current smokers were more likely to have moderate or high disease activity compared with former and never smokers (P < 0.001 for both). There was a gradient of worsening CVD risk factor profiles (lipoproteins and blood pressure) from never to former to current smokers. Furthermore, former and never smokers had significantly lower CVD event rates compared with current smokers [hazard ratio 0.70 (95% CI 0.51, 0.95), P = 0.02 and 0.48 (0.34, 0.69), P < 0.001, respectively]. The CVD event rates for former and never smokers were comparable. Conclusion: Smoking cessation in patients with RA was associated with lower disease activity and improved lipid profiles and was a predictor of reduced rates of CVD events

Leishmania-Induced Inactivation of the Macrophage Transcription Factor AP-1 Is Mediated by the Parasite Metalloprotease GP63

Leishmania parasites have evolved sophisticated mechanisms to subvert macrophage immune responses by altering the host cell signal transduction machinery, including inhibition of JAK/STAT signalling and other transcription factors such as AP-1, CREB and NF-κB. AP-1 regulates pro-inflammatory cytokines, chemokines and nitric oxide production. Herein we show that upon Leishmania infection, AP-1 activity within host cells is abolished and correlates with lower expression of 5 of the 7 AP-1 subunits. Of interest, c-Jun, the central component of AP-1, is cleaved by Leishmania. Furthermore, the cleavage of c-Jun is dependent on the expression and activity of the major Leishmania surface protease GP63. Immunoprecipitation of c-Jun from nuclear extracts showed that GP63 interacts, and cleaves c-Jun at the perinuclear area shortly after infection. Phagocytosis inhibition by cytochalasin D did not block c-Jun down-regulation, suggesting that internalization of the parasite might not be necessary to deliver GP63 molecules inside the host cell. This observation was corroborated by the maintenance of c-Jun cleavage upon incubation with L. mexicana culture supernatant, suggesting that secreted, soluble GP63 could use a phagocytosis-independent mechanism to enter the host cell. In support of this, disruption of macrophage lipid raft microdomains by Methyl β-Cyclodextrin (MβCD) partially inhibits the degradation of full length c-Jun. Together our results indicate a novel role of the surface protease GP63 in the Leishmania-mediated subversion of host AP-1 activity

Nutritional Modulation of Immune and Central Nervous System Homeostasis: The Role of Diet in Development of Neuroinflammation and Neurological Disease

The gut-microbiome-brain axis is now recognized as an essential part in the regulation of systemic metabolism and homeostasis. Accumulating evidence has demonstrated that dietary patterns can influence the development of metabolic alterations and inflammation through the effects of nutrients on a multitude of variables, including microbiome composition, release of microbial products, gastrointestinal signaling molecules, and neurotransmitters. These signaling molecules are, in turn, implicated in the regulation of the immune system, either promoting or inhibiting the production of pro-inflammatory cytokines and the expansion of specific leukocyte subpopulations, such as Th17 and Treg cells, which are relevant in the development of neuroinflammatory and neurodegenerative conditions. Metabolic diseases, like obesity and type 2 diabetes mellitus, are related to inadequate dietary patterns and promote variations in the aforementioned signaling pathways in patients with these conditions, which have been linked to alterations in neurological functions and mental health. Thus, maintenance of adequate dietary patterns should be an essential component of any strategy aiming to prevent neurological pathologies derived from systemic metabolic alterations. The present review summarizes current knowledge on the role of nutrition in the modulation of the immune system and its impact in the development of neuroinflammation and neurological disease

Predictors of health care drop-out in an inception cohort of patients with early onset rheumatoid arthritis

Abstract Background RA patients who eventually dropped out of treatment and out of the health care system had potentially disastrous consequences for their health-related quality-of-life outcomes. Objectives of the study were to identify predictors of health care drop out (HDO) in an inception and ongoing cohort of patients with recent onset RA. Methods Charts from patients attending an early arthritis clinic from February 2004 to December 2015, and standardized follow-up evaluations were reviewed. Patients with HDO (cases) were defined when they did not return back to the clinic for a schedule visit for at least one year. Persistence with therapy was defined as length of time patients complied with RA-treatment. A case-control nested within a cohort design was used to compare baseline and cumulative (up to HDO or equivalent follow-up) variables between cases and paired controls (patients compliant with scheduled visits). Cox regression analysis was used to investigate predictors of HDO. The study was approved by the Institutional Review Board and patients gave written informed consent to have their data published. Results Data from 170 patients (89.4% female, [mean±SD] age: 38.2±12.6 years) with ≥1 year of follow-up were analyzed; up to December 2015, (median, interquartile rage) follow-up was 86.6 months (43.2–123) during which 35 (20.6%) patients had HDO after 41.1 months (12.1–58.7). Baseline and cumulative variables related to disease activity, treatment and persistence with therapy entered regression models; cumulative number of flares, number of disease-modifying anti-rheumatic drugs /patient and persistence <50% emerged as predictors of HDO. Five cases returned back after (median, range) drop out time of 3.8 years (2.3–5.8); they exhibited higher disability and poorer function than paired controls and outcomes were sustained up to their last follow-up. Conclusions In a real clinical setting of an EAC, failure to control disease activity, intensive treatment and poor persistence with therapy predicted HDO. Abandonment of health care had a negative impact on patient outcomes and was sustained even after health care was reinitiated

Validation of a risk perception questionnaire developed for patients with rheumatoid arthritis.

BackgroundRisk perception is a multidimensional phenomenon that describes the individual's judgment of the likelihood of experiencing something unpleasant. Risk perception helps to understand how rheumatoid arthritis patients perceive disease-related-risks. We developed and validated a risk perception questionnaire for Spanish speaking rheumatoid arthritis patients.MethodsThe questionnaire development and validation was performed in 3 steps, using respective convenience samples. Step-1 included the conceptual model construction, 20 patient's interviews to identify components from the conceptual model-dimensions and 11 healthcare provider´s consultations who identified RA related manifestations/complications (network and frequencies analysis). Step-2 consisted of item generation and reduction and questionnaire feasibility (n = 100). Step-3 consisted of the questionnaire psychometric validation (n = 270), which included content, face, construct (exploratory factor analysis) and criterion validity (logistic regression analysis) and consistency and stability (Cronbach's α and test-retest).ResultsSamples were representative of typical RA outpatients. Initial conceptual model included 7 dimensions, 3 for probability and 1 each, for responsibility, prevention, control and for severity (Step-1). The final version was considered feasible by the patients and included 27 items (Step-2). A five-factor model was most appropriated and resulted in 68.8% of the variance explained: Cronbach's α = 0.90, intraclass-correlation-coefficient = 0.93 (95% CI = 0.90-0.95). A positive relation between number of external criteria from the charts and risk perception was found; all items had ≥80% agreement from experts; patients agreed about item´s semantic clarity (89%) and format adequacy (97%), (Step-3).ConclusionsThe risk perception questionnaire was valid and reliable to evaluate risk perception construct in RA outpatients; it can be incorporated to routine care and clinical research, and guide interventions to improve patient's health behaviors

“Efecto de la restricción calórica en la activación de la microglía en ratones BALB/c”

La microglía es la célula inmunocompetente del sistema nervioso central, su función es preservar la homeostasis y funcionamiento adecuado del mismo; sin embargo, en un ambiente de inflamación crónica se le ha relacionado con daño al tejido nervioso. La restricción calórica (RC) es un método dietético empleado para retrasar la aparición de enfermedades crónico-degenerativas y la inflamación crónica, además de mejorar la efectividad de las funciones leucocitarias en la homeostasis del organismo. El objetivo de este estudio fue analizar el efecto que tiene la restricción calórica en las funciones de la microglía. Se obtuvieron células mononucleares purificadas de cerebro y médula espinal de ratones BALB/c clasificados como ad libitum (AL), con restricción calórica (RC; 30% de reducción en la ingestión de alimentos) o con dieta hiper-energética (HE; suplementado con sacarosa al 40% en el agua para beber), durante 4 semanas. Las células obtenidas fueron analizadas por citometría de flujo, empleando anticuerpos para los marcadores CD45, CD11b, MHC-I, MHC-II, CD80 y CD86. El consumo de alimento, agua y peso corporal fueron monitoreados a lo largo del estudio. Los resultados muestran que los ratones con RC ingirieron una mayor cantidad de líquido, menor cantidad de alimento y ganaron menos peso corporal que los ratones del grupo AL. No se observaron diferencias en estos parámetros entre los grupos HE y AL. La RC aumentó significativamente la expresión de MHC-I en las células de la microglía en comparación con los grupos AL y HE, junto con una tendencia para el grupo RC a expresar menor CD80 y mayor CD86. Nuestros resultados sugieren que la microglía en animales bajo RC presenta un fenotipo que puede favorecer la tolerancia inmunológica al incrementar la presentación de antígenos propios en ausencia de co-estimulación, lo que puede favorecer la homeostasis del tejido nervioso en condiciones normales