This study used an in vivo mouse model to analyze the response of dendritic cells (DCs) in Peyer's patches (PPs) within the first 48 h of infection with the wild-type murine rotavirus EDIM (EDIMwt). After the infection, the absolute number of DCs was increased by 2-fold in the PPs without a modification of their relative percentage of the total cell number. Also, the DCs from PPs of infected mice showed a time-dependent migration to the subepithelial dome (SED) and an increase of the surface activation markers CD40, CD80, and CD86. This response was more evident at 48 h postinfection (p.i.) and depended on viral replication, since DCs from PPs of mice inoculated with UV-treated virus did not show this phenotype. As a result of the activation, the DCs showed an increase in the expression of mRNA for the proinflammatory cytokines interleukin-12/23p40 (IL-12/23p40), tumor necrosis factor alpha (TNF-α), and beta interferon (IFN-β), as well as for the regulatory cytokine IL-10. These results suggest that, a short time after rotavirus infection, the DCs from PPs play a critical role in controlling the infection and, at the same time, avoiding an excessive inflammatory immune response.
Health-related quality of life (HRQOL) measurements provide valuable information about the psychological and social impact of treatment on patients with cystic fibrosis (CF). This study evaluated the HRQOL of Brazilian patients with CF and assessed the changes in HRQOL domains over 1 year after dornase alfa (Pulmozyme) introduction.One hundred fifty-six stable patients with CF and 89 caregivers answered the Portuguese-validated version of the Cystic Fibrosis Questionnaire-Revised (CFQ-R) at baseline (T(0)), and at 3 (T(1)), 6 (T(2)), 9 (T(3)), and 12 (T(4)) months of follow-up. Eighteen patients were excluded because they did not fulfill the inclusion criteria. The patients were analyzed in two groups: those aged 6-11 years and those aged 14 years and older. ANOVA for observed repeated results and the last observation carried forward (LOCF) method for missing data were used for the statistical analysis.After 1 year of follow-up, there was significant improvement in respiratory symptoms (T(4) - T(0) = 8.1; 95% confidence interval (95% CI) = [2.1;14.0]; effect size (ES) = 0.35; P < 0.001), Emotional Functioning (T(4) - T(0) = 5.6; 95% CI = [1.1;10.1]; ES = 0.31; P < 0.05), Social Functioning (T(4) - T(0) = 6.0; 95% CI = [1.3;11.7]; ES = 0.31; P < 0.05), Body Image (T(4) - T(0) = 11.9; 95% CI = [4.1;19.7]; ES = 0.42; P < 0.05), and Treatment Burden (T(4) - T(0) = 5.3; 95% CI = [0.3;10.3]; ES = 0.24; P < 0.05) domains in the younger group. A significant improvement in Role Functioning (T(4) - T(0) = 6.1; 95% CI = [1.1;11.1]; ES = 0.40; P < 0.05), Body Image (T(4) - T(0) = 12.6; 95% CI = [3.5;21.7]; ES = 0.46; P < 0.05), and Weight (T(4) - T(0) = 11.7; 95% CI = [1.8;21.6]; ES = 0.40; P < 0.05) was obtained in the older group. The caregivers' CFQ-R showed improvements in the Digestive Symptoms (T(4) - T(0) = 5.5; 95% CI = [1.5;9.4]; ES = 0.30; P < 0.05), Respiratory Symptoms (T(4) - T(0) = 7.6; 95% CI = [3.9;11.4]; ES = 0.48; P < 0.05), and Weight (T(4) - T(0) = 10.1; 95% CI = [1.6;18.6]; ES = 0.26; P < 0.05) domains.The introduction of dornase alfa improved the HRQL of the patients with CF during the first year of treatment.
Entre los principales problemas para el desarrollo del cultivo de la yuca (Manihot esculenta Crantz) en Venezuela esta la carencia de buen material de siembra. Tradicionalmente, la yuca se propaga por estacas, siendo esto una fuente importante en la diseminacion de plagas y enfermedades. El uso de plantas in vitro permite obtener material de siembra sano y vigoroso; sin embargo, su adaptacion en campo requiere mayor atencion en el control de malezas o arvenses. El presente trabajo evaluo el efecto de 3 herbicidas, fluometuron, S-metolacloro, pendimetalin, en comparacion con el desyerbe manual, durante el establecimiento en campo de plantas in vitro de yuca. Los ensayos se realizaron en San Pablo, Edo. Yaracuy. Se uso un diseno de bloques al azar con cuatro repeticiones. Aunque los resultados no mostraron diferencias significativas en el porcentaje de supervivencia de las plantulas, su crecimiento fue significativamente superior (p <0,05) en parcelas tratadas con fluometuron y S-metolacloro con respecto al control manual. No se encontro diferencias entre tratamientos en el control general de arvenses, pero el S-metolacloro mostro mejor control de especies de hoja ancha. Se recomienda usar S-metolacloro y fluometuron el mismo dia del transplante para mejorar la competitividad de las plantulas.
Abstract Endothelial dysfunction (ED) is a key factor for the development of cardiovascular diseases. Due to its chronic, life-threatening nature, ED only can be studied experimentally in animal models. Therefore, this work was aimed to characterize a murine model of ED induced by a daily intraperitoneal administration of angiotensin II (AGII) for 10 weeks. Oxidative stress, inflammation, vascular remodeling, hypertension, and damage to various target organs were evaluated in treated animals. The results indicated that a chronic intraperitoneal administration of AGII increases the production of systemic soluble VCAM, ROS and ICAM-1 expression, and the production of TNFα, IL1β, IL17A, IL4, TGFβ, and IL10 in the kidney, as well as blood pressure levels; it also promotes vascular remodeling and induces non-alcoholic fatty liver disease, glomerulosclerosis, and proliferative retinopathy. Therefore, the model herein proposed can be a representative model for ED; additionally, it is easy to implement, safe, rapid, and inexpensive.
OBJECTIVE: To describe the clinical impact of the first year treatment with dornase alfa, according to age groups, in a cohort of Brazilian Cystic Fibrosis (CF) patients. METHODS: The data on 152 eligible patients, from 16 CF reference centers, that answered the medical questionnaires and performed laboratory tests at baseline (T0), and at six (T2) and 12 (T4) months after dornase alfa initiation, were analyzed. Three age groups were assessed: six to 11, 12 to 13, and >14 years. Pulmonary tests, airway microbiology, emergency room visits, hospitalizations, emergency and routine treatments were evaluated. Student's t-test, chi-square test and analysis of variance were used when appropriated. RESULTS: Routine treatments were based on respiratory physical therapy, regular exercises, pancreatic enzymes, vitamins, bronchodilators, corticosteroids, and antibiotics. In the six months prior the study (T0 phase), hospitalizations for pulmonary exacerbations occurred in 38.0, 10.0 and 61.4% in the three age groups, respectively. After one year of intervention, there was a significant reduction in the number of emergency room visits in the six to 11 years group. There were no significant changes in forced expiratory volume in one second (VEF1), in forced vital capacity (FVC), in oxygen saturation (SpO2), and in Tiffenau index for all age groups. A significant improvement in Shwachman-Kulczychi score was observed in the older group. In the last six months of therapy, chronic or intermittent colonization by P. aeruginosa was detected in 75.0, 71.4 and 62.5% of the studied groups, respectively, while S. aureus colonization was identified in 68.6, 66.6 and 41.9% of the cases. CONCLUSIONS: The treatment with dornase alfa promoted the maintenance of pulmonary function parameters and was associated with a significant reduction of emergency room visits due to pulmonary exacerbations in the six to 11 years age group, with better clinical scores in the >14 age group, one year after the intervention.
CD8+ T lymphocytes are one of the main effector cells of the immune system, they protect the organism against intracellular threats such as viruses and bacteria, as well as neoplasms. It is currently well established that CD8+ T cells have distinct immune responses, given by their phenotypes Tc1, Tc2, Tc17, and TcReg. The cellular plasticity of such phenotypes depends on the presence of different combinations of cytokines in the extracellular medium. It is known that metabolic imbalances play an important role in immune response, but the precise role of metabolic disturbances on the differentiation and function of CD8+ T cells, however, has not been explored. In this work, we used a computational model to explore the potential effect of metabolic alterations such as hyperglycemia, high alcohol consumption, dyslipidemia, and diabetes on CD8+ T cell differentiation. Our model predicts that metabolic alterations preclude the effector function of all CD8+ T cell phenotypes except for TcReg cells. It also suggests that such inhibition originates from the increase of reactive oxygen species in response to metabolic stressors. Finally, we simulated the outcome of treating metabolic-inhibited CD8+ T cells with drugs targeting key molecules such as mTORC1, mTORC2, Akt, and others. We found that overstimulation of mTORC2 may restore cell differentiation and functions of all effector phenotypes, even in diabetic patients. These findings highlight the importance of our predictive model to find potential targets to strengthen immunosuppressed patients in chronic diseases, like diabetes.
espanolEl ocumo, Xanthosoma sagittifolium (L.) Schott, y el taro, Colocasia esculenta (L.) Schott son plantas herbaceas de la familia de las Araceas. Son plantas perennes que crecen en zonas tropicales, y cuya importancia radica en el consumo del cormo o tallo subterraneo modificado como organo de reserva. El metodo de multiplicacion comunmente utilizado es por fracciones vegetativas, lo que conlleva a una baja tasa de multiplicacion y a la dispersion de enfermedades. La importancia del establecimiento y multiplicacion in vitro de plantas de ambas especies con el objeto de producir semilla libre de patogenos. El objetivo del trabajo fue estudiar las condiciones optimas para la multiplicacion in vitro de plantas de ocumo y taro. Cormos de ambas especies fueron sometidos a desinfeccion superficial con detergentes liquidos, alcohol y cloro comercial (2,5%). Para el establecimiento inicial de las especies, los meristemas fueron colocados en medio MS-2% sacarosa y concentraciones hormonales de 0,1 mg l-1 bencil aminopurina (BAP) y 0,01 mg l-1 acido naftalenacetico (ANA). En cuanto a la proliferacion de brotes, se disenaron medios de cultivo con 1 mg l-1 BAP, 2 mg l-1 BAP, 1 mg l-1 BAP–3 mg l-1 AG3, 1 mg l-1 BAP–0,05 mg l-1 AG3–0,02 mg l-1 ANA y 1 mg l-1 BAP–0,5 mg l-1 AG3–0,02 mg l-1 ANA. Los resultados mostraron que la mejor tasa de proliferacion se logra con el medio MS-2% sacarosa-1 mg l-1 BAP con valores similares de las tasas de multiplicacion en ambas especies (4,6-4,7 plantulas/explante/4 semanas). Los medios y las condiciones de cultivo senaladas han permitido la multiplicacion rutinaria de las especies por un periodo mayor a los 4 anos. EnglishCocoyam, Xanthosoma sagittifolium (L.) Schott and taro, Colocasia esculenta (L.) Schott are edible herbaceous plants of the Aracea family. They grow in the tropics and their modified stems or corms, are consumed as a staple due to their high starch content. The most common reproduction method for these species is by vegetative cuttings, with low propagation rates and disease dissemination, requiring the procurement of pathogen free plants of both species. The aim of this work was to study optimal conditions for in vitro micropropagation of cocoyam and taro plants. In order to reach the aim, corms of both species were surface sterilized with dish liquid detergent, alcohol and bleach (2,5%). To establish the species in vitro, meristems were cultured in MS-2% sucrose and 0,1 mg l-1 BA - 0,01 mg l-1 NAA. Shoot proliferation was induced in MS-2% sucrose media supplemented with 1 mg l-1 BA, 2 mg l-1 BA, 1 mg l-1 BA–3 mg l1 AG3, 1 mg l-1 BA–0,05 mg l-1 GA3–0,02 mg l-1 NAA y 1 mg l-1 BA–0,5 mg l1 GA3–0,02 mg l-1 NAA. Results showed that the best proliferation rates were obtained with MS-2% sucrose -1 mg l-1 BA. Similar multiplication rates were obtained for both species (4,6-4,7 plants/explant/4 weeks). The methodology presented in this paper allowed the maintenance of cocoyam and taro for more than four years.