RESUMO
Instrumental appetitive extinction involves the reduction of a previously reinforced response when its occurrence is no longer rewarded. Two experiments with terrestrial toads (Rhinella arenarum) tested whether the occurrence of a nonreinforced response is necessary for response extinction by varying the time of exposure to nonrewarded goal-box stimuli across groups. In Experiment 1, toads that received the same acquisition training (15 sessions, 1 session/day, 300â¯s of access to water in the goal box) were randomly assigned to two groups. In Group 600 (n=12), animals spent 600â¯s in the goal box in 8 daily extinction sessions (water present but inaccessible). In Group 0 (n=11), toads performed the runway response (i.e., walking from the start to the goal box) but were removed as soon as they entered the goal box, thus having minimal exposure to nonrewarded goal-box stimuli. The runway response was weakened in Group 600 across extinction trials, but exhibited little change in Group 0. In Experiment 2, toads were randomly assigned to two groups after the same acquisition training. Group 0 (n=7) was treated the same as Group 0 in the previous experiment. In Group RI (retention interval, n=7), toads remained in their home cage for 13 days. Finally, all animals received 4 extinction sessions with 300â¯s in the empty goal box. There was little behavioral change in Group 0 during the 13 sessions with minimal exposure to the goal box. In extinction, both groups reduced their runway response at similar rates. Although the procedures were instrumental, extinction of the runway response in toads can be accounted for in terms of a Pavlovian approach response to stimuli paired with reward and nonreward in the goal box.
Assuntos
Condicionamento Clássico , Condicionamento Operante , Extinção Psicológica , Animais , Extinção Psicológica/fisiologia , Condicionamento Clássico/fisiologia , Condicionamento Operante/fisiologia , Recompensa , Masculino , Reforço Psicológico , Feminino , Comportamento Animal/fisiologia , Bufonidae/fisiologia , Bufo arenarum/fisiologiaRESUMO
Introducción: Es probable que el SARS-CoV-2 favorezca el paso de infección a enfer medad tuberculosa. Si bien la información es limitada, existen avances en la comprensión de la interacción COVID-19 y tuberculosis. Nuevas investigaciones arrojaron similitudes inesperadas en la patogenia y evolución de la coinfección. Linfopenia prolongada, hipe rinflamación, lesión del tejido pulmonar y desequilibrio en los subconjuntos de células T CD4+ asociados con COVID-19 podrían propagar la infección por M. tuberculosis y progresión de la enfermedad. Casos clínicos: Presentamos tres pacientes jóvenes, sin comorbilidades, con factores de riesgo para infección tuberculosa latente, diagnosticados de tuberculosis pulmonar posterior cursado COVID-19 leve, de tratamiento sintomático (no corticoideo). Discusión: Estos casos plantean el probable impacto del SARS-CoV-2 en el paso de infección tuberculosa latente a enfermedad, excluida la ya demostrada influencia de los corticoides y formas graves de COVID-19. Existe cada vez más evidencia que refuerza esta idea.
Introduction: SARS-CoV-2 is likely to favor the transition from infection to tuberculosis disease. Although information is limited, there is progress in understanding the inter action between COVID-19 and Tuberculosis. New investigations yielded unexpected similarities in the pathogenesis and evolution of the coinfection. Prolonged lymphopenia, hyperinflammation, lung tissue injury, and imbalance in CD4+ T-cell subsets associated with COVID-19 could propagate M. tuberculosis infection and disease progression. Clinical cases: we present three young patients, without comorbidities, with risk factors for Latent Tuberculous Infection, diagnosed with pulomonary Tuberculosis post mild COVID-19, treated symptomatically (not corticosteroids). Discussion: These cases raise the probable impact of SARS-CoV-2 in the transition from Latent Tuberculous Infection to disease, excluding the already proven influence of corticosteroids and severe forms of COVID-19. There is increasing evidence to sup port this idea.
RESUMO
The existence of a third root in the mandibular first molars may have implications for certain dental treatments; however, its greatest relevance could be in anthropological and forensic sciences, because its prevalence varies significantly according to ethnic groups. The purpose of this research was to determine the prevalence of radix entomolaris (RE) in a sample of Chilean people. A random sample of 1330 digital periapical radiographs of endodontically treated mandibular first molars (551 males and 779 females, aged between 18 and 87 years) were evaluated. The prevalence of RE, its distribution by sex and root canal lengths were determined. Evidence demonstrated that the formation of RE is associated with ancestry and its frequency is variable according to populations studied, being more frequent in Asians and Native Americans. The prevalence of RE in the studied people was 3.16%, similar to frequencies reported in European individuals (3.4%-4.2%). The 61.90% of RE were located at the right side of the mandible and 38.10% at the left side. The average working length of RE was 19.52 mm. No statistically significant differences in frequencies were observed by sex (p = 0.19). The prevalence of RE varies among continental population groups. However, due to human migration, the frequency of this physical trait could be modified in specific geographic regions. The observed prevalence of RE in the study group was similar to the prevalence ranges observed for European ancestry populations and it was considerably lower than the data reported for non-Europeans. The absence of sexual dimorphism is consistent with results of previous studies performed worldwide.
Assuntos
Dentição , Raiz Dentária , Masculino , Feminino , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Chile/epidemiologia , Raiz Dentária/diagnóstico por imagem , Dente Molar , Etnicidade , MandíbulaRESUMO
Chloroquine (CQ) has been widely used for many years against malaria and various viral diseases. Its important use and high potential to being persistent make it of particular concern for ecotoxicological studies. Here, we evaluated the toxicity of CQ alone and in combination with copper (Cu) to the euryhaline rotifer Proales similis. All experiments were carried out using chronic toxicity reproductive five-day tests and an application factor (AF) of 0.05, 0.1, 0.3, and 0.5 by multiplying the 24-h LC50 values of CQ (4250 µg/L) and Cu (68 µg/L), which were administered in solution. The rate of population increase (r, d-1) ranged from 0.50 to 52 (controls); 0.20 to 0.40 (CQ); 0.09 to 0.43 (Cu); and -0.03 to 0.30 (CQ-Cu) and showed significant decrease as the concentration of both chemicals in the medium increased. Almost all tested mixtures induced synergistic effects, mainly as the AF increased. We found that the presence of Cu intensifies the vulnerability of organisms to CQ and vice versa. These results stress the potential hazard that these combined chemicals may have on the aquatic systems. This research suggests that P. similis is sensitive to CQ as other standardized zooplankton species and may serve as a potential test species in the risk assessment of emerging pollutants in marine environments.
Assuntos
Cobre , Rotíferos , Animais , Cloroquina/toxicidade , Cobre/toxicidade , Dose Letal Mediana , Testes de Toxicidade CrônicaRESUMO
Describir e identificar las razones por las cuales los padres o tutores no completaron el calendario de vacunación infantil en un Centro de Atención Primaria de Salud de la Ciudad de Corrientes en el año 2021. Metodología: Estudio descriptivo, transversal. Población: padres o tutores de niños con esquemas incompletos. Recolección de datos mediante encuesta validada en prueba piloto. Los datos plasmados en una matriz fueron sometidos a análisis descriptivos. Se contó con aval del Comité de Ética. Resultados: La muestra se integró con 53 unidades de análisis. Edad media 28 años; 79% eran las madres; 62% ya tenían dos o más hijos; 74% eran soltero/as; 47% no había concluido el secundario o la primaria; la mayoría eran desempleados o percibían planes sociales. El 66% pensaba que las vacunas curaban enfermedades;89% que las prevenían y 89% pensaban que eran seguras. Fuentes de información: el equipo médico y enfermería, 17% de familiares o amigos, 30% en internet o medios de comunicación. En motivosde incumplimiento, lo más frecuente falta de vacunas (31%), horarios de trabajo de padres o tutor (15%), enfermedades del infante (10%). Conclusión: La información sobre vacunas era brindada por equipo de salud, familias y medios de comunicación. Aunque afirmaban que prevenían enfermedades y eran seguras muchos sostenían que curaban enfermedades. Se señalaron como motivos del incumplimiento falta de vacunas, horarios laborales de los entrevistados y enfermedades del menor, restricciones horariasdel vacunatorio y por la pandemia[AU]
Describe and identify the reasons why parents or guardians did not complete the childhood vaccination schedule in a Primary Health Care Center of the City of Corrientes in the year 2021. Methodology: Descriptive, cross-sectional study. Population: parents or guardians of children with incomplete schemes. Data collection through a survey validated in a pilot test. The data captured in a matrix were subjected to descriptive analysis. It was endorsed by the Ethics Committee. Results: The sample was integrated with 53 units of analysis. Mean age 28 years; 79% were mothers; 62% already had two or more children; 74% were single; 47% had not completed secondary or primary school; most were unemployed or received social plans. 66% thought that vaccines cured diseases; 89% prevented them and 89% thought they were safe. Sources of information: the medical and nursing team, 17% from family or friends, 30% on the internet or the media. In non-compliance reasons, the most frequent lack of vaccines (31%), parent or guardian work schedules (15%), infant diseases (10%). Conclusion: The information on vaccines was provided by the health team, families and the media. Although they claimed that they prevented diseases and were safe, many maintained that they cured diseases. Reasons for non-compliance were noted as lack of vaccines, work schedules of the interviewees and illnesses of the minor, time restrictions of the vaccination and those given by the pandemic[AU]
Descrever e identificar os motivos pelos quais os pais ou responsáveis não completaram o calendário de vacinação infantil em um Centro de Atenção Primária à Saúde da Cidade de Corrientes no ano de 2021. Metodologia: Estudo descritivo, transversal. População: pais ou responsáveis de crianças com esquemas incompletos. Coleta de dados por meio de questionário validado em teste piloto. Os dados capturados em uma matriz foram submetidos à análise descritiva. Foi aprovado pelo Comitê de Ética. Resultados: A amostra foi integrada com 53 unidades de análise. Idade média 28 anos; 79% eram mães; 62% já tinham dois ou mais filhos; 74% eram solteiros; 47% não concluíram o ensino médio ou fundamental; a maioria estava desempregada ou recebia planos sociais. 66% achavam que as vacinas curavam doenças; 89% os preveniram e 89% acharam que eram seguros. Fontes de informação: equipe médica e de enfermagem, 17% de familiares ou amigos, 30% na internet ou na mídia. Nos motivos de não conformidade, a falta de vacinas mais frequente (31%), horários de trabalho dos pais ou responsáveis (15%), doenças infantis (10%). Conclusão: As informações sobre vacinas foram fornecidas pela equipe de saúde, famílias e mídia. Embora afirmassem que preveniam doenças e eram seguros, muitos sustentavam que curavam doenças. Os motivos da não adesão foram apontados como falta de vacinas, horários de trabalho dos entrevistados e doenças do menor, restrições de horário da vacinação e as dadas pela pandemia[AU]
Assuntos
Humanos , Masculino , Feminino , Atenção Primária à Saúde , Atitude Frente a Saúde , Poder Familiar , Programas de Imunização , Cooperação e Adesão ao Tratamento , Estudos TransversaisRESUMO
AIMS: Previous studies in TB patients showed an immuno-endocrine imbalance characterized by a disease-severity associated increase in plasma levels of proinflammatory cytokines and glucocorticoids (GCs). To analyze the potential immunomodulatory effect of circulating GCs over peripheral blood mononuclear cells (PBMC) from TB patients, we investigated the expression of positively (anti-inflammatory-related genes ANXA1; FKBP51; GILZ, NFKBIA, and NFKBIB) and negatively (inflammatory genes: IL-6, IL-1ß, and IFN-γ) Glucocorticoids Receptors (GR)-regulated genes. Plasma concentrations of cytokines and hormones, together with specific lymphoproliferation were also assessed. MATERIALS AND METHODS: Gene expression was quantified by RT-qPCR, specific lymphoproliferation by 3H-thymidine incorporation, whereas plasma cytokines and hormones levels by ELISA. KEY FINDINGS: Transcripts of ANXA1, GILZ, NFKBIB, and NFKBIA appeared significantly increased in patients, whereas FKBP51, IL-6, IL-1ß, and NF-κB remained unchanged. Upon analyzing according to disease severity, mRNA levels for ANXA1 and NFKBIB were even higher in moderate and severe patients. GILZ was increased in moderate cases, with NFKBIA and IL-1 ß being higher in severe ones, who also displayed increased GRß transcripts. TB patients had reduced plasma DHEA concentrations together with increased pro and anti-inflammatory cytokines (IFN-γ, IL-6, and IL-10) cortisol and cortisol/DHEA ratio, more evident in progressive cases, in whom their PBMC also showed a decreased mycobacterial-driven proliferation. The cortisol/DHEA ratio and GRα expression were positively correlated with GR-regulated genes mainly in moderate patients. SIGNIFICANCE: The increased expression of cortisol-regulated anti-inflammatory genes in TB patients-PBMC, predominantly in progressive disease, seems compatible with a relatively insufficient attempt to downregulate the accompanying inflammation.
Assuntos
Receptores de Glucocorticoides , Tuberculose Pulmonar , Citocinas/metabolismo , Desidroepiandrosterona/farmacologia , Glucocorticoides/farmacologia , Humanos , Hidrocortisona/metabolismo , Interleucina-6/metabolismo , Leucócitos Mononucleares/metabolismo , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Tuberculose Pulmonar/genética , Tuberculose Pulmonar/metabolismoRESUMO
RESUMEN Introducción: Los trastornos intraventriculares de la conducción constituyen una manifestación habitual en los pacientes con enfermedad de Chagas con función ventricular izquierda conservada. Se desconoce si su presencia puede estar asociada a una mayor actividad inflamatoria. Objetivos: Determinar si existe una correlación entre los niveles de interleuquinas y la presencia de trastornos intraventriculares de la conducción en pacientes con serología positiva para enfermedad de Chagas y fracción de eyección ventricular izquierda conservada. Material y métodos: Se evaluó a 22 pacientes con edades comprendidas entre 21 y 80 años, seropositivos para enfermedad de Chagas, de más de 20 años de evolución y fracción de eyección ventricular izquierda mayor del 50%. Se analizó, además, un grupo control de 14 individuos sanos. Se determinaron las concentraciones en plasma de IFN-γ, IL-1β, IL-6, IL-10, IL-12 (p70), IL-15, IL-17A, MCP-1/CCL2, MIP-1 a/CCL3, TNF-a e IL-2. Se consideró trastornos intraventriculares de la conducción a la presencia de bloqueo de rama derecha, hemibloqueo anterior izquierdo o bloqueo de rama izquierda. Resultados: De los 22 pacientes con serología positiva para enfermedad de Chagas, 10 presentaron trastornos de la intraventriculares de la conducción (45,4%). En el grupo con trastornos intraventriculares de la conducción, se observaron niveles elevados de interleuquinas de alto efecto inflamatorio como INF-γ, IL-15, IL-2 (p70), IL-12, MP1-a, en comparación al grupo control, además de presentar altos valores de IL-10 como mecanismo modulador de una respuesta inmunitaria excesiva. Conclusiones: La asociación entre niveles elevados de interleuquinas y la presencia de trastornos intraventriculares de la conducción plantea un posible proceso inflamatorio crónico para su desarrollo en pacientes chagásicos con fracción de eyección ventricular izquierda conservada.
ABSTRACT Background: Intraventricular conduction disturbances are common in patients with Chagas disease and preserved left ventricular ejection fraction, but their association with higher inflammatory activity is unknown. Objectives: The aim of this study was to determine the presence of an association between interleukin levels and intraventricular conduction disturbances in patients with positive serology for Chagas disease and preserved left ventricular function. Methods: Twenty-two patients between 22 and 80 years of age with positive serology test for Chagas disease with more than 20 years progression and left ventricular ejection fraction ≥50% were included in the study and compared with a control group of 14 healthy individuals. Plasma levels of IFN-γ, IL-1β, IL-6, IL-10, IL-12 (p70), IL-15, IL-17A, MCP-1/CCL2, MIP-1 a/CCL3, TNF-a and IL-2 were measured in patients and controls. Right bundle branch block, left anterior hemiblock or left bundle branch block were considered intraventricular conduction disturbances. Results: Among the 22 patients with positive serology for Chagas disease, 10 presented intraventricular conduction disturbances (45.4%). This group had elevated levels of interleukins with high inflammatory effect such as INF-γ, IL-15, IL-2, IL-12, MIP-1 a, compared with the control group, and high levels of IL-10 as a regulatory mechanism of an excessive immune response. Conclusions: The association between elevated levels of inflammatory interleukins and intraventricular conduction disturbances suggests that chronic inflammation may play a role in the development of these abnormalities in patients with positive serology for Chagas disease and preserved left ventricular ejection function.
RESUMO
Systemic lupus erythematosus is characterized by high levels of IgG class autoantibodies that contribute to the pathophysiology of the disease. The formation of these autoantibodies occurs in the germinal centers, where there is cooperation between follicular T helper cells (TFH) and autoreactive B cells. Prolactin has been reported to exacerbate the clinical manifestations of lupus by increasing autoantibody concentrations. The objective of this study was to characterize the participation of prolactin in the differentiation and activation of TFH cells, by performing in vivo and in vitro tests with lupus-prone mice, using flow cytometry and real-time PCR. We found that TFH cells express the long isoform of the prolactin receptor and promoted STAT3 phosphorylation. Receptor expression was higher in MRL/lpr mice and correlative with the manifestations of the disease. Although prolactin does not intervene in the differentiation of TFH cells, it does favor their activation by increasing the percentage of TFH OX40+ and TFH IL21+ cells, as well as leading to high serum concentrations of IL21. These results support a mechanism in which prolactin participates in the emergence of lupus by inducing overactive TFH cells and perhaps promoting dysfunctional germinal centers.
Assuntos
Centro Germinativo/imunologia , Interleucinas/metabolismo , Lúpus Eritematoso Sistêmico/imunologia , Nefrite Lúpica/imunologia , Prolactina/metabolismo , Receptores OX40/metabolismo , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Autoanticorpos/metabolismo , Células Cultivadas , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Endogâmicos MRL lpr , Receptores OX40/genética , Receptores da Prolactina/metabolismo , Fator de Transcrição STAT3/metabolismo , Regulação para CimaRESUMO
Self-reactive immature B cells are eliminated through apoptosis by tolerance mechanisms, failing to eliminate these cells results in autoimmune diseases. Prolactin is known to rescue immature B cells from B cell receptor engagement-induced apoptosis in lupus-prone mice. The objective of this study was to characterize in vitro prolactin signaling in immature B cells, using sorting, PCR array, RT-PCR, flow cytometry, and chromatin immunoprecipitation. We found that all B cell maturation stages in bone marrow express the prolactin receptor long isoform, in both wild-type and MRL/lpr mice, but its expression increased only in the immature B cells of the latter, particularly at the onset of lupus. In these cells, activation of the prolactin receptor promoted STAT3 phosphorylation and upregulation of the antiapoptotic Bcl2a1a, Bcl2l2, and Birc5 genes. STAT3 binding to the promoter region of these genes was confirmed through chromatin immunoprecipitation. Furthermore, inhibitors of prolactin signaling and STAT3 activation abolished the prolactin rescue of self-engaged MRL/lpr immature B cells. These results support a mechanism in which prolactin participates in the emergence of lupus through the rescue of self-reactive immature B cell clones from central tolerance clonal deletion through the activation of STAT3 and transcriptional regulation of a complex network of genes related to apoptosis resistance.
Assuntos
Prolactina/metabolismo , Fator de Transcrição STAT3/metabolismo , Animais , Apoptose , Camundongos , Camundongos Endogâmicos MRL lprRESUMO
Resumen Comprender un texto es una actividad cognitiva compleja que implica la construcción de una representación mental coherente en la memoria. Un proceso importante para ello es la generación de inferencias. La memoria de trabajo ha mostrado ser un factor cognitivo importante para explicar las diferencias en comprensión e inferencias, al igual que la capacidad de sostener la atención. El propósito del presente trabajo consiste en estudiar la relación entre la memoria de trabajo y la atención sostenida en la comprensión de narraciones en niños de 5 y 6 años. Para ello, se trabajó con una muestra de 100 niños, quienes escucharon tres textos narrativos y respondieron preguntas acerca de su contenido literal e inferencial, y además realizaron dos pruebas de memoria de trabajo y una de atención sostenida. Los resultados indican que los niños de 6 años muestran desempeños mejores y significativos en la comprensión de información literal y en la respuesta a preguntas de inferencia que los niños de 5 años. Además, el análisis de correlación mostró que las medidas de comprensión se hallan vinculadas a medidas de atención sostenida y a medidas de memoria de trabajo. El análisis de senderos sugiere que, en niños de 5 y 6 años, las mejoras logradas en la comprensión general como producto de la edad están mediadas, en parte, por la capacidad del niño para mantener la atención en la narración y almacenar temporalmente la información recibida en la memoria de trabajo mientras la escucha.
Abstract Text comprehension involves the construction of a coherent mental representation, which requires the person to build bridges between the new information and the background knowledge. In adults, establishing associations between information provided by the text is frequently an automatic skill, while for children it implies an important cognitive effort. This ability develops gradually over time and is connected to the generation of inferences. Working memory and the ability to sustain attention are considered two crucial processes for comprehension. The purpose of this study is to analyze the role of working memory and sustained attention in the comprehension of narratives in 5 and 6-year-old children. The study included 100 children of 5 and 6 years of age, of both sexes, that participated with the informed consent of their parents. Three oral texts were narrated to the children by a professional storyteller. For each text, six questions were asked: three of literal content and three of inferential content. Additionally, two working memory tasks were administered with one task of sustained attention. Three analyses were performed: First, a correlation analysis, to study the associations between comprehension, working memory, and sustained attention measures. Then, a comparison analysis of comprehension, working memory, and sustained attention scores between ages 5 and 6. And finally, a path analysis to study the role of age, sustained attention, and working memory on comprehension. Spearman Rho analyses in the whole sample show that literal comprehension had a significant correlation with forward digit span (Rho = .37, p < .001), backward digit span (Rho = .37, p < .001), and with the sustained attention task (Rho = -.37, p < .001). Inferences showed a significant correlation with forward digit span (Rho = .36, p < .001), backward digit span (Rho = .46, p < .001), and with the sustained attention task (Rho = -.37, p < .001). Sustained attention measures showed a significant correlation with forward digit span (Rho = -.34, p < .001) and with backward digit span (Rho = -.37, p < .001). The comparison analysis indicated significant differences between 5- and 6-year-olds in sustained attention measures (t(98) = 3.08, SEM = 5.41, p < .01), literal comprehension (t(98) = 4.05, SEM = 0.59, p < .001), and inferences (U = 750.50, z = 3.50, p < .001), but not in forward digit span (t(98) = 1.43, SEM = 0.34, p = .16) and backward digit span (U = 1043.50, z = 1.49, p = .14). A model of interrelation was proposed with age as independent variable, comprehension as dependent variable, and working memory and sustained attention as mediating variables, being comprehension, a latent factor formed by literal comprehension and inferences, and working memory another latent factor formed by forward digits and backward digits span. The path analysis showed a good fit of the data to the model (c2(5) = 1.93, p = .86; AGFI = .97, CFI = .99, TLI = .99, RMSEA = .00). The analysis showed that 6-year-olds perform better than 5-year-olds in literal and inferential information, and in sustained attention, but not in working memory. The correlation analyses, on the other hand, indicated that comprehension measures are associated to working memory and sustained attention scores and the path analysis indicated that both working memory and sustained attention play a role in comprehension. This suggests that, in 5 and 6-year-olds, age has an effect on the comprehension of general information and the ability to generate inferences, but this effect is mediated, in part, by the child's ability to sustain attention on the narration and to temporarily store the information received while listening to it.
RESUMO
Pulmonary tuberculosis (PTB), caused by Mycobacterium tuberculosis (Mtb), is a major health problem worldwide, further aggravated by the convergence of type 2 diabetes mellitus (DM) which constitutes an important risk factor for TB development. The worse scenario of patients with PTB and DM may be partly related to a more unbalanced defensive response. As such, newly diagnosed PTB patients with DM (TB+DM, n = 11) or not (TB, n = 21), as well as DM (n = 18) patients and pair matched controls (Co, n = 22), were investigated for the circulating immuno-endocrine-metabolic profile (ELISA), along with studies in peripheral blood mononuclear cells (PBMC) analyzing transcript expression (RT-qPCR) of mediators involved in glucocorticoid functionality. Given the hyperglycemic/hypercortisolemic scenario of TB+DM patients, PBMC were also exposed to stress-related cortisol concentrations (0.1 and 1 µM) and supraphysiologic glucose doses (10, 20, and 40 mM) and assessed for the specific response against Mtb stimulation (lymphoproliferation, -thymidine incorporation-, and cytokine production -bead-cytometry). All TB patients displayed increased plasma amounts of cortisol, growth hormone -hGH-, and proinflammatory mediators. In turn, TB+DM showed even higher levels of interferon gamma -IFN-γ- and hGH (vs. TB), or IL-6, C reactive protein, cortisol and hGH (vs. DM). Both DM groups had equally augmented values of IL-10. All TB patients showed decreased dehydroepiandrosterone- sulfate concentrations, even more in TB+DM cases. Leptin was also decreased in both TB cases, particularly in the TB group, revealing a lower body mass index, as well. Unlike PBMC from TB cases showing a decreased relationship between the glucocorticoids receptor (GR) isoforms (GRα/GRß; functional isoform/negative isoform), cells from TB+DM patients had no changes in this regard, along with an increased expression of 11-beta hydroxysteroid dehydrogenase type-1, the enzyme facilitating intracellular cortisone to cortisol conversion. TB+DM patients also showed an increased Mtb antigen-driven lymphoproliferation. Compared to TB, DM and HCo counterparts, PBMC from TB+DM patients had a biased Th1 response to Mtb stimulation (increased IL-2 and IFN-γ production), even when exposed to inhibitory cortisol doses. TB+DM patients show a more unbalanced immuno-endocrine relationship, respect the non-diabetic counterparts, with a relative deficiency of cortisol immunomodulatory influences, despite their more favorable microenvironment for cortisol-mediated immune effects.
Assuntos
Diabetes Mellitus Tipo 2 , Sistema Endócrino/fisiopatologia , Hidrocortisona/sangue , Sistema Imunitário/fisiopatologia , Tuberculose , Adulto , Estudos de Casos e Controles , Células Cultivadas , Comorbidade , Citocinas/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/imunologia , Feminino , Humanos , Hidrocortisona/farmacologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/patologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/imunologia , Tuberculose/sangue , Tuberculose/complicações , Tuberculose/epidemiologia , Tuberculose/imunologiaRESUMO
It is well-established that infectious stress activates the hypothalamus-pituitary-adrenal axis leading to the production of pituitary adrenocorticotropin (ACTH) and adrenal glucocorticoids (GCs). Usually, GC synthesis is mediated by protein kinase A (PKA) signaling pathway triggered by ACTH. We previously demonstrated that acute murine Chagas disease courses with a marked increase of GC, with some data suggesting that GC synthesis may be ACTH-dissociated in the late phase of this parasitic infection. Alternative pathways of GC synthesis have been reported in sepsis or mental diseases, in which interleukin (IL)-1ß, prostaglandin E2 (PGE2), and/or cAMP-activated guanine nucleotide exchange factor 2 (EPAC2) are likely to play a role in this regard. Accordingly, we have searched for the existence of an ACTH-independent pathway in an experimental model of a major parasitic disease like Chagas disease, in addition to characterizing potential alternative pathways of GC synthesis. To this end, C57BL/6 male mice were infected with T. cruzi (Tc), and evaluated throughout the acute phase for several parameters, including the kinetic of GC and ACTH release, the adrenal level of MC2R (ACTH receptor) expression, the p-PKA/PKA ratio as ACTH-dependent mechanism of signal transduction, as well as adrenal expression of IL-1ß and its receptor, EPAC2 and PGE2 synthase. Our results reveal the existence of two phases involved in GC synthesis during Tc infection in mice, an initial one dealing with the well-known ACTH-dependent pathway, followed by a further ACTH-hyporesponsive phase. Furthermore, inflamed adrenal microenvironment may tune the production of intracellular mediators that also operate upon GC synthesis, like PGE2 synthase and EPAC2, as emerging driving forces for GC production in the advanced course of Tc infection. In essence, GC production seems to be associated with a biphasic action of PGE2, suggesting that the effect of PGE2/cAMP in the ACTH-independent second phase may be mediated by EPAC2.
RESUMO
Quorum-sensing (QS) mechanisms are important in intra- and inter-specific communication among bacteria. We investigated QS mechanisms in Bradyrhizobium japonicum strain CPAC 15 and Azospirillum brasilense strains Ab-V5 and Ab-V6, used in commercial co-inoculants for the soybean crop in Brazil. A transconjugant of CPAC 15-QS with partial inactivation of N-acyl-homoserine lactones (AHLs) was obtained and several parameters were evaluated; in vitro, CPAC 15 and the transconjugant differed in growth, but not in biofilm formation, and no differences were observed in the symbiotic performance in vivo. The genome of CPAC 15 carries functional luxI and luxR genes and low amounts of three AHL molecules were detected: 3-OH-C12-AHL, 3-OH-C14-AHL, and 3-oxo-C14-AHL. Multiple copies of luxR-like genes, but not of luxI are present in the genomes of Ab-V5 and Ab-V6, and differences in gene expression were observed when the strains were co-cultured with B. japonicum; we may infer that the luxR-genes of A. brasilense may perceive the AHL molecules of B. japonicum. Soybean symbiotic performance was improved especially by co-inoculation with Ab-V6, which, contrarily to Ab-V5, did not respond to the AHLs of CPAC 15. We concluded that A. brasilense Ab-V5, but not Ab-V6, responded to the QS signals of CPAC 15, and that the synergistic interaction may be credited, at least partially, to the QS interaction. In addition, we confirmed inter- and intra-species QS communication between B. japonicum and A. brasilense and, for Azospirillum, at the strain level, impacting several steps of the symbiosis, from cell growth to plant nodulation and growth.
Assuntos
Acil-Butirolactonas/metabolismo , Azospirillum brasilense/fisiologia , Bradyrhizobium/fisiologia , Glycine max/microbiologia , Interações Microbianas/fisiologia , Percepção de Quorum/fisiologia , Simbiose/fisiologia , Azospirillum brasilense/genética , Azospirillum brasilense/crescimento & desenvolvimento , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biofilmes/crescimento & desenvolvimento , Bradyrhizobium/genética , Bradyrhizobium/crescimento & desenvolvimento , Brasil , Técnicas de Cocultura , Regulação Bacteriana da Expressão Gênica , Percepção de Quorum/genética , Proteínas Repressoras/genética , Simbiose/genética , Transativadores/genética , Fatores de Transcrição/genéticaRESUMO
We investigated the effects of Azospirillum brasilense strains Ab-V5 and Ab-V6 in the induction of mechanisms of systemic acquired resistance (SAR) and induced system resistance (ISR) on maize (Zea mays L.) plants. Under normal growth conditions, the treatments consisted of the standard inoculation of cells at sowing, and leaf spray of cells or their metabolites at the V2.5 growth stage; under saline stress (170 mM NaCl), the treatment consisted of standard single and co-inoculation of A. brasilense and Rhizobium tropici. The main compounds in the Azospirillum metabolites were identified as indole-3-acetic acid (IAA) and salicylic acid (SA). Under normal conditions, A. brasilense cells applied at sowing or by leaf spray increased the activities of catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA) in leaves, and of ascorbate peroxidase (APX) in roots; however, interestingly, in general the highest activities were observed by leaf spray of metabolites. Under normal conditions, the highest levels of salicylic acid (SA) and jasmonic acid (JA) were achieved in leaves by leaf spray of metabolites, of SA in roots by leaf spray of cells, and of JA in roots by standard inoculation and leaf spray of metabolites. Under saline stress, plant protection occurred via SA and abscisic acid (ABA), but not JA. In general, inoculation resulted in further increases in SA in leaves and roots, and ABA in leaves. We hypothesize that A. brasilense confers protection to maize plants by simultaneous induction of JA and SA pathways, and, under saline stressing conditions, by SA and ABA pathways.
Assuntos
Antioxidantes/metabolismo , Azospirillum brasilense/metabolismo , Zea mays/metabolismo , Ácido Abscísico/metabolismo , Catalase/metabolismo , Ciclopentanos/metabolismo , Ácidos Indolacéticos/metabolismo , Malondialdeído/metabolismo , Oxilipinas/metabolismo , Folhas de Planta/enzimologia , Raízes de Plantas/enzimologia , Ácido Salicílico/metabolismo , Estresse Fisiológico , Superóxido Dismutase/metabolismo , Zea mays/enzimologia , Zea mays/microbiologiaRESUMO
Tuberculosis (TB) caused by Mycobacterium tuberculosis is a health problem worldwide. Patients with pulmonary TB show a neuro-immune-endocrine imbalance characterized by an impaired cellular immunity together with increased plasma levels of cortisol, pro- and anti-inflammatory cytokines and markedly decreased dehydroepiandrosterone (DHEA) levels. Extending these findings, we now investigated the immune-endocrine profile of TB patients undergoing specific treatment. Patients (n = 24) were bled at diagnosis (T0), 2, 4, 6 months after treatment initiation and 3 months following its completion. At T0, TB patients showed increased plasma levels of interleukin-6 (IL-6), C reactive protein, interferon-gamma (IFN-γ) and transforming growth factor beta (TGF-ß). These mediators decreased during treatment, reaching levels similar to those from healthy controls (n = 26). Specific treatment led to an increased lymphoproliferative response along with clinical improvement. Newly diagnosed patients had low levels of DHEA, with increased cortisol amounts and cortisol/DHEA ratio, which normalized upon specific treatment. As regards glucocorticoid receptors (GR), TB patients at diagnosis presented a reduced mRNA GRα/GRß ratio in their peripheral blood mononuclear cells. Furthermore, multivariate analysis showed that cortisol/DHEA ratio was positively associated with inflammatory mediators for which this ratio may constitute a disease biomarker. Anti-mycobacterial treatment results in a better immune-endocrine scenario for the control of physiopathological processes accompanying disease development and hence implied in clinical recovery.
Assuntos
Antituberculosos/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Leucócitos Mononucleares/efeitos dos fármacos , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose Pulmonar/tratamento farmacológico , Adulto , Proteína C-Reativa/genética , Proteína C-Reativa/imunologia , Estudos de Casos e Controles , Desidroepiandrosterona/sangue , Etambutol/uso terapêutico , Feminino , Regulação da Expressão Gênica/imunologia , Humanos , Hidrocortisona/sangue , Interferon gama/genética , Interferon gama/imunologia , Interleucina-6/genética , Interleucina-6/imunologia , Isoniazida/uso terapêutico , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/microbiologia , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/crescimento & desenvolvimento , Mycobacterium tuberculosis/patogenicidade , Pirazinamida/uso terapêutico , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/imunologia , Rifampina/uso terapêutico , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/imunologia , Resultado do Tratamento , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologiaRESUMO
Objetivo: Establecer los umbrales específicos de referencia de cada uno de los parámetros de función tiroidea en cada trimestre de la gestación y determinar el impacto del uso de umbrales no específicos en el diagnóstico de las alteraciones funcionales en el primer trimestre. Métodos: Entre enero y septiembre de 2014 se contactaron 759 mujeres embarazadas con edad mayor de 18 años y sin alteraciones funcionales tiroideas conocidas. Tras excluir a todas las pacientes que no completaron el seguimiento durante toda la gestación y las que presentaron inmunidad tiroidea positiva, 411 gestantes configuraron nuestra población de referencia. Se determinaron los niveles de TSH, T4L y T3L en cada trimestre, los anticuerpos antiperoxidasa tiroidea y antitiroglobulina en el primero y se recogió una muestra de orina en los trimestres primero y tercero para la determinación del yodo urinario. Resultados: Un total de 411 gestantes completaron el seguimiento en los 3 trimestres. Un 38,69% consumían sal yodada y un 72,20% suplementos yodados. Los valores de referencia de TSH expresados como mediana y percentiles 2,5 y 97,5 fueron: 1,53 μUI/ml (0,26-3,95), 1,90 μUI/ml (0,78-3,85) y 1,89 μUI/ml (0,71-3,61) en el primer, segundo y tercer trimestre, respectivamente. El nivel de yoduria fue de 171,31 μg/l (90,7-274,9) en el primer trimestre y de 190,37 μg/l (96,44-360,38) en el tercero. La aplicación en el primer trimestre de los umbrales propuestos por las sociedades internacionales ocasionaría una clasificación errónea del 19,8% de las gestantes en relación con su función tiroidea, mientras que los umbrales no específicos de nuestro laboratorio lo harían en el 8,52%. Conclusiones: La utilización de umbrales no específicos para el diagnóstico de las alteraciones funcionales tiroideas durante la gestación ocasiona un importante porcentaje de errores de clasificación, contribuyendo a una atención inadecuada.
en
Assuntos
Humanos , Feminino , Gravidez , Padrões de Referência , Testes de Função Tireóidea/classificação , Complicações na Gravidez , Doenças da Glândula Tireoide/diagnóstico , Glândula Tireoide/fisiopatologia , Iodo/urinaRESUMO
El objetivo de este trabajo es estudiar la relación entre la atención sostenida y el conocimiento previo con la comprensión de narraciones en niños de 4 años de edad. La muestra comprendía 30 niños a los que se les presentaron dos cuentos y se les solicitó que respondieran una serie de preguntas para evaluar comprensión de información literal y la generación de inferencias. Se utilizaron además una prueba de atención sostenida y un cuestionario de conocimiento previo. Los resultados demuestran la existencia de una asociación entre la comprensión de textos y el conocimiento previo, y se observa una relación diferenciada del conocimiento previo con distintos aspectos de la comprensión, comprobándose una asociación con la habilidad para generar inferencias, no así con la comprensión de información de tipo literal. Además, la atención sostenida posee valor predictivo sobre la comprensión de texto global, específicamente sobre la comprensión de información de tipo literal.
The aim of this project is to study the relationship between sustained attention and prior knowledge with narrative comprehension in 4 years-old children. For that purpose, two narrative stories and a questionnaire to assess comprehension of literal information and inference generation were administrated to 30 children. Also, a sustained attention test and a prior knowledge questionnaire were administrated. Results showed an association between text comprehension with prior knowledge, and an association of sustained attention with different aspects of text comprehension, observing an association with the ability to generate inferences, but not with literal information comprehension. Also, a predictive role of sustained attention on global comprehension and more specifically on literal information comprehension was found.
Assuntos
Pré-Escolar , Criança , Narração , Compreensão , AtençãoRESUMO
Prolactin has an immunomodulatory effect and has been associated with B-cell-triggered autoimmune diseases, such as systemic lupus erythematosus (SLE). In mice that develop SLE, the PRL receptor is expressed in early bone marrow B-cells, and increased levels of PRL hasten disease manifestations, which are correlated with a reduction in the absolute number of immature B-cells. The aim of this work was to determine the effect of PRL in an in vitro system of B-cell tolerance using WEHI-231 cells and immature B-cells from lupus prone MRL/lpr mice. WEHI-231 cells express the long isoform of the PRL receptor, and PRL rescued the cells from cell death by decreasing the apoptosis induced by the cross-linking of the B-cell antigen receptor (BCR) as measured by Annexin V and active caspase-3. This decrease in apoptosis may have been due to the PRL and receptor interaction, which increased the relative expression of antiapoptotic Bcl-xL and decreased the relative expression of proapoptotic Bad. In immature B-cells from MRL/lpr mice, PRL increased the viability and decreased the apoptosis induced by the cross-linking of BCR, which may favor the maturation of self-reactive B-cells and contribute to the onset of disease.