Systemic effects in naïve mice injected with immunomodulatory lectin ArtinM

<div><p>Toll-like receptors (TLR) contain N-glycans, which are important glycotargets for plant lectins, to induce immunomodulation. The lectin ArtinM obtained from <i>Artocarpus heterophyllus</i> interacts with TLR2 N-glycans to stimulate IL-12 production by antigen-presenting cells and to drive the immune response toward the Th1 axis, conferring resistance against intracellular pathogens. This immunomodulatory effect was demonstrated by subcutaneously injecting (s.c.) ArtinM (0.5 μg) in infected mice. In this study, we evaluated the systemic implications of ArtinM administration in <i>naïve</i> BALB/c mice. The mice were s.c. injected twice (7 days interval) with ArtinM (0.5, 1.0, 2.5, or 5.0 μg), LPS (positive control), or PBS (negative control) and euthanized after three days. None of the ArtinM-injected mice exhibited change in body weight, whereas the relative mass of the heart and lungs diminished in mice injected with the highest ArtinM dose (5.0 μg). Few and discrete inflammatory foci were detected in the heart, lung, and liver of mice receiving ArtinM at doses ≥2.5 μg. Moreover, the highest dose of ArtinM was associated with increased serum levels of creatine kinase MB isoenzyme (CK-MB) and globulins as well as an augmented presence of neutrophils in the heart and lung. IL-12, IFN-γ, TNF-α, and IL-10 measurements in the liver, kidney, spleen, heart, and lung homogenates revealed decreased IL-10 level in the heart and lung of mice injected with 5.0 μg ArtinM. We also found an augmented frequency of T helper and B cells in the spleen of all ArtinM-injected <i>naïve</i> mice, whereas the relative expressions of T-bet, GATA-3, and ROR-γt were similar to those in PBS-injected animals. Our study demonstrates that s.c. injection of high doses of ArtinM in <i>naïve</i> mice promotes mild inflammatory lesions and that a low immunomodulatory dose is innocuous to <i>naïve</i> mice.</p></div

RELAÇÃO ENTRE SÍNDROME DE BURNOUT, ANSIEDADE E QUALIDADE DE VIDA ENTRE ESTUDANTES DE CIÊNCIAS DA SAÚDEdoi: http://dx.doi.org/10.5892/ruvrd.v12i1.1471

Este estudo teve por objetivo determinar a prevalência da Síndrome de Burnout e dimensões (exaustão emocional, descrença, eficácia profissional) e avaliar sua relação com transtorno de ansiedade e com percepção do nível de qualidade de vida entre estudantes de Ciências da Saúde. Caracteriza-se como estudo transversal analítico, tendo sido utilizados para coleta de dados: Maslach Burnout Inventory Student Survey, Inventário de Ansiedade Traço-Estado, WHOQOL-Bref, Critério de Classificação Econômica Brasil e Questionário demográfico-socioeconômico, condições de saúde e discentes. Identificaram-se prevalências da Síndrome de Burnout em 65,1% dos estudantes (n=229); alto nível de exaustão emocional em 35,2% (n=124); alto nível de descrença em 35,8% (n=126) e baixo nível eficácia profissional em 30,4% (n=107). Registrou-se maior chance de desenvolver Síndrome de Burnout entre estudantes sem filhos, com altos índices de ansiedade-traço e com baixa percepção do nível de qualidade de vida no domínio físico. Maiores chances de desenvolver exaustão emocional foram evidentes entre aqueles com altos índices de ansiedade-estado e com baixa percepção do nível de qualidade de vida no domínio psicológico. Maior chance de desenvolver a dimensão eficácia profissional entre aqueles com altos índices de ansiedade-estado e com baixa percepção do nível de qualidade de vida no domínio social. Constatou-se relação entre SB e suas dimensões com transtorno de ansiedade e com percepção do nível de qualidade de vida, evidenciando a necessidade de se adotar medidas de enfrentamento da síndrome para possível redução do transtorno de ansiedade e promoção do nível de qualidade de vida entre estudantes de Ciências da Saúde

Relação entre síndrome de burnout, ansiedade e qualidade de vida entre estudantes de ciências da saúde

Este estudo teve por objetivo determinar a prevalência da Síndrome de Burnout e dimensões (exaustão emocional, descrença, eficácia profissional) e avaliar sua relação com transtorno de ansiedade e com percepção do nível de qualidade de vida entre estudantes de Ciências da Saúde. Caracteriza-se como estudo transversal analítico, tendo sido utilizados para coleta de dados: Maslach Burnout Inventory Student Survey, Inventário de Ansiedade Traço-Estado, WHOQOL-Bref, Critério de Classificação Econômica Brasil e Questionário demográfico-socioeconômico, condições de saúde e discentes. Identificaram-se prevalências da Síndrome de Burnout em 65,1% dos estudantes (n=229); alto nível de exaustão emocional em 35,2% (n=124); alto nível de descrença em 35,8% (n=126) e baixo nível eficácia profissional em 30,4% (n=107). Registrou-se maior chance de desenvolver Síndrome de Burnout entre estudantes sem filhos, com altos índices de ansiedade-traço e com baixa percepção do nível de qualidade de vida no domínio físico. Maiores chances de desenvolver exaustão emocional foram evidentes entre aqueles com altos índices de ansiedade-estado e com baixa percepção do nível de qualidade de vida no domínio psicológico. Maior chance de desenvolver a dimensão eficácia profissional entre aqueles com altos índices de ansiedade-estado e com baixa percepção do nível de qualidade de vida no domínio social. Constatou-se relação entre SB e suas dimensões com transtorno de ansiedade e com percepção do nível de qualidade de vida, evidenciando a necessidade de se adotar medidas de enfrentamento da síndrome para possível redução do transtorno de ansiedade e promoção do nível de qualidade de vida entre estudantes de Ciências da Saúde

Body weight variation and relative organs mass of <i>naïve</i> BALB/c mice after ArtinM administration.

<p>(<b>A</b>) The protocol of ArtinM administration includes two subcutaneous injections, 10 and 3 days before the mice were euthanized (adapted from Coltri et al. [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0187151#pone.0187151.ref022" target="_blank">22</a>]). An identical protocol was used for PBS or LPS injection in the negative and positive control groups, respectively. (<b>B</b>) The body weight was first determined on day -10, and the daily subsequent determinations allowed calculating the weight variations in relation to the first value. (<b>C–G</b>) On day 0, the mass of spleen (<b>C</b>), liver (<b>D</b>), kidney (<b>E</b>), lung (<b>F</b>), and heart (<b>G</b>) was measured, and the quotient between the organ mass and the body weight was used to express the organ relative mass (mg/body weight) for each mice. (<b>A</b>–<b>G</b>) Results are expressed as mean ± SD, and the differences were considered significant when p < 0.05 (*) compared to the PBS control group.</p

Blood leukogram of <i>naïve</i> BALB/c mice after ArtinM administration.

<p>Total and differential leukocyte counting was performed in blood samples obtained at days 0 (<b>A</b>), -9 (<b>B</b>), -8 (<b>C</b>), -2 (<b>D</b>), and -1 (<b>E</b>) from animals that received ArtinM at the doses specified in each panel, LPS (positive controls), or PBS (negative controls). Results are expressed as mean ± SEM (<b>A</b>) and mean ± SD (<b>B-E</b>). Differences were considered significant when p < 0.05 (*) compared to the PBS control group.</p

Relative expression of transcription factors related to the differentiation of T helper cells in the spleen of <i>naïve</i> BALB/c mice after ArtinM administration.

<p>Total RNA was extracted from the mice spleen harvested at day 0. The total RNA was reverse-transcribed into cDNA, and the relative expression of T-bet (<b>A</b>), GATA-3 (<b>B</b>), and ROR-γt (<b>C</b>) was determined by real-time quantitative PCR. Animals received ArtinM at the specified doses, PBS (negative control), or LPS (positive control). The values were normalized to β-actin expression. Results are expressed as mean ± SD, and the levels of relative expression were compared to the PBS control group. Differences were considered significant when p < 0.05 (*) compared to the PBS control group.</p

Relative frequency of cell populations in the spleen of <i>naïve</i> BALB/c mice after ArtinM administration.

<p>Cell suspension prepared from the mice spleen harvested at day 0 was assessed by flow cytometry. The frequency of CD4+ T (<b>A</b>), CD8+ T (<b>B</b>), B (<b>C</b>), and CD11b+ cells (<b>D</b>) was determined by reacting the cells with anti-CD4 FITC, anti-CD8 FITC, anti-CD3 PE, anti-CD19 PE, and anti-CD11b PE antibodies. Animals received ArtinM at the specified doses, PBS (negative control), or LPS (positive control). Results are expressed in percentage and are represented as mean ± SD. Differences were considered significant when p < 0.05 (*) compared to the PBS control group.</p

Histopathology of the heart, lung, and liver of <i>naïve</i> BALB/c mice receiving ArtinM.

<p>The panels show representative sections (6 μm) of the organs from mice injected with various ArtinM doses or those of the positive (LPS) and negative (PBS) controls groups. The sections were stained with hematoxylin and eosin (H&E), and images were captured using a microscope (Nikon Eclipse 50i) coupled to a digital camera (Evolution MP 5.0). The yellow arrows indicate the presence of inflammatory infiltrate at the perivascular, peribronchial, or periductal regions. Magnification bars = 100 μm for all the tissues sections.</p

Serum biochemical parameters of <i>naïve</i> BALB/c mice receiving ArtinM.

<p>The serum levels of CPK (<b>A</b>), CK-MB (<b>B</b>), GOT (<b>C</b>), GPT (<b>D</b>), alkaline phosphatase (<b>E</b>), urea (<b>F</b>), total protein (<b>G</b>), albumin (<b>H</b>), and globulin (<b>I</b>) were determined in samples harvested at day 0 from mice that received ArtinM at the specified dose (x axis). PBS and LPS was administered to the negative and positive controls, respectively. Results are expressed as mean ± SD, and differences were considered significant when p < 0.05 (*) compared to the PBS control group.</p

Cytokine levels in tissues of <i>naïve</i> BALB/c mice after ArtinM administration.

<p>The levels of IL-12p40, IFN-γ, TNF-α, and IL-10 in the supernatant of organ homogenates obtained at the day 0 were assessed by ELISA. The organs were heart (<b>A</b>–<b>D</b>), lung (<b>E</b>–<b>H</b>), liver (<b>I</b>–<b>L</b>), kidney (<b>M</b>–<b>P</b>), and spleen (<b>Q</b>–<b>T</b>). Animals received ArtinM at the specified doses, PBS (negative control), or LPS (positive control). Results are expressed as mean ± SD, and the differences were considered significant when p < 0.05 (*) compared to the PBS control group.</p