Avaliação da influência dos marcadores inflamatórios na mortalidade de pacientes com AVC isquêmico

À medida que a população envelhece e a expectativa de vida aumenta, a incidência global e a prevalência de AVC isquêmico tendem a aumentar significativamente. Nesse contexto, surge a necessidade de avaliar novos marcadores preditores de mortalidade, como a contagem absoluta de monócitos, relação linfócitos sobre monócitos, relação neutrófilos sobre linfócitos e níveis de proteína C reativa ultrassensível, que além de serem de fácil acesso e baixocusto, sugerem indicar desfecho no paciente com AVC agudo. O objetivo deste estudo foi avaliar a associação dos marcadores inflamatórios com a mortalidade de pacientes com AVC isquêmico. Métodos: trata-se de um estudo retrospectivo observacional a partir de prontuários eletrônicos e exames laboratoriais de pacientes com AVC isquêmico em uma unidade hospitalar de Cascavel/PR. Umaanálise estatística descritiva foi conduzida para determinar o perfil dospacientes segundo o desfecho e aplicado um modelo de regressãologística para verificar as variáveis associadas a mortalidade. Foramconsiderados significativos apenas os dados com p-valor 0,05.Resultados: Dos 65 pacientes que foram admitidos no estudo, 50receberam alta hospitalar e 15 foram a óbito no hospital. Entre osmarcadores inflamatórios, a relação de neutrófilos sobre linfócitos(OR 1,55; p-valor 0,01) mostrou-se significativamente associada amaior chance de óbito. Os pacientes que faleceram apresentaramníveis superiores de PCR ultrassensível, maior contagem absoluta demonócitos, relação linfócitos sobre monócitos diminuída, e relaçãoneutrófilos sobre linfócitos elevada. Conclusão: a relação de neutrófilos sobre linfócitos elevada pode estar significativamente associada ao desfecho desfavorável após um AVC isquêmico

Vagotomy diminishes obesity in cafeteria rats by decreasing cholinergic potentiation of insulin release

CAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORHerein, we investigated whether subdiaphragmatic vagotomy has benefits on obesity, body glucose homeostasis, and insulin secretion in cafeteria (CAF)-obese rats. Wistar rats were fed a standard or CAF diet for 12 weeks. Subsequently, CAF rats were randomly submitted to truncal vagotomy (CAF Vag) or sham operation (CAF Sham). CAF Sham rats were hyperphagic, obese, and presented metabolic disturbances, including hyperinsulinemia, glucose intolerance, insulin resistance, hyperglycemia, and hypertriglyceridemia. Twelve weeks after vagotomy, CAF Vag rats presented reductions in body weight and perigonadal fat stores. Vagotomy did not modify glucose tolerance but normalized fed glycemia, insulinemia, and insulin sensitivity. Isolated islets from CAF Sham rats secreted more insulin in response to the cholinergic agent, carbachol, and when intracellular cyclic adenine monophosphate (cAMP) is enhanced by forskolin or 3-isobutyl-1-methylxanthine. Vagotomy decreased glucose-induced insulin release due to a reduction in the cholinergic action on beta-cells. This effect also normalized islet secretion in response to cAMP. Therefore, vagotomy in rats fed on a CAF-style diet effectively decreases adiposity and restores insulin sensitivity. These effects were mainly associated with the lack of cholinergic action on the endocrine pancreas, which decreases insulinemia and may gradually reduce fat storage and improve insulin sensitivity.Herein, we investigated whether subdiaphragmatic vagotomy has benefits on obesity, body glucose homeostasis, and insulin secretion in cafeteria (CAF)-obese rats. Wistar rats were fed a standard or CAF diet for 12 weeks. Subsequently, CAF rats were randomly submitted to truncal vagotomy (CAF Vag) or sham operation (CAF Sham). CAF Sham rats were hyperphagic, obese, and presented metabolic disturbances, including hyperinsulinemia, glucose intolerance, insulin resistance, hyperglycemia, and hypertriglyceridemia. Twelve weeks after vagotomy, CAF Vag rats presented reductions in body weight and perigonadal fat stores. Vagotomy did not modify glucose tolerance but normalized fed glycemia, insulinemia, and insulin sensitivity. Isolated islets from CAF Sham rats secreted more insulin in response to the cholinergic agent, carbachol, and when intracellular cyclic adenine monophosphate (cAMP) is enhanced by forskolin or 3-isobutyl-1-methylxanthine. Vagotomy decreased glucose-induced insulin release due to a reduction in the cholinergic action on beta-cells. This effect also normalized islet secretion in response to cAMP. Therefore, vagotomy in rats fed on a CAF-style diet effectively decreases adiposity and restores insulin sensitivity. These effects were mainly associated with the lack of cholinergic action on the endocrine pancreas, which decreases insulinemia and may gradually reduce fat storage and improve insulin sensitivity724625633CAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORCAPES - COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIORsem informaçã

Diabetes Mellitus: Um estudo epidemiológico retrospectivo e observacional

ABSTRACT: Diabetes mellitus is a chronic disease in which hyperglycemia occurs and causes several changes throughout the patients' lives. Given the changes in all areas due to Covid-19, the epidemiological study carried out showed a drop in the incidence of cases of Diabetes Mellitus diagnosed in the period from January 1 2015 to July 31 2021, which may be related to the direction of the outpatients clinics for the exclusive care of patients who have contracted covid-19.RESUMO: O diabetes mellitus é uma doença crônica em que ocorre hiperglicemia e acarreta em várias alterações ao longo da vida dos pacientes. Diante das mudanças em todos os âmbitos devido a Covid-19, o estudo epidemiológico realizado mostrou queda na incidência dos casos de Diabetes Mellitus diagnosticado no período de 01 janeiro de 2015 até 31 de julho de 2021, podendo ser relacionado ao direcionamento dos ambulatórios para o atendimento exclusivo de pacientes que contraíram a covid-19.&nbsp

Toxoplasma gondii chitinase induces macrophage activation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Toxoplasma gondii is an obligate intracellular protozoan parasite found worldwide that is able to chronically infect almost all vertebrate species, especially birds and mammalians. Chitinases are essential to various biological processes, and some pathogens rely on chitinases for successful parasitization. Here, we purified and characterized a chitinase from T. gondii. The enzyme, provisionally named Tg_chitinase, has a molecular mass of 13.7 kDa and exhibits a Km of 0.34 mM and a Vmax of 2.64. The optimal environmental conditions for enzymatic function were at pH 4.0 and 50 degrees C. Tg_chitinase was immunolocalized in the cytoplasm of highly virulent T. gondii RH strain tachyzoites, mainly at the apical extremity. Tg_chitinase induced macrophage activation as manifested by the production of high levels of pro-inflammatory cytokines, a pathogenic hallmark of T. gondii infection. In conclusion, to our knowledge, we describe for the first time a chitinase of T. gondii tachyzoites and provide evidence that this enzyme might influence the pathogenesis of T. gondii infection.Toxoplasma gondii is an obligate intracellular protozoan parasite found worldwide that is able to chronically infect almost all vertebrate species, especially birds and mammalians. Chitinases are essential to various biological processes, and some pathoge1012112FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOCNQP - CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICOFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)FAPESP [2013/10741-8]2013/10741-8SEM INFORMAÇÃOThis study was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (Grant number 2013/10741-8). Additional financial help was provided by Conselho Nacional de Desenvolvimento Científico e Tecnológico, and Fundação de Apoio ao Ensino, Pe

Toxoplasma gondii Chitinase Induces Macrophage Activation.

Toxoplasma gondii is an obligate intracellular protozoan parasite found worldwide that is able to chronically infect almost all vertebrate species, especially birds and mammalians. Chitinases are essential to various biological processes, and some pathogens rely on chitinases for successful parasitization. Here, we purified and characterized a chitinase from T. gondii. The enzyme, provisionally named Tg_chitinase, has a molecular mass of 13.7 kDa and exhibits a Km of 0.34 mM and a Vmax of 2.64. The optimal environmental conditions for enzymatic function were at pH 4.0 and 50 °C. Tg_chitinase was immunolocalized in the cytoplasm of highly virulent T. gondii RH strain tachyzoites, mainly at the apical extremity. Tg_chitinase induced macrophage activation as manifested by the production of high levels of pro-inflammatory cytokines, a pathogenic hallmark of T. gondii infection. In conclusion, to our knowledge, we describe for the first time a chitinase of T. gondii tachyzoites and provide evidence that this enzyme might influence the pathogenesis of T. gondii infection

The absence of either CD14 or CD36 does not affect the TLR activation triggered by rPCN.

<p>HEK293T were cotransfected with CD14 and/or CD36 along with TLR2/1 (A) or TLR2/6 (B). The total amount of DNA in each transfection was kept constant by adding empty expression vector. The HEK293T cells were stimulated with rPCN (1.25 µg/mL), which was previously incubated with polymyxin to neutralize LPS. The positive controls were Pam3CysSK4 (P3C) for TLR2/1 and FSL-1 for TLR2/6. Medium was used as negative control for cell stimulation (white bars). Results are representative of three independent experiments. Statistical differences were assessed by comparing the response of cells lacking one of the co-receptors to the response of cells expressing both co-receptors, under similar stimuli. Values are the mean ± S.D. *** p<0.001.</p

Therapeutic groups.

a<p>PBS alone.</p><p>Therapeutic groups.</p

Morphometry of lung granulomas and analysis of fungal burden in infected animals treated with rPCN.

<p>Each group of mice was either not treated (PBS) or therapeutically treated according to protocols G1–G4 (see <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0003317#s2" target="_blank">Material and Methods</a>). Panel A: Number of granulomas per mm² of tissue. Panel B: Granuloma area, in µm². Panel C: Pulmonary CFU recovery. For morphometric analysis, the Image J program, developed by Wayne Rasband of the National Institute of Mental Health, was used. Bars depict the mean and SD. * p<0.05; ** p<0.01; *** p<0.001 <i>vs.</i> the PBS group.</p

Therapeutic administration of rPCN increases proinflammatory cytokine and NO production.

<p>Lung homogenates were analyzed for IL-12p40 (A), IFN-γ (B), TNF-α (C), IL-10 (D), IL-4 (E), and NO (F) concentrations. Data represent the mean and SD of five mice per group; the experiments were performed in triplicate. * p<0.05; ** p<0.01; *** p<0.001 <i>vs.</i> the PBS group.</p