Inflammasome activation and IL-1 signaling during placental malaria induce poor pregnancy outcomes.

Placental malaria (PM) is associated with severe inflammation leading to abortion, preterm delivery, and intrauterine growth restriction. Innate immunity responses play critical roles, but the mechanisms underlying placental immunopathology are still unclear. Here, we investigated the role of inflammasome activation in PM by scrutinizing human placenta samples from an endemic area and ablating inflammasome components in a PM mouse model. The reduction in birth weight in babies from infected mothers is paralleled by increased placental expression of AIM2 and NLRP3 inflammasomes. Using genetic dissection, we reveal that inflammasome activation pathways are involved in the production and detrimental action of interleukin-1ß (IL-1ß) in the infected placenta. The IL-1R pharmacological antagonist Anakinra improved pregnancy outcomes by restoring fetal growth and reducing resorption in an experimental model. These findings unveil that IL-1ß-mediated signaling is a determinant of PM pathogenesis, suggesting that IL-1R antagonists can improve clinical outcomes of malaria infection in pregnancy.

The Impact of Immunosuppressive Drugs on Human Placental Explants.

The use of immunosuppressive drugs guarantees the vitality of the graft and allows gestation in spite of intercurrences such as prematurity and intrauterine growth restriction. However, little is known about the direct effects of immunosuppressive drugs on placental cells. We investigated the effects of immunosuppressive drugs in the chorionic villous explants from human term placentas of healthy gestations. Human placental explants from term gestations (37-39 week gestational age, n = 12) were exposed to cyclosporine A (CSA, 0, 62.5, 125, 1250 ng/mL) or azathioprine (AZA, 0, 5, 10, 100 ng/mL) separately or, in combination for up to 48 hours. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays showed a significant decrease in the explant metabolic activity between AZA and the control group (24 hours, 100 ng/mL, 48 hours, all concentrations, P < .005). Cyclosporin A (CsA) reduced cell activity when associated with AZA (48 hours, P < .005). Fibrinoid deposits increased in AZA-treated explants alone (5 ng/mL, 48 hours; 10 ng/mL, 24-48 hours; P < .005) or when associated with CsA (10 AZA/125 CsA, P < .05), whereas in CsA treatment alone, there was an augment in syncytial knots (24-48 hours, P < .005). The sFLT1 gene (24 hours, P < .05) and protein (P < .005) expression increased in AZA and CsA-treatments separately or in combination (P < .05). Placental growth factor increased in AZA (24 hours, 10 ng/mL) and CsA (125 ng/mL; P < .05). In conclusion, our data indicate that AZA primarily acts on the villous metabolism, perturbing placental homeostasis. Since these drugs may alter the balance of angiogenic factors in its selection for clinical application, their impact on the behavior of placental villous should be considered.

Qualidade de vida e independência funcional de idosos frequentadores do clube do idoso do município de Sorocaba / Quality of life and functional independence of the elderly goers to the elderly house in the city of Sorocaba

INTRODUÇÃO: Nos últimos anos a expectativa de vida vem aumentando em todo o mundo. A manutenção da capacidade funcional e da qualidade de vida (QV) dessa população é um dos desafios da atualidade. OBJETIVO: Avaliar a QV e a independência funcional de idosos frequentadores do Clube do Idoso do município de Sorocaba e investigar a correlação entre essas medidas. MÉTODOS: Participaram idosos de ambos os sexos com idade ≥60 anos. Foram utilizados: Instrwumento de Caracterização Sociodemográfica; World Health Organization Quality of Life Assessment-Old (WHOQOL-OLD) e Medida de Independência Funcional (MIF). Análises estatísticas realizadas: teste de Mann-Whitney e teste de Kruskal-Wallis para comparação entre os escores e o coeficiente de correlação de postos de Spearman para verificar a correlação entre os instrumentos. RESULTADOS: Participaram 71 idosos, 69,01% mulheres, 56,34% com idade entre 60 e 69 anos, 33,80% casados e 83,10% aposentados. Não houve diferenças significativas quanto ao sexo para os dois instrumentos e quanto à idade nos escores do WHOQOL-OLD. Os idosos ≥80 anos apresentaram queda da independência funcional (p<0,001) e aqueles com mais anos de estudo apresentaram maior independência funcional e avaliaram melhor a QV global. Houve correlação diretamente proporcional entre escores da MIF e QV. CONCLUSÃO: Este estudo apontou que a funcionalidade está diretamente ligada à QV. Daí a importância dos grupos de terceira idade como forma de favorecer a prática de atividade física e aumentar a interação social, fatores essenciais na proteção e promoção da saúde e da QV dessa população.

INTRODUCTION: In the last years, life expectancy has been increasing all over the world. Preserving the functional capacity and the quality of life (QOL) of this population is one of the current challenges. OBJECTIVE: Assess the QOL and the functional independence of the elderly attending the Elderly Club in the Municipality of Sorocaba and to investigate the correlation among these measures. Methods: Elderly men and women aged ≥60 years old participated in the assessment. The instruments used were Sociodemographic Characterization Instrument; World Health Organization Quality of Life Assessment ­ Old (WHOQOL-OLD) and Functional Independence Measure (FIM). Statistical analysis: Mann-Whitney and Kruskal-Wallis tests to compare the scores and Correlation of Spearman to check the correlation between instruments. RESULTS: Seventy-one elderly participated, being 69.01% women, 56.34% between 60 and 69 years old, 33.80% married and 83.10% retired. There were not significant differences regarding sex between the two instruments and, in the scores of WHOQOL-OLD, regarding age. The elderly aged ≥80 years old showed a decline in the functional independence (p<0.001) and those with more years of study showed a better functional independence and assessed better the global QOL. There was a directly proportional correlation between the scores of the MIF and the QOL. CONCLUSION: This study indicated that the functionality is directly linked to QOL. Hence the importance of the elderly groups as a way of encouraging the practice of physical activities and increasing social interaction, essential factors for the protection and promotion of health and QOL of this population.