RESUMO
Aedes aegypti and Aedes albopictus are the main vectors of arboviruses such as Dengue, Chikungunya and Zika, causing a major impact on global economic and public health. The main way to prevent these diseases is vector control, which is carried out through physical and biological methods, in addition to environmental management. Although chemical insecticides are the most effective strategy, they present some problems such as vector resistance and ecotoxicity. Recent research highlights the potential of the imidazolium salt "1-methyl-3-octadecylimidazolium chloride" (C18MImCl) as an innovative and environmentally friendly solution against Ae. aegypti. Despite its promising larvicidal activity, the mode of action of C18MImCl in mosquito cells and tissues remains unknown. This study aimed to investigate its impacts on Ae. aegypti larvae and three cell lines of Ae. aegypti and Ae. albopictus, comparing the cellular effects with those on human cells. Cell viability assays and histopathological analyses of treated larvae were conducted. Results revealed the imidazolium salt's high selectivity (> 254) for mosquito cells over human cells. After salt ingestion, the mechanism of larval death involves toxic effects on midgut cells. This research marks the first description of an imidazolium salt's action on mosquito cells and midgut tissues, showcasing its potential for the development of a selective and sustainable strategy for vector control.
Assuntos
Aedes , Imidazóis , Inseticidas , Larva , Aedes/efeitos dos fármacos , Animais , Larva/efeitos dos fármacos , Imidazóis/toxicidade , Imidazóis/farmacologia , Inseticidas/toxicidade , Inseticidas/farmacologia , Humanos , Mosquitos Vetores/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Controle de Mosquitos/métodosRESUMO
Acute lymphoblastic leukemia (ALL), a complex malignancy, displays varying expression profiles of PIP4K2-related genes in adult patients. While PIP4K2A expression is elevated in ALL bone marrow cells compared to healthy bone marrow cells, PIP4K2B is downregulated, and PIP4K2C remains relatively unchanged. Despite the correlation between increased PIP4K2A expression and increased percentage of peripheral blood blasts, clinical outcomes do not strongly correlate with the expression of these genes. Here we investigated the therapeutic potential of three PIP4K2 inhibitors (THZ-P1-2, a131, and CC260) in ALL cell models. THZ-P1-2 emerges as the most effective inhibitor, inducing cell death and mitochondrial damage while reducing cell viability and metabolism significantly. Comparative analyses highlight the superior efficacy of THZ-P1-2 over a131 and CC260. Notably, THZ-P1-2 uniquely disrupts autophagic flux and inhibits the PI3K/AKT/mTOR pathway, indicating a distinct molecular mechanism. In summary, our findings elucidate the differential expression of PIP4K2-related genes in ALL and underscore the potential role of PIP4K2A in disease pathogenesis. The therapeutic promise of THZ-P1-2 in ALL treatment, along with its distinct effects on cell death mechanisms and signaling pathways, enriches our understanding of PIP4K2's involvement in ALL development and offers targeted therapy prospects.
Assuntos
Fosfotransferases (Aceptor do Grupo Álcool) , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Linhagem Celular Tumoral , Transdução de Sinais/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/antagonistas & inibidores , Autofagia/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico , Apoptose/efeitos dos fármacosRESUMO
BACKGROUND: Yoga practice can increase blood flow in the genital area, increase muscular strength, and improve body perception, which is related to sexual function. This study aimed to summarize the available evidence about the effects of yoga on sexual function in adults. METHODS: Systematic searches of five databases were conducted from inception to April 28, with the last update on September 28, 2023. Randomized clinical trials (RCTs) that compared yoga with nonintervention control groups on sexual function in adults. Risk of bias and certainty of evidence were assessed by the Cochrane risk of bias tool 2, and the GRADE approach, respectively. Summary effect size measures were calculated using a random-effects model estimation and are reported as standardized mean differences and 95% confidence intervals. Reporting followed the PRISMA guidelines. RESULTS: Ten RCTs that comprised 730 adults (range mean age, 26.64-68.2 years; 680 [93.2 %] women) were included. For the primary outcome, yoga intervention was associated with a significant small improvement in sexual function (-0.31; -0.47 to -0.15, p = 0.0002), with some concerns about risk of bias in nine RCTs (90%) and low-certainty evidence. Subgroup analyses revealed that yoga interventions performed by women (-0.36; -0.52 to -0.21, p < 0.00001), healthy individuals (-0.38; -0.59 to -0.16, p = 0.0006), or middle-aged individuals (-0.44; -0.63 to -0.25, p < 00001) significantly improved sexual function compared with control groups. CONCLUSION: Yoga was associated with a small improvement in sexual function compared with nonintervention control groups in adults. However, high-quality, larger RCTs are required to draw more definitive conclusions.
Assuntos
Ensaios Clínicos Controlados Aleatórios como Assunto , Yoga , Humanos , Feminino , Adulto , Masculino , Disfunções Sexuais Fisiológicas/terapia , Pessoa de Meia-Idade , Comportamento Sexual , IdosoAssuntos
Azacitidina , Humanos , Azacitidina/administração & dosagem , Azacitidina/uso terapêutico , Masculino , Feminino , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/uso terapêutico , América do Sul , Esquema de Medicação , Pessoa de Meia-Idade , IdosoRESUMO
El artículo discute algunos apuntes epistemológicos presentes en los trabajos de Canguilhem, Foucault y Kuhn y sus implicaciones para la caracterización de la racionalidad de la medicina científica. La delimitación del concepto de enfermedad, constructo fundamental por tratarse del objeto de conocimiento de la medicina, es abordado en el análisis de Canguilhem para la formación teórica de los conceptos de lo normal y lo patológico, y en la interpretación foulcaltiana que identifica el desplazamiento epistemológico que da origen al método clínico como modelo de práctica subyacente a los procesos de intervención en salud. La perspectiva socio-constructivista de L. Fleck es representada como posibilidad de abordaje epistemológico para explicar la dinámica de transformación, instauración y extensión de los hechos científicos, atribuyendo importancia a los elementos históricos y sociales como posibilidad de interpretar la complejidad en el área de la salud.
This article discusses some epistemological aspects of Canguilhem, Foucault and Kuhn's work and their implication in the characterization of Medicine's scientific rationale. The delimitation of the disease concept, which is fundamental for being Medicine's object of knowledge, is considered in Canguilhem's analysis of the theoretical formation of the concepts of what is normal or pathologic and in Foucault's interpretation that identifies the epistemological hallmark that gives origin to the clinical method as a subjacent model to all health intervention processes. Ludwik Fleck's socio constructivist perspective is presented as a possibility to epistemologically approach the dynamics of transformation, instauration and extension of scientific facts, placing special importance on the historical and social elements as a possibility to interpret health's complexity.
RESUMO
El artículo discute algunos apuntes epistemológicos presentes en los trabajos de Canguilhem, Foucault y Kuhn y sus implicaciones para la caracterización de la racionalidad de la medicina científica. La delimitación del concepto de enfermedad, constructo fundamental por tratarse del objeto de conocimiento de la medicina, es abordado en el análisis de Canguilhem para la formación teórica de los conceptos de lo normal y lo patológico, y en la interpretación foulcaltiana que identifica el desplazamiento epistemológico que da origen al método clínico como modelo de práctica subyacente a los procesos de intervención en salud. La perspectiva socioconstructivista de L. Fleck es representada como posibilidad de abordaje epistemológico para explicar la dinámica de transformación, instauración y extensión de los hechos científicos, atribuyendo importancia a los elementos históricos y sociales como posibilidad de interpretar la complejidad en el área de la salud.(AU)
This article discusses some epistemological aspects of Canguilhem, Foucault and Kuhns work and their implication in the characterization of Medicines scientific rationale. The delimitation of the disease concept, which is fundamental for being Medicines object of knowledge, is considered in Canguilhems analysis of the theoretical formation of the concepts of what is normal or pathologic and in Foucaults interpretation that identifies the epistemological hallmark that gives origin to the clinical method as a subjacent model to all health intervention processes. Ludwik Flecks socio constructivist perspective is presented as a possibility to epistemologically approach the dynamics of transformation, instauration and extension of scientific facts, placing special importance on the historical and social elements as a possibility to interpret healths complexity.(AU)
Assuntos
Ciências da Saúde , Conhecimento , Filosofia MédicaRESUMO
El trígono arterio-venoso del corazón, de Brocq & Mouchet, está formado por la intersección de tres vasos cardíacos, la vena cardíaca magna y las arterias circunfleja e interventricular anterior, los cuales se encuentran en la porción superior del ventrículo izquierdo, entre el cono arterial y la aurícula izquierda, en la cara pulmonar o izquierda del corazón. Con el objetivo de conocer la incidencia, conformación y contenido del trígono aludido, estudiamos 26 corazones formolizados, correspondientes a cadáveres de individuos brasileños, adultos, de ambos sexos. El trígono fue encontrado en 23 corazones (88 por ciento). Clasificamos el trígono de acuerdo a su forma y encontramos los siguientes padrones: "abierto inferiormente" (52 por ciento); "cerrado" (35 por ciento); "completamente abierto" (9 por ciento) y "abierto superiormente" (4 por ciento). El área del trígono fue en promedio de 369 mm2. En todos los casos en que el trígono estuvo presente, la arteria diagonal recorría su interior y, en 87 por ciento de los casos habían otras ramas ventriculares izquierdas menores que variaron entre 1 y 4. El trígono arterio-venoso de Brocq & Mouchet se localiza en un área frecuentemente sometida a procesos quirúrgicos y por el hecho de coexistir innumerables vasos de calibre menor, existe un importante riesgo de lesión.