Neutrophils in Rheumatoid Arthritis: A Target for Discovering New Therapies Based on Natural Products

Rheumatoid arthritis (RA) is a systemic autoimmune disorder with an important inflammatory component in joints. Neutrophils are the most abundant leukocytes in inflamed joints, and play an essential role in the initiation and progression of RA. Neutrophil effector mechanisms include the release of proinflammatory cytokines, reactive oxygen and nitrogen species (ROS and RNS), and granules containing degradative enzymes, which can cause further damage to the tissue and amplify the neutrophil response. Therefore, the modulation of neutrophil migration and functions is a potential target for pharmacological intervention in arthritis. The pharmacologic treatment options for RA are diverse. The current treatments are mostly symptomatic and have side effects, high costs, and an increased risk of malignancies. Because of these limitations, there is a growing interest in the use of natural products as therapies or adjunct therapies. Herbal products have attracted considerable interest over the past decade because of their multiple beneficial effects such as their antioxidant, anti-inflammatory, antiproliferative, and immunomodulatory properties. This chapter focuses on the role of neutrophils in the pathogenesis of arthritis and the action of substances from natural products as putative antirheumatic therapies

Multiple Organ Dysfunction During Severe Malaria: The Role of the Inflammatory Response

Severe malaria is a systemic illness characterized by the dysfunction of one or more peripheral organs, such as the lungs [acute respiratory distress syndrome (ARDS)] and kidneys [acute kidney injury (AKI)]. Several clinical and experimental studies suggest that features of the inflammatory response are related to the multi-organ dysfunction observed in severe malaria. Our group has been dedicated to studying the roles of pro- and anti-inflammatory mediators in the multi-organ dysfunction observed in experimental severe malaria, especially in the lungs, kidneys, and brain. Herein, we explore severe malaria as a pathology derived from intense inflammatory responses in different organs and further distinguish and compare these organ-specific inflammatory responses. The pathophysiological mechanism of severe malaria is not fully elucidated; however, it is important to study it as a complex inflammatory response assembled by different actors, each one orchestrating a different mechanism

Qualidade de vida do idoso na comunidade: aplicação da Escala de Flanagan

The aim of this study was to evaluate the satisfaction degree of the elderly people regarding their quality of life. Data were obtained by a questionnaire characterizing the sample with a scale of quality proposed by Flanagan, using the interview technique. Among 128 elderly people, authors verified a insufficient degree of satisfaction. The dimensions of the quality of life pointed out by the Flanagan's scale were: personal development and fulfillment; family relations; social participation; welfare and material support; learning and friendship. The authors concluded that the Flanagan's scale presents limitations as a result of the subjectivity of the concept of quality.Este estudio pretendió valorar la satisfacción de los ancianos en relación a su calidad de vida. Los datos fueron obtenidos por medio de un cuestionario que caracterizaba la muestra y la escala de calidad de vida de Flanagan, utilizando la técnica de entrevista. La muestra fue constituida por 128 ancianos. En los resultados, comprobamos que la satisfacción de estos ancianos fue regular. Las dimensiones de la calidad de vida apuntadas en escala de Flanagan fueron: desarrollo personal y realización, relaciones con familiares, participación social, bienestar físico y material, amistad y aprendizaje. Concluimos que esta escala presenta limitaciones en virtud del carácter subjetivo del concepto de calidad.Esse estudo objetivou avaliar a satisfação de idosos em relação à sua qualidade de vida. Os dados foram obtidos através de questionário que caracterizava a amostra e a Escala de Qualidade de Vida de Flanagan, utilizando-se a técnica de entrevista. A amostra foi constituída por 128 idosos. Nos resultados, verificamos que a satisfação desses idosos mostrou-se regular. As dimensões da qualidade de vida apontadas na escala de Flanagan foram: desenvolvimento pessoal e realização; relações com familiares; participação social; bem-estar físico e material; amizade e aprendizagem. Concluímos que essa Escala apresenta limitações em virtude do caráter subjetivo do conceito de qualidade

Mefloquine–oxazolidine derivatives, derived from mefloquine and arenecarbaldehydes: In vitro activity including against the multidrug-resistant tuberculosis strain T113

AbstractTen new mefloquine–oxazolidine derivatives, 4-[(1S,8aR)-3-(aryl)hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinoline (1: aryl=substituted phenyl) and 4-[(1S,8aR)-3-(heteroaryl)hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinoline [2: heteroaryl=5-nitrothien-2-yl (2a); 5-nitrofuran-2-yl (2b) and 4H-imidazol-2-yl) (2c)], have been synthesized and evaluated against Mycobacterium tuberculosis. Compounds 1f (aryl=3-ethoxyphenyl), 1g (Ar=3,4,5-(MeO)3-C6H2) and 2c were slightly more active than mefloquine (MIC=33μM) with MICs=24.5, 22.5 and 27.4, respectively, whereas compounds 1e (aryl=3,4-(MeO)2-C6H3) and 2a (MICs=11.9 and 12.1μM, respectively) were ca. 2.7 times more active than mefloquine, with a better tuberculostatic activity than the first line tuberculostatic agent ethambutol (MIC=15.9). The compounds were also assayed against the MDR strain T113 and the same MICs were observed. Thus the new derivatives have advantages over such anti-TB drugs as isoniazid, rifampicin, ethambutol and ofloxacin, for which this strain is resistant. The most active compounds were not cytotoxic to Murine Macrophages Cells in a concentration near their MIC values

Leukotriene B4 mediates γδ T lymphocyte migration in response to diverse stimuli

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141926/1/jlb0323.pd

Cortes comerciales y característica de la canal de borregos y cabritos suplementados con bloques multinutricionales

 Objective. Aimed to identify the weight and yield of the commercial cuts, muscularity, and adiposity in the carcasses of sheep and goats grazing in the Caatinga supplemented with different sources of supplementations; these include feed-blocks. Material and methods. Sixty non-castrated males an initial average body weight of 18.63 ± 1.93 kg were used: 30 goats and 30 sheep all animals did not have a defined breed standard (WDBS). The experimental design used was entirely randomized (DIC), in factorial scheme 3x2 (three types of supplementation: mineral salt, MBs and MBs + buffel hay, and two species: sheep and goats) and 10 replications. Animals were raised in a rangeland grazing system in an area with vegetation characteristic of Caatinga ecosystem under three types of supplementation: 1: only mineral salt; 2: Feed blocks (MBs); and 3: MBs + buffel hay There were measured the weight, yield and the components of left half-part of carcass of lambs and kids. Results. The sheep were superior to goats in carcass conformation, loin-eye area, index of muscularity of the leg and compactness index of the leg while the goats were superior to sheep in leg muscles weight. Conclusions. Sheep and Goats, when fed with supplementation of pasture feeding blocks in the Caatinga ecosystem; Supplementation with mineral salt and Multinutritional Blocks with and without Buffel can be used to improve herds in the caatinga, with similar results among the three. Sheep show more adiposity of meat than goats, in contrast, goats have higher musculature than sheep when fed with feed blocks.Objetivo. Con el objetivo de identificar el peso y rendimiento de los cortes comerciales, musculatura y adiposidad en las canales de borregos y cabritos pastando en la Caatinga suplementado con diferentes fuentes de suplementos; Estos incluyen bloques de alimentación. Material y métodos. Se utilizaron 60 machos no castrados con un peso corporal medio inicial de 18,63 ± 1,93 kg: 30 borregos y 30 cabritos, todos los animales no tenían un estándar de raza definido (WDBS). El diseño experimental utilizado fue totalmente al azar (DIC), en esquema factorial 3x2 (tres tipos de suplementación: sal mineral, MBs y MBs + heno buffel, y dos especies: borregos y cabritos) y 10 repeticiones. Los animales fueron criados en un sistema de pastoreo de pastizales en un área con vegetación característica del ecosistema de Caatinga bajo tres tipos de suplementación: 1: sal mineral solamente; 2: Bloques de alimentación (MBs); Y 3: MBs + heno buffel Se midió el peso, el rendimiento y los componentes de la mitad izquierda de la carcasa de corderos y cabritos. Resultados. Las cordeiros fueron superiores a las cabritos en conformación de carcasas, área de lomo, índice de musculatura de la pierna y índice de compacidad de la pierna mientras que las cabritos fueron superiores a las cordeiros en el peso de los músculos de las piernas. Conclusión. Cordeiros y cabritos, cuando se alimentan con suplementos de bloques de alimentación de pasto en el ecosistema de Caatinga; La suplementación con sal mineral y Bloques Multinutritivos con y sin Buffel puede ser utilizada para mejorar los rebaños en la caatinga, con resultados similares entre los tres. Las cordeiros muestran más adiposidad de carne que las cabritos, en contraste, las cabritos tienen mayor musculatura que las cordeiros cuando se alimentan con bloques de alimentación

LPS Induces mTORC1 and mTORC2 Activation During Monocyte Adhesion

Monocyte adhesion is a crucial step in transmigration and can be induced by lipopolysaccharide (LPS). Here, we studied the role of mammalian target of rapamycin (mTOR) complexes, mTORC1 and mTORC2, and PKC in this process. We used THP-1 cells, a human monocytic cell line, to investigate monocyte adhesion under static and flow conditions. We observed that 1.0 μg/mL LPS increased PI3K/mTORC2 pathway and PKC activity after 1 h of incubation. WYE-354 10−6 M (mTORC2/mTORC1 inhibitor) and 10−6 M wortmannin avoided monocyte adhesion in culture plates. In addition, WYE also blocked LPS-induced CD11a expression. Interestingly, rapamycin and WYE-354 blocked both LPS-induced monocyte adhesion in a cell monolayer and actin cytoskeleton rearrangement, confirming mTORC1 involvement in this process. Once activated, PKC activates mTORC1/S6K pathway in a similar effect observed to LPS. Activation of the mTORC1/S6K pathway was attenuated by 10−6 M U0126, an MEK/ERK inhibitor, and 10−6 M calphostin C, a PKC inhibitor, indicating that the MEK/ERK/TSC2 axis acts as a mediator. In agreement, 80 nM PMA (a PKC activator) mimicked the effect of LPS on the activation of the MEK/ERK/TSC2/mTORC1/S6K pathway, monocyte adhesion to ECV cells and actin cytoskeleton rearrangement. Our findings show that LPS induces activation of mTOR complexes. This signaling pathway led to integrin expression and cytoskeleton rearrangement resulting in monocyte adhesion. These results describe a new molecular mechanism involved in monocyte adhesion in immune-based diseases