Nitric oxide modulates interleukin-2-induced proliferation in CTLL-2 cells

The role of the L-arginine–nitric oxide metabolic pathway was explored for interleukin-2-induced proliferation in the cytotoxic T lymphocyte clone CTLL-2. Specific inhibition of nitric oxide synthase significantly diminished, in a concentration-dependent manner, 3H-thymidine uptake of CTLL-2 cells in response to different concentrations of interleukin 2. Withdrawal of L-arginine from culture medium resulted as potent as the higher inhibition obtained when blocking nitric oxide synthase with L-arginine analogues. Furthermore, intermedial concentrations of Larginine and exogenous nitric oxide donors were found for achieving optimal IL2-induced proliferation of CTLL-2. These findings prompted us to suggest that intra- and/or inter-cellular nitric oxide signalling may contribute to the modulation of the IL2 mitogenic effect upon cytotoxic T lymphocytes

CATENIN-DEPENDENT AND -INDEPENDENT FUNCTIONS OF VASCULAR ENDOTHELIAL CADHERIN

Vascular endothelial cadherin (VE-cadherin, cadherin-5, or 7B4) is an endothelial specific cadherin that regulates cell to cell junction organization in this cell type. Cadherin linkage to intracellular catenins was found to be required for their adhesive properties and for localization at cell to cell junctions. We constructed a mutant form of VE-cadherin lacking the last 82 amino acids of the cytoplasmic domain. Surprisingly, despite any detectable association of this truncated VE-cadherin to catenin-cytoskeletal complex, the molecule was able to cluster at cell-cell contacts in a manner similar to wild type VE-cadherin. Truncated VE-cadherin was also able to promote calcium-dependent cell to cell aggregation and to partially inhibit cell detachment and migration from a confluent monolayer. In contrast, intercellular junction permeability to high molecular weight molecules was severely impaired by truncation of VE-cadherin cytoplasmic domain. These results suggest that the VE-cadherin extracellular domain is enough for early steps of cell adhesion and recognition. However, interaction of VE-cadherin with the cytoskeleton is necessary to provide strength and cohesion to the junction. The data also suggest that cadherin functional regulation might not be identical among the members of the family

INFLUENCIA DEL pH EN LAS RELACIONES MICROBIANAS DE LA CAVIDAD BUCAL. REVISIÓN BIBLIOGRÁFICA

El pH es el grado de acidez de una solución. En cavidad bucal, el pH define diferentes sucesos tanto bioquímicos como microbiológicos, entre los factores que ejercen influencia en todos estos eventos intrabucales encontramos: 1) capacidad buffer salival, la saliva no estimulada es de pH ligeramente ácido, la saliva estimulada posee pH básico. 2) carbohidratos exógenos. 3) bacterias acidógenas de la biopelícula dental, las cuales coexisten en microambientes altamente organizados, pudiendo metabolizar rápidamente ciertos azúcares a glucanos y productos finales ácidos. 4) agentes químicos, tales como hidróxido de calcio, el cual libera iones hidroxilos al medio, alcalinizándolo y haciéndolo no viable para el metabolismo bacteriano; clorhexidina, antiséptico de gran sustantividad, activo en bacterias Gram positivas y Gram negativas; fluoruros, que exhiben capacidad de inhibición metabólica, mecanismo antiadherente, producción de cambios en la carga superficial del diente. 5) azúcares alcoholes edulcorantes (xilitol), presenta la propiedad de retardar el flujo metabólico de ciertas bacterias cariogénicas

Lobenzarit disodium inhibits the constitutive NO–cGMP metabolic pathways. Possible involvement as an immunomodulatory drug

Lobenzarit disodtulIl (CCA) is a novel immunomodulatory drug useful in the treatment of chronic inflammations. Its principal mechanism of action seems to be through enhancing the T suppressor/T helper lymphocyte ratio. However, the molecular basis for these actions remains unclear. In this study it was found that CCA inhibits the production of guanosine 3',5'-cyclic monophosphate almost completely when present in concentrations of 1 mM. Further results demonstrated that such inhibition could also be explained by interference in constitutive nitric oxide generation. In addition to previous findings, more insight into the molecular mechanism of action of CCA is provided

El receptor 2 de VEGF (VEGFR2) y el receptor 1 de la PTH (PTH1R) actúan como mediadores de la respuesta antiapoptótica al estímulo mecánico en las células osteocíticas MLO-Y4

Mechanical stimulation plays a crucial role in bone mineral maintenance. This stimulation prevents osteocyte apoptosis by a mechanism that involves β-catenin accumulation and nuclear translocation of extracellular-signal-regulated kinases (ERKs). The vascular endothelial growth factor (VEGF) and parathyroid hormone-related protein (PTHrP) modulate bone formation, although their interaction with osteocytes is unknown. In this paper we have considered the possible role of VEGF (VEGFR2) 2 receptor and PTH (PTH1R) type 1 receptor in the anti-apoptotic response to mechanical stimulation of MLO-Y4 osteocyte-like cells. The cells were subjected to mechanical stress by laminar fluid flow (10 min, 10 dinas/cm ) or hypotonic shock (240 mOsm, 1h), or stimulated with VEGF 165 2 or PTHrP (1-36). We also compared the effects of overexpressed VEGFR2 and mechanical stimulation of these cells. Mechanical stimulation, VEGF or PTHrP (1-36) stimulated cellular viability and β-catenin stabilization in a similar manner, associated with its localization in the membrane. Mechanical stimulation increased PTH1R presence in the membrane. VEGFR2 inhibition as well as the PTHrP (7-34) antagonist reduced these effects. On the other hand, VEGFR2 overexpression in MLO-Y4 cells mimicked the mechanical stimulation effect on β-catenin and cellular viability. Our findings support a functional role for both systems, VEGF/VEGFR2 and PTHrP/PTH1R, in the early response to mechanical stimulation in promoting osteocyte-like viability.La estimulación mecánica juega un papel fundamental en el mantenimiento de la masa ósea. Dicha estimulación previene la apoptosis de los osteocitos por un mecanismo que implica la acumulación de β-catenina y la translocación nuclear de quinasas reguladas por señales extracelulares (ERK). El factor de crecimiento del endotelio vascular (VEGF) y la proteína relacionada con la parathormona (PTHrP) modulan la formación ósea, aunque su interacción con los osteocitos es desconocida. En el presente estudio hemos evaluado el posible papel del receptor 2 del VEGF (VEGFR2) y del receptor tipo 1 de PTH (PTH1R) en la respuesta antiapoptótica a la estimulación mecánica en células osteocíticas MLO-Y4. Las células se sometieron a estrés mecánico por flujo laminar de fluido (10 min, 10 dinas/cm ) o choque hipotónico (240 mOsm, 1h), o estimuladas con VEGF 165 2 o PTHrP (1-36). Además, comparamos los efectos de sobre-expresar VEGFR2 y el estímulo mecánico en estas células. La estimulación mecánica, el VEGF o la PTHrP (1-36), de manera similar, estimularon la viabilidad celular y la estabilización de β-catenina, relacionada con su localización en la membrana. Además, la estimulación mecánica aumentó la presencia del PTH1R en la membrana. La inhibición del VEGFR2 así como el antagonista PTHrP (7-34) disminuyeron estos efectos. Por otro lado, la sobre-expresión del VEGFR2 en las células MLO-Y4 mimetizó el efecto del estímulo mecánico sobre la β-catenina y la viabilidad celular. Estos hallazgos apoyan un papel funcional de ambos sistemas, VEGF/VEGFR2 y PTHrP/PTH1R, en la respuesta temprana a la estimulación mecánica para promover la viabilidad osteocítica

Independent and combined influence of neonatal and current body composition on academic performance in youth: The UP & DOWN Study

Backgrounds: Unhealthy body composition is a cause for concern across the lifespan. Objective: The objective of this study was to examine the independent and combined associations between neonatal and current body composition with academic performance among youth. Methods: This cross-sectional study was conducted with a total of 1557 youth (745 girls) aged 10.4 ± 3.4 years. Birth weight and length at birth were self-reported. Current body composition was assessed by body mass index (BMI), waist circumference (WC) and percentage of body fat (BF%). Academic performance was assessed through schools records. Results: Birth weight was related to all academic variables in boys, independent of potential confounders, including BMI; whereas WC, BMI and BF% were related to all academic performance indicators in both boys and girls, independent of potential confounders, including birth weight (all P  <  0.05). In addition, the combined adverse effects of low birth weight and current overweight on academic performance were observed in both boys and girls for grade point average (GPA) indicator. Boys in the group with none adverse effect had significantly higher scores in GPA (score +0.535; 95% confidence interval, 0.082–0.989) than boys in the group of both adverse effects (P  <  0.007); among girls, GPA score was higher in the group with none adverse effect than in the groups with one or two adverse effects (P for trend = 0.029). Conclusions: Neonatal and current body composition, both independently and combined, may influence academic performance in youth