TNF-α Affects Signature Cytokines of Th1 and Th17 T Cell Subsets through Differential Actions on TNFR1 and TNFR2

Tumor necrosis factor (TNF)-α is a pleiotropic cytokine implicated in the etiology of several autoimmune diseases, including rheumatoid arthritis (RA). TNF-α regulates diverse effector functions through the activation of TNF-α receptor (TNFR)1 and TNFR2. Although the detrimental role of this cytokine has been addressed in distinct disease settings, the effects of TNF-α on cytokine production by isolated CD4⁺ T helper type 1 (Th1) and Th17 cells, two T cell subpopulations that contribute to the pathogenesis of RA, have not been completely elucidated. Here, we show that TNF-α promotes a reduction and expansion in the frequency of both T cell subsets producing IFN-γ and IL-17, respectively. Selective blockade of TNFR1 or TNFR2 on Th1 and Th17 cells revealed that TNFR2 mediates the decrease in IFN-γ production, while signaling through both receptors augments IL-17 production. We also demonstrate that Th1, but not Th17 cells from RA patients present lower levels of TNFR1 compared to healthy controls, whereas TNFR2 expression on both T cell types is similar between patients and controls. Since TNF-α receptors levels in RA patients are not significantly changed by the therapeutic blockade of TNF-α, we propose that targeting TNFR2 may represent an alternative strategy to normalize the levels of key cytokines that contribute to RA pathogenesis.     

Swarm intelligence for traffic light scheduling: Application to real urban areas

Congestion, pollution, security, parking, noise, and many other problems derived from vehicular traffic are present every day in most cities around the world. The growing number of traffic lights that control the vehicular flow requires a complex scheduling, and hence, automatic systems are indispensable nowadays for optimally tackling this task. In this work, we propose a Swarm Intelligence approach to find successful cycle programs of traffic lights. Using a microscopic traffic simulator, the solutions obtained by our algorithm are evaluated in the context of two large and heterogeneous metropolitan areas located in the cities of Málaga and Sevilla (in Spain). In comparison with cycle programs predefined by experts (close to real ones), our proposal obtains significant profits in terms of two main indicators: the number of vehicles that reach their destinations on time and the global trip time.     

Intraindividual variability in infant behavior.

Longitudinal observational data of infant crying, fretting/fussing, and smiling and the time spent in physical contact with the mother were used in a study on behavioral variability. The infants were followed weekly for a 15-month period. Evidence was found of an important intraindividual variability in the studied behaviors, specifically between the ages of 0 and 5 months, 5 and 10 months, but not between 10 and 15 months. Results are discussed and analyzed in the light of earlier literature. The possible functions and the factors underlying variability in development as well as its methodological implications are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The Influence of Oxygen Volumetric Mass Transfer Rates on Cyclodextrin Glycosyltransferase Production by Alkaliphilic Bacillus circulans in Batch and Fed-Batch Cultivations

In this work, the influence of oxygen mass transfer rates on the production of cyclodextrin glycosyltransferase (CGTase) by the alkaliphilic bacterium Bacillus circulans ATCC 21783 was investigated. Experimental design and response surface methodology were applied to optimize agitation speed and air flow rate in batch cultivations, in order to identify their significant effects and interactions with the synthesis of CGTase. Results were expressed as the volumetric mass transfer rates of oxygen (k_la, [per hour]). The maximal CGTase productivity of 155 U mL⁻¹ h⁻¹ was achieved with k_la of 48 h⁻¹. CGTase production was also studied in fed-batch cultures using the optimized parameters obtained in the batch experiments. The maximal CGTase productivity on fed-batch cultivations was 137 U mL⁻¹ h⁻¹ with feeding rates of starch at 0.17 g L⁻¹ h⁻¹.     

Guest Editorial

Multimedia Tools and Applications -     

Development and validation of a dissolution test for lodenafil carbonate based on in vivo data

Introduction: Lodenafil carbonate is a phosphodiesterase type 5 inhibitor used for the treatment of erectile dysfunction. Currently, there is no dissolution test reported for lodenafil carbonate and this drug is not listed in any pharmacopoeia.

Objective: The present study focused on the development and validation of a dissolution test for lodenafil carbonate tablets, using a simulated absorption profile based on in vivo data.

Methods: The appropriate conditions were determined after testing sink conditions. Different conditions as medium, surfactant concentration and rotation speed were evaluated. The percentage of dose absorbed was calculated by deconvolution, using the Wagner–Nelson method.

Results: According to the obtained results, the use of 0.1?M HCl?+?1.5% SLS (900?mL, at 37?+?0.5?°C) as the dissolution medium, paddles at 25?rpm were considered adequate. The samples were quantified by UV spectroscopy at 295?nm and the validation was performed according to international guidelines. The method showed specificity, linearity, accuracy and precision, within the acceptable range. Kinetics of drug release was better described by the first-order model.

Conclusion: The proposed dissolution test can be used for the routine quality control of lodenafil carbonate in tablets.     

Nano and micro architectures for self-propelled motors

Self-propelled micromotors are emerging as important tools that help us understand the fundamentals of motion at the microscale and the nanoscale. Development of the motors for various biomedical and environmental applications is being pursued. Multiple fabrication methods can be used to construct the geometries of different sizes of motors. Here, we present an overview of appropriate methods of fabrication according to both size and shape requirements and the concept of guiding the catalytic motors within the confines of wall. Micromotors have also been incorporated with biological systems for a new type of fabrication method for bioinspired hybrid motors using three-dimensional (3D) printing technology. The 3D printed hybrid and bioinspired motors can be propelled by using ultrasound or live cells, offering a more biocompatible approach when compared to traditional catalytic motors.     

The Generation of Nitric Oxide from Aldehyde Dehydrogenase-2: The Role of Dietary Nitrates and Their Implication in Cardiovascular Disease Management

Reduced bioavailability of the nitric oxide (NO) signaling molecule has been associated with the onset of cardiovascular disease. One of the better-known and effective therapies for cardiovascular disorders is the use of organic nitrates, such as glyceryl trinitrate (GTN), which increases the concentration of NO. Unfortunately, chronic use of this therapy can induce a phenomenon known as “nitrate tolerance”, which is defined as the loss of hemodynamic effects and a reduction in therapeutic effects. As such, a higher dosage of GTN is required in order to achieve the same vasodilatory and antiplatelet effects. Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is a cardioprotective enzyme that catalyzes the bio-activation of GTN to NO. Nitrate tolerance is accompanied by an increase in oxidative stress, endothelial dysfunction, and sympathetic activation, as well as a loss of the catalytic activity of ALDH2 itself. On the basis of current knowledge, nitrate intake in the diet would guarantee a concentration of NO such as to avoid (or at least reduce) treatment with GTN and the consequent onset of nitrate tolerance in the course of cardiovascular diseases, so as not to make necessary the increase in GTN concentrations and the possible inhibition/alteration of ALDH2, which aggravates the problem of a positive feedback mechanism. Therefore, the purpose of this review is to summarize data relating to the introduction into the diet of some natural products that could assist pharmacological therapy in order to provide the NO necessary to reduce the intake of GTN and the phenomenon of nitrate tolerance and to ensure the correct catalytic activity of ALDH2.