The Immunoregulatory Actions of DHEA in Tuberculosis, A Tool for Therapeutic Intervention?

Dehydroepiandrosterone (DHEA) is an androgen synthesized by the adrenal cortex, which is an intermediary in the biosynthesis of sex hormones, such as testosterone and estradiol. DHEA mostly circulates as a conjugated ester, in the form of sulfate (DHEA-S). There exist several endogenous factors able to influence its synthesis, the most common ones being the corticotrophin-releasing hormone (CRH), adrenocorticotrophin (ACTH), growth factors, and proinflammatory cytokines, among others. Like other steroid hormones, DHEA, can alter the functioning of immune cells and therefore the course of diseases exhibiting an immune-inflammatory component, mostly from autoimmune or infectious nature. We herein review the role played by DHEA during a major infectious disease like tuberculosis (TB). Data recorded from TB patients, mouse models, or in vitro studies show that DHEA is likely to be implied in better disease control. This provides a stimulating background for carrying out clinical studies aimed at assessing the usefulness of DHEA as an adjuvant in TB patients.

Controlled degradability of PCL-ZnO nanofibrous scaffolds for bone tissue engineering and their antibacterial activity.

Up to date, tissue regeneration of large bone defects is a clinical challenge under exhaustive study. Nowadays, the most common clinical solutions concerning bone regeneration involve systems based on human or bovine tissues, which suffer from drawbacks like antigenicity, complex processing, low osteoinductivity, rapid resorption and minimal acceleration of tissue regeneration. This work thus addresses the development of nanofibrous synthetic scaffolds of polycaprolactone (PCL) - a long-term degradation polyester - compounded with hydroxyapatite (HA) and variable concentrations of ZnO as alternative solutions for accelerated bone tissue regeneration in applications requiring mid- and long-term resorption. In vitro cell response of human fetal osteoblasts as well as antibacterial activity against Staphylococcus aureus of PCL:HA:ZnO and PCL:ZnO scaffolds were here evaluated. Furthermore, the effect of ZnO nanostructures at different concentrations on in vitro degradation of PCL electrospun scaffolds was analyzed. The results proved that higher concentrations ZnO may induce early mineralization, as indicated by high alkaline phosphatase activity levels, cell proliferation assays and positive Alizarin-Red-S-stained calcium deposits. Moreover, all PCL:ZnO scaffolds particularly showed antibacterial activity against S. aureus which may be attributed to release of Zn2+ ions. Additionally, results here obtained showed a variable PCL degradation rate as a function of ZnO concentration. Therefore, this work suggests that our PCL:ZnO scaffolds may be promising and competitive short-, mid- and long-term resorption systems against current clinical solutions for bone tissue regeneration.

Rapid Reconstitution Packages (RRPs) implemented by integration of computational fluid dynamics (CFD) and 3D printed microfluidics.

Rapid Reconstitution Packages (RRPs) are portable platforms that integrate microfluidics for rapid reconstitution of lyophilized drugs. Rapid reconstitution of lyophilized drugs using standard vials and syringes is an error-prone process. RRPs were designed using computational fluid dynamics (CFD) techniques to optimize fluidic structures for rapid mixing and integrating physical properties of targeted drugs and diluents. Devices were manufactured using stereo lithography 3D printing for micrometer structural precision and rapid prototyping. Tissue plasminogen activator (tPA) was selected as the initial model drug to test the RRPs as it is unstable in solution. tPA is a thrombolytic drug, stored in lyophilized form, required in emergency settings for which rapid reconstitution is of critical importance. RRP performance and drug stability were evaluated by high-performance liquid chromatography (HPLC) to characterize release kinetics. In addition, enzyme-linked immunosorbent assays (ELISAs) were performed to test for drug activity after the RRPs were exposed to various controlled temperature conditions. Experimental results showed that RRPs provided effective reconstitution of tPA that strongly correlated with CFD results. Simulation and experimental results show that release kinetics can be adjusted by tuning the device structural dimensions and diluent drug physical parameters. The design of RRPs can be tailored for a number of applications by taking into account physical parameters of the active pharmaceutical ingredients (APIs), excipients, and diluents. RRPs are portable platforms that can be utilized for reconstitution of emergency drugs in time-critical therapies.