Alpha-lipoic acid (ALA) has been used as a dietary supplement at different doses in patients with diabetes mellitus type 2 (T2DM) due to its antioxidant, anti-inflammatory, and hypoglycemic effects. However, the reports on the effects of ALA are controversial. For this reason, the purpose of the present study was to determine the effect of 600 mg/day of ALA on the markers of oxidative stress (OxS) and inflammation and RAGE in older adults with T2DM. A quasiexperimental study was carried out with a sample of 135 sedentary subjects (98 women and 37 men) with a mean age of64±1years, who all had T2DM. The sample was divided into three groups: (i) experimental group (EG) with 50 subjects, (ii) placebo group (PG) with 50 subjects, and control group (CG) with 35 subjects. We obtained the following measurements in all subjects (pre- and posttreatment): glycosylated hemoglobin (HbA1c), receptor for advanced glycation end products (RAGE), 8-isoprostane, superoxide dismutase (SOD), glutathione peroxidase (GPx), total antioxidant status (TAS), and inflammatory (CRP, TNF-α, IL-6, IL-8, and IL-10) markers. Regarding the effect of ALA on HbA1c, a decrease was observed in the EG (baseline8.9±0.2vs. posttreatment8.6±0.3) and the PG (baseline8.8±0.2vs. posttreatment8.4±0.3) compared to the CG (baseline8.8±0.3vs. six months9.1±0.3) although the difference was not statistically significant (p<0.05). There was a statistically significant decrease (p<0.05) in the blood concentration of 8-isoprostane in the EG and PG with respect to the CG (EG: baseline100±3vs. posttreatment57±3, PG: baseline106±7vs. posttreatment77±5, and CG: baseline94±10vs. six months107±11pg/mL). Likewise, a statistically significant decrease (p<0.05) in the concentration of the RAGE was found in the EG (baseline1636±88vs. posttreatment1144±68) and the PG (baseline1506±97vs. posttreatment1016±82) compared to CG (baseline1407±112vs. six months1506±128). A statistically significant decrease was also observed in all markers of inflammation and in the activity of SOD and GPx in the CG with respect to the EG and PG. Our findings suggest that the administration of ALA at a dose of 600 mg/day for six months has a similar effect to that of placebo on oxidative stress, inflammation, and RAGE in older adults with T2DM. Therefore, higher doses of ALA should be tried to have this effect. This trial is registered with trial registration numberISRCTN13159380.

In this work, a new simplified method to find the fluidity enhancement of a non-Newtonian liquid under a pulsating (time-dependent) pressure gradient is analyzed. The fluidity enhancement is predicted by means of a Taylor series expansion of the flow rate in the vicinity of the applied wall stress. This expansion is shown to render the same results as several perturbation techniques used at length in the literature. Both new and the conventional perturbation methods are equivalent in their predictions of the fluidity enhancement. Even though the flow and rheology behavior are modeled using the Bautista-Manero-Puig constitutive equation, it is shown that the prediction of the fluidity enhancement does not depend on the constitutive model employed, but a condition of shear thinning behavior of the fluid is necessary for it. Flow enhancement is predicted using rheological data for blood since this fluid naturally flows under a pulsatile pressure gradient. The flow enhancement equation is found to have a similar form as the equation of the Rabinowitsch formalism in fully developed Poiseuille flow. This simplified technique will help in saving machine time for numerical predictions in computational blood flow simulations.

Context: Drug polymorphism could affect drug product dissolution, manufacturability, stability and bioavailability/bioequivalence. The impact of polymorphism on the manufacturability and in vitro dissolution profiles of sulindac capsules has not been studied yet. Objective: To evaluate the impact of polymorphism on the manufacturability and in vitro dissolution of sulindac hard gelatin capsules. Materials and methods: Sulindac crystal forms I and II (SLDI and SLDII, respectively) were prepared and characterized. Powder formulations containing one of the polymorphs, lactose and magnesium stearate (at three different levels) were prepared and their flow properties determined. Hard gelatin capsules were filled with the formulations and tested for fill-weight variations. Drug dissolution for SLDI- and SLDII-containing hard gelatin capsules was determined. Results: Differences in flow properties for each polymorph were observed, as well as for their formulations, which in turn affected capsule weight homogeneity. Statistically significant differences in the rate and extent of drug release were observed between SLDI- and SLDII-containing capsules. Discussion: Formulations containing SLDI showed a better manufacturability and a better dissolution profile than those with SLDII. Conclusion: Sulindac crystalline form I was the best candidate for hard gelatin capsule formulation because of its technological and in vitro dissolution properties.

Flexoelectric actuation employs an applied electric field to induce membrane curvature, which is the mechanism utilized by the outer hair cells (OHC) present in the inner ear. The model developed for this study, representing the OHC, integrates two key components: (i) an approximation of the flexoelectric membrane shape equation for circular membranes attached to the inner surface of a circular capillary, and (ii) the coupled capillary flow of contacting liquid viscoelastic phases characterized by the Tanner-Power law rheological equation of state. A second-order non-linear differential equation for average curvature has been derived, and a robust numerical method has been programmed. This model simplifies to a linear model used previously. The main challenge involves identifying and describing the enhancement in curvature change rate. It was observed that low symmetry, low viscosity, and soft membrane and shear-thickening behavior of the phases enhance the curvature change rate. Additionally, there exists a critical electric field frequency value that maximizes the curvature change rate (resonance effect). The current theory, model, and computational simulations add to the ongoing development comprehension of how biological membrane shape actuation through electromechanical couplings.