Diffusivity of drug actives in transdermal drug delivery (TDD)

Transdermal Drug Delivery (TDD) through skin patches has many advantages including the following: slow and continuous administration of the therapeutic over long periods of time, timely dosage, accessibility, kinetic maneuverability, elimination of the “First Pass Effect” and negative side effects on the digestive tract. All of the above justify investment into further development of TDD therapies, despite the skin permeability restrictions posed on size and charge by the skin. As skin permeability varies between all individuals based on age, ethnicity and lifestyle, the determination of the proper drug dosages to be contained in the skin patch is highly reliant on clinical trials. The objective of this research is to further investigate the application of components of a modified Duda-Zalinsky Equation (DZE) for drug diffusivity through a polymer matrix, to account for physical enhancers added to the Heated Lidocaine-Tetracaine Patch based on diffusivity results obtained from tests run in a Franz Cell apparatus. Pre-clinical trials computational estimation of the drug’s diffusion properties with respect to the polymer matrix and skin will provide for safer clinical trials, with testing dosages that are closer to the therapeutic drug concentration in the blood

Sensitivity-bandwidth limit in a multi-mode opto-electro-mechanical transducer

An opto--electro--mechanical system formed by a nanomembrane capacitively coupled to an LC resonator and to an optical interferometer has been recently employed for the high--sensitive optical readout of radio frequency (RF) signals [T. Bagci, \emph{et~al.}, Nature {\bf 507}, 81 (2013)]. Here we propose and experimentally demonstrate how the bandwidth of such kind of transducer can be increased by controlling the interference between two--electromechanical interaction pathways of a two--mode mechanical system. With a proof--of--principle device \new{operating at room temperature, we achieve a sensitivity of 300 nV/Hz^(1/2) over a bandwidth of 15 kHz in the presence of radiofrequency noise, and an optimal shot-noise limited sensitivity of 10 nV/Hz^(1/2) over a bandwidth of 5 kHz. We discuss strategies for improving the performance of the device, showing that, for the same given sensitivity, a mechanical multi--mode transducer can achieve a bandwidth} significantly larger than that of a single-mode one

Quantum dynamics of a vibrational mode of a membrane within an optical cavity

Optomechanical systems are a promising candidate for the implementation of quantum interfaces for storing and redistributing quantum information. Here we focus on the case of a high-finesse optical cavity with a thin vibrating semitransparent membrane in the middle. We show that robust and stationary optomechanical entanglement could be achieved in the system, even in the presence of nonnegligible optical absorption in the membrane. We also present some preliminary experimental data showing radiation-pressure induced optical bistability.Comment: 6 pages, 2 figures. Work presented at the conference QCMC 2010 held on 19-23 July 2010 at the University of Queensland, Brisbane, Australi

Type 2 diabetes and reduced exercise tolerance: A review of the literature through an integrated physiology approach

The association between type 2 diabetes mellitus (T2DM) and heart failure (HF) is well established. Early in the course of the diabetic disease, some degree of impaired exercise capacity (a powerful marker of health status with prognostic value) can be frequently highlighted in otherwise asymptomatic T2DM subjects. However, the literature is quite heterogeneous, and the underlying pathophysiologic mechanisms are far from clear. Imaging-cardiopulmonary exercise testing (CPET) is a non-invasive, provocative test providing a multi-variable assessment of pulmonary, cardiovascular, muscular, and cellular oxidative systems during exercise, capable of offering unique integrated pathophysiological information. With this review we aimed at defying the cardiorespiratory alterations revealed through imaging-CPET that appear specific of T2DM subjects without overt cardiovascular or pulmonary disease. In synthesis, there is compelling evidence indicating a reduction of peak workload, peak oxygen assumption, oxygen pulse, as well as ventilatory efficiency. On the contrary, evidence remains inconclusive about reduced peripheral oxygen extraction, impaired heart rate adjustment, and lower anaerobic threshold, compared to non-diabetic subjects. Based on the multiparametric evaluation provided by imaging-CPET, a dissection and a hierarchy of the underlying mechanisms can be obtained. Here we propose four possible integrated pathophysiological mechanisms, namely myocardiogenic, myogenic, vasculogenic and neurogenic. While each hypothesis alone can potentially explain the majority of the CPET alterations observed, seemingly different combinations exist in any given subject. Finally, a discussion on the effects -and on the physiological mechanisms-of physical activity and exercise training on oxygen uptake in T2DM subjects is also offered. The understanding of the early alterations in the cardiopulmonary response that are specific of T2DM would allow the early identification of those at a higher risk of developing HF and possibly help to understand the pathophysiological link between T2DM and HF

Computation of Electrostatic Field near Three-Dimensional Corners and Edges

Theoretically, the electric field becomes infinite at corners of two and three dimensions and edges of three dimensions. Conventional finite-element and boundary element methods do not yield satisfactory results at close proximity to these singular locations. In this paper, we describe the application of a fast and accurate BEM solver (which usesexact analytic expressions to compute the effect of source distributions on flatsurfaces) to compute the electric field near three-dimensional corners and edges. Results have been obtained for distances as close as 1$\mu m$ near the corner/edge and good agreement has been observed between the present results and existing analytical solutions.Comment: Presented in International Conference on Computational and Experimental Engineering and Sciences held at IIT Madras, Chennai, India, during 1-6 December, 200

Heavy oxygen recycled into the lithospheric mantle

Magmas in volcanic arcs have geochemical and isotopic signatures that can be related to mantle metasomatism due to fluids and melts released by the down-going oceanic crust and overlying sediments, which modify the chemistry and mineralogy of the mantle wedge. However, the effectiveness of subduction-related metasomatic processes is difficult to evaluate because the composition of arc magmas is often overprinted by interactions with crustal lithologies occurring during magma ascent and emplacement. Here, we show unequivocal evidence for recycling of continental crust components into the mantle. Veined peridotite xenoliths sampled from Tallante monogenetic volcanoes in the Betic Cordillera (southern Spain) provide insights for mantle domains that reacted with Si-rich melts derived by partial melting of subducted crustal material. Felsic veins crosscutting peridotite and the surrounding orthopyroxene-rich metasomatic aureoles show the highest 18O/16O ratios measured to date in upper mantle assemblages worldwide. The anomalously high oxygen isotope compositions, coupled with very high 87Sr/86Sr values, imply the continental crust origin of the injected melts. Isotopic anomalies are progressively attenuated in peridotite away from the veins, showing 18O isotope variations well correlated with the amount of newly formed orthopyroxene. Diffusion may also affect the isotope ratios of mantle rocks undergoing crustal metasomatism due to the relaxation of 18O isotope anomalies to normal mantle values through time. Overall, the data define an O isotope “benchmark” allowing discrimination between mantle sources that attained re-equilibration after metasomatism ( requiring at least 5 Myr) and those affected by more recent subduction-derived enrichment processes