PRELIMINARY STUDIES ON BRAIN TARGETING OF INTRANASAL ATOMOXETINE LIPOSOMES

Objective: The objective of the present study was to evaluate the enhancement in brain uptake of liposomes containing atomoxetine (ATX-Lipo) for intranasal delivery in the management of Attention Deficit Hyperactivity Disorder (ADHD).Methods: ATX-Lipo and ATX mucoadhesive liposomes (ATX-Muco Lipo) with and without a vasoconstrictor phenylephrine (PHE) were prepared by lipid film hydration method and characterized for physicochemical parameters. Biodistribution and pharmacokinetic evaluation of ATX-Lipo in the brain and blood of Sprague Dawley rats following intranasal (i. n.) and intravenous (i. v.) administrations were examined using optimized technetium-labeled ([99]m Tc-labeled) atomoxetine formulations. Gamma scintigraphy imaging was performed in Sprague Dawley rats.Results: ATX-Lipo and ATX-Muco Lipo were found to be stable with average particle size of 404.35±1.86 nm and 510.50±1.22 nm respectively.[99]mTc tagged ATX-Lipo, ATX-Muco Lipo, ATX+PHE-Muco Lipo and ATX solution were found to be stable and suitable for in vivo studies. On comparing ATX concentrations after i. n. administrations of ATX-Lipo, ATX-Muco Lipo and ATX+PHE-Muco Lipo and i. v. administration of ATX-Lipo, brain/blood uptake ratios (BBR) at 30 min were found to be 0.161, 1.255, 0.331, and 0.003 respectively. These results revealed effective brain targeting following i. n. administration of mucoadhesive ATX liposomes. Higher drug targeting efficiency (% DTE) and direct transport percentage (%DTP) for mucoadhesive liposomes indicated considerable brain targeting from ATX-Muco liposomes. Gamma scintigraphy imaging of the rat brain conclusively demonstrated the greater extent of transport of atomoxetine by ATX+PHE-Muco Lipo (i. n.), when compared with ATX solution (i. n.) into the rat brain.Conclusion: This preliminary investigation demonstrates a considerable extent of transport of ATX into the brain through i. n. ATX+PHE-Muco Lipo, which may prove to be a new platform for better management of ADHD.Keywords: Intranasal delivery, Brain targeting, Mucoadhesive liposomes, Vasoconstrictor, Radiolabeling, Drug targeting efficiency, Direct transport percentage, Gamma scintigraphy

Abstract sentence representations in 3-year-olds: Evidence from language production and comprehension

We use syntactic priming to test the abstractness of the sentence representations of young 3-year-olds (35-42 months). In describing pictures with inanimate participants, 18 children primed with passives produced more passives (11 with a strict scoring scheme, 16 with lax scoring) than did 18 children primed with actives (2 on either scheme) or 12 children who received no priming (0). Priming was comparable to that reported for older children and adults. Comprehension of reversible passives with animate participants before and after priming was above chance but did not improve as a result of priming. Young 3-year-olds represent sentences abstractly, have syntactic representations for noun, verb, "surface subject", and "surface object", have semantic representations for "agent" and "patient", and flexibly map the relation between syntax and semantics. Taken together with research on syntactic categories in 2-year-olds, our results provide empirical support for continuity in language acquisition

Do two and three year old children use an incremental first-NP-as-agent bias to process active transitive and passive sentences? : A permutation analysis

We used eye-tracking to investigate if and when children show an incremental bias to assume that the first noun phrase in a sentence is the agent (first-NP-as-agent bias) while processing the meaning of English active and passive transitive sentences. We also investi-gated whether children can override this bias to successfully distinguish active from passive sentences, after processing the remainder of the sentence frame. For this second question we used eye-tracking (Study 1) and forced-choice pointing (Study 2). For both studies, we used a paradigm in which participants simultaneously saw two novel actions with reversed agent-patient relations while listening to active and passive sentences. We compared English-speaking 25-month-olds and 41-month-olds in between-subjects sentence struc-ture conditions (Active Transitive Condition vs. Passive Condition). A permutation analysis found that both age groups showed a bias to incrementally map the first noun in a sentence onto an agent role. Regarding the second question, 25-month-olds showed some evidence of distinguishing the two structures in the eye-tracking study. However, the 25-month-olds did not distinguish active from passive sentences in the forced choice pointing task. In contrast, the 41-month-old children did reanalyse their initial first-NP-as-agent bias to the extent that they clearly distinguished between active and passive sentences both in the eye-tracking data and in the pointing task. The results are discussed in relation to the development of syntactic (re)parsing

Kinetics of Discontinuous Precipitation and Dissolution in a Nickel 2.1 AT% Indium Alloy

The kinetics of discontinuous precipitation and discontinuous dissolution in a Ni - 2.1 at.% In alloy were investigated in the temperature range of 796 K to 998 K using light and electron microscopy. The velocities and interlamellar spacings were experimentally determined and analysed on the basis of several theories. Petermann and Hornbogen\u27s theory was found to be suitable for analysing the kinetics of both discontinuous precipitation and dissolution. Discontinuous precipitaton was also analysed using theories proposed by Turnbull, Aaronson and Liu, Calm, Shapiro and Kirkadly, Sundquist and Hillert. It was observed that the Dbh values for precipitation extrapolate well into those obtained for dissolution. The diffusivities obtained for discontinuous precipitation and dissolution are in good agreement with the diffusivities of indium in a stationary nickel grain boundary. This shows that both reactions are controlled by grain boundary diffusion and that the diffusivities are of the same order of magnitude in stationary and moving grain boundaries. Comparison of the data obtained with that of Abdou et. al in a Ni-2.0 at% alloy also shows good agreement

Vibrations of laminated beams

Governing equations in the form of simultaneous ordinary differential equations have been derived for natural vibration analysis of isotropic laminated beams. This formulation includes significant secondary effects such as transverse shear and rotatory inetia. Through a numerical example, the influence of these secondary effects has been studied