Relationships between the particle velocity and introduction of drug-loaded microparticles into the skin in a microparticulate bombardment system

Recently, it has been suggested that a microparticulate bombardment system would be a very useful tool for the delivery of a variety of powdered drugs as an alternative to parenteral injection via a needle. However the relationship between the particle dynamics and introduction into the skin has not been researched using this system. In the present study, we analyzed the velocity of microparticles bombarded by the Helios(TM) gun system under various conditions using particle image velocimetry (PIV). The particle kinetic energy, which depended on the particle velocity and particle mass, was increased with increasing helium pressure and particle size, decreasing bombardment dose, resulting in the increased percentage introduction and relative bioavailability (F(0-24 h)). The particle velocity had a greater influence than the particle mass. Therefore, in order to be the most effective system for introduction into the skin, it is necessary to use a high helium pressure and microparticles of high density. However, it is also necessary to consider the skin damage after bombardment.     

Quantitative assessment of regional systolic and diastolic functions and temporal heterogeneity of myocardial contraction in patients with myocardial infarction using cine magnetic resonance imaging and Fourier fitting

Purpose

The objective of this study is to determine regional left ventricle (LV) function and temporal heterogeneity of LV wall contraction by analyzing regional time–volume curve (TVC) after Fourier fitting and to assess altered systolic and diastolic functions and temporal indices of myocardial contraction in infarcted segments in comparison with noninfarcted myocardium in patients with myocardial infarction (MI).

Methods

Steady-state cine magnetic resonance (MR) and late gadolinium-enhanced (LGE) MR images were acquired using a 1.5-T MR system in 60 patients with MI. Regional LV function was determined by analyzing regional TVC in 16 segments. The fitted regional TVC was generated by Fourier curve fitting with five harmonics. Regional LV ejection fraction (EF), peak ejection rate (PER), peak filling rate (PFR), time to end-systole and time to peak filling (TPF) were determined from TVC and the first derivative curve.

Results

On LGE MR imaging (MRI), MI was observed in 307 of 960 segments (32.0%). Regional EF and PER averaged in LGE segments were 49.3±14.5% and 2.83±0.65 end-diastolic volume (EDV)/s, significantly lower than those in normal segments (66.7±11.9% and 3.63±0.60 EDV/s, P<.001 and P<.01, respectively). In addition, regional PFR, an index of diastolic function, was significantly reduced in LGE segments (1.94±0.54 vs. 2.86±0.68 EDV/s, P<.01). Time to end-systole and TPF were significantly greater in LGE segments (380.2±57.6 and 169.3±45.4 ms) than in normal segments (300.9±55.1 and 132.3±43.0 ms, P<.01 and P<.01, respectively).

Conclusions

Analysis of regional TVC on cine MRI after Fourier fitting allows quantitative assessment of regional systolic and diastolic LV functions and temporal heterogeneity of LV wall contraction in patients with MI.     

A stereoselective synthesis of dl-3-epiuleine

A stereoselective synthesis of an indole alkaloid, 3-epiuleine, in racemic form is described. The key step involved is the ethylation of readily accessible compound $\text{5}$ with Et₂CuLi.     

Distributed-feedback vertical cavity structures for optically pumped solid-state organic lasers

Theoretical analysis of threshold gain and absorption efficiency is presented for a vertical-cavity surface-emitting organic laser by using transfer matrix method. Pyrromethene 567 dye doped in a polymer film is examined for verification of the active material with an InGaN cyan LED as a pump source. By alternately stacking high- and low-refractive-index active polymer films, modeling results indicate that the threshold gain can be reduced and the absorption efficiency at the pump wavelength can be improved compared with those of a vertical cavity with a dielectric mirror stack. The absorption efficiency of the distributed-feedback resonator is not practically degraded even if the pump wavelength is located near the stopband.     

Total synthesis of (±)-cannabisativine

Total synthesis of the Cannabis alkaloid cannabisativine ($\text{1}$) was stereoselectively achieved for the first time in a racemic form starting from a dihydropyridine derivative ($\text{2}$) by way of $\text{3}$, $\text{4}$, and $\text{5}$.     

Identification of a Conformational Equilibrium That Determines the Efficacy and Functional Selectivity of the μ‐Opioid Receptor

G‐protein‐coupled receptor (GPCR) ligands impart differing degrees of signaling in the G‐protein and arrestin pathways, in phenomena called “biased signaling”. However, the mechanism underlying the biased signaling of GPCRs is still unclear, although crystal structures of GPCRs bound to the G protein or arrestin are available. In this study, we observed the NMR signals from methionine residues of the μ‐opioid receptor (μOR) in the balanced‐ and biased‐ligand‐bound states. We found that the intracellular cavity of μOR exists in an equilibrium between closed and multiple open conformations with coupled conformational changes on the transmembrane helices 3, 5, 6, and 7, and that the population of each open conformation determines the G‐protein‐ and arrestin‐mediated signaling levels in each ligand‐bound state. These findings provide insight into the biased signaling of GPCRs and will be helpful for development of analgesics that stimulate μOR with reduced tolerance and dependence.     

Bis(2,6-dimethoxyphenyl) sulfide, selenide and telluride, and their derivatives

2,6-Dimethoxyphenyl derivatives of sulfur, selenium, and tellurium, such as ΦEEΦ, Φ₂E, ΦSeH, [MeΦ₂E]X (X=MeSO₄, ClO₄), Φ₂EO · xH₂O, [Φ₂EOR]ClO₄, [Φ₂EOH]ClO₄ (R=Me, Et), Me₂SnCl₂ · 2Φ₂EO (E=S, Se) [Φ=2,6-(MeO)₂C₆H₃; E=S, Se, Te] have been prepared, and their properties compared with common phenyl derivatives. The reaction rates of Φ₂E with dimethyl sulfate and butyl bromide increased in the order E=S<Se<Te, which were compared with those of Ph₃M and Φ₃M, M=P>As>Sb. These reactivities are parallel with the electrochemical oxidation potentials reported for Ph₂E and with the first ionization potentials reported for Ph₃M. The rate of Φ₂Te was faster than that of Ph₃P and slightly faster than that of Φ₃Sb. From the reactivity of [Φ₂E-Me]⁺ salts with nucleophiles, the E⁺–Me bond strengths were estimated to increase in the order E=Se<S<Te. The reaction rates of Φ₂EO with dimethyl sulfate increased in the order E=S<Se<Te, and the respective rate of Φ₂EO was faster than that of Φ₂E. The origins of these reactivities and bond strengths are discussed.     

Berberine alkaloid: Quantum chemical study of different forms by the DFT and MP2 methods

The stable structures and electronic properties for the berberine cation as well as possible ammonium, carbinol and amino-aldehyde forms of protoberberine salts in the presence of hydroxyl ions were investigated by the B3LYP/6-31G(d,p) and MP2/6-31++G(d,p) methods. The geometry optimizations by both methods lead to the nonplanar propeller-twisted and buckled structure for the all forms. The obtained bond lengths and bond angles agree with the experimental values. The comparison of total energies elucidates that the amino-aldehyde form is the most preferable tautomer in gas phase, while the carbinol form is less stable. The least stable tautomer is the ammonium form.     

The Atiyah-Singer index theorem as passage to the classical limit in quantum mechanics

A new approach to the Atiyah-Singer index theorem is described, using the technique of continuous fields ofC ^*-algebras. The proof is given in the case of elliptic pseudodifferential operators on ℝ ⁿ .