Validation of an LC method to determine skin retention profile of genistein from nanoemulsions incorporated in hydrogels

Recent studies have shown the effect of soy isoflavones in preventing skin photoaging and photocarcinogenesis, especially for genistein (GEN). Nanoemulsions have been proposed as a delivery system for GEN administration due to the low water solubility of this isoflavone. This article describes the validation of an isocratic liquid chromatography method to determine GEN in porcine ear skin layers from nanoemulsions before and after incorporation into hydrogels. The analyses are performed on a reversed-phase C18 column using a mobile phase composed of methanol-water (70:30, v/v) under acid conditions (at pH 3.0) and UV detection at 270 nm. The method is linear in the range of 0.1-10 μg/mL (r(2) > 0.999) in the presence of skin extracts. The low limit of quantitation is estimated as 0.1 μg/mL. No interferences from formulation excipients or skin layer compounds are detected. The RSD values for intra- and inter-day precision are lower than 15%. Recovery ranged from approximately 90% to 110%. The method is applied to estimate GEN retention in the skin from formulations using Franz diffusion cells. The highest amount of GEN is detected in the epidermis (185 μg/cm(2)). In conclusion, the method proved to be specific, precise, and accurate in determining GEN amounts from formulations in skin retention studies.     

Microsystems for biomimetic stimulation of cardiac cells

The heart is a complex integrated system that leverages mechanoelectrical signals to synchronize cardiomyocyte contraction and push blood throughout the body. The correct magnitude, timing, and distribution of these signals is critical for proper functioning of the heart; aberrant signals can lead to acute incidents, long-term pathologies, and even death. Due to the heart's limited regenerative capacity and the wide variety of pathologies, heart disease is often studied in vitro. However, it is difficult to accurately replicate the cardiac environment outside of the body. Studying the biophysiology of the heart in vitro typically consists of studying single cells in a tightly controlled static environment or whole tissues in a complex dynamic environment. Micro-electromechanical systems (MEMS) allow us to bridge these two extremes by providing increasing complexity for cell culture without having to use a whole tissue. Here, we carefully describe the electromechanical environment of the heart and discuss MEMS specifically designed to replicate these stimulation modes. Strengths, limitations and future directions of various designs are discussed for a variety of applications.     

A stochastic interactive model for the diffusion of information

Two important generalizations of information diffusion models are the presence of stochastic effects and the possibility of arbitrary patterns of influence among individuals. A Markov random fields model includes both of these features. Under very weak assumptions, there is a unique equilibrium distribution of information patterns for given stochastic (local) interactions among a finite population. This has implications for policies to influence the transmission of information. The dynamic behavior of a special and simple case of the model tends to approximate the standard (logistic) diffusion curve. For an infinite population, uniqueness of equilibrium distributions may fail; some sufficient conditions to ensure uniqueness are given.     

Families of completely positive maps associated with monotone metrics

An operator convex function on (0,∞)$(0,\infty )$ which satisfies the symmetry condition k(x⁻¹)=xk(x)$k(x^{-1})=xk(x)$ can be used to define a type of non-commutative multiplication by a positive definite matrix (or its inverse) using the primitive concepts of left and right multiplication and the functional calculus. The operators for the inverse can be used to define quadratic forms associated with Riemannian metrics which contract under the action of completely positive trace-preserving maps.     

Quantitation of melatonin and n-acetylserotonin in human plasma by nanoflow LC-MS/MS and electrospray LC-MS/MS

Melatonin (MEL) and its chemical precursor N-acetylserotonin (NAS) are believed to be potential biomarkers for sleep-related disorders. Measurement of these compounds, however, has proven to be difficult due to their low circulating levels, especially that of NAS. Few methods offer the sensitivity, specificity and dynamic range needed to monitor MEL and its precursors and metabolites in small blood samples, such as those obtained from pediatric patients. In support of our ongoing study to determine the safety, tolerability and PK dosing strategies for MEL in treating insomnia in children with autism spectrum disorder, two highly sensitive LC-MS/MS assays were developed for the quantitation of MEL and precursor NAS at pg/mL levels in small volumes of human plasma. A validated electrospray ionization (ESI) method was used to quantitate high levels of MEL in PK studies, and a validated nanospray (nESI) method was developed for quantitation of MEL and NAS at endogenous levels. In both assays, plasma samples were processed by centrifugal membrane dialysis after addition of stable isotopic internal standards, and the components were separated by either conventional LC using a Waters SymmetryShield RP18 column (2.1?×?100 mm, 3.5?μm) or on a polyimide-coated, fused-silica capillary self-packed with 17?cm AquaC18 (3?μm, 125??). Quantitation was done using the SRM transitions m/z 233?→?174 and m/z 219?→?160 for MEL and NAS, respectively. The analytical response ratio versus concentration curves were linear for MEL (nanoflow LC: 11.7-1165 pg/mL, LC: 1165-116,500 pg/mL) and for NAS (nanoflow LC: 11.0-1095 pg/mL).     

The influence of intramolecular hydrogen bonding on the structure and E ↔ Z photoisomerization of urocanic acid derivatives

The molecular structures and E ? Z photoisomerization reactions of methyl urocanate and several urocanamides were investigated. All of the Z isomers possess intramolecular hydrogen bonds. The intramolecular hydrogen bonds may influence the efficiency of photoisomerization but do not totally inhibit its occurrence. The relative energies of the electronic absorption of the E and Z isomers depends on the mode of hydrogen bonding and are accurately predicted in the case of methyl urocanate using INDO/S-CI calculations. The solvent dependence of the absorption spectra of methyl urocanate can be related to the effects of inter- and intramolecular hydrogen bonding.     

Copolymerization of carbon dioxide and propylene oxide using an aluminum porphyrin system and its components

The catalytic activities of tetraphenylporphinatoaluminum chloride (TPPAlCl) and its propylene oxide adduct (TPPAl(PO)₂Cl) were investigated in detail together with a quarternary salt Et₄NBr for the copolymerization of carbon dioxide and propylene oxide. In addition, for the components and starting raw materials of the catalyst systems, catalytic activities were examined for the copolymerization. The TPPAlCl catalyst delivered oligomers containing ether linkages to a large extent, regardless of its PO adduction. And cyclic propylene carbonate, as byproduct, was formed in a very small portion. Using the TPPAlCl coupled with Et₄NBr as a catalyst system, the formation of ether linkages was reduced significantly in the copolymerization; however, the obtained oligomer still contained ether linkages of 25.0 mol % in the backbone. On the other hand, the formation of cyclic carbonate was increased to 22.4 mol % relative to the oligomer product. The results indicate that the salt, which was coupled with the TPPAlCl catalyst, plays a key role in reducing the formation of ether linkage in the oligomer and, however, in enhancing the formation of cyclic carbonate. Similar results were obtained for the copolymerization catalyzed by the TPPAl(PO)₂Cl/Et₄NBr system. That is, the formation of ether linkages was not restricted further by the PO adduction of the TPPAlCl component in the catalyst system. Only oligomers with a relatively high molecular weight were produced. This indicates that the PO adduction of the TPPAlCl component contributes highly to the initiation and propagation step in the oligomerization, consequently leading to a relatively high molecular weight oligomer. In contrast, the Et₄NBr, as well as the Et₂AlCl, produced only cyclic carbonate in a very low yield. Furthermore, tetraphenylporphine exhibited no catalytic activity, regardless of using together with Et₄NBr. On the other hand, the Et₂AlCl coupled with Et₄NBr provided a low molecular weight oligomer having ether linkages of 92.3 mol % in addition to the cyclic carbonate. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 3329–3336, 1999     

In situ infrared spectroscopy study on imidization reaction and imidization-induced refractive index and thickness variations in microscale thin films of a poly(amic ester)

Poly(amic ester) (PAE) is a soluble precursor of polyimide that has attracted interest from both the microelectronic and the flat-panel display industries because of its several important advantages, including excellent solubility, high hydrolytic stability, and solvent-free film formation, over the polyimide precursor, poly(amic acid), for which monomer-polymer equilibration always occurs in solution due to its carboxylic acid groups. In this study, poly(3,4'-oxydiphenylene pyromellitamic diethyl ester) (PMDA-3,4'-ODA PAE) was chosen as a PAE precursor, and its thermal imidization behavior in microscale thin films was investigated quantitatively for the first time using time-resolved infrared (IR) spectroscopy. In addition, the variations of the film refractive index and thickness with temperature and time were determined in detail from the time-resolved IR spectra and are fully interpreted in this paper by considering the imidization kinetics of the precursor.     

Substituent,solvent and steric effects on the electrochemical reduction of aziridinium salts

The polarographic behavior of a series of N,N-dimethyl-2-arylaziridinium fluorosulfonates was investigated as another example of ring-opening reactions of this important class of compounds. Half-wave potentials showed that in water reduction was facilitated by electron-donating groups. This unusual result was explained in terms of electron transfer to an aminocarbonium ion-like species. In methylene chloride, however, two one-electron waves were observed, with the first showing a normal substituent effect (? = 0.17 ± 0.03 V). This result indicated direct electron transfer to the aziridinium ion itself to form a radical species which was detected by cyclic voltammetry. Reasons for the change in mechanism are presented, and E_1/2 values for selected aziridinium salts illustrate the importance of steric effects on the reduction process.