Development of a bioanalytical method for the quantification of sinococuline in human plasma and its application in phase I clinical pharmacokinetic study

A selective, highly sensitive, precise, and novel bioanalytical method has been developed and validated to quantify sinococuline, an active constituent present in the phytopharmaceutical drug product containing Cocculus hirsutus plant extract, in vivo. Chromatographic separation was achieved on a Luna Omega Polar-C18 bonded analytical column maintained at 45°C. The isocratic mobile phase consisted of methanol and ammonium formate buffer (60:40, v/v) at acidic pH with a low flow rate of 0.250 mL/min. Detection was performed on an API 4000 mass spectrometer using electrospray ionization in positive polarity and multiple reaction monitoring mode to achieve a lower limit of quantification of 1.50 ng/mL. Excellent accuracy and precision were obtained after extracting the analyte from plasma samples using a chemical analogue as an internal standard in the absence of an isotope-labeled compound. The extraction efficacy was evidenced from recovery study, and the analyte was found to be stable in plasma. Validation study demonstrated linearity with coefficient of correlation, r ≥ 0.99, and minimal matrix effect. This bioanalytical method was successfully applied to evaluate pharmacokinetic parameters of sinococuline from a phase I clinical trial of an aqueous extract of C. hirsutus in healthy human volunteers.     

Activity of microemulsion-based nanoparticles at the human bio-nano interface: concentration-dependent effects on thrombosis and hemolysis in whole blood

Background: Although microemulsion-based nanoparticles (MEs) may be useful for drug delivery or scavenging, these benefits must be balanced against potential nanotoxicological effects in biological tissue (bio-nano interface). We investigated the actions of assembled MEs and their individual components at the bio-nano interface of thrombosis and hemolysis in human blood. Methods: Oil-in-water MEs were synthesized using ethylbutyrate, sodium caprylate, and pluronic F-68 (ME4) or F-127 (ME6) in 0.9% NaCl_w/v. The effects of MEs or components on thrombosis were determined using thrombo-elastography, platelet contractile force, clot elastic modulus, and platelet counting. For hemolysis, ME or components were incubated with erythrocytes, centrifuged, and washed for measurement of free hemoglobin by spectroscopy. Results and conclusions: The mean particle diameters (polydispersity index) for ME6 and ME4 were 23.6 ± 2.5 nm (0.362) and 14.0 ± 1.0 nm (0.008), respectively. MEs (0, 0.03, 0.3, 3 mM) markedly reduced the thromboelastograph maximal amplitude in a concentration-dependent manner (49.0 ± 4.2, 39.0 ± 5.6, 15.0 ± 8.7, 3.8 ± 1.3 mm, respectively), an effect highly correlated (r2 = 0.94) with similar changes caused by pluronic surfactants (48.7 ± 10.9, 30.7 ± 15.8, 20.0 ± 11.3, 2.0 ± 0.5) alone. Neither oil nor sodium caprylate alone affected the thromboelastograph. The clot contractile force was reduced by ME (27.3 ± 11.1–6.7 ± 3.4 kdynes/cm², P = 0.02, n = 5) whereas the platelet population not affected (175 ± 28–182 ± 23 10⁶/ml, P = 0.12, n = 6). This data suggests that MEs reduced platelet activity due to associated pluronic surfactants, but caused minimal changes in protein function necessary for coagulation. Although pharmacological concentrations of sodium caprylate caused hemolysis (EC₅₀ = 213 mM), MEs and pluronic surfactants did not disrupt erythrocytes. Knowledge of nanoparticle activity and potential associated nanotoxicity at this bio-nano interface enables rational ME design for in vivo applications.     

A flexible and generic approach to dynamic modelling of supply chains

In this paper, we present a new modelling approach for realistic supply chain simulation. The model provides an experimental environment for informed comparison between different supply chain policies. A basic simulation model for a generic node, from which a supply chain network can be built, has been developed using an object-oriented approach. This generic model allows the incorporation of the information and physical systems and decision-making policies used by each node. The object-oriented approach gives the flexibility in specifying the supply chain configuration and operation decisions, and policies. Stochastic simulations are achieved by applying Latin Supercube Sampling to the uncertain variables in descending order of importance, which reduces the number of simulations required. We also present a case study to show that the model is applicable to a real-life situation for dynamic stochastic studies.     

Some inequalities for the polar derivative of a polynomial

LetP(z) be a polynomial of degreen which does not vanish in |z|<1. In this paper, we estimate the maximum and minimum moduli of thekth polar derivative ofP(z) on |z|=1 and thereby obtain compact generalizations of some known results, which among other results, yields interesting refinements of Erdos-Lax theorem and a theorem of Ankeny and Rivlin.     

Diastereoselective formation of 2-aryl-3-arenesulfonyl 4-ethyl-1,3-oxazolidines: An X-ray crystallographic and H NMR study

N-Arylsulfonamides of (R)- and (S)-2-amino-1-butanol, on condensation with aromatic aldehydes produced diastereomerically pure 2-aryl-3-arenesulfonyl 4-ethyl-1,3-oxazolidines. The absolute configurations of one enantiomeric pair have been determined from two fully refined X-ray structures, supplemented by nmr data.     

某些查耳酮化合物的发光

本文叙述了两个同质查耳酮系列的合成.一个带有查耳酮中心链(系列Ⅰ),另一个是系列Ⅰ的酯类(系列Ⅱ).研究了每个系列中三种化合物的发光,发现两个系列的所有化合物都能见到发光.系列Ⅰ中的化合物在峰值为360nm处可见到发光,而系Ⅱ列中的化合物未能观测到这一波长的发光.然而,在峰值为470nm处两者均可见到发光.得出的结论是,消除非键电子微扰作用的氢键是系列Ⅰ中的化合物在360nm处出现发光的原因.     

Application of the finite Hankel transform to a diffusion problem without azimuthal symmetry

The problem treated in this paper concerns calculating the evolution of the pressure in a single-phase, slightly compressible fluid in a porous medium consisting of communicating layers. The fluid is produced through a point sink located on the side of an otherwise sealed cylindrical wellbore. This location of the sink causes the flow around the wellbore to be azimuthally asymmetric.The problem is solved through successive application of Laplace, finite Fourier and finite Hankel transforms. Although apparently straightforward, this approach leads to serious numerical difficulties. The published form of the inversion formula for the finite Hankel transform leads to inaccurate computation for the higher azimuthal modes even with 128 bit arithmetic. An alternative form is developed which enables accurate evaluation of the solution with the more practical 64 bit arithmetic. The technique for two-layer solution presented here can be directly extended to a problem with a larger number of communicating layers. This is the first instance of successful application of the finite Hankel transform to an azimuthally asymmetric diffusion problem.     

Micro-mechanical behaviors of SMA composite materials under hygro-thermo-elastic strain fields

An analytical procedure to evaluate the behavior of shape memory alloy (SMA) composite under hygrothermal environment is presented. The SMA wires are considered as inclusions embedded in a homogeneous matrix medium of the composite. The inhomogeneity associated with the phase transformation and thermal strains in the SMA wire as well as the hygrothermal strain in the matrix is homogenized using Eshelby’s equivalent inclusion method. In the present work, a similar approach adopted for SMA composites by Marfia and Sacco [Marfia, S., Sacco, E., 2005. Micromechanics and homogenisation of SMA-wire-reinforced materials. J. Appl. Mech. 72 (2), 259–268.] is considered in order to validate the response of SMA composite subjected to thermo-elastic strain field. However, in the present approach, certain modifications and new derivations for the inelastic strain tensors is carried out. First, the constitutive laws for the SMA wire and matrix are expressed in terms of the average strain in the composite. The evolutionary equations used to characterize the pseudoelastic (PE) behavior of the SMA wire are redefined in terms of the eigen strains (phase transformation and thermal strains) occurring in the SMA wire, which are then expressed in terms of the average strain in the composite. Further, the SMA composite constitutive law under coupled hygro-thermo-elastic strain fields is proposed. The generic homogenized hygric and thermal inelastic composite tensors required for the proposed hygro-thermo-elastic constitutive law are derived. Finally, the SMA composite lamina is characterized using Eshelby’s equivalent inclusion method. Using the proposed modifications and derivations, the analytical results are validated for the case of thermo-elastic strain fields and the procedure is then extended to evaluate the SMA composite behavior under hygro-thermo-elastic strain fields. The results include the effect of thermo-elastic and hygro-thermo-elastic strains on the transformation stresses and the nature of hysteresis due to hygric and thermo-elastic strains.     

AUTOMATED WIND TUNNEL MEASUREMENTS

It is common practice in power transmission to use bundled overhead electrical conductors because the lower rate of corona discharge, compared with single conductors, makes the bundle attractive for high voltages. However, secondary problems may arise from the vibrations induced by the aerodynamic forces which act on the leeward conductors as a result of their immersion in the wake of a windward conductor. Thus, in addition to possible aeolian and galloping oscillations observed for a single conductor, bundle conductors may also be subjected to wake-induced oscillations. ^1,2 Although extensive research has been done on the aeroelastic behavior of single and bundled conductors which are bare, little is known about the galloping or wake oscillation characteristics of given bundle conductors which, depending upon the environmental conditions during the formation of ice, may have five or so representative shaped cross-sections. One important task involves the aerodynamic quasi-static force and moment measurements in a wind tunnel using full scale conductor cross-sections each of which must be rotated through many angles at different spacings. Such measurements are repetitive as well as tediously time consuming and, hence, are beneficially automated. A reliable, accurate and inexpensive automated apparatus is described in this paper which permits the aerodynamic measurements to be performed efficiently and without intervention. Most importantly, it relieves the operator of the usual responsibility for manually controlling the separation and orientation of the sections as well as the need to manually compensate fluctuations in the free stream air speed. For simplicity, the apparatus is detailed in the context of a twin bundle conductor.