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.     

A comprehensive experimental and improved kinetic modeling study on the pyrolysis and oxidation of propyne

To improve our understanding of the combustion characteristics of propyne, new experimental data for ignition delay times (IDTs), pyrolysis speciation profiles and flame speed measurements are presented in this study. IDTs for propyne ignition were obtained at equivalence ratios of 0.5, 1.0, and 2.0 in ‘air’ at pressures of 10 and 30 bar, over a wide range of temperatures (690–1460 K) using a rapid compression machine and a high-pressure shock tube. Moreover, experiments were performed in a single-pulse shock tube to study propyne pyrolysis at 2 bar pressure and in the temperature range 1000–1600 K. In addition, laminar flame speeds of propyne were studied at an unburned gas temperature of 373 K and at 1 and 2 bar for a range of equivalence ratios. A detailed chemical kinetic model is provided to describe the pyrolytic and combustion characteristics of propyne across this wide-ranging set of experimental data. This new mechanism shows significant improvements in the predictions for the IDTs, fuel pyrolysis and flame speeds for propyne compared to AramcoMech3.0. The improvement in fuel reactivity predictions in the new mechanism is due to the inclusion of the propyne + H?₂ reaction system along with ?H radical addition to the triple bonds of propyne and subsequent reactions.     

Evaluation of the magnetic moments of radium isotopes

Using the relativistic linked cluster many-body perturbation procedure we have obtained the hyperfine field at the nucleus of the Ra⁺ ion in the²S_1/2 ground state. There is good agreement between the calculated magnetic moment of²¹³Ra and the results of a recent Zeeman measurement by the collinear laser beam technique. Detailed comparison is carried out between our result and earlier ones.     

An experimental and kinetic modeling study of the auto-ignition of natural gas blends containing C1–C7 alkanes

Ignition delay time measurements for multi-component natural gas mixtures were carried out using a rapid compression machine at conditions relevant to gas turbine operation, at equivalence ratios of 0.5–2.0 in ‘air’ in the temperature range 650–1050 K, at pressures of 10–30 bar. Natural gas mixtures comprising C₁–C₇ n-alkanes with methane as the major component (volume fraction: 0.35–0.98) were considered. A design of experiments was employed to minimize the number of experiments needed to cover the wide range of pressures, temperatures and equivalence ratios. The new experimental data, together with available literature data, were used to develop and assess a comprehensive chemical kinetic model. Replacing 1.875% methane with 1.25% n-hexane and 0.625% n-heptane in a mixture containing C₁–C₅ components leads to a significant increase in a mixture's reactivity. The mixtures containing heavier hydrocarbons also tend to show a strong negative temperature coefficient and two-stage ignition behavior. Sensitivity analyses of the C₁–C₇ blends have been performed to highlight the key reactions controlling their ignition behavior.     

Engineered Bio-inspired Multifunctional Peptide- and Protein-based Therapeutic Biomolecules for Better Wound Care

Developing non-immunogenic therapeutic biomolecules for facilitating blood clotting followed by wound healing via therapeutic angiogenesis, still remains a formidable challenge. Excessive blood loss of accident victims and battalions cause a huge number of deaths worldwide. Patients with inherited bleeding disorders face acute complications during injury and post-surgery. Biologically-inspired peptide-based hemostat can act as a potential therapeutic for handling coagulopathy. Additionally, non-healing wounds for patients having ischemic diseases can cause severe clinical complications. Advancement in stabilized growth-factor-based proangiogenic therapy may offer effective possibilities for the treatment of ischemic pathology. This review will discuss nature-inspired biocompatible stabilized peptide- and protein-based molecular medicines to serve unmet medical challenges for handling traumatic coagulopathy and impaired wound healing.     

Theory of hyperfine interactions in lithiumlike systems

The valence, exchange core polarization and correlation contributions to the magnetic hyperfine constants in the ground states of the lithiumlike ions Be⁺, B²⁺, C³⁺, N⁴⁺, O⁵⁺, F⁶⁺, Ne⁷⁺ and Bi⁸⁰⁺ are investigated using relativistic many-body perturbation theory. Radiative corrections have also been studied. Comparison is made with available experimental data and the trends in the various contributions are analyzed.     

Affine and polynomial mutual information coregistration for artifact elimination in diffusion tensor imaging of newborns

We have investigated the use of two different image coregistration algorithms for identifying local regions of erroneously high fractional anisotropy (FA) as derived from diffusion tensor imaging (DTI) data sets in newborns. The first algorithm uses conventional affine registration of each of the diffusion-weighted images to the unweighted (b = 0) image for each slice, while the second algorithm uses second-order polynomial warping. Similarity between images was determined using the mutual information (MI) criterion, which is the preferred 'cost' criterion for coregistration of images with significantly different image intensity distributions. We have found that subtle differences exist in the FA values resulting from affine and second-order polynomial coregistration and demonstrate that nonlinear distortions introduce artifacts of spatial extent similar to real white matter structures in the newborn subcortex. We show that polynomial coregistration systematically reduces the presence of erroneous regions of high FA and that such artifacts can be identified by visual inspection of FA maps resulting from affine and polynomial coregistrations. Furthermore, we show that nonlinear distortions may be particularly pronounced when acquiring image slices of axial orientation at the height of the nasal cavity. Finally, we show that third-order polynomial MI coregistration (using the images resulting from second-order coregistration as input) has no observable effect on the resulting FA maps.     

Design and synthesis of triptycene based fluorescent polymer with pendent triazole: Effect of functionality on host–guest interaction

Fluorescent materials have emerged as one of the promising candidates for chemical sensing due to their high sensitivity towards analytes that are relatively electron deficient such as nitroaromatics (NACs). Herein, four new 1,2,3‐triazole functionalized dibromo monomers ( 2‐5 ) have been synthesized. These dibromo monomers ( 2‐5 ) have been subsequently polymerized with 2,6‐diethynyltriptycene ( DET ) to yield four new ethynyl linked polymers ( P2‐P5 ) with 1,2,3‐triazole pendent. These polymers are organosoluble, amorphous in nature and have high thermal stability [T_d > 289 °C and high char yield (>73%) at 800 °C]. Interestingly these new polymers ( P2‐P5 ) are highly fluorescent in solution (Φ = 0.37–0.43 in DCM) relative to the polymer ( P1 ) that does not have the 1,2,3‐triazole motif as a pendent. The host–guest interaction between these polymers ( P1‐P5 ) and electron deficient molecules (PA and C₆₀) has been investigated. The Stern–Volmer quenching constant (K_SV) data suggest that the interaction of picric acid and polymers increases significantly in presence of 1,2,3‐triazole linked pendent group whereas in case of C₆₀, the K_SV value decrease considerably in presence of 1,2,3‐triazole linked pendent. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017 , 55, 3725–3735