Degradation kinetics of fluvoxamine in buffer solutions: In silico ADMET profiling and identification of degradation products by LC-MS/ESI

The kinetics of hydrolysis of fluvoxamine maleate (FLV) has been investigated over the pH range 1.0–12.0 at 40, 60 and 80 °C. FLV degradation follows pseudo-first-order kinetics which is consistent with the kinetics of drugs that are not readily dissolved in aqueous medium. The hydrolytic degradation rate constant (k_obs) range from 0.92 (pH 6.0) to 13.8 × 10⁻⁴ min⁻¹ (pH 1.0). The k_obs represents the sum of six different degradation rate constants; the k_H has been found to be higher than k_OH. The FLV exhibits a typical rate- pH profile with a flat bottom over the pH range 3.0–6.0 which indicates its maximum stability at pH 6.0. Ten FLV degradants have been predicted by Zeneth software and among them four degradation products (D1, D2, D3 and D4) have been identified in degraded samples. The in-silico pharmacokinetics and toxicity of degradation products have been determined using Swiss ADME and admetSAR software. The toxicity profile reveals that D2 is both AMES toxic and carcinogenic while the rest of the products are non-AMES toxic and non-carcinogenic. All of the degradation products are high in causing fish toxicity thus their presence in pharmaceutical waste is alarming for environmental safety.     

First report of the nutritional profile and antioxidant potential of Holothuria arguinensis,a new resource for aquaculture in Europe

This work reports for the first time the nutritional profile and antioxidant potential of the edible sea cucumber Holothuria arguinensis from the North-eastern Atlantic. H. arguinensis has high levels of protein, with the amino acids profile dominated by alanine, glycine and proline and low lysine/arginine ratios. Its carbohydrate and energetic contents are also low as well as the total lipid levels, although its lipid profile is rich in polyunsaturated fatty acids (PUFA), especially arachidonic, eicosapentaenoic and docosahexaenoic acids. In addition, H. arguinensis has high levels of calcium. The water and ethanol extracts show ability to scavenge free radicals and to chelate copper and iron ions. Our results indicate that H. arguinensis has a balanced nutritional quality suitable for human consumption. In addition, it contains compounds with antioxidant potential; thus its intake can contribute for a healthy and well-balanced diet.     

The flow simulation of a low-specific-speed high-speed centrifugal pump

In this paper a general three-dimensional simulation of turbulent fluid flow is presented to predict velocity and pressure fields for a centrifugal pump. A commercial CFD code was used to solve the governing equations of the flow field. In order to study the most suitable turbulence model, three known turbulence models of standard k–ε, RNG and RSM were applied. The complex flow configuration required us to use around 5,800,000 cells, and 12 computational nodes (processors) for parallel computing. Simulation results in the form of characteristic curves were compared with available experimental data, and an acceptable agreement was obtained. Additionally, effect of number of blades on the efficiency of pump was studied. The number of blades was changed from 5 to 7. The results show that the impeller with 7 blades has the highest head coefficient. Finally, it was observed also that the position of blades with respect to the tongue of volute has great effect on the start of the separation. Thus, to analyze the effect of blade number on the characteristics of the pump, the position of blade and tongue should be similar to each other. Investigations of this kind may help to reduce the required experimental work for the development and design of such devices.     

Chromatographic determination of some biomarkers of liver cirrhosis and hepatocellular carcinoma in Egyptian patients

Metabolomics has been shown to be an effective tool for disease diagnosis, biomarker screening and characterization of biological pathways. A total of 140 subjects were included in this study; urine metabolomes of patients with liver cirrhosis (LC, n = 40), patients with hepatocellular carcinoma (HCC; n = 55) and healthy male subjects (n = 45) as a control group were studied. Gas chromatography/mass spectrometry‐based urine metabolomics profiles were investigated for all participants. Diagnostic models were constructed with a combination of marker metabolites, using principal components analysis and receiver operator characteristic curves. A total of 57 peaks could be auto‐identified of which 13 marker metabolites (glycine, serine, threonine, proline, urea, phosphate, pyrimidine, arabinose, xylitol, hippuric acid, citric acid, xylonic acid and glycerol) were responsible for the separation of HCC group from healthy subjects. Also, eight markers metabolites (glycine, serine, threonine, proline, citric acid, urea, xylitol and arabinose) showed significant differences between the LC group and healthy subjects. No significant difference was detected between HCC and LC groups regarding all these metabolites. Metabolomic profile using GC–MS established an optimized diagnostic model to discriminate between HCC patients and healthy subjects; also it could be useful for diagnosis of LC patients. However, it failed to differentiate between HCC and LC patients.     

Spectroscopic ellipsometry of very thin tantalum pentoxide on Si

Variable angle spectroscopic ellipsometry of very thin T₂O₅ layers on Si and the previously published appropriate algorithm for data interpretation have been successfully applied in terms of accurate characterization of very thin T₂O₅/Si systems. The simulation procedure following a simple three and four layered model was used assuming an existence of inhomogeneous interfacial layers. Quantitative determination of the thicknesses and composition identification were achieved, both for the top T₂O₅ layer and for an interfacial layer. The constituents in the interfacial layer and its depth profiles were recognized.     

Biotransformation and metabolic profile of anemoside B4 with rat small and large intestine microflora by ultra‐performance liquid chromatography–quadrupole time‐of‐flight tandem mass spectrometry

Pulsatilla chinensis (Bunge) Regel is commonly used in Asia, and anemoside B4 (AB4) is its major saponin, with diverse pharmaceutical effects. Previous studies showed that intestinal flora plays an important role in the metabolism of herbs administered orally. In this study, the metabolic profile of AB4 with microflora in rat small and large intestines in vitro was investigated. Gut microflora was collected from different intestinal segments and anaerobically incubated with AB4 at 37°C for 24, 48, 72 and 96 h, respectively. A total of 10 metabolites were detected and identified by ultra‐ performance liquid chromatography/quadrupole time‐of‐flight mass spectrometry, involving the products of oxygenation and deglycosylation reactions. Gut microflora in the large intestine generated more comprehensive metabolic pathways, which appears to be attributable to the wider range of bacterial types and numbers of bacteria. Human cancer cell lines SMMC‐7721, Hela and MCF‐7 were treated with metabolite pools by MTT assay, together with M6 as the greatest deglycosylation product. As a result, M6 exhibited a reduction in cell viability of SMMC‐7721 with an IC₅₀ value of 22.28 ± 1.26 μg/mL. The present study provided scientific evidence for AB4 metabolism in small and large intestines, which is helpful to reveal the active forms of AB4 in vivo .     

Numerical simulation of core convection by a multi-layer semi-implicit spherical spectral method

A semi-implicit multi-layer spherical spectral method for simulating stellar core convection is described. The fully compressible three-dimensional hydrodynamic equations with rotation and energy generation are solved. Prognostic variables are expressed as finite sums of spherical harmonics in the horizontal directions and handled by the finite difference method in the radial direction. The stratified approximation is used to simplify the nonlinearity to quadratic. A multi-layer scheme is employed to overcome the time step problem arising from shrinking grid sizes in the physical space near the center of the star. Despite of the different spectral truncations in different layers, round-off conservation of the total mass and total angular momentum of the whole domain can be maintained, and were confirmed numerically. The code is parallelized; with 12 processors the speedup factor is about 9. The solutions of model core convection with and without rotation are discussed.     

Temporal contrast improvement in chirped pulse amplification systems by a four-grating compressor and by spectral modifications

The quest for higher peak focused intensities and better temporal contrast drives one to improve the design of all possible stages of the chirped pulse amplification (CPA) system. In this paper, we have analyzed the role of dispersion and spectral profile on the temporal shape and contrast ratio of the output pulse of a CPA system. The simulations indicate that an initial sech² or a Gaussian pulse in the CPA system is best for a good contrast ratio. Incorporating a four-grating based pulse compressor in the CPA system improves the contrast as well as provides the flexibility to compensate the dispersion upto the fourth order. The simulations also detail the effect of spectral profile tailoring on the contrast ratio and peak power.     

Mechanistic aspects of the dehydration and dehydrohalogenation of halo-hydroxyformaldoxime conformers. A quantum chemical model study

A detailed exploration of the configurational and conformational space of chloro- and bromo-hydroxyformaldoximes, Xhfaox (X = Cl, Br) has been carried out with the aid of the B3LYP level of density functional theory, using the 6-31G(d,p) basis set. The most stable configuration in each series of the Clhfaox and Brhfaox conformers corresponds to the Z-s-cis, s-trans configuration, while the highest energy Z-(s-trans, s-cis) conformers were found at 7.0(7.6) and 6.0(6.6) kcal mol(-1), respectively, at the B3LYP(QCISD(T)) levels of theory. Saddle points were also located on the PES of the Clhfaox and Brhfaox compounds corresponding to Z-(s-cis, s-cis) conformers at 13.8(14.9) and 13.6(14.6) kcal mol(-1), respectively, at the B3LYP(QCISD(T)) levels. Upon dehydration Xhfaox could afford a number of isomeric CXNO species. The dehydration processes of Xhfaox are predicted to be endothermic, the computed heats of reactions found in the range of 20.5 to 86.2 kcal mol(-1) and 15.9 to 100.4 kcal mol(-1) at the B3LYP and QCISD(T) levels, respectively. The reaction pathways for the addition of water to halo-fulminates yielding the most stable Xhfaox conformers was predicted to be concerted with a single transition structure, but are asynchronous with activation barriers of 32.8 and 43.0 kcal mol(-1) for the chloro- and bromo-derivatives, respectively. The PES governing the isomerization reactions of the CXNO isomers have also been calculated, and possible isomerization pathways have been delineated. Upon dehydrohalogenation the Xhfaox conformers yield hydroxy-isocyanate or hydroxy-fulminate, the former being more stable by 31.8(18.8) kcal mol(-1) at the B3LYP(QCISD(T)) levels of theory. The reaction pathways for the addition of HX to hydroxy-isocyanate were predicted to be slightly exothermic, the heats of reactions being -3.2 and -5.5 kcal mol(-1), respectively, and have to surmount high activation barriers of 39.7 and 35.0 kcal mol(-1), respectively. Similarly, the addition of HX to hydroxy-fulminate was predicted to be much more exothermic, the heats of reactions being -34.7 and -37.3 kcal mol(-1), respectively, and have to surmount much lower activation barriers of only 10.5 and 7.5 kcal mol(-1) respectively, at the B3LYP level. Finally, calculated structures, relative stability, and bonding properties of all stationary points located on the PES of the systems and reactions studied are thoroughly discussed with respect to computed electronic properties.