Generation and detection of levuglandins and isolevuglandins in vitro and in vivo

Levuglandins (LGs) and isolevuglandins (isoLGs), formed by rearrangement of endoperoxide intermediates generated through the cyclooxygenase and free radical induced oxidation of polyunsaturated fatty acids (PUFAs), are extraordinarily reactive, forming covalent adducts incorporating protein lysyl ε-amino groups. Because they accumulate, these adducts provide a dosimeter of oxidative injury. This review provides an updated and comprehensive overview of the generation of LG/isoLG in vitro and in vivo and the detection methods for the adducts of LG/isoLG and biological molecules in vivo.     

Determination of diazepam and nordazepam in milk and plasma in the presence of oxazepam and temazepam

For studies on the excretion of drugs into milk a sensitive high-performance liquid chromatographic assay was developed to quantitate diazepam and nordazepam in the milk and plasma of humans and rabbits in the presence of their major metabolites, oxazepam and temazepam. Flurazepam was used as an internal standard. The assay involves extractions with diethyl ether and an additional acid clean-up step. Chromatographic separation was achieved by a LiChrospher 60 RP-select B (5 microns) column and KH2PO4- acetonitrile (69:31, v/v) adjusted to pH 2.80 as a mobile phase. The same extraction and chromatographic conditions were suited to both types of samples, milk and plasma. The limits of determination using ultraviolet detection at 241 nm was for diazepam 20 ng/ml and for nordazepam 15 ng/ml. The absolute recoveries of diazepam, nordazepam and flurazepam in human milk were 84, 86 and 92% and in human plasma 97, 89 and 94%, respectively. The within- and between-day accuracy and precision for diazepam and nordazepam in milk and plasma at all concentrations tested (20-1500 ng/ml) were better than 8%. The high fat content which occurs in rabbit milk presented no limitation for the extraction of lipophilic diazepam: the method was successfully used to monitor milk and plasma concentrations of diazepam and nordazepam in lactating New Zealand White rabbits during 26-h infusions of diazepam (1.4 mg/h).     

Coassembly of Nanorods and Nanospheres in Suspensions and in Stratified Films

The entropically driven coassembly of nanorods (cellulose nanocrystals, CNCs) and nanospheres (dye‐labeled spherical latex nanoparticles, NPs) was studied in aqueous suspensions and in solid films. In mixed CNC‐latex suspensions, phase separation into an isotropic latex‐NP‐rich and a chiral nematic CNC‐rich phase took place; the latter contained a significant amount of latex NPs. Drying the mixed suspension resulted in CNC‐latex films with planar disordered layers of latex NPs, which alternated with chiral nematic CNC‐rich regions. In addition, fluorescent latex NPs were embedded in the chiral nematic domains. The stratified morphology of the films, together with a random distribution of latex NPs in the anisotropic phase, led to the films having close‐to‐uniform fluorescence, birefringence, and circular dichroism properties.     

Enthalpies of solution of purine and adenine in water and in dimethylsulfoxide

Journal of Solution Chemistry - Enthalpies of solution of purine and adenine in water and in demethylsulfoxide were measured calorimetrically in the temperature range 25–40°C. ΔH s...     

Electrochemical Fluorination of Benzamide and Acetanilide in Anhydrous HF and in Acetonitrile

Electrochemical fluorination of benzamide in anhydrous hydrogen fluoride does not involve the amide group but occurs exclusively at the aromatic ring, yielding isomeric fluoro- and difluorobenzamides and 3,3,6,6-tetrafluoro-1,4-cyclohexadienecarboxamide. Electrochemical fluorination of benzamide in acetonitrile as solvent gives the same products, as well as benzonitrile and its fluorinated derivatives and products of hydrolysis and fluorination of acetonitrile. Electrochemical fluorination of acetanilide in anhydrous HF leads to complete tarring of the reaction mixture, while its fluorination in acetonitrile results in selective formation of m-fluoroacetanilide.     

Comparison and correlation of in vitro, in vivo and in silico evaluations of alpha, beta and gamma cyclodextrin complexes of curcumin

In the present study investigated the effect of curcumin (CUR) alpha (α), beta (β) and gamma (γ) cyclodextrin (CD) complexes on its solubility and bioavailability. CUR the active principle of turmeric is a natural antioxidant agent with potent anti-inflammatory activity along with chemotherapeutic and chemopreventive properties. Poor solubility and poor oral bioavailability are the main reasons which preclude CUR use in therapy. Extent of complexation was β-CD complex (82 %) > γ-CD (71 %) > α-CD (65 %). Pulverization method resulted in significant enhancement of CUR (0.002 mg/ml) solubility with CUR α-CD complex (0.364 mg/ml) > CUR β-CD complex (0.186 mg/ml) > CUR γ-CD complex (0.068 mg/ml). Gibbs-free energy and in silico molecular docking studies favour formation of α-CD complex > β-CD complex > γ-CD complex. With reference to CUR, relative bioavailability of CUR α-CD, CUR β-CD and CUR γ-CD complexes were 460, 365 and 99 % respectively. CUR–CD complexes exhibited increased bioavailability with an increase in t_½, tmax, Cmax, AUC, Ka, and MRT; and a decrease in Ke, clearance and Vd values. AUC increase was CUR α-CD complex > CUR β-CD complex > CUR γ-CD complex. Significant difference (p < 0.05) was observed between CUR α-CD complex and CUR γ-CD complex by one-way ANOVA and Dunnett’s post hoc test for multiple comparison analysis. Correlation observed between in vitro, in vivo and in silico methods indicates potential of in silico and in vitro methods in CD selection.     

Homo- and hetero-complexes of exchangeable apolipoproteins in solution and in lipid-bound form

The self-association state of human plasma apolipoprotein E (apoE) in solution and in complexes with dimyristoylphosphatidylcholine (DMPC) varying in stoichiometry was studied in sub-micromolar concentration range by gel filtration, fluorescence anisotropy, fluorescence quenching and energy transfer measurements with apolipoprotein labeled with lysine-specific fluorescent dyes. Together, these results confirm the equilibrium scheme for various apoE structures in solution: oligomer (in aged preparations) <==> 'closed' tetramer <==> 'open' tetramer ('molten globule' state) <==> native or partially denatured monomer <==> fully denatured monomer. Within DMPC:apoE discoidal complex (125:1) the apolipoprotein association state seems to be intermediate between that in solution and in larger vesicular complex (1000:1); for both complexes, the degree of exposure of fluorescein chromophores into water phase decreased. Hetero-associates of apoA-I and apoC-III-1 in solution and in the complexes with DMPC appear to behave similarly to apoE. When extrapolated to native HDL particles, 'molten globule' state seems to be a structure responsible for the interaction of exchangeable apolipoproteins with phospholipid. For a first time, the location of various apolipoprotein molecules on disc periphery was confirmed. The lysine residue(s) seems to locate closely to reacting residue(s) within apolipoprotein molecules in associates, however, with different package constraints for discoidal versus vesicular complexes with phospholipid.     

Structure of dimethoxyamine in the crystalline and gaseous phases and in solution

Conclusions It has been established by the methods of x-ray diffraction analysis and electron diffraction analysis and measurements of the dipole moments and the birefringence that in the crystalline and gaseous phases, as well as in solution, N,N-dimethoxyamine has a gauche-gauche conformation, which is stipulated by a stabilizing nO-N-O* orbital interaction. The geometric parameters of the molecule have been determined.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 10, pp. 2235–2242, October, 1986.     

Fluorimetric quantification of clodronate and alendronate in aqueous samples and in serum

The bisphosphonates clodronate and alendronate are drugs in the therapy of osteoporosis or Paget's disease. They are highly hydrophilic and therefore of low oral bioavailability. Determination methods for bisphosphonates are often laborious and expensive equipment is needed. The presented quantification method based on kinetic measurement of the fluorescence decrease of an Al³⁺-morin complex can be used to determine the bisphosphonate content in aqueous and plasma samples. The intra- and inter-assay accuracies were found to be within 98.8% and 102.3% of the target samples for clodronate and within 97.2% and 105.0% of the target samples for alendronate. The LOQ was defined as 15.6 ng/ml for clodronate and 62.5 ng/ml for alendronate. In serum samples, intra- and inter-assay accuracy was found to be within 99.0% and 101.6% of the target samples for clodronate and within 97.8% and 102.6% of the target samples for alendronate. In serum samples, the LOQ was defined as 1.55 mg/ml for clodronate and 0.39 mg/ml for alendronate. Though less sensitive in serum, the presented method could support research on the development of drug delivery systems in vitro and in vivo for the investigated and other structurally related bisphosphonates.     

Identification and characterization of in vitro and in vivo fidarestat metabolites: Toxicity and efficacy evaluation of metabolites

The progression of diabetic complications can be prevented by inhibition of aldose reductase and fidarestat considered to be highly potent. To date, metabolites of the fidarestat, toxicity, and efficacy are unknown. Therefore, the present study on characterization of hitherto unknown in vitro and in vivo metabolites of fidarestat using liquid chromatography–electrospray ionization tandem mass spectrometry (LC/ESI/MS/MS) is undertaken. In vitro and in vivo metabolites of fidarestat have been identified and characterized by using LC/ESI/MS/MS and accurate mass measurements. To identify in vivo metabolites, plasma, urine, and feces samples were collected after oral administration of fidarestat to Sprague–Dawley rats, whereas for in vitro metabolites, fidarestat was incubated in human S9 fraction, human liver microsomes, and rat liver microsomes. Furthermore, in silico toxicity and efficacy of the identified metabolites were evaluated. Eighteen metabolites have been identified. The main in vitro phase I metabolites of fidarestat are oxidative deamination, oxidative deamination and hydroxylation, reductive defluroniation, and trihydroxylation. Phase II metabolites are methylation, acetylation, glycosylation, cysteamination, and glucuronidation. Docking studies suggest that oxidative deaminated metabolite has better docking energy and conformation that keeps consensus with fidarestat whereas the rest of the metabolites do not give satisfactory results. Aldose reductase activity has been determined for oxidative deaminated metabolite (F‐1), and it shows an IC50 value of 0.44 μM. The major metabolite, oxidative deaminated, did not show any cytotoxicity in H9C2, HEK, HEPG2, and Panc1 cell lines. However, in silico toxicity, the predication result showed toxicity in skin irritation and ocular irritancy SEV/MOD versus MLD/NON (v5.1) model for fidarestat and its all metabolites. In drug discovery and development research, it is distinctly the case that the potential for pharmacologically active metabolites must be considered. Thus, the active metabolites of fidarestat may have an advantage as drug candidates as many drugs were initially observed as metabolites.     

Photodimerisation of glycothymidines in solution and in micelles

Glycothymidines were designed and synthesized as a new class of functional glycomimetics in which a photochemical [2+2] cycloaddition of the thymine moiety induces structural changes of carbohydrate presentation. To test if photodimerisation of these glycothymidines is feasible within an array of molecules, the photochemical reaction was investigated using NMR and NMR diffusion experiments in solution as well as in the supramolecular context of detergent micelles that mimic cellular membranes.     

Thermodynamics of solvation and association in solutions of fluorosiloxane rubber and polychloroprene in organic liquids

The enthalpy of dissolution and concentration dependences of the enthalpy of dilution of solutions of fluorosiloxane rubber and polychloroprene in different organic liquids are determined by means of isothermal microcalorimetry. It is established that the processes of polychloroprene dissolution are accompanied by exothermic effects, while those of fluorosiloxane rubber are accompanied by endothermic effects. The calorimetric data are analyzed using the UNIQUAC model to calculate the model parameters associated with the local concentrations of components in the solution that characterize solvation and association. It is shown that the local distribution of the solvent molecules in the polychloroprene solution differed only slightly from the average over the volume, while the process of solvent association predominated in the solution of fluorosiloxane rubber.     

钢铁中稀土合金化的内耗研究及其理论

扼要地回顾了稀土钢及其合金化研究的发展历程；阐明合金化、合金化耗及用内耗研究合金化的基本思想和铁内耗谱及其机制等理论理论基础；介绍了用内耗方法研究钢中稀土合金化取得的进展；最后，从钢中稀土的作用结构材料的发展，展望了用稀土处理钢的前景。     

Synthesis and evaluation of antitumour activity in vitro and in vivo of chrysin salicylate derivatives

A series of chrysin salicylate derivatives as potential antitumour agents were synthesised and evaluated their antitumour activities in vitro and in vivo. Most of the compounds exhibited moderate to good activities against MCF-7 cells, HepG2 cells, MGC-803cells and MFC cells. Among them, compound 3f showed the most potent activity against MGC-803 cells and MFC cells with IC₅₀ values of 23.83 ± 3.68 and 27.34 ± 5.21 μM, respectively. The flow cytometry assay reconfirmed that compound 3f promoted the occurrence of tumour cells’ G1/S block under the inhibiting effect of compound 3f. Compound 3f possessed higher antitumour efficacy in tumour-bearing mice, compared with the positive control 5-Fu and the blank control saline.     

Analysis of anisotropic polarizability of molecules in the gas phase and in liquids and solutions

Conclusions The anisotropic polarizabilities of molecules in the gas phase and in dilute solutions in isotropic solvents, as determined from data on Rayleigh light scattering and the Kerr effect, are completely consistent with each other.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya No. 2, pp. 335–339, February, 1981.     

Determination of chlorpyrifos and acephate in tropical soils and application in dissipation studies

A rapid and accurate method for the extraction and determination of the two organophosphorus insecticides, chlorpyrifos and acephate in top- and subsoil materials of three tropical clayey soils from Sarawak has been developed. Soil samples were extracted with ethyl acetate and the pesticides were determined by GC-FPD. High recoveries of 76–102% and 76–100% were obtained for acephate and chlorpyrifos respectively, at fortification levels of 0.01, 0.1 and 1 mg kg^?1 with standard deviations below 9.0%. The addition of water prior to the extraction was important for obtaining high and reproducible recoveries. The method did not require clean-up of the extracts prior to GC analysis and could be detected down to 0.01 mg kg^?1. A field study was conducted using the modified method to measure the degradation kinetics and migration of acephate and chlorpyrifos in one of the soils over a period of 84 days. The degradation of acephate and chlorpyrifos were rapid with half-lives of 3.3 and 8.7 days, respectively. Both pesticides were detected in subsoils 2 h after application at the deepest (50 cm) soil layers examined and at concentrations up to 5.42 mg kg^?1. Subsoil concentrations of acephate were higher than for chlorpyrifos, and subsoil concentrations of acephate peaked after it had started to degrade in the top soil. The subsoil concentrations of the pesticides were attributed to transport with soil particles (chlorpyrifos) and via solution (acephate) through pores and cracks present in the soil profiles. The study demonstrates the high mobility of even strongly retained and fast degrading pesticides under tropical humid conditions.     

Photoisomerization of azobenzenes and spirocompounds in nematic and in twisted nematic liquid crystals

Samples of a nematic mixture of ZLI1132 and of a twisted nematic mixture composed of ZLI1132 and chiral inductor S811, including 1%-10% (w/w) 4-N,N-dimethylaminoazobenzene (DAB), (4'-nitro)-4-N,N-dimethylaminoazobenzene (NDAB), spiropyran (SP), or spirooxazine (SO) were irradiated to produce the photochromic transformation of the dopant. The changes in the system were monitored by time-resolved transmission spectroscopy, time-resolved birefringence, or polarized Raman scattering. The medium sensitivity of the kinetics and spectroscopy of some of the probes was used to derive information on polarity of the medium. In the systems studied, apart from the changes in absorption spectrum, great changes in birefringence can be photoinduced and the order of the nematic phase can be changed in either direction, depending on the dopant. The open form of SP can discriminate orientation polarity. Although the polarity parallel to the mesogenic director is similar to that for acetone, the perpendicular orientation has a polarity similar to acetonitrile. In agreement with this observation, the kinetics of the Z --> E isomerization of NDAB, oriented parallel to the mesogenic director, also experiences a polarity similar to that for acetone. The decay rate constant of the open form of SP displays a linear relationship between its Arrhenius parameters, which is universal in a great variety of homogeneous solvents, solvent mixtures, and liquid crystals, therefore validating the hypothesis that the same type of transformation is observed in all these cases, namely, the decay of the open form monomer. The dopants used have been proven to be adequate probes of bulklike properties in locally heterogeneous systems as liquid crystals.     

Spectrofluorimetric determination of melamine formaldehyde in solid and liquid forms and in wastewater

A new, simple and sensitive spectrofluorimetric method for determination of trace amount of melamine formaldehyde (MF) was developed. In phosphate buffer solution of pH 7.4 MF can remarkably quench the luminescence intensity of toluylene red (NR) at λ_em = 590 nm due to formation of NR-MF ion associate complex. The luminescence intensity of NR-MF complex was in proportion to the concentration of MF and used as photo probe for its determination. The dynamic range for the determination of MF is 7.5–52.5 ppm with detection limit of 4.4 ppm. The method is relatively free from interferences from coexisting substances and used successfully for the determining of MF in powder and liquid forms and in wastewater produced from MF industries. The average recoveries and standard deviations of 98.3 ± 0.6, 98.1 ± 0.6 and 97.3 ± 0.5% were achieved for determination of MF in solid, liquid forms and wastewater, respectively     

Gasification in air and in steam of a partly demineralized and heat-treated coal

The gasification in air and in steam of a bituminous coal from Belmez (Cordoba, Spain) (SAO) and of samples resulting either from acid treatment (HCl, SAH; HNO₃ SAN and HF, SAF) or from thermal treatment (SAOC) has been studied under dynamic conditions. For gasification in air, the sequence of variation of the reactivity is SAN > SAF>SAH>SAO at lower gasification temperatures, and SAF>SAH>SAN>SAO at higher treatment temperatures. In steam, however, the sequence is SAF>SAO, SAH>SAN in the whole interval of gasification temperatures. SAOC shows a reactivity much lower than SAO in both reactant gases. The results are explained by considering the feasible effects of the treatments on the textural characteristics and on the chemical surface of the coal.     

Heterogeneity in copper and glycan content of ceruloplasmin in human serum differs in health and disease

Crossed immunoelectrophoresis of human serum revealed two heterogeneity types of ceruloplasmin with different electrophoretic migration. The two types both consisted of peptides with Mr 150,000, 100,000 and 45,000, which were interpreted as native ceruloplasmin and two hydrolytic fragments. The two types were different in copper content, and one type could reversibly be changed into the other. The glycan microheterogeneity of ceruloplasmin was analyzed by crossed affinoimmunoelectrophoresis with free Lens culinaris agglutinin (LCA) and wheat germ agglutinin (WGA). A third of the ceruloplasmin molecules, both high and low copper type, bound to LCA and two thirds to WGA. The heterogeneity and the microheterogeneity of ceruloplasmin in two groups of patient sera were compared to sera from healthy individuals. The ceruloplasmin type with respect to copper content was a much better factor than either glycan microheterogeneity or total serum concentration in discriminating between the three groups.