Metabolic profiling of human lung cancer blood plasma using 1H NMR spectroscopy

Lung cancer (both small cell and non-small cell) is the second most common cancer in both men and women. The article represents results of evaluating of the plasma metabolic profiles of 100 lung cancer patients and 100 controls to investigate significant metabolites using 400 MHz 1H NMR spectrometer. The results of multivariate statistical analysis show that a medium-field NMR spectrometer can obtain the data which are already sufficient for clinical metabolomics

Genome Characterization of a Pathogenic Porcine Rotavirus B Strain Identified in Buryat Republic, Russia in 2015

Citation: Alekseev, K.P.; Penin, A.A.; Mukhin, A.N.; Khametova, K.M.; Grebennikova, T.V.; Yuzhakov, A.G.; Moskvina, A.S.; Musienko, M.I.; Raev, S.A.; Mishin, A.M.; Kotelnikov, A.P.; Verkhovsky, O.A.; Aliper, T.I.; Nepoklonov, E.A.; Herrera-Ibata, D.M.; Shepherd, F.K.; Marthaler, D.G. Genome Characterization of a Pathogenic Porcine Rotavirus B Strain Identified in Buryat Republic, Russia in 2015. Pathogens 2018, 7, 46.An outbreak of enteric disease of unknown etiology with 60% morbidity and 8% mortality in weaning piglets occurred in November 2015 on a farm in Buryat Republic, Russia. Metagenomic sequencing revealed the presence of rotavirus B in feces from diseased piglets while no other pathogens were identified. Clinical disease was reproduced in experimentally infected piglets, yielding the 11 RVB gene segments for strain Buryat15, with an RVB genotype constellation of G12-P[4]-I13-R4-C4-M4-A8-N10-T4-E4-H7. This genotype constellation has also been identified in the United States. While the Buryat15 VP7 protein lacked unique amino acid differences in the predicted neutralizing epitopes compared to the previously published swine RVB G12 strains, this report of RVB in Russian swine increases our epidemiological knowledge on the global prevalence and genetic diversity of RVB

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Reaction pathway and kinetic study of 4,5-dihydroxyimidazolidine-2-thione synthesis by HPLC and NMR

Process of 4,5-dihydroxyimidazolidine-2-thione (DHIT) synthesis from thiourea and glyoxal is studied. Formation of imidazole-2-thiones and 4,5-dihydroxyimidazolidin-2-one as byproducts is confirmed by NMR. The kinetics of the scalable DHIT synthesis process is studied by HPLC, and the kinetic parameters of the model based on the proposed reaction scheme are calculated. The model correctly describes the kinetics of the DHIT formation and thiourea consumption

Мочевина құрамындағы биологиялық белсенді қосылыстарды анықтауға арналған 1D және 2D NMR спектроскопиясы

Urea (carbamide) is the main end product of amino acids' metabolism in mammals. Extensive research in the field of urea chemistry has contributed to the creation of many biologically active and other compounds based on the carbamide fragment NH–CO–NH. The substituting groups of urea directly affect its properties and characteristics which are reflected in the NMR spectral data and this circumstance can be the basis for the identification of urea derivatives. In this work, chemical shifts in the NMR spectra of urea and its acyclic structure, barbituric series, imidazolidinone series and bicyclic structure derivatives were studied and identified. A system analysis was carried out to determine the effect of the type of substituents on the positions of signals of the NH-CO-NH fragment in the NMR spectra. The possibility of 2D NMR spectroscopy using to simplify the identification procedure for complex mixtures was shown in the paper. The combined use of 1D and 2D NMR spectroscopy is convenient and informative to establish the structure of biologically active compounds. These methods make it possible to determine the presence and type of impurities, as well as to establish the destruction processes leading to the corresponding impurities

Metabolic profiling of human lung cancer blood plasma using 1H NMR spectroscopy

Lung cancer (both small cell and non-small cell) is the second most common cancer in both men and women. The article represents results of evaluating of the plasma metabolic profiles of 100 lung cancer patients and 100 controls to investigate significant metabolites using 400 MHz 1H NMR spectrometer. The results of multivariate statistical analysis show that a medium-field NMR spectrometer can obtain the data which are already sufficient for clinical metabolomics

Rotational Barriers in N-Benzhydrylformamides: An NMR and DFT Study

N-Benzhydrylformamides are pharmacologically active compounds with anticonvulsant, enzyme-inducing, antihypoxic, and other types of biological activity. The conformational behavior of benzhydrylformamides is determined to a great extent by the presence of substituents at the nitrogen atom and in the ortho-position(s) of the diphenylmethane moiety. Particularly, the NMR spectra of these compounds often contain two sets of signals originating from different orientations of the formyl group. With the use of the dynamic NMR method and DFT calculations, we investigated the internal rotations of aromatic and formyl fragments and estimated the corresponding rotational barriers in N-benzhydrylformamide (BHFA), N-methyl-N-benzhydrylformamide (BHFA-NMe), and in a series of ortho-halogen-substituted N-benzhydrylformamides. It was found that the DFT method at M06-2X/6-311+G* level of theory satisfactorily reproduces the experimental barrier ΔG298≠(Formyl) of the formyl group rotation in BHFA-NMe. In BHFA, BHFA-NMe, and in the ortho-halogen derivatives, the calculated ΔG298≠(Formyl) values are close to each other and lie within 20–23 kcal/mol. On the other hand, the ortho-substituents significantly hinder the rotation of aryl fragment with ΔG298≠(Aryl) values varying from 2.5 kcal/mol in BHFA to 9.8 kcal/mol in ortho-iodo-N-benzhydrylformamide