Comparative studies of O,O-dialkyl-O-chloromethylchloroformimino phosphates: interaction with neuropathy target esterase and acetylcholinesterase

Acetylcholinesterase (AChE) and neuropathy target esterase (neurotoxic esterase, NTE) are two major target enzymes for organophosphorus (OP) esters. The relative potency of an OP ester to react with AChE or with NTE in vitro correlates with its relative potency in vivo to cause acute toxicity (death) or organopohosphate-induced delayed neurotoxicity (OPIDN). On this basis extrapolation from in vitro to in vivo data now seems justifiable to predict risk of OPIDN. The kinetics of NTE and AChE inhibition by experimental pesticides of the general formula (RO)2P(O)ON=CClCH2Cl, where R = methyl, ethyl, isopropyl, propyl, isobutyl, butyl, pentyl, has been studied. Compounds with short R (methyl, ethyl) were shown to be far more potent inhibitors of AChE than NTE. Both anti-NTE activity, selectivity for NTE and, correspondingly, the propensity of compounds to cause OPIDN rise with increasing their hydrophobicity. A high value of ki(NTE)/ki(AChE) for R = pentyl suggests that this compound would have the potential to cause OPIDN at doses lower than the LD50. A quantitative structure-activity relationships (QSAR) analysis indicated that NTE and AChE have different structural and electronic requirements for their respective OP inhibitors.     

Lipanor treatment of atherogenic hyperlipoproteinemia

AIM: The study of the hypolipidemic efficiency, safety and tolerance of ciprofibrate (lipanor) in therapy of atherogenic hyperlipoproteinemia. MATERIALS AND METHODS: The trial included 14 hypertensive postmenopausal females, 14 patients with diabetes mellitus type II, 14 males with coronary heart disease and primary hyperlipoproteinemia (total cholesterol > 6.5 mmol/l, triglycerides < 4.5 mmol/l under low-cholesterol diet). Lipanor was given for 12 weeks in a daily single dose 100 mg in the morning. Lipids and other biochemical indices were measured in a fasting state after 1 and 3 months of lipanor treatment. RESULTS: After 1 month of lipanor treatment there was a 22-30%, 24-49% decrease in the level of low-density lipoprotein cholesterol, triglycerides, respectively. High-density lipoprotein cholesterol increased by 16%. The hypolipidemic effect of lipanor persisted for 3 months during which triglycerides continued to fall (up to 38.5%). Lipanor was well tolerated, only one patient with diabetes mellitus had hyperactivity of creatine phosphokinase manifesting with clinical symptoms (the drug was discontinued). 3 patients developed mild side effects. Alkaline phosphatase activity inhibited in all the groups by 25-41%. CONCLUSION: Lipanor is a highly effective, safe hypolipidemic drug with good tolerance. It can be recommended for correction of atherogenic hyperlipoproteinemia in patients at high risk of atherosclerosis progression.     

Gas chromatography in express diagnosis of candidiasis and monitoring of antifungal therapy efficacy by D-arabinitol and mannose levels in pediatric patients]

Methods for preventing and treating Ebola virus hemorrhagic fever are not still available despite the fact that this virus have been studied for 20 years. Methods of immunization of the animals (sheep, goats) non-susceptible to Ebola virus with live virus preparations were developed to obtain the hyperimmune anti-Ebola virus sera required to have highly immune antivirus gamma-globulins. These methods made it possible to obtain the immune sera having high virus-neutralizing antibodies. Caprine immunoglobulins were obtained from sera by fractionation of immune sera by Kohn's method. The neutralization indices of the immunoglobulins obtained were at least Ig. When administered in the first hours of infection, the protective effect of these preparations was shown on guinea pigs infected with LD50 of the strain pathogenic to the animals. Preclinical trials of these immunoglobulins on laboratory animals and clinical trials on volunteers were performed. The preparation was used as a preventive agent when accidents took place at the laboratory working with Ebola virus. The similar preparation from equine sera having high neutralizing and protective properties was elaborated at the Virological Center, Microbiological Institute, Russian Ministry of Defense. Its prophylactic efficiency was also shown in infected gamadrias.     

The effect of insulin on the function of the lysosomal apparatus of the neutrophilic leukocytes during the formation of a stress syndrome

In experiments on male rabbits with the lack of insulin it is been revealed violations after the past immobilization the intensivity and duration of neutrophilic leukocytosis decrease, contents of lysosomes in neutrophils, activity of acid phosphatase. By lysosomal ferments don't determine the can observer discordance of processes of coagulation, fibrinolysis, kininogenesis.     

Granulometric Analysis of Powder Materials Used for Producing Samples by Method of Selective Laser Melting

Metallurgist - The paper discusses the aspects of granulometric and morphological analysis of powders used in the technology of selective laser melting. Studies have been carried out to obtain...     

TiN/Cr/Al2O3 and TiN/Al2O3 hybrid coatings structure features and properties resulting from combined treatment

New experimental results are presented on the structure and the elemental and phase composition of hybrid coatings, which were deposited on a substrate of AISI 321 stainless steel using a combination of plasma-detonation, vacuum-arc and subsequent High-Current Electron Beam (HCEB) treatment. We found that an increase in energy density intensified mass transfer processes and resulted in changes in aluminum oxide phase composition (γ → α and β → α). Also we observed the formation of a nanocrystalline structure in Al₂O₃ coatings. Electron beam treatment of a hybrid coating surface induced higher adhesion, decreased the intensity of surface wear and increased corrosion resistance in a sulphuric acid solution. The corrosion resistance of the coatings was studied in several electrolytic solutions (0.5 M H₂SO₄, 1 M HCl, 0.75 M NaCl) using electrochemical techniques. In most cases the corrosion resistance was improved, except those in NaCl solutions. The nano-hardness of the protecting coating was 13 GPa before electron beam melting and 9 GPa after it (as a result of TiN and Al₂O₃ sub-layers mixing).     

A method for calculating the tangent on the basis of the Hough transform

A method for calculating the tangent direction for a digital curve on the basis of the Hough transform is proposed. The initial data for the Hough transform are taken from tables of angular intervals obtained from a catalog of digital curves. Such a catalog is constructed for a chosen size of the local window on the basis of a specially developed indexation of curves. When determining the intervals of tangent directions for the catalog of curves, several methods of parameterization are used: straight line, elliptic or sinusoidal arc, and superposition of harmonics. The curve selection criterion is the maximum curvature of the corresponding smooth parametric curves. This makes it possible to adapt the method to a class of initial curves. Comparison with earlier-developed methods has demonstrated a significant increase in accuracy, especially with an increase in the curvature.     

Erratum to: Minimizing total tardiness on parallel machines with preemptions

In this note, we correct a mistake which was made in the paper “Minimizing Total Tardiness on Parallel Machines with Preemptions” (see J Schedul 15:193–200, 2012).     

Human immunodeficiency virus 1 (HIV-1)-specific reverse transcriptase (RT) inhibitors may suppress the replication of specific drug-resistant (E138K)RT HIV-1 mutants or select for highly resistant (Y181C-->C181I)RT HIV-1 mutants

Mutant HIV-1 that expresses a Glu138-->Lys substitution in its RT [(E138K)RT] is resistant to the HIV-1-specific RT inhibitor 2',5'-bis-O-(tert-butyldimethylsilyl)-3'-spiro-5"-(4"-amino-1",2"- oxathiole-2",2"-dioxide)pyrimidine (TSAO). However, cell cultures infected with this mutant were completely protected against virus-mediated destruction by micromolar concentrations of the HIV-1-specific RT inhibitors tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one and -thione (TIBO), nevirapine, and bis(heteroaryl)piperazine (BHAP). In contrast, cells infected with a virus mutant that expresses a Tyr181-->Cys substitution in its RT [(Y181C)RT] were not protected by nevirapine and TIBO and were only temporarily protected by BHAP. HIV-1 mutant that emerged under the latter conditions contained a Cys181-->Ile substitution in their RT [(LC181I)RT]. This mutant proved highly resistant to all HIV-1-specific RT inhibitors tested, except for several 1-(2-hydroxyethoxymethyl)-6-(phenylthio)thymine (HEPT) derivatives. When recombinant (C181I)RT was evaluated for susceptibility to the HIV-1-specific RT inhibitors, it was resistant to all inhibitors except the HEPT compounds. Since a (Y181F)RT HIV mutant strain was isolated from cells infected with (Y181C)RT HIV-1 and treated with BHAP, we postulate that the Ile codon was derived from a Cys-->Phe transversion mutation (TGT-->TTT), followed by a Phe-->Ile transversion mutation (TTT-->ATT).