Results of intensive phase tretament of tuberculosis treatment according to CYP2E1 genotype

The polymorphism of the gene of cytochrome P-450 2E1 (CYP2E1) that participate in metabolism of antituberculosis agent isoniazid may influence on effectiveness of tuberculosis (TB) treatment. Aim of research: to detect the peculiarities of pulmonary TB course and outcome after in -patient treatment according to CYP2E1 genotype of the patients with primary TB. Materials and methods: analysis of medical cards from 86 patients with primary pulmonary tuberculosis at the end of hospital treatment in Odessa regional antituberculosal dispensary was conducted in 2012 year with consideration of CYP2E1 genotype. Results: the obtained data has proved that at the beginning of treatment there was no significant difference between TB patients concerning the signs of destruction, infiltration and disintegration according to CYP2E1 polymorphism, however the patients with CD, DD genotype more frequently had sings of dissemination and destruction in pulmonary tissues than the patients with CC genotype. At the end of in-patient treatment the patients with CD, DD genotype more often exhibited signs of infiltration of pulmonary tissues and longer remained smear-positive according to cultural method, than the patients with CC genotype. Despite of CYP2E1 genotype around 25% of tuberculosis patients had multidrug resistant strains of M.tuberculosis in the end of in-patient treatment. It will be important to check in coming researches an influence of CYP2E1 polymorphism in TB-patients on toxicity of antituberculosis therapy

Outcomes of tuberculosis treatment depending on CYP2C19 genotype

As proven earlier, in patients with tuberculosis (TB) the concentration of antituberculosis drugs like isoniazid and rifampicin may differ depending on polymorphism of CYP2C19. The aim of the research was to determine the peculiarities of the pulmonary TB course and its outcome after the in-patient treatment depending on CYP2C19 genotype of the patients. The analysis of medical cards from 83 patients with the primary pulmonary tuberculosis at the end of the in-patient treatment in Odessa regional TB dispensary was conducted in 2012 with consideration of CYP2C19 genotype. At the beginning of the treatment the processes of disintegration were 3 times less in patients with *1/*1 genotype than in patients with *1/*2 genotype (10.3% versus 31.8%; P<0.05; χ2=5.40), and 6.5 times less than in individuals with *2/*2 genotype (10.3% versus 66.7%; P<0.05; χ2=7.94). At the end of the in-patient treatment the signs of pulmonary destruction were 6.5 times more common in individuals with *1/*1 genotype than in individuals with *1/*2 genotype (29.3 versus 4.5; Р<0.05; χ2=5.61). The signs of resorption and consolidation in the pulmonary tissue were observed in 74.1% of the patients with *1/*1 genotype, 95.5% of the patients with *1/*2 genotype and 66.7% of the patients with *2/*2 genotype. There were no significant differences between groups in relation to duration of the treatment and development of drug-resistance

An impact of CYP3A4 *1B polymorphism on rifampicin metabolism

Until now, the enzyme systems responsible for biotransformation of the antituberculous drug rifampicin remain unknown. The aim of research was an investigation of the candidate enzymes involved in the biotransformation of rifampicin using the computer system PASS and an experimental study concerning the effect of the polymorphism of the biotransformation gene CYP3A4 *1B on the level of rifampicin in the blood of patients with pulmonary tuberculosis (РTB).The probability (Pa) of certain pharmacological activity and the effect on putative enzyme systems of the human body of rifampicin has been calculated by the PASS method. Polymerase chain reaction revealed the polymorphism of the CYP3A4 *1B gene among healthy volunteers as well as patients with РTB.With a high degree of probability, according to PASS calculations, it was predicted that rifampicin undergo metabolism with the CYP3A4 enzyme - probability (Ra) were 0.891. According to the genotype CYP3A4 *1B, 95.3% of the healthy donors carried a homozygous wild-type gene (i.e., had high enzymatic activity) - AA genotype; the rest 4.7% - were carriers of the heterozygous AG genotype (moderate enzyme activity).The polymorphism of CYP3A4 *1B genotypes and alleles in the south-west of Ukraine was close to the results obtained in European countries. 91.4% and 8.6% of the patients with РTB had AA and AG genotype, correspondently. Thus, among the patients with РTB, the AG genotype was more often observed than among healthy volunteers. There was no significant difference in rifampicin concentration among РTB-patients concerning CYP3A4 * 1B polymorphism

Critical behavior of frustrated systems: Monte Carlo simulations versus Renormalization Group

We study the critical behavior of frustrated systems by means of Pade-Borel resummed three-loop renormalization-group expansions and numerical Monte Carlo simulations. Amazingly, for six-component spins where the transition is second order, both approaches disagree. This unusual situation is analyzed both from the point of view of the convergence of the resummed series and from the possible relevance of non perturbative effects.Comment: RevTex, 10 pages, 3 Postscript figure

Polymorphism of cytochrome Р-450 2E1 gene in Odessa region healthy volunteers

Значні міжетнічні відмінності щодо поліморфізму генів біотрансформації ліків мають значення для дії багатьох лікарських препаратів. Тому метою даної роботи було дослідження поліморфізму гена цитохрому P-450 2E1 (CYP2E1) серед здорових добровольців на прикладі Одеського регіону. Для цього визначали наявність мутації у 6-му інтроні CYP2E1 за допомогою ферменту ендонуклеази DraI і полімеразної ланцюгової реакції. Відповідно до генотипу CYP2Е1, зі 112 здорових донорів 82,1 % індивідів були носіями гомозиготного дикого типу гена *DD, решта 17,9 % мали генотип *CD; носії генотипу *CС були відсутні. Жодних суттєвих відмінностей щодо віку, статі, групи крові серед носіїв різних генотипів і алелів CYP2Е1 не спостерігалося. Поліморфізм генотипів і алелів CYP2Е1 на Півдні України був близьким до результатів досліджень у країнах Європи, включаючи Російську Федерацію і Туреччину, і суттєво відрізнявся від даних, отриманих у Південно-Східній Азії (Малайзія, Китай) і США.The significant inter-ethnic differences concerning polymorphism of biotransformation genes affect the activities of numerous medicines. That is why the aim of current research was an investigation of polymorphism of cytochrome P-450 2E1 (CYP2E1) in healthy volunteers in Odessa region. So, it was studied a presence of mutation in 6th intron CYP2E1 with the help of DraI endonuclease and polymerase chain reaction. According to CYP2Е1 genotype out of 112 donors 82,1 % carried homozygote wild type of gene *DD, others — 17,9 % had *CD genotype; carriers of *CС genotype were absent. There were no significant differences in CYP2Е1 genotype according to age, sex, blood group. The polymorphism of CYP2E1 genotype on south of Ukraine was close with results from European countries, including Russia and Turkey and varied from data of South-East Asia (Malaysia, Chine) and USA

Biochemical markers and cells count in peripheral blood in patients with tuberculosis according to CYP2C9 genotype

Целью работы было исследование течения туберкулеза легких в зависимости от полиморфизма цитохрома-Р450 2С9 (CYP2С9) согласно клеточному составу и биохимическим показателям крови. Был проведен анализ медицинских карт 83 больных с впервые диагностированным туберкулезом легких в начале и при завершении стационарного лечения в Одесском областном противотуберкулезном диспансере в 2012 году. Как в начале, так и при завершении стационарного лечения больные с генотипами *2/*3, *3/*3 имели наибольший уровень эритроцитов и гемоглобина и самый низкий уровень СОЭ, что свидетельствует о меньшей выраженности явлений интоксикации. Также у этой группы больных отмечались наиболее высокие показатели АлТ и ГГТ, что свидетельствует о большем риске токсичности противотуберкулезной терапии у носителей генотипов *2/*3, *3/*3 по сравнению с носителями генотипов *1/*1, *1/*2, *1/*3.The aim of present work was detection of peculiarities of pulmonary tuberculosis course depending on cytochrome-450 2C9 (CYP2C9) polymorphism according on cellular content of cells count and biochemical markers of the blood. it was done analysis of 83 medical card of primary pulmonary tuberculosis at the beginning and at the end of in-patient treatment in Odessa district dispensary in 2012 y. At the beginning and at the end of in-patient treatment the patients with genotype *2/*3, *3/*3 have had the highest level of erythrocytes and hemoglobin, and the lowest level of erythrocytes sedimentation rate that witnessed the slight intoxication. Also in this group of patients it was found the highest level of alanine aminotransferase and gamma glutathione transferase that have proved higher risk of toxicity of antituberculosis therapy in the carriers of *2/*3, *3/*3 genotype relatively to carriers of *1/*1, *1/*2, *1/*3 genotypes

Hygienic substantiation of calculating models for predicting toxicity of different classes insecticides (first part).

This work is the first part of our study to develop alternative experimental mathematic models for predicting toxicity of insecticides. In the first stage, calculations will be carried out and the most reliable models will be proposed. In the second – a statistical analysis and comparative estimation of the toxicometric parameters obtained experimentally and calculated according to the proposed equations. The purpose of the research is the scientific substantiation of the calculation models for predicting toxicity of insecticides of different classes. Data on the physico-chemical properties and toxicometry parameters of fungicides are taken from the PPDB pesticides database. Insecticides of such chemical classes as derivatives of tetram and tetronic acids, benzoylureas, carbamates, neonicotinoids, pyrethroids, organophosphorus compounds, avermectins were selected for analysis. It has been established that there is a significant positive correlation between NO(A)EL in the chronic experiment of all insecticides, the median lethal doses at oral administration (LD50 per os) of pyrithoids and neonicotinoids, and the molecular weight (at p&lt;0.05). There is a significant negative correlation between the toxicometry parameters of all insecticides and their individual groups (pyrithoids, neonicotinoids, organophosphorus compounds) and melting temperature and the octanol-water partition coefficient, log Po/w (at p&lt;0.05). It is proved that the proposed calculation models for predicting insecticide hazards are adequate according to Fisher's criterion, and the coefficients of regression equations are reliable according to Student's criterion (p&lt;0,05)

Spin Stiffness of Stacked Triangular Antiferromagnets

We study the spin stiffness of stacked triangular antiferromagnets using both heat bath and broad histogram Monte Carlo methods. Our results are consistent with a continuous transition belonging to the chiral universality class first proposed by Kawamura.Comment: 5 pages, 7 figure

A characterization of those automata that structurally generate finite groups

Antonenko and Russyev independently have shown that any Mealy automaton with no cycles with exit--that is, where every cycle in the underlying directed graph is a sink component--generates a fi- nite (semi)group, regardless of the choice of the production functions. Antonenko has proved that this constitutes a characterization in the non-invertible case and asked for the invertible case, which is proved in this paper

Emission of charged particles from excited compound nuclei

The formation of excited compound nucleus (CN) and its statistical decay is investigated within the dinuclear system (DNS) model.The initial DNS is formed in the entrance channel when the projectile is captured by a target, and then the evolution of DNS in mass asymmetry coordinate leads to formation of the hot CN. The emission barriers for complex fragments were calculated within the DNS model by using the double folding procedure for the interaction potential. It is shown that cross sections for complex fragment emission become larger when excited CN is more neutron deficient. This approach gives also an opportunity to calculate the new neutron deficient isotopes production cross sections and can be applied to describe the hot fission of heavy systems.The model was tested by comparison of calculated results with experimental dat