Measurement of the average time-integrated mixing probability of b-flavored hadrons produced at the Fermilab Tevatron

We have measured the number of like-sign (LS) and opposite-sign (OS) lepton pairs arising from double semileptonic decays of b and (b) over bar hadrons, pair produced at the Fermilab Tevatron collider. The data samples were collected with the Collider Detector at Fermilab during the 1992-1995 collider run by triggering on the existence of mumu or emu candidates in an event. The observed ratio of LS to OS dileptons leads to a measurement of the average time-integrated mixing probability of all produced b-flavored hadrons which decay weakly, (χ) over bar =0.152+/-0.007 (stat)+/-0.011 (syst), that is significantly larger than the world average (χ) over bar =0.118+/-0.005

The frequency of CYP2C19 genetic polymorphisms in Russian patients with peptic ulcers treated with proton pump inhibitors

DA Sychev,1,2 NP Denisenko,1,2 ZM Sizova,2 AV Grachev,3 KA Velikolug4 1Russian Medical Academy of Post-Graduate Education, 2I.M. Sechenov First Moscow State Medical University, 3SM-Clinic, 4Out-patient department Number 51 branch 3, Moscow, Russia Introduction: Proton pump inhibitors, which are widely used as acid-inhibitory agents for the treatment of peptic ulcers, are mainly metabolized by 2C19 isoenzyme of cytochrome P450 (CYP2C19). CYP2C19 has genetic polymorphisms, associated with extensive, poor, intermediate or ultra-rapid metabolism of proton pump inhibitors. Genetic polymorphisms of CYP2C19 could be of clinical concern in the treatment of peptic ulcers with proton pump inhibitors. Aim: To investigate the frequencies of CYP2C19*2, CYP2C19*3, and CYP2C19*17 alleles and genotypes in Russian patients with peptic ulcers. Methods: We retrospectively reviewed the cases of 971 patients of Caucasian origin with Russian nationality from Moscow region with endoscopically and histologically proven ulcers, 428 males (44%) and 543 females (56%). The mean age was 44.6±11.9 years (range: 15–88 years). DNA was extracted from ethylenediaminetetraacetic acid whole blood samples (10 mL). The polymorphisms CYP2C19 681G>A (CYP2C19*2, rs4244285), CYP2C19 636 G>A (CYP2C19*3, rs4986893) and CYP2C19 -806 C>T (CYP2C19*17, rs12248560) were evaluated using real-time polymerase chain reaction. Results: Regarding CYP2C19 genotype, 317 patients (32.65%) out of 971 were CYP2C19*1/*1 carriers classified as extensive metabolizers. Three hundred and eighty-six (39.75%) with CYP2C19*1/*17 or CYP2C19*17/*17 genotype were ultra-rapid metabolizers. Two hundred and fifty-one people (25.85%) were intermediate metabolizers with CYP2C19*1/*2, CYP2C19*2/*17, CYP2C19*1/*3, CYP2C19*3/*17 genotypes. Seventeen patients (1.75%) with CYP2C19*2/*2, CYP2C19*3/*3, CYP2C19*2/*3 genotypes were poor metabolizers. The allele frequencies were the following: CYP2C19*2 – 0.140, CYP2C19*3 – 0.006, CYP2C19*17 – 0.274. Conclusion: There is a high frequency of CYP2C19 genotypes associated with modified response to proton pump inhibitors in Russian patients with peptic ulcers. Genotyping for CYP2C19 polymorphisms is suggested to be a useful tool for personalized dosing of proton pump inhibitors. Keywords: CYP2C19, proton pump inhibitors, peptic ulcer, Russia

MicroRNA and vascular pathology of the eye

Since the discovery of microRNAs just a few decades ago, our knowledge of these molecules and their potential as diagnostic biomarkers and therapeutic targets has significantly expanded. There is an ongoing discussion in the scientific community about the possibility of using microRNA for the diagnosis of cardiovascular diseases. It has been shown recently that levels of some microRNAs vary in vascular eye disorders, such as age-related macular degeneration and diabetic retinopathy. However, despite serious advances in our understanding of microRNA’s role in eye pathology, we still do not know whether it is possible to use microRNA as a biomarker for central retinal vein occlusion. Perhaps, the discovery of such candidate microRNAs will help in making the timely diagnosis and improve the quality of medical care in patients with retinal vein occlusion.</jats:p

The frequency of SLCO1B1*5 polymorphism genotypes among Russian and Sakha (Yakutia) patients with hypercholesterolemia

Dmitrij Alekseevitch Sychev,1 Grigorij Nikolaevich Shuev,2 Jana Valer&#39;evna Chertovskih,3 Nadezhda Romanovna Maksimova,3 Andrej Vladimirovich Grachev,1 Ol&#39;ga Aleksandrovna Syrkova2 1Department of Internal Medicine and Clinical Pharmacology, Russian Medical Academy of Postgraduate Education, Moscow, 2Faculty of Postgraduate Education, Far Eastern State Medical University, Khabarovsk, 3Genetic Laboratory, Ammosov North-Eastern Federal University, Yakutsk, Russian Federation Introduction: Statins are the most commonly prescribed medicines for treatment of hypercholesterolemia. At the same time, up to 25% of patients cannot tolerate or have to discontinue the statin therapy due to statin-induced myopathy. In a majority of cases, statin-induced myopathy is attributed to SLCO1B1 gene polymorphism. The strongest association between statin-induced myopathy and SLCO1B1 gene polymorphism was described for simvastatin. Our research was focused on the frequency of SLCO1B1*5 genetic variant in the Russian population and in the native population of Sakha (Yakutia).Materials and methods: A total of 1,071 hyperlipidemic Russian and 76 hyperlipidemic Sakha (Yakutian) patients were included in the study. Genotypes of SLCO1B1*5 (c.521T&gt;C, rs4149056) were determined with polymerase chain reaction amplification. The results of our study were compared with data about hyperlipidemic patients in available publications.Results: In the Russian population 665 (62%) patients had TT genotype of SLCO1B1*5, 346 (32%) patients had TC genotype, and in 60 patients (6%) CC variant was found (Hardy&ndash;Weinberg&#39;s chi-square test was 3.1 P=0.21). In comparison with Brazil, France, the People&#39;s Republic of China, Japan, and the native population of Sakha (Yakutia), C-allele, which causes an increased risk of statin-induced myopathy, was found significantly more often in the Russian population. In the native population of Sakha (Yakutia) SLCO1B1 polymorphism was TT &ndash; 62 (82%), TC &ndash; 11 (14%), CC &ndash; 3 (4%) (Hardy&ndash;Weinberg&#39;s chi-square test was 5.13 P=0.077). In comparison with data from Brazil, France, the People&#39;s Republic of China, and Japan, C-allele frequency in the Sakha (Yakutian) population was not significantly different.Conclusion: Thus, we have studied the incidence of pathologic SLCO1B1 c.521C-allele in Russian and Sakha hyperlipidemic patients. The presence of SLCO1B1 C-allele in patients with hyperlipidemia forces us to be more careful in hypolipidemic drug prescription, especially statins, according to a higher risk of statin-induced myopathy development. The fact that SLCO1B1 C-allele is rarer among Sakha patients, could be interesting from the point of studying adverse drug effects frequency and statins&#39; effectiveness.Keywords: Russian, Sakha (Yakutia), pharmacogenetics, SLCO1B1, statins, myopath

The correlation between CYP2D6 isoenzyme activity and haloperidol efficacy and safety profile in patients with alcohol addiction during the exacerbation of the addiction

Dmitry Alekseevich Sychev,1 Mikhail Sergeevich Zastrozhin,1&ndash;3 Valery Valerieevich Smirnov,4 Elena Anatolievna Grishina,1 Ludmila Mikhailovna Savchenko,1 Evgeny Alekseevich Bryun1,2 1Russian Medical Academy of Postgraduate Education, Ministry of Health of the Russian Federation, 2Department of Public Health, Moscow Research and Practical Centre for Narcology, 3Peoples&rsquo; Friendship University of Russia, 4National Research Center, Institute of Immunology Federal Medical-Biological Agency of Russia, Moscow, Russia Background: Today, it is proved that isoenzymes CYP2D6 and CYP3A4 are involved in metabolism of haloperidol. In our previous investigation, we found a medium correlation between the efficacy and safety of haloperidol and the activity of CYP3A4 in patients with alcohol abuse.Objective: The aim of this study was to evaluate the correlation between the activity of CYP2D6 and the efficacy and safety of haloperidol in patients with diagnosed alcohol abuse.Methods: The study involved 70 men (average age: 40.83&plusmn;9.92 years) with alcohol addiction. A series of psychometric scales were used in the research. The activity of CYP2D6 was evaluated by high-performance liquid chromatography with mass spectrometry using the ratio of 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline to pinoline. Genotyping of CYP2D6 (1846G&gt;A) was performed using real-time polymerase chain reaction.Results: According to results of correlation analysis, statistically significant values of Spearman correlation coefficient (rs) between the activity of CYP2D6 and the difference of points in psychometric scale were obtained in patients receiving haloperidol in injection form (Sheehan Clinical Anxiety Rating Scale =-0.721 [P&lt;0.001] and Udvald for Kliniske Undersogelser Side Effect Rating Scale =0.692 [P&lt;0.001]) and in those receiving haloperidol in tablet form (Covi Anxiety Scale =-0.851 [P&lt;0.001] and Udvald for Kliniske Undersogelser Side Effect Rating Scale =0.797 [P&lt;0.001]).Conclusion: This study demonstrated the correlations between the activity of CYP2D6 isozyme and the efficacy and safety of haloperidol in patients with alcohol addiction. Keywords: haloperidol, biotransformation, CYP2D6, side effects, alcohol addictio

Water-in-oil emulsion foaming by thiourea nitrosation: reaction and mass transfer

A study has been undertaken into the chemical production of gas bubbles within a concentrated water-in-oil emulsion, typical of those used as emulsion explosives. Chemical foaming was initiated by the introduction of a concentrated sodium nitrite solution to the emulsion, and the measurement of the decreasing emulsion density with time served to estimate the rate of nitrogen production. A conversion of emulsion density to nitrite ion concentration facilitated a kinetic analysis of the data. The change in nitrite ion concentration follows a rate equation which indicates that the rate-limiting reaction step corresponds to the N-nitrosation of thiourea by ON⁺, with an apparent rate constant of 0.22 M⁻¹ s⁻¹ at 25 °C. Tests over a temperature range of 25 to 50 °C yielded an activation energy of 59 kJ mol⁻¹. A mass-transfer model describing the rate of diffusion between aqueous droplets is presented. This model suggests that chemical kinetics, rather than molecular diffusion, is the rate-limiting phenomenon in the foaming of emulsions. Supporting this finding, the kinetic experiments in emulsion returned very similar results to previous experiments performed in aqueous media under similar conditions

Do CYP2C19 and ABCB1 gene polymorphisms and low CYP3A4 isoenzyme activity have an impact on stent implantation complications in acute coronary syndrome patients?

Eric Rytkin,1 Karin B Mirzaev,1 Elena A Grishina,1 Valeriy V Smirnov,2 Kristina A Ryzhikova,1 Zhannet A Sozaeva,1 Michael Iu Giliarov,2 Denis A Andreev,2 Dmitriy A Sychev1 1Russian Medical Academy of Continuous Professional Education, 2I.M. Sechenov First Moscow State Medical University, Ministry of Health of the Russian Federation, Moscow, Russian Federation Aim: The aim of this study was to determine the impact of CYP2C19 and ABCB1 gene polymorphisms and CYP3A4 isoenzyme activity on stent implantation complications among patients with an acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI).Patients and methods: Seventy-six patients (median age 63, range 37&ndash;91 years) with an ACS who underwent PCI were screened for CYP2C19 and ABCB1 gene polymorphisms with real-time polymerase chain reaction: CYP2C19*2, CYP2C19*17, and ABCB1 3435. CYP3A4 isoenzyme activity was determined by urine cortisol and 6-beta-hydroxycortisol levels. Stent implantation complications such as stent thrombosis (n=2) and restenosis (n=1) were observed among drug-eluting stent recipients.Results: Low mean 6-beta-hydroxycortisol/cortisol ratio is indicative of impaired CYP3A4 activity and was associated with higher risk of thrombosis (&beta; coefficient=0.022, SE 0.009, p=0.021 in the linear regression model). The increase in the length of the implanted stent was associated with higher risk of restenosis (&beta;&nbsp;coefficient=0.006, SE=0.002, p=0.001 in the linear regression model). The presence of the CYP2C19*2 polymorphism did not affect the incidence of stent thrombosis (&beta;&nbsp;coefficient=&minus;1.626, SE=1.449, p=0.262 in the logistic regression model), nor did the CYP2C19*17 (&beta;&nbsp;coefficient=&minus;0.907, SE=1.438, p=0.528 in the logistic regression model) and ABCB1 3435 polymorphisms (&beta;&nbsp;coefficient=1.270, SE=1.442, p=0.378 in the logistic regression model).Conclusion: We did not find evidence that the presence of CYP2C19*2, CYP2C19*17, and ABCB1 3435 polymorphisms may jeopardize the safety of stent implantation in patients with an ACS. Patients with low CYP3A4 isoenzyme activity may have increased risk of stent thrombosis. Keywords: acute coronary syndrome, clopidogrel, complications, polymorphism, stents&nbsp