Unrecorded alcohol consumption in Russia: toxic denaturants and disinfectants pose additional risks

In 2005, 30% of all alcohol consumption in Russia was unrecorded. This paper describes the chemical composition of unrecorded and low cost alcohol, including a toxicological evaluation. Alcohol products (n=22) from both recorded and unrecorded sources were obtained from three Russian cities (Saratov, Lipetsk and Irkutsk) and were chemically analyzed. Unrecorded alcohols included homemade samogons, medicinal alcohols and surrogate alcohols. Analysis included alcoholic strength, levels of volatile compounds (methanol, acetaldehyde, higher alcohols), ethyl carbamate, diethyl phthalate (DEP) and polyhexamethyleneguanidine hydrochloride (PHMG). Single samples showed contamination with DEP (275–1269 mg/l) and PHMG (515 mg/l) above levels of toxicological concern. Our detailed chemical analysis of Russian alcohols showed that the composition of vodka, samogon and medicinal alcohols generally did not raise major public health concerns other than for ethanol. It was shown, however, that concentration levels of DEP and PHMG in some surrogate alcohols make these samples unfit for human consumption as even moderate drinking would exceed acceptable daily intakes

CONSERVATIVE THERAPY IN MYOCARDIAL INFARCTION: THE IMPACT OF GENETIC FACTORS

Recently, myocardial infarction is a significant medical and social problem. Mortality in one year after infarction remains high, regardless the therapy with all recommended for the prognosis improvement medications. As one of probable reasons for adverse prognosis could be considered drug tolerance, related to genes polymorphism, responsible for pharmacokinetics and pharmacodynamics of the drugs. Current review summarizes some available at the moment literature data in the genes SLCO1B1, LIPC, CYP2C19, АСЕ, ADRB1 polymorphism influence on the effectiveness of myocardial infarction therapy, that might be useful for further scientific investigation or improvement of long term treatment of this disease by personalization of drug therapy

The Narimanov-Moiseev multimodal analysis of nonlinear sloshing in circular conical tanks

The chapter reports mathematical aspects of the Narimanov–Moiseev multimodal modelling for the liquid sloshing in rigid circular conical tanks, which perform small-magnitude oscillatory motions with the forcing frequency close to the lowest natural sloshing frequency. To derive the corresponding nonlinear modal system (of ordinary differential equations), we introduce an infinite set of the sloshing-related generalised coordinates governing the free-surface elevation but the velocity potential is posed as a Fourier series by the natural sloshing modes where the time-depending coefficients are treated as the generalised velocities. The employed approximate natural sloshing modes exactly satisfy both the Laplace equation and the zero-Neumann boundary condition on the wetted tank walls. The Lukovsky non-conformal mapping technique transforms the inner (conical) tank (physical) domain to an artificial upright circular cylinder, for which the single-valued representation of the free surface is possible. Occurrence of secondary resonances for the V-shaped truncated conical tanks is evaluated. The Narimanov–Moiseev modal equations allow for deriving an analytical steady-state (periodic) solution, whose stability is studied. The latter procedure is illustrated for the case of longitudinal harmonic excitations. Standing (planar) waves and swirling as well as irregular sloshing (chaos) are established in certain frequency ranges. The corresponding amplitude response curves are drawn and extensively discussed

ASPECTS OF LIPID-LOWERING THERAPY WITH ATORVASTATIN IN PATIENTS WITH MYOCARDIAL INFARCTION FROM THE PERSPECTIVE OF PERSONALIZED MEDICINE

Aim. To analyze the impact of the SLCO1B1*5 (c.521T&gt; C) and LIPC (C514T) genes polymorphisms on the efficacy of atorvastatin therapy and the incidence of the combined endpoint in patients after myocardial infarction (MI).Material and methods. 121 patients with MI aged 45-75 years were included into the study. All patients were prescribed atorvastatin. A group of 65 people in whom lipid levels were studied at baseline and after 3 months of atorvastatin treatment was formed to evaluate the efficacy of statin therapy. Genetic polimorphism of SLCO1B1*5 (c.521T&gt; C) and LIPC (C514T) was determined using polimerase chain reaction. The prognosis was assessed by clinical outcomes after 3 months of follow-up, based on the achievement of the combined endpoint MACE (Major Adverse Cardiac Events), which included cardiovascular deaths, recurrent MI, hospitalization for progressive angina, unplanned coronary revascularization.Results. Patients with SLCO1B1 c.521СC genotype had no significant reduction in the levels of atherogenic lipids (p&gt;0.05), while patients with TT and TC genotypes demonstrated significant reduction in atherogenic cholesterol fractions (p&lt;0.05). Allelic polymorphism of LIPC (C514T) gene has no influence on the atorvastatin treatment efficacy. The SLCO1B1 and LIPC (C514T) genes polymorphism has no impact on the three-month prognosis after MI.Conclusion. The SLCO1B1 polymorphism should be taken into consideration while personalised prescribing of atorvastatin to patients with MI.</p

The gene polymorphism of beta1-adrenoreceptor, postinfarction myocardial remodeling and cardiovascular risk: is there any correlation?

The influence of gene polymorphisms ADRB1 (Ser49Gly), ADRB1 (Arg389Gly) on myocardial remodeling and 12-month prognosis of patients with ST-segment elevation myocardial infarction (STEMI) was studied. The gene polymorphisms ADRB1 (Ser49Gly) and ADRB1 (Arg389Gly) does not affect myocardial remodeling. Ser49 allele is associated with a greater incidence of acute coronary events, such as death from cardiovascular causes, repeated non-fatal myocardial infarction, unplanned coronary revascularization, hospitalization for progressive angina pectoris within a year after STEMI. The Gly49 allele and the Gly49Gly genotype are associated with a favorable prognosis within a year after STEMI. The gene polymorphism ADRB1 (Arg389Gly) does not affect the prognosis after STEMI

PREDICTORS OF LONG-TERM PROGNOSIS OF MYOCARDIAL INFARCTION: FOCUS ON THE PHARMACOKINETICS

Aim: to analyze the prognostic value of gene polymorphisms ACE (D/I), SLCO1B1 (Val174Ala), LIPC (C514T), CYP2C19*2, CYP2C19*3, ADRB1 (Ser49Gly), ADRB1 (Arg389Gly) of patients with ST-segment elevation myocardial infarction (STEMI).Materials and methods. 155 patients with STEMI from 45 to 75 years of age were involved into the study. All patients were prescribed all recommended preparations improving prognosis (statins, angiotensin-converting enzyme inhibitors, beta-blockers, clopidogrel as part of dual antiplatelet therapy) from the fi rst day of hospitalization. Prognosis was assessed by endpoints: cardiovascular mortality, nonfatal myocardial infarction throughout 12 months.Results. Carriers genotypes *1*2 and *1*3 had in 3,27 times higher risk of recurrent myocardial infarction within 1 year from the STEMI (р=0,03). There was no effect of gene polymorphisms ACE (D/I), SLCO1B1 (Val174Ala), LIPC (C514T), ADRB1 (Ser49Gly), ADRB1 (Arg389Gly) on the probability of recurrent myocardial infarction (p&gt;0,05). Associative links studied polymorphisms with the cardiovascular mortality is not installed (p&gt; 0,05)

Полиморфизм гена CYP2C19 и его влияние на долгосрочный прогноз при инфаркте миокарда

Background: Despite advanced in interventional and medical treatment, mortality after myocardial infarction (MI) remains high, which necessitates the search for predictors of poor outcome. An association between the gene CYP2C19 alleles with lower functional activity and the rates of cardiovascular events has been found. In a number of studies, negative impact of the *2 and *3 alleles of this polymorphic gene on the post-infarction course was shown. However, in most of these studies the patients were followed up from 3 months to 1 year. Aim: To evaluate the effect of CYP2C19 gene polymorphism (*2, *3) on the long-term prognosis in patients with a history of ST-segment elevation myocardial infarction (STEMI). Materials and methods: This open-label prospective two-center study included 145 patients aged 45 to 75 years with a history of STEMI. For 1 year from STEMI on, all the patients were taking medications recommended for outcome improvement, such as statins, clopidogrel as a component of dual antiplatelet therapy, beta-blockers, angiotensin converting enzyme inhibitors. The outcomes were assessed at 12 months by the endpoints of cardiovascular death and recurrent non-fatal MI, and at 5 years by the endpoints of overall mortality and recurrent non-fatal MI. Results: During one year of the follow up, 7 of 145 patients (4.8%) died from cardiovascular causes. Recurrent MI occurred in 8.3% (n = 12) of the patients. The carriers of *1*2 and *1*3 genotypes of the polymorphic CYP2C19 gene were 3.27-fold more likely to experience recurrent MI within 1 year, compared to the carriers of other genotypes (relative risk = 3.27 [95% confidence interval 1.03; 10.36], p = 0.03). After 5 years of the follow up, this association has disappeared. No influence of the assessed polymorphisms on overall and cardiovascular mortality was found (p 0.05). One hundred and seven (107) patients were followed up for 5 years; 14 (13.0%) of them died, other 15 patients (14.0%) had recurrent MIs. Conclusion: *2 and *3 alleles of the polymorphic CYP2C19 gene responsible for the metabolism of clopidogrel, are risk factors of an unfavorable 12-month outcome after STEMI. Subsequently, the influence of the CYP2C19 gene polymorphism on the outcomes evades and is not associated with a 5-year prognosis. To improve post-STEMI outcomes at 1 year, it is necessary to implement the earliest personalized approached to antiplatelet treatment based on the results of the CYP2C19 gene polymorphism analysis.Обоснование. Несмотря на достижения интервенционных и медикаментозных методов лечения, смертность после инфаркта миокарда (ИМ) остается высокой, что актуализирует поиск предикторов неблагоприятного прогноза. Установлена ассоциативная связь носительства аллелей со сниженной функциональной активностью гена CYP2C19 с частотой возникновения сердечно-сосудистых событий. В ряде исследований показано негативное влияние *2 и *3 аллельных вариантов данного полиморфного гена на течение постинфарктного периода. Однако в большинстве из них период наблюдения варьировал в диапазоне от 3 месяцев до 1 года. Цель оценить влияние полиморфизма гена CYP2C19 (*2, *3) на долгосрочный прогноз у пациентов, перенесших ИМ с подъемом сегмента ST. Материал и методы. В открытое проспективное двуцентровое исследование включено 145 пациентов в возрасте от 45 до 75 лет, перенесших ИМ с подъемом сегмента ST. В течение 1 года после ИМ все пациенты принимали рекомендованные для улучшения прогноза препараты статины, клопидогрел в составе двойной антиагрегантной терапии, бета-адреноблокаторы, ингибиторы ангиотензинпревращающего фермента. Прогноз оценивался спустя 12 месяцев по достижению конечных точек: смерть от сердечно-сосудистых причин и повторный нефатальный ИМ, а также через 5 лет по достижению таких конечных точек, как общая летальность и повторный нефатальный ИМ. Результаты. В течение 1 года наблюдения из 145 респондентов от сердечно-сосудистых причин умерли 4,8% пациентов (n = 7), повторный нефатальный ИМ зарегистрирован у 8,3% (n = 12). Носители генотипов *1*2 и *1*3 полиморфного гена CYP2C19 были в 3,27 раза больше подвержены возникновению повторного ИМ в течение 1 года по сравнению с обладателями других генотипов (относительный риск 3,27; 95% доверительный интервал [1,03; 10,36], р = 0,03). По истечении пятилетнего периода наблюдения данная ассоциативная связь нивелируется. Влияния изучаемых полиморфизмов на общую и сердечно-сосудистую летальность не установлено (р 0,05). За пятилетний период прослежено 107 человек. Из них умерли 14 (13,0%), еще у 15 (14,0%) пациентов произошел повторный нефатальный ИМ. Заключение. Генотипы *1*2 и *1*3 полиморфного гена CYP2C19, ответственного за метаболизм клопидогрела, служат факторами риска неблагоприятного 12-месячного прогноза после перенесенного ИМ с подъемом сегмента ST. В последующем влияние полиморфизма гена CYP2C19 на исходы нивелируется и не имеет ассоциативной связи с пятилетним прогнозом. Для улучшения годового прогноза ИМ с подъемом сегмента ST необходим как можно более ранний персонализированный подход к выбору антиагрегантной терапии, основанный на результатах генетического анализа по полиморфному гену CYP2C19