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Ultrasonic methods determining volume of cavities of ventricles of the heart
• для конуса: KN = —;
4
п
• для цилиндра: KN = —;
4
Сф
• для призмы: KN =---.
d г
ф
Для других известных геометрических фигур также можно определит конкретные значения KN.
Предложенный метод позволяет достичь следующего положительного эффекта:
резкое уменьшение времени анализа данных эхокардиографического обследования; установление более точного измерения объема полостей желудочков сердца и надежно ставить диагноз для пациента. тестирование имеющейся известной геометрической фигуры (шар, конус, эллипсоид и др.) предложенной формулой, пять раз точнее, чем предложенные формулы [4; 6]. предложенные формулы строго математически обоснованы, и каждый ее член имеет физический смысл.
Список литературы:
1. Мухарлямов Н. М., Беленков Ю. Н. Ультразвуковая диагностика в кардиологии. - М.: «Медицина», 1981. - 157 с.
2. Клиническая ультразвуковая диагностика./Под ред. Мухарлямова. - М., 1987. - Т. 1. - 185 с.
3. Толыжников В. А., Семенова Е. Н. Основные принципы расчета объемных показателей сердца.// Кардиология, - 1987. - Т. 27. 6, - С. 119-123.
4. Алпатов А. В. Способ определения объема полостей желудочков сердца.//Авторское свидетельство №2194450, - 2002.
5. Teichholz L. E., Kreulen T., Herman M. V., Gorlin R. Problems in echocardiographic volume determinations: echocardiographic-angiographic correlations in presence or absence of asynergy.//Amer. J. Cardiology. - 1976. - Vol. 3. - P. 7.
6. Abdikarimov F. B., Navruzov Q. N., Khujatov N. J. New way scoping of a cavity of the left ventricle of heart according to an echocardiography.//European Science review, - Vienna, - № 2. - 2014. (March-Aprel), - Р. 44-46.
Bychkov Eugene Nikolaevich, Saratov State Medical University n. a. VI. Razumovsky
Russian Ministry of Health, Associate Professor of psychiatry, narcology, psychotherapy and clinical psychology department, PhD
Borodulin Vladimir Borisovich, Saratov State Medical University n. a. VI. Razumovsky
Russian Ministry of Health, Head of the biochemistry department, prof., MD
Barylnik Julia Borisovna, Saratov State Medical University n. a. VI. Razumovsky
Russian Ministry of Health, Head of psychiatry, narcology, psychotherapy and clinical psychology department, MD Samoylova Daria Dmitrievna, Saratov State Medical University n. a. VI. Razumovsky Assistant of psychiatry, narcology, psychotherapy and clinical psychology department, PhD
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Section 1. Clinical medicine
Filippova Natalia Valerevna, Saratov State Medical University n. a. V. I. Razumovsky
Russian Ministry of Health, Assistant of psychiatry, narcology, psychotherapy and clinical psychology department, PhD E-mail: [email protected]
The analysis of detoxication genes’ polymorphism at development of a “detoxication syndrome” in drug-addicted patients with various experience of narcotics use
Abstract: The molecular genetics represents important branch of biomedical researches as many processes in organism are determined genetically. It is necessary to consider a role of a molecular and genetic factor for successful symptomatic treatment of drug-addicted patients. It is connected with that fact that biochemical indicators can reflect the metabolic processes proceeding in an organism of people with drug addiction, and determined by a genetic factor. It is possible to carry detoxication of narcotics, their penetration into tissues of a brain and processes of drugs removal from an organism to such processes. At drug-addicted subjects there is an interaction between a hepatic and kidney parenchyma during the utilization of narcotics in liver with the subsequent their removal through kidneys. That’s why the condition of detoxication genes in hepatocytes is one of the indicators in processes of an inactivation of narcotic preparations and their efficiency. The carriage of two polymorphic variants CC on genes of UGT2B7 and UGT1A1 can be considered as adverse sign of genetic polymorphism at the drug-addicted people which, on the one hand, will lead to accumulation of indirect bilirubin in blood, and, on the other hand, will induce to increase a drug dose for achievement of narcotic effect.
Keywords: drug addiction, detoxication, genetic polymorphism.
Relevance of research. Sharp poisoning with narcotic substances and chronic narcotic intoxication is even more often met in practice of psychiatrists, experts in narcology, forensic scientists, therapists and doctors of other specialties.
In West countries about 15 % of the population use narcotic drugs, drug-addicted patients make up to 5-7 %. In the last decade the narcotization level of Russian population sharply increased, and the prognosis of this situation is poor. The illicit receipt of such synthetic and semi-synthetic drugs as ephedrone, methamphetamine, benzedrine, phencyclidine, fentanyl, trimetilfentanit, etc. promptly increased. The HIV epidemic wave basically connected (in 79.9 % of cases) with drugs use began in Russia. The growth of a narcotization caused increase of an incidence and mortality among addicts, thus in 50.9 % of cases any somatic diseases, including the infectious served as its reasons.
Despite a wide range of medical and social measures for fight against drug addiction, including
actions for toughening of legislative control of production and use of drugs, the share of the population (especially young) involved in the use of narcotic substances steadily grows. At the same time the efficiency of antinarcotic programs remains rather low.
There are many means in nature having psychotropic effect which are little studied and can be used as narcotic substances in the future. It is known because of detection in various biological objects of new substances with narcotic action testifies. By annually chemical way new psychotropic drugs are synthesized. The list of chemicals with psychotropic and (or) narcotic action is very extensive and is currently insufficiently studied. Thus the set of substances which definition in biological environments and tissues during judicial and chemical research can be undertaken in the conditions of modern daily expert practice is also limited.
Pharmacogenetics is a science about genetically caused individual reaction of an organism to medicines. It’s basic conceptual provisions are based
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The analysis of detoxication genes’ polymorphism at development of a “detoxication syndrome” in drug-addicted...
on the principles of a genetic variety of the person connected with existence of genetic polymorphism. Depending on specific features of a genome different individuals can keep stability or, on the contrary, find hypersensibility to the damaging agents and medicines [2]. The majority of xenobiotics, getting to an organism, don’t render direct biological effect and are exposed to various transformations, so-called biotransformation, that is a series of metabolic reactions that are brought out of an organism [4; 6; 15]. Reactions of biotransformation are controlled by special enzymes of detoxication system. The hereditary changes of activity of such enzymes and/or imbalance in their work caused by genetic polymorphism lead to inadequate reaction of an organism to various xenobiotics. Undesirable collateral reactions or absence of therapeutic effect at reception of medicines can turn out to be consequence of it. Existence of exact data on chemical structure of medicine, the biomechanism of it’s action and about the enzymatic systems controlling this process, added with data on a structure of the corresponding genes promotes a rapid progress of a pharmacogenetics as to one of the most perspective sections of molecular medicine. Moreover, identification of associations of polymorphic options of genes with various individual sensitivity to medicines allows not only to specify pathogenesis of the disease, but also to develop optimum strategy of treatment taking into account biochemical identity of the patient [2; 3; 6; 9].
As the beginning of any clinical symptomatology the changes at the molecular level which precede Table 1. - Total number of the (
development of a full-fledged picture of a disease act. Identification of similar molecular markers represents a separate task and depends on understanding the researcher of an ultimate goal. It is possible to speak about peculiar “design” or “skeleton” of the conducted researches for obtaining information on progressing of a disease and early diagnostics of initial forms of this or that pathology.
Especially it should be noted the value of molecular and genetic researches as many processes in an organism are determined genetically, and for successful symptomatic treatment of drug-addicted patients it is necessary to consider a role of a molecular and genetic factor as biochemical indicators can reflect the metabolic processes proceeding in an organism of the persons having drug addiction, and determined by a genetic factor [2; 7]. It is possible to carry to such processes, in particular, a narcotics detoxication, their penetration into tissues of a brain and processes of removal of drugs from an organism [5; 7; 8].
Materials and methods of research
The research was conducted within five years (from 2007 to 2011). It included 250 patients with chronic opium drug addiction which led to development of hepatic and renal pathology, and also arterial hypertension and a chronic illness of kidneys.
To all patients the standard clinical tool examination was conducted. In the table 1 the distribution of the examined drug-addicted people by gender and age criteria is specified.
The distribution of the examined patients depending on duration of narcotics use is presented in the table 2.
imined drug-addicted patients
Gender Age
18-29 y. o. 30-49 y. o. 50-60 y. o.
Abs. number % Abs. number % Abs. number %
Male 102 40.8 63 25.2 39 15.6
Female 23 9,2 12 4.8 11 4.4
Total (n=250) 125 50 75 30 50 20
Table 2. - Total number of patients with various experience of the drugs use
Gender Experience of the drugs use
2-3 years 4-5 years 6-8 years More than 9 years
Abs. number % Abs. number % Abs. number % Abs. number %
Male 32 12.8 70 28 63 25.2 39 15.6
Female 18 7.2 5 2 12 4.8 11 4.4
Total (n=250) 50 20 75 30 75 30 50 20
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Section 1. Clinical medicine
The research of genes polymorphism in this work was conducted on hydrogel biochips and consisted of the following stages:
A. Allocation of leucocytes from blood by a method of A. Boyum (1968) in V. V. Novitsky’s modification, 2004.
B. Allocation of DNA from leucocytes by the protocol of “Wizard” [Genomic DNA Purification Kit A 1120] with the use of “Promega” firm reactants.
C. Carrying out two rounds of multiplex PCR for an operating of DNA fragments, necessary for the analysis defining existence of genetic polymorphism with simultaneous introduction of a fluorescent tag to PCR products (a technique of Institute of molecular biology ofW. A. Engelgardt RAHN).
D. Hybridization - interaction of fluorescent and marked products of PCR with probes on the biochip and the analysis of fluorescence of elements of the biochip with use of a universal hardware-software complex (IMB technique ofW. A. Engelgardt RAHN).
Carrying out polymerase chain reaction was made in two stages with addition of the primers specific to the studied genes. The fluorescent marking of the PCR-product was carried out at the second stage of PCR using the dye of a pentametine row. Thus the primer containing a fluorescent tag was added to PCR-mix in higher concentration, than not marked primer, so that only one marked chain was mainly acquired. During the further hybridization there was a specific interaction of molecules probes and a molecule target by the principle of a complementarity on the biochip. Hybridization mix was denatured completely within 5 minutes at 95 °C, cooled in ice, applied on the biochip and incubated within 10-12 hours at 37 °C. After the end of an incubation and removal of hybridization mix, the surface of the biochip was dried up by compressed air and the registration of fluorescent signals by means of the portable analyzer supplied with the software of “Imagewer” was carried out (Institute of molecular biology ofW. A. Engelgardt RAHN, Russia). The picture of hybridization represents distribution of fluorescence signals, the brightest in points of specific binding of the probe and the target. The method of DNA chips use is high informative, allows to analyze up to 50 polymorphic options of genes with an accuracy more than 99 %.
Results and their discussion
As a result of this research the new concept “a detoxication syndrome” at drug-addicted patients is offered. The purpose of this concept is objectiveness of an assessment of bilirubin, morphine and other xenobiotics, including medicines detoxication processes. These processes take place on the basis of polymorphisms of genes identification. These genes are directly involved in processes of a xenobiotics detoxication, and intensity of these or those biochemical ways of xenobiotics transformation which is expressed in change of metabolites concentration or activity of the enzymes which are directly involved in processes of a xenobiotics detoxication.
It is known that at parenteral introduction of morphine-6-glucuronide the activity of this metabolite is approximately twice higher in comparison with morphine [10; 12]. Against regular reception of morphine inside the serumal concentration of morphine-6-glucuronide usually surpasses the concentration of morphine, and during the long narcotization the narcotic effects are caused mainly by this metabolite [13; 14]. Morfin-6-glucuronide is removed by kidneys and collects at a renal failure in blood that explains lengthening and strengthening of morphine effect at patients with a chronic renal failure [11]. On the other hand, the interaction of morphine-6-glucuronide with erythrocytes will promote development of a hypoxia in tissues.
As a result of the conducted research polymorphism of the genes belonging to families UDF-glucuroniltransferase UGT1 and UGT2, namely UGT1A1 and UGT2B7 which are responsible for interaction of glucuronic acid and bilirubin — UGT1A1 and also for interaction of glucuronic acid and morphine — UGT2B7 was found.
In 27 % of cases the СС-polymorphism carriage was established, in 15 % — a carriage of TT polymorphism and polymorphism С/T in the 3rd intron of a gene of UGT1A1 was found in 58 % of carriers. The carriage ofpolymorphism of CC at people with narcotic dependence leads to decrease in a glucuron-idation of bilirubin and increase of its level in blood.
At addicts with various experience of drugs use the polymorphism of UGT2B7 gene on a polymorphic marker of C802T was distributed as follows: 22 % of carriers had CC polymorphism, at 13 % of
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The analysis of detoxication genes’ polymorphism at development of a “detoxication syndrome” in drug-addicted...
carriers polymorphism of a TT met and 65 % had C/T polymorphism. It should be noted that the carriage of a CC genotype on a polymorphic C802T marker of a gene of UGT2B7 leads to the low speed of a glucuronidation of morphine that, in turn, causes low concentration morphine-6-glucuronide and morphine-3-glucuronide in blood, and, therefore, leads to low narcotic effect. The similar situation causes the necessity of the raised drug doses use for narcotic effect achievement.
Thus, the carriage of two polymorphic variants CC on genes of UGT2B7 and UGT1A1 can be considered as an adverse sign of genetic polymorphism at the people having drug addiction which, on the one hand, will lead to accumulation of indirect bilirubin in blood, and, on the other hand, will induce to increase a drug dose for narcotic effect achievement.
A certain interest represents carrying out of molecular and genetic researches at people with drug addiction having arterial hypertension against the CRF development for the purpose of the genes participating both in a narcotics detoxication, and metabolism of various medicines used for symptomatic or pathogenetic treatment of a chronic renal failure and arterial hypertension identification.
The GSTT1 gene belongs to genes of glutathio-netransferase superfamily a class 6 and is localized in a locus 22qll.2 together with GSTT2 gene identical for 55 % to GSTT1 gene. The same as GSTM1 gene, GSTT1 gene participates in a glutathione -mediated detoxication of peroxide lipids oxidation, free radicals and alkylation of proteins products. GSTT1 polymorphism (as well as GSTM1 gene) is caused by existence/lack of an extended deletion which results in total absence of a protein product (“zero” allele). According to existing facts frequency of homozygotes on a “zero” allele in the Russian population makes 15-20 %.
The conducted researches showed the presence of heterozygotes (lack of deletion on fatherly and presence of deletion on a maternal chromosome, or on the contrary — presence of a deletion on fatherly chromosome and lack of a deletion on maternal chromosome) on this polymorphism in 68 % of cases on GSTM1 gene. Lack of deletion in a gene as polymorphism, that is “wild” type, made 30 %, heterozygotes with a deletion of a gene made 68 % and
homozygotes with deletion in a gene on maternal and fatherly chromosomes were presented 2 % of all quantity of the studied samples.
People who quite often have drug addiction use the crude drugs containing such impurity as ace-tylcodeine, barbiturates, an acetonitrile, epoxides, gasolines of various extent of cleaning, caffeine, etc. It is obvious that load ofliver cells therefore increases repeatedly and demands turning on of additional mechanisms for an inactivation of the xenobiotics which got to an organism. Such multipurpose metabolites take part in processes of a detoxication as UDF-glucuronic acid, glutathione, NADF*N2, molecular oxygen and others.
Increase of all types of hypoxia at addicts (respiratory, cardiovascular, erythrocyte and tissue) will change a cellular metabolism towards prevalence in cells cytoashes of anaerobic processes. Increase of anaerobic processes leads to decrease in concentration of ATP and reduction of a power charge of cells that involves decrease in all plastic processes in liver cells including decrease in concentration of such important makroerg as GTF, CTF and UTF. The last metabolite is especially important as takes part in formation of UDF-glucuronic acid — the central metabolite of the detoxication processes proceeding in hepatocytes, and participating in formation including bilirubin-glucuronides and morphine-glucuronides.
It is obvious that switching of a glucuronic acid metabolism on formation of bigger quantity will lead morphine-glucuronides in comparison with bilirubin-glucuronodes to increase of concentration of indirect bilirubin in blood serum and further to development of a hepatotoxic syndrome. Certainly, it is also necessary to consider polymorphism of the genes which are taking part both in a bilirubin detoxication and in formation of morphine-glucuronide in hepatocytes with its subsequent exit in blood and penetration through a blood-brain barrier (BBB). In this case it is about genes of UGT2B7 and UGT1A1, MRD1.
Existence ofpolymorphic option CC in all three specified genes will lead to decrease in a glucuronidation of morphine and bilirubin at simultaneous decline in the ability of morphine to get through a blood-brain barrier that will lead to desire of the drug addict to raise a drug dose for achievement of appropriate narcotic effect.
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Section 1. Clinical medicine
On the other hand, the “fast” acetylizers coded reduction bilirubin-glucuronide owing to a con-by UGT2B7 gene with polymorphism of T/T will sumption of UDF-glucuronic acid on morphine-intensively translate morphine in its derivative mor- glucuronide formation and to increase of indirect
phine-glucuronide that will lead to concentration bilirubin in blood (fig. 1).
Fig. 1. Metabolism change at addicts using morphine, xenobiotics and various impurity. Designations: BBB-blood-brain barrier, PAH-polycyclic aromatic hydrocarbons, D3 - D-3 vitamin
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The analysis of detoxication genes’ polymorphism at development of a “detoxication syndrome” in drug-addicted...
Use of glutathione in the detoxication processes with the participation of GSTT1 and GSTM1 genesis one of important mechanisms of an inactivation of the organic compounds coming in the form of impurity with the main narcotic preparations to the addict’s organism. Glutathione consists of three amino acids, and the metabolism of each of these amino acids is an important element in its receiving. Polymorphism of a gene of MTHFR changes a cysteine metabolism that is followed by increase of concentration of the homocysteine in blood and urine acting as a cysteine amino acid exchange marker. Glutamine amino acid also is a part of glutathione and at violation of its exchange concentration of glutathione will also decrease.
Conclusion. At drug-addicted subjects there is interaction between a hepatic and kidney parenchyma in the course of narcotics utilization in liver with the subsequent their removal through kidneys. Therefore the condition of detoxication genes in hepatocytes is one of the indicators determining processes of narcotics inactivation and their efficiency. The carriage of two polymorphic options CC on genes of UGT2B7 and UGT1A1 can be considered as adverse sign of genetic polymorphism at the people having drug addiction which, on the one hand, will lead to accumulation of indirect bilirubin in blood, and, on the other hand, will induce to increase a drug dose for narcotic effect achievement.
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2. Goldenkova-Pavlov I. V. The comparative analysis of results of a phenotyping and genotyping on polymorphism of N-acetylation at person./I. V. Goldenkova-Pavlov, S. A. Bruskin, R. M. Abdeev and oth-er//Genetics: magazine of the Russian Academy of Sciences. - 2006. - T. 42. - No. 8. - P. 1143-1150.
3. Minushkina L. O. The genes of angiotensin-converting enzyme, NO- synthetase and endotelina-1 and a hypertrophy of a myocardium of the left ventricle at patients with a hypertensive illness of Yakutia aboriginals./L. O. Minushkina//Cardiology. - 2005. - No. 1. - P. 41-45.
4. Suleymanov S. Sh. Features of functioning of system of xenobiotics biotransformation in adaptive reactions and pathology of the small people of Far North./N. L. Suleymanov. - Synopsis... MD - 1997. - 47 s.
5. Cattaneo M. Hyperhomocysteinemia, Atherosclerosis and Thrombosis./M. Cattaneo//Thromb. Haemost. - 1999. - 81. - P. 165-176.
6. Hein D. W. Molecular genetics and epidemiology of the NAT1 and NAT2 acetylation polymorphisms./ D. W. Hein, M. A. Doll, A. J. Fretland//Cancer Epidemiol. Biomarkers Prev. - 2000. - № 9 (1). - Р. 29-42.
7. Heux S. The methylentetrahydrofolate reductase gene variant (C677T) as a risk factor for essential hypertension in Caucasians./S. Heux, F. Morin, R. A. Lea//Hypertens. Res. - 2004. - Vol. 27, - № 9. -P. 663-667.
8. Miyamoto Y. Endothelial nitric oxide synthase gene is positively associated with essential hypertension./ Y. Miyamoto, Y. Saitio, N. Kajiyama et al.//Hypertension. - 1998. - 32. - Р. 3-8.
9. Oparil S. Pathogenesis of hypertension./S. Oparil, A. Zaman, D. A. Calhoun//Ann. Intern. Med. -2003. - 139. - P. 761-776.
10. Osborne R. Analgesic activity of morphine-6-glucuronide./R. Osborne, S. Joel, D. Trew, M. Slevin// Lancet. - 1988. - P. 828.
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14. Portenoy R. K. The metabolite morphine-6-glucuronide contributes to the analgesia produced by morphine infusion in patients with pain and normal renal function./R. K. Portenoy, H. T. Thaler, C. E. Intur-risi, H. Friedlander-Klar, K. M. Foley//Clin. Pharmacol. Ther. - 1992. - 51: 422-431.
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Dmitrieva Oksana Alekseevna, Leonenko Ekaterina Andreevna, Vozhzhova Victoria Nicolaevna,
Pisanko Gennady Gennadevich, Stavropol State Medical University, Students the Faculty of Therapeutic
Karpov Sergey Mihailovich, Professor, MD, Head of the Department of Neurology
Shevchenko Peter Petrovich, assistant professor of neurology E-mail: [email protected]
The degree of disorder of the patients’ psycho-emotional sphere with epilepsy
Abstract: Epilepsy — is a chronic disease which is shown spontaneously with the approach of generalized convulsive attacks and possible variants of inconvulsive current. Here register the disorder of the psycho -emotional sphere which the weight depends on the form of the disease. Epilepsy is a not only medical, but also social problem. Except the attacks, the disease can be followed by also progressing changes of the personality.
Keywords: inherent (idiopathic) epilepsy, secondary (symptomatic) epilepsy, psycho -emotional sphere, patient, disease, attacks.
Actuality. According to the European committee on epilepsy, about 50 million people or 0.5-1 % of the world’s population suffer from this disease. Thus, there is none the less than one attack is transferred by 5 % of the population during the life; the disease is lifelong for 20-30 % of patients. In Russia according to Ministry of Health of the Russian Federation, epilepsy is found with the frequency from 1.1 to 8.9 cases for 1000 people. The risk of developing of epilepsy depends on age: more often the children are ill with it till 15 years and the persons are ill who older than 65 years. In Russia, in 2011, 38,505 patients are registered with the diagnosis which established for the first time.
The objective of research. To analyse the degree of the importance of a disease for society, to give a result of this pathology for the patient.
Results. In change of the patient’s identity note the delay of psychological development, and also the manifestation of egoism, the slowed-down thought and excessive attention to insignificant details. For the patient is characterized by the sharp changes of mood (from unnatural and friendly, to maliciously and aggressive), he can’t allocate the main thing, the vocabulary (oligofaziya) decreases, memory becomes worse, the intelligence destroys, up to full weak-minded. 70 % cases are related to primary or inherent (idiopathic) form for which the reason remains unknown. This form of the disease is characterized by the prompt destruction of the patient’s psychology and intelligence. Epilepsy is a consequence of any disease in other 30 %. This form is called a secondary (symptomatic), it has less significant action the patient’s intelligence. Secondary epilepsy is dangerous
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