CC BY
30
nification are intended for identification of a number of correlation links, the most important of which are:
- cause and effect interrelations of OR factors and types of health losing and job capacity working in certain industries of economy, productions and employment a long time by the certain occupation causing risk of the production caused and occupational morbidity, an industrial traumatism as which consequences temporary and (or) fixed disability and a lethal outcome acts;
- a probability of manifestation of OR and degree (severity) of their consequences — in specific occupational groups and at an individual level is estimated when cases of approach losing of a temporary and/or fixed working capacity including resulting in disability are analyzed;
- an age of affected persons in production (because of DHPF or adverse psychophysiological factors of labor process), so-called an average age of disability because of an occupational accident or an average age of the dead in production;
- OR factors, probability of their manifestation and degree (severity) of their consequences, on the one hand, and types of provided compensation payments, and duration of benefits receipt or retiring income, on the other hand.
There are developments in the field of classification of labour conditions in a workplace with a description of consequences work-
ing in optimum, admissible or harmful working conditions in the Research institute of sanitation, hygiene and occupational diseases of the Ministry of Health of the Republic of Uzbekistan.
Conclusions. Thus, study results have been shown:
- a high prognostic importance of laboratory and functional researches in identification of before clinical signs of lungs diseases during a long work in the conditions of dust content of air coal dust;
- a prevalence of fungal diseases among miners depends on age, service years of underground work and working conditions, and also a great importance isolation of the production territories, general shower and changing rooms, wearing uniform and a closed footwear.
Recommendations. It is necessary for sorting out of a complex problems arising in case of an OR assessment of energy industry employees:
- to integrate characteristics of labour conditions factors by transition from regulation of separate parameters of factors to the complex indicators gathering parameters family which are mutually compensating or strengthening action of each other.
- to use algorithm of probability calculation oflosing by worker of working capacity depending on a condition of labour conditions in a workplace and individual OR depending on labour conditions and worker health state.
References:
1. Клименко А. И., Кяро В. А., Ибрагимов Г. М., Красников С. Я. Решение вопросов энергоснабжения в угольной промышленности. Горный вестник Узбекистана. 2004 (1 (16)): 8-13.
2. Узбекистан планирует увеличить добычу угля в два раза. [Электронный ресурс]. http://uzdaily.uz/articles-id-20435.htm//. Дата посещения - 20.03.2015.
3. Измеров Н. Ф., Тарасова Л. А., Кузьмина Л. П. Проблема сердечно-сосудистой патологии в медицине труда. Гигиена труда и медицинская экология; 2004 (4): 77-85.
4. Хван Т. А., Хван П. А. Основы экологии. Серия «Учебники и учебные пособия». Ростов на-Д: Феникс; 2001: 256.
5. Международная организация труда МОТ-СУОТ. IL0-0SH:2001. Руководство по системам управления охраной труда. -Женева; 2003: 19.
6. Калмыков А. А. Иммунновоспалительные аспекты патогенеза профессионального бронхита в сочетании с артериальной гипертензией. Автореф. дисс. канд. мед. наук. - Харьков; 2007: 36.
Akilov Khabibulla Ataullaevich, d. m.s., professor, Head of Children Surgery Department of Republican Research Center of the Emergency Medical Care, pro-rector on education, Head of Children Surgery Department of Tashkent
Post-graduate Medical Institute Saidov Farkhod Khamidovich, Senior researcher of Children Surgery Department of Tashkent Post graduate Medical Institute, E-mail: medsaidov@mail.ru
Comparative evaluation of the colon microbiocenosis in children with chronic colostasis on the background of surgical treatment
Abstract: The results of the state of intestinal microflora were investigated and studied in 71 children with chronic colostasis. Of them in 12 (16,9%) children the dysbacteriosis of intestine of the 1st degree was found, of the 2nd degree — in 29 (40,8%) children, of the 3d degree — in 30 (42,2%) children. The 3-d degree of colostasis developed mostly often in the patients at the stage of decompensation (70,8%).
Keywords: chronic colostasis, microbiocenosis, dysbiosis, children.
Background. The multiple literature data indicate that colosta- clinical and laboratory methods of diagnosis of the patients with sis is increasingly being recognized both among children and adults colostasis and for determination of the need in operative treatment [3; 7; 9; 13]. In a number of works parallel with other diagnostic there is shown microbiological diagnosis, that is, determination of
the intestinal dysbacteriosis [1; 4;10; 12]. To the most significant causes leading to disturbance of microbiocnosis there are attributed antibacterial therapy, hormone therapy, use of cytostatics, radiation therapy, the factor of nutrition; acute infectious diseases of the gastrointestinal tract; stresses; biorhythms disturbance, travelling, attenuation of the immune status and internal diseases, first of all of the organs of gastrointestinal tract, that is, theme of our research [2; 5; 6; 8; 11].
The purpose of research. To study on microbiocenosis of the colon intestine in children with chronic colostasis.
Material and methods. We investigated and studied on the results of the state of intestinal microflora in 71 children with chronic colostasis who were on the stationary treatment at the department ofpe-diatric surgery of the Republican Research Center of the Emergency Medical care from 2010 to 2015. The patients were divided into three groups in relation to the degree of compensation of the chronic colostasis. At the compensated stage the deviations from N-parameters were related to the prevailed number ofthe lactose negative intestinal colon bacilli (in 4 out of 22-18,3%) and decrease in quantity of such symbiotic intestine microorganisms as enterococci (45,5%) as well as lactobacteria (45,5%) and bifidobacteria (27,3%). In all patients (100%) of this group there were normal titres of the colon bacilli; hemolytic forms of the escherichia were identified in 6 (27,3%) patients; coagulase negative staphylococci were found in 4 (18,3%) patients and Proteidae — in 9,8%. However analysis of the concentration of studied microorganisms showed that these changes were insignificant. Thus, titre of all lactose negative E.coli was 10 6, that is, only one point higher than norm; titre of enterococci in 4 out of 5 patients was also reduced by one point — from 10 5 to 106, lactic acid bacilli in 8 out of 10 patients from 10 7 to 10 6, bifidobacteria have reduced titres from 10 8 to 10 7 in all 6 patients.
In the subcompensated stage the deviations from norm were found in the same indicators, but there was added reduction of E.coli (in 8 patients, 32%), appearance of Candida, higher level of identified hemolytic colon bacilli (32%) and significantly more marked decrease in lactic acid bacilli in 20 (80,0%) out of 25 patients. In the majority of cases the titres of the identified microorganisms changed compared with norm by 1-2 points, for example, the level of normal colon bacilli reduced in the majority of patients (7) to 10 6, and only in one child — to 10 5; tires of lactose negative E.coli were higher than one point in 3 patients (10 6) and than two points (10 7) in 2 patients. The similar tendency was noted among the concentrations of enterococci, lactic acid bacilli and bifidobacteria.
In the decompensated stage of colostasis all above shown changes were more marked — this is related to quantity of patients with deviations from norm and titres of the microorganisms identified. Thus, reduction of the quantity of colon bacilli by 2-3 points (10 5-10 4) was observed in a half of patients of this group; titres of biochemical inactive E.coli in the majority ofpatients (4) increased by 3 point (to 10 8). More significantly reduction of the titres was revealed in bifidobacteria — from 13 patients with reduced quantity of these microorganisms in
10 children titres fell by 4 points (10 5), and in lactic acid bacilli, respectively, in 20 out of 23 patients by three points (10 4). Besides, in the patients with decompensated stage of colostasis there were identified P.aeruginosa (12,5%) and S.aureus (8,3%) — bacteria characterized by high potential ability to produce toxins.
Results and discussion.
There were expected more marked changes in the microecology of the intestine at the decompensated stage of colostasis (Table I).
Table 1. - Character of changes of intestinal microflora in chronic constipation before treatment (at admission) in 71 children
Quantitative changes of the microbial landscape in 71 patients Quantity of patients in relation to stage of compensation of chronic colostasis
Compensated stage of 22 patients Subcompen-sated stage in 25 patients Decompen-sated stage in 24 patients Totally 71 patients Norm
Reduction of the total quantity of the colon bacillus <10 7 8 (32%) 10 (41,7%) 18 (25,4%) 107-108
Increase in number of lactose negative colon bacilli >10 5 4 (18,2%) 5 (20%) 6 (25%) 15 (21,1%) < 105
Hemolytic colon bacilli 3 (13,6%) 7 (28,0%) 12 (50%) 22 (31,0%) 0
Other opportunistic enterobacteria Pr.vulgaris 2 (9,1%) Pr.mirabilis 3 (12%) 5 (7%) < 104
Increase in quantity of nonfermen-tative bacteria >10 4 P.aeruginosa 3 (12,5%) 3 (4,2%) < 10 3 - < 104
Staphylococci (saprophytic, epidermal) 4 (18,2%) 2 (8,3%) 6 (8,5%) < 104
Staphylococcus aureus 2 (8,3%) 2 (2,8%) 0
Reduction of enterococci quantity <10 5 5 (22,7%) 6 (24%) 8 (33,3%) 19 (26,8%) 105-108
Reduction of quantity of lactoba-cilli<10 7 10 (45,5%) 20 (80%) 23 (95,8%) 53 (74,6%) 107-108
Reduction of quantity of bifidobacteria <10 9 6 (27,3%) 6 (24%) 13 (54,2%) 25 (35,2) 10 9-10 10
Increase in quantity of Candida fungi>10 4 6 (24%) 8 (33,3%) 14 (19,7%) < 10 3- < 10 4
Conclusion: In all 71 patients there were revealed features of dysbacteriosis.
On the basis of analysis of the data obtained all the patients with chronic colostasis independently on the stage of compensation were
considered as persons with dysbacteriosis. The complex therapy of dysbacteriosis (vitamins, diet, probiotics and others) contributed to the normalization of the every day stool and improvement of the general state in 96,3% of children.
It should be noted that dysbacteriosis of the 4 stage in the studied patients was not revealed because there was not defined full absence of bifidoflora with considerable decrease in lactoflora with simultaneous change of the quantity of the colon bacilli and increase of nonspecific for healthy human opportunistic bacteria. Dysbacteriosis of the first degree was diagnosed in the patients with insignificant changes in the aerobic-facultative flora (E.coli in the first turn) and absence of change of the lacto- and bifidoflora. The quantitative and qualitative changes of the colon bacilli and other opportunistic bacteria on the background of insignificant quantitative reduction (by one-two stages) of bifidoflora and lactoflora were attributed to the dysbacteriosis of the 2 degree. The 3 degree of dysbacteriosis is characterized by significant reduction (to 105) of bifidobacteria in combination with reduction of lactoflora and acute change of the level of normal colon bacilli. On the basis of this approach an according to the recommendations in the patients with chronic colostasis of the various stage of compensation there was established diagnosis:
At compensated stage in 22 patients:
Dysbacteriosis of the 1st degree — 10 (45,5%) of the 2d degree — 12 (54,5%). At the subcompensated stage in 25 patients:
Dysbacteriosis of the 1st degree — 2 (8,0%) of the 2 d degree — 10 (40,0%) of the 3d degree — 13 (52%). At the decompensated stage in 24 patients:
Dysbacteriosis of the 2d degree — 7 (29,2%) of the 3 degree — 17 (70,8).
In comparison with control indicators obtained in 71 patients at admission to the hospital with parameters after performance of conservative treatment in a number of cases there was observed their restoration. Thus, in the patients after treatment the normal colon bacillus was reduced only in 8 patients or in 18,6%, while before treatment they were 25,3%; inactive in relation to enzymes E.coli was found also less frequently — 13,9% compared with 21,2%; deviation among the enterococci also reduced from 26,8% before treatment and to 16,3% after treatment, respectively; lower parameters were obtained in relation to bifidobacteria (from 35,2% to 23,3%) and Candida fungus (from 19,6% to 11,6%). However the most important in the recovery of intestinal microflora there were changes in the lactic acid bacilli: if before treatment in the control in 74,7% of children the quantity of lactic acid bacilli was reduced, than after conservative treatment this indicator was 34,8% p<0,01). About significant restoration of the intestinal microflora after treatment there were indicated statistically reliable reduction of the identification of hemolytic colon bacilli (13,9% compared to 36,6%, p<0,01) and absence of the opportunistic enterobacteria. At the same time after treatment the blue pus bacilli was revealed in 3 patients (7,0%), and pathogenic staphylococcus in 2 (4,6%) patients which were typical representatives of the hospital flora. Totally, evaluating quantitative and qualitative parameters of intestinal microbiosis in the patients treated by conservative approach it was found that in 23 (53,4%) patients microbiocenosis was not recovered completely.
Group of operated patients included 19 children, of them only 3 patients had subcompensated stage of chronic colostasis, and in 16 — decompensated stage.
Table 2. - The state of intestinal biocenosis in children with chronic constipation after operative method of treatment in 19 patients
Quantitative changes of microbial landscape in 19 patients Quantity of patients in relation to stage of compensation of chronic colostasis
Subcompensated stage in 3 patients Decompensated stage in 16 patients Totally 19 patients Norm
Decrease in the total quantity of colon bacilli <10 7 1 (33,3%) 1 (6,25%) 2 (10,5%) 107-108
Increase in the quantity of lactose negative colon bacilli >10 5 2 (12,5%) 2 (10,5%) < 10 5
Hemolytic colon bacilli 2 (12,5%) 2 (10,5%) 0
Other opportunistic enterobacteria Kl.pneumoniae 1 (12,5%) 1 (5,3%) < 10 4
Increase in quantity of nonfermentative bacteria >10 4 Ps. Aeruginosa 1 (12,5%) 1 (5,3%) < 10 3 - < 104
Staphylococci (saprophytic, epidermal) < 104
Staphylococcus aureus 2 (12,5%) 2 (10,5%) 0
Decrease in quantity of enterococci <10 5 1 (33,3%) 1 (6,25%) 2 (10,5%) 10 5-10 8
Decrease in quantity of lactic acid bacilli <10 7 1 (33,3%) 4 (25%) 5 (26,3%) 10 7-10 8
Decrease in quantity of bifidobacteria <10 9 1 (33,3%) 4 (25%) 5 (26,3%) + 10 9 -+10 10
Increase in quantity of Candida fungi >10 4 1 (33,3%) 3 (18,8) 4 (21,1%) < 10 3 - < 10 4
Conclusion: in 4 (21,2%) patients who underwent operative method of treatment disbiosis was not recovered.
In spite of small quantity of the operated patients difference in the parameters of intestinal microbiocenosis with control (group of patients at admission) was rather marked. Thus, deviations from norm in the colon bacilli were higher than in control 2,4 times (25,4% and 10,5%), lactose negative colon bacilli — 2 times (21,2% and 10,5%), enterococci 2,5 times (26,8% and 10,5%), bifidobacteria -1,3 times (35,2% and 26,3%). Statistically reliable results were obtained in determination of hemolytic colon bacilli, this indicator reduced from 36,6% at admission to 10,5% after operation (p<0,05).
However, the most significant decrease was noted in relation to lactic acid bacilli — from 74,6% before operation and 26,3% after operation (x2-P<0.01) (Table 3).
According to the above presenting criteria about stages of dysbacteriosis, intestinal microbiocenosis in the patients with chronic colostasis after operative intervention was not recovered in 4 patients (21,0%). Comparison of this parameter with group of patients, receiving conservative treatment showed that restoration of the intestinal microbiocenosis in the patients after operative treatment appeared to be more effective than conservative treatment and statistically reliable (x2-4,3, p<0,05).
Table 3. - Comparison of the indicators of intestinal disbiosis in children with chronic colostasis at admission with group of children after operative treatment
Major parameters of disbiosis Quantity of patients with deviation from N in 71 patients at admission (control) Quantity of patients with deviation from N in 19 patients after operative treatment x2 P
Decrease in total quantity of colon bacilli <10 7 18 (25,3%) 2 (10,5%) X2 - 1,4 Р >0,05
Increase in quantity of lactose negative colon bacilli >10 5 15 (21,2) 2 (10,5%) X2 - 0,5 Р >0,05
Hemolytic colon bacilli 26 (36,6) 2 (10,5%) X2 - 3,8 Р <0,05
Other opportunistic enterobacteria (P. Vulgaris 2 P.mlrabilis -3) -5 (7,0) K.pneumoniae -1 Р >0,05
Increase in quantity of nonfermentative bacteria бактерий >10 4 0 Ps.aeruginosa - 1 Р >0,05
Staphylococci (saprophytic, epidermal) 6 (8,4%) - Р >0,05
Staphylococcus aureus 2 (2,8) 2 (10,5%) x2 - 0,6 Р >0,05
Decrease in quantity of enterococci <10 5 19 (26,8%) 2 (10,5%) X2 - 1,4 Р >0,05
Decrease in quantity of lactobacilli<10 7 53 (74,6%) 5 (26,3%) X2 - 13,2 Р <0,01
Decrease in quantity ofbifidobacteria <109 25 (35,2%) 5 (26,3%) x2 - 0,2 Р >0,05
Increase in quantity of Candida fungi >10 4 14 (19,6) 4 (21) Р >0,05
The above presented data showed that statistically reliable reduction of the lactic acid bacilli have been determined practically in all groups ofpatients with chronic colostasis; less marked but constantly the microflora deficit has been found. It is known that almost in all the schemes of treatment of dysbacteriosis including also dysbacteriosis in chronic constipations the dufalac is prescribed. Because of lactulose in the intestinal flora the production of the short-chain fatty acids increased that improved trophic of the intestinal epithelium, and this, in its turn, increased in water and electrolytes absorption, normalized motor function. Thus, the wide use of dufalac in the complex therapy of the patients with chronic colostasis is advisable, because it is the strong activator of the colonizational resistance in the patients with disturbances of the normal microbiocenosis.
Conclusions. 1. In all studied patients (71 children, 100%) with chronic colostasis there was identified intestinal dysbacteriosis of 1st degree in 12 (16,9%) children, of2d degree — in 29 (40,8%),
of 3d degree — in 30 (42,2%) children. The dysbacteriosis of 3d degree developed mostly often in the patients at the stage of decompensation (70,8%).
2. At the decompensated stage of chronic colostasis compared with compensated and subcompensated stages the deviations from norm were noted in the most important parameters of microbiocenosis, that is, reduction of the quantity of normal esherichia (P<0,05),. Lactic acid bacilli (P<0,01), bifidobacteria (P<0,05).
3. According to the quantitative and qualitative parameters of intestinal microbiocenosis in the patients treated with conservative method in 23 (53,4%) patients microbiocenosis was not restored completely, in the operated patients this parameter was in 4 (21,1%) (p<0,05).
4. The operative way of the treatment of chronic colostasis resulted in restoration of the normal ecology of the intestine in 15 (78,9%) children.
References:
1. Ardatskaya M. D. Intestinal microbiocenosis and its role in the development and maintenance of the intestinal tract disease//Novosti medicine I farmacii. - 2010. - № 11-12. - P. 331-332.
2. Lenushkin A. I., Kirgizov I. V. About prophylactic role of lactulose in relation to new interpretation of the chronic colostasis in chil-dren//Voproci practicheskoy pediatrii. - 2007. - T.2, N 4. - P. 23-26.
3. Minushkin O. N., d. m.s. Ardatskaya M. D. Intestinal dysbacteriosis (dysbiosis): the modern presentation, diagnosis and therapeutic correction//Educational-methodical user's guide for physicians and postgraduate students of the circles of postgraduate education for doctors. - Moscow, 2008.
4. Parfenov A. I., Clinical problems of dysbacteriosis//Russian Gastroentorologicheskiy jurnal. - 1999. - N 4. - P. 49-55.
5. Tkachenko E. I., prof. Suvorova A. N. Dysbiosis of the intestine. Handbook on diagnosis and treatment. - SPb.: Speclit, 2007, 238 p.
6. Khavkin A. I., Belmer S. B. Microbiology of the intestine: methods of nonspecific correction//Children's gastroenterology and nutri-ciology. - 2003. - N 13. - P. 772-775.
7. Anderson D., Engemann J., Harrell L. et al. Predictors of Mortality in Patients with Bloodstream Infection Due to Ceftazidime-Resistant Klebsiella pneumoniae//J. Antimicrobial Agents and Chemotherapy. - 2006. - Vol. 50. - No. 5. - P. 1715-1720.
8. Bouhnik Y., Neut C., Raskine L., Michel C., Riottot M., Andrieux C., Guillemot F., Dyard F., Flourie B. Prospective, randomized, parallel-group trial to evaluate the effects of lactulose and polyethylene glycol-4000 on colonic flora in chronic idiopathic constipation/Aliment. Pharmacol. Ther. - 2004. - Vol. 19 (8). - P. 889-899.
The role of genes of the folate cycle in the development of antiphospholipid syndrome in the Uzbek population
9. Eili Klein, David L. Smith, and Ramanan Laxminarayan. Hospitalizations and Deaths Caused by Methicillin-Resistant Staphylococcus aureus, United States, 1999-2005//EID Journal Home. - 2007. - Vol.13, N 12.
10. Thomas C. M., Versalovic J. Probiotics-host communication modulation of signaling pathways in the intestine//Gut Microbes. - 2010. -Vol 1, N. 3. - P. 1-16.
11. Schneider-Lindner V. et al. Antibacterial drugs and the risk of community-associated methicillin-resistant Staphylococcus aureus in children//Arch Pediatr Adolesc Med. Published online August 1, 2011.
12. Wunderink R. G., Niederman M. S., Kollef M. H. et al. Linezolid in Methicillin Resistant Staphylococcus aureus Nosocomial Pneumonia: A Randomized, Controlled Study//Clin Infect Dis. - 2012. - Vol 54, N 5. - P. 621-629.
13. Yamada K., Yanagihara K., Hara Y. et al. Clinical features of bacteremia caused by methicillin-resistant Staphylococcus aureus in a tertiary hospital. Tohoku//J Exp Med. - 2011. - Vol.224, 1. - P. 61-67.
Akramhodzhaeva Dilfuza Shakarimovna, Junior Scientific Researcher of the Institute of Immunology of the Academy Kamalov Zaynitdin Sayfutdinovich, Head of the Laboratory of Immunoregulation of the Institute of Immunology of the Academy MD, Professor
E-mail: zay_kamal@ramdler.ru Khegai Tatiana Rudolfovna, Head of the Laboratory of Human Genomics of the Institute of Immunology of the Academy MD Zakhidova Nadira Erkinovna, Junior Research Assistant, of the Laboratory of Human Genomics of the Institute of Immunology of the Academy MD of Sciences of the Republic of Uzbekistan
The role of genes of the folate cycle in the development of antiphospholipid syndrome in the Uzbek population
Abstract: When comparing of frequencies of genotypes of the studied polymorphic markers we have been established the genetic associations of the genes of folate cycle to the development of antiphospholipid syndrome. The results of this study demonstrate the relationship risk of antiphospholipid syndrome in the Uzbek population with carriage of A alleles of rs1805087 polymorphism, and rs1805087 polymorphism of AA genotypes and AA genotype of the rs1801131 polymorphic marker.
Keywords: Antiphospholipid syndrome (APS), the genes of folate cycle, allele frequency, polymorphism of genes, genetic association.
Antiphospholipid syndrome (APS) — clinical and laboratory syndrome characterized by venous and arterial thrombosis, pathology of pregnancy and some other less common clinical manifestations and laboratory disorders, pathogenesis associated with the synthesis of antiphospholipid antibodies (aPL) [1; 2].
APS — a complex and insufficiently developed problem. This is explained by the heterogeneity of pathogenetic mechanisms that underlie the APS, the lack of reliable clinical and laboratorial indicators to predict the risk of recurrence of thrombosis. Currently, there are no generally accepted international standards of the treatment tactics of patients with various forms of APS and the proposed recommendations are based primarily on the results of the "open" tests or retrospective analysis of outcomes of the disease [3-11]. The approaches to prevention and treatment of atherosclerotic vascular lesions, often develops in patients with APS are not enough studied [12; 3].
In the population, according to the American authors, APS occurs in 5% of cases [15]. In our country, such studies have not been undertaken. Antiphospholipid syndrome is observed in women 2-5 times more often than in men, and, if the initial ratio of the number of patients with APS women and men is 4: 1, then the sec-
ondary form of the disease, this figure rises to 7: 1, which is probably due to greater susceptibility ofwomen to systemic connective tissue diseases [14]. The investigations of HLA antigens (human leucoc-ites antigen) showed that in patients with APS often than in the population found HLA: DR4, DR7, DRw53, suggesting a possible genetic predisposition to the disease [13]. The literature describes familial cases of APS, constituting, according to some authors, up to 2% [14]. It is possible that there are two forms of the disease: sporadic and familial.
The genes of the folate cycle involved in processes of remeth-ylation may also be considered as potential candidates genes in the development of the APS syndrome.
The Violation of the processes ofremethylation (formation ofme-thionine from homocysteine), which occurs because of the MTHFR enzyme MTRR deficiency and leads to the development of a number of pathological conditions, such as atherosclerosis; atherothrombosis; cleft neural tube defect; heart attacks and disruption of chromosome segregation in oogenesis. Methylation of DNA is a methyl group to join in the composition cytosine CpG-dinucleotide in C5 position of the cytosine ring.
