Introduction. Contamination of drinking water with chemicals of man-made origin generates negative trends in prevalence of digestive system diseases and, above all, chronic inflammatory diseases of the upper gastrointestinal tract [1, 3]. The presence of residual hyperchlorination products and heavy metals in drinking water causes the occurrence of additional cases of gastroduodenal disease at the level of 18 % annually, increases the number of children with abnormal and complicated forms of gastroduodenal diseases, including hypotrophic and atrophic chronic gastroduodenitis (CGD) [1, 2, 4]. The likelihood of hypotrophic and atrophic damages developing of the mucous membranes of the stomach and duodenal ulcer (DU), the causes of their genesis remain the most debated issues of pediatric gastroenterology [2, 4]. Some researchers see the correlation between the CGD and adverse effects of chemicals of man-made origin [2, 5]. However, pathogenetic factors for CGD development, associated with exposure to chemicals of man-made origin, remain under-investigated.
The aim of this study was to investigate the pathogenesis of CGD Hp (–) in children consuming drinking water with high concentration of manganese and hyperchlorination products (chloroform).
Materials and methods. The study group comprised 116 children with CGD Hp (–) aged 7–10 years (8,6 ± 1,2 years), living on the territory with unsatisfactory quality of drinking water in terms of sanitary-chemical parameters (content of chloroform – to 2,7 MAC, manganese – to 3,3 MAC). The comparison group consisted of 56 children with CGD Hp (–) of the same age (8,4 ± 1,4 years, p ? 0,05), living in the area where drinking water quality complies the hygienic standards. The air quality in the living territories of the children from both groups corresponded to hygienic requirements. The groups have been matched by gender. All children had negative results of “Helika test” and ELISA blood test for antibodies to Helicobacter pylori.
Chemical-analysis study of manganese in blood has been performed by atomic absorption spectrophotometry method on the spectrophotometer AAnalyst produced by PERKIN-ELMER (USA); detection of chloroform – by gas chromatography on the chromatograph “Chromatec-Crystal-5000” with the halogen-selective detector.
The clinical examination of children included: socio-medical questionnaires, analysis of outpatient-card of development, examination by pediatrician, gastroenterologist, neurologist. Autonomic nervous system status assessment has been carried out with the use of cardiorhythmographic programme “Poly-Spectrum”. The assessment was based on the cardiac rhythm mathematical analysis. Ultrasound scan of liver, gallbladder, biliary tract, stomach and duodenum has been performed according to standard procedures on the unit “Toshiba VIAMO” (Japan) using convex (1,9–6,0 MHz) and linear (7,0–14,0 MHz) multi-frequency sensors. Fibrogastroduodenoscopy has been carried out according to standard procedures with mucosal biopsy of 2 sites. Analysis of the information has been performed with the use of statistical methods (Statistica 6.0) and with the help of specially designed software, coupled with MS-Office applications. For the comparison of quantitative characters two-sample Student t-test has been used; evaluation of dependencies between the characters has been performed by the method of regression analysis.
Results of the study. All children, included in the study group, were born from 1–3 pregnancies, had no congenital abnormalities of the gastrointestinal tract, carried to full-time (95 % – study group and 94,1 % – comparison group; p = 0.34), had close weighty growth parameters at birth (3241,3 ± 154,6 g and 51,2 ± 0,6 cm – study group; 3132,4 ± 162,4 g and 50,37 ± 1,56 cm – comparison group; p = 0,43–0,48) and Apgar score (8,12 ± 0,20 scores vs. 8,58 ± 0,10 scores; p = 0,20). The frequency of recording in the history of acute intestinal infections in the two groups did not differ (10,3 and 12,5 % respectively, p = 0,67). Most children (79.3 % and 73,2 % respectively, p = 0,37) were raised in families with middle-income (12–14 thousand rubles per family member), lived in comfortable housing and used tap water without further purification (95 and 87,5 %, respectively, p = 0,24). Violations of the nutritional status of children was noted by 32.8 % of parents of children in the study group and 25 % – in the comparison group (p = 0,29). Duration of the disease in children of the study groups was 2,1 ± 1,1 and 1,9 ± 1,2, respectively (p = 0,72).
During the chemical-analysis studies of blood it was found: manganese concentration in children of the study group was 0,0283 ± 0,0042 mkg/cm3 (reference concentration – mkg/cm3 0,011, p < 0,01); chloroform – 0,019891 ± 0,006675 mkg/cm3 (reference concentration – mkg/cm3 0,0, p < 0,01). In the comparison group the manganese concentration was 0,011389 ± 0,001434 mkg/cm3 (p < 0,01 to the study group), chloroform – 0,002009 ± 0,000701 mkg/cm3 (p < 0,01 to the study group). In general, the concentration of manganese in children of the study group exceeded the rate in the comparison group by 2,6 times (p < 0,01), chloroform – by 10 times (p < 0,001).
The comparative analysis of the incidence of complaints of gastrointestinal character showed that children in the study group noted more frequently decreased appetite (91,4 and 61 %, respectively, p = 0,04), gaseous eructation (45,5 % vs. 25,4 %, p = 0,03), abdominal pain (58,6 % vs. 37,2 %, p = 0,03), localized in the epigastrium (58,2 % vs. 23,2 %, p ? 0,001) or right upper quadrant (61,2 % vs. 32,1 %, p ? 0,001), disorders of intestinal habits (78,5 % vs. 57,1 %, p = 0,004). Among the complaints of astheno-vegetative character the most frequently mentioned included: sweating (37,1 % vs. 10,9 %, p = 0,02), fatigue (16,4 and 8,6 %, respectively, p = 0,04), transport intolerance (6,9 and 5,4 %, p = 0,82). In children of the study group the hepatobiliary dysfunction symptoms were recorded 1,4 times more likely (87,9 and 64,3 %, respectively, p = 0,001). The significant causal relationship of probability of the development of biliary tract disease with the elevated blood levels of chloroform (R2 = 0,29; F = 36,92; p = 0,001) and diseases of the nervous system of functional nature – with the high concentration of manganese and chloroform (R2 = 0,50–0,77; F = 93,67–109,62; p = 0,01–0,001) has been determined.
The predominant type of vegetative tonus in children of the study group was eutonia (50 %), but in 37,5 % vagotonic option was revealed, which is 1.9 times higher than in the comparison group (20 %, p = 0,02). In the study group the sympathicotonic type of autonomic reactivity was observed in only 25 %, which is 1,2 times less frequently than in the comparison group (30 %, OR = 1,2, CI = 1,1–1,7, p = 0,04), the predominant type was hypersympathicotonic (62,5 %); in the comparison group this option was met 1,5 times less frequently – 43,3 % (OR = 1,45, CI = 1,16–3,11). The direct significant correlations of elevated blood manganese and initial development of vagotonia (R2 = 0,41; F = 98,72; p = 0,01) have been established; elevated blood manganese and hypersympathicotonic type of autonomic reactivity (R2 = 0,37; F = 87,54; p = 0,01). During the ultrasound scan of hepatobiliary area the reactive changes of the liver in the study group were recorded 7 times more frequently (31,7 % vs. 4,5 %, p = 0,01), in addition, 1,6–1,7 times more frequently the biliary dysfunction of hypokinetic type took place (80,2 % vs. 50 %, p = 0,001) and an increase in the linear dimensions of the liver (12,2 and 7,0 %, respectively, OR = 1,74, CI = 1,32–3, 76, p = 0,05). There was a significant correlation between the elevated chloroform concentration in children’s blood and the development of reactive changes of the liver (R2 = 0,39; F = 76,83; p = 0,01), higher concentration of manganese in blood and presence of biliary dysfunction of hypokinetic type (R2 = 0,41; F = 99,23; p = 0,01).
During the ultrasound scan of the gastroduodenal area a moderate amount of fluid in the stomach was determined in children of the study group 3 times more frequently than in the comparison group (33 and 11 %, respectively, p = 0,003). Physiological variant of motor function of the stomach and duodenum in children of the study group was met 2 times rarer (14 % versus 28 %, p = 0,03). Duodeno-gastric, duodeno-bulbar, bulbo-gastric reflux was detected in the study group 1,4–1,5 times more frequently (OR = 1,41–1,52; CI 1,12–3,87, p = 0,01–0,03). The causal link of the high concentration of manganese in blood and the impaired motor function of the stomach and duodenum (R2 = 0,25–0,52; F = 46,5–119,18; p = 0,01–0,001) was found.
During the endoscopy the incidence of atrophic and hypotrophic changes of antral gastric mucosa in the study group was 3,4 times higher than the comparison group (18,1 % versus 5,4 %, p = 0,01). The causal link of the high concentation of manganese in blood and the atrophic and hypotrophic changes of the gastric mucosa (R2 = 0,21–0,36; F = 58,11–94,32; p = 0,01) has been established.
Discussion. The results of the performed study suggest that in children consuming water of inadequate quality (concentration of hyperchlorination and manganese products > 1MAC), the chloroform and manganese concentration in blood substantially exceeds the reference level. It has been found that the elevated concentration of chloroform and manganese in blood contributes to the development of autonomic parasympathetic dysfunction by parasympathetic type, reactive changes of the liver, biliary dysfunction of hypokinetic type and dysmotility of the stomach and duodenum by the hyperkinetic type. The effect on the gastric mucosa of bile acids results in solubilization of the lipid surface of epithelial layers’ membrane. According to the literature [2, 4] the lecithin contained in the bile by the action of pancreatic juice phospholipase is biotransformed in lysolecithin, which in case of contact with the stomach has a strong cytotoxic effect on the epithelium and the subsequent development of hypotrophic processes. The biliary dysfunction by the hypokinetic type initiated by chemical toxicants combined with hyperkinetic disorders of gastroduodenal sphere underlie the development of the sub- and atrophic changes in the mucosa of the stomach and duodenum. The emerging technologies of prevention should be aimed not only at increasing the activity of the processes of biotransformation of chemicals and their elimination, but also at the correction of autonomic dysfunction, gastroduodenal and biliary motility.
The work is submitted to the International Scientific Conference “Fundamental research”, Israel (tel Aviv), October, 16–23, 2014,came to the editorial office оn 11.07.2014.