[Is suprastenotic dilatation a mandatory symptom of impaired bile outflow?].

OBJECTIVE: To study the rate, nature, and symptoms of bile flow impairments running without developing suprastenotic dilatation. MATERIAL AND METHODS: A total of 1082 patients undergoing endoscopic retrograde cholangiopancreatography for the differential diagnosis of jaundices were followed up. According to the diameter of the common bile duct, the patients were classified into cholangioectasia and non-cholangioectasia groups. The investigators studied the causes of bile evacuation disorders; the levels of bilirubin, hepatic transferases, and alkaline phosphatase; the duration and periodicity of obstructive jaundice; extended compression of suprastenotic dilatation; the occurrence of other symptoms; and the efficiency of additional procedures for the differential diagnosis of hepatic and obstructive jaundices. RESULTS: There was no suprastenotic dilatation in 11 cases: in noncircular amorphous internal hepatocholedochal blocks, in cicatrical stenoses of the hepatocholedoch, in excessive metastatic spread into the hepatic portal and parenchyma, extended stenosis of the common bile duct does not lead to intrahepatic cholangiectasia. In 9 cases, instrumental palpation and aspiration biopsy were used to visualize common bile duct stenosis in order to elucidate its nature, degree, and rigidity. Endobiliary stenting was employed for the differential diagnosis of jaundices. CONCLUSION: No suprastenotic dilatation was seen in 0.8% of patients with organic bile flow impairment. In these cases, obstacles to bile flow may be suggested by clear-cut variations in the diameter of the hepaticocholedoch and its deformity. The absence of suprastenotic dilatation may be partly explained by excessive metastatic liver involvement and malignant hepatoduodenal ligament infiltration. When suprastenotic dilatation is absent, instrumental palpation and diagnostic and therapeutic stenting may be used for the differential diagnosis of obstructive and hepatic jaundices.

[Study of cytogenetic and cytotoxic effect of non-contact electrochemically-activated waters in the five organs of rats].

For the first time the multiorgan karyological analysis of five organs of rats was applied for the study of the cytogenetic and cytotoxic action of the four types of non-contact electrochemically activated water in the 30-days in vivo experiment. The effects of investigated waters were not detected in bone marrow polychromatic erythrocytes. "Anolyte" (ORP = -362 mV) did not have a negative effect on rats. "Catholyte-5" (ORP = +22 mV) and "Catholyte-25" (ORP = -60 mV) induced cytogenetic abnormalities in the bladder and fore stomach. The same catholytes and "Catholyte-40" (ORP = -10 mV) changed the proliferation indices: increased the mitotic index in the fore stomach epithelium and reduced the frequency of binucleated cells in the fore stomach, bladder and lungs. The increase in the rate of cells with cytogenetic abnormalities on the background of the promotion of mitotic activity can be considered as a manifestation of the negative effect, typical for catolytes, but the effect of each out of them has its own features.

[Harmonization with international approaches to guidance documents on methods of assessment of the mutagenic properties of chemical environmental factors].

Evaluation of mutagenic activity--an indispensable element of the toxicological characteristics of chemicals in their hygienic regulation. In the article there is performed an analysis of the adopted in the Organization for Economic Cooperation and Development (OECD) and in Russia guidance documents on methods of assessment of the mutagenic properties of chemicals. In the OECD there are 17 manuals, each of which describes a single method, in Russia there were approved five guidance documents for specific groups of chemicals (drugs, pesticides, nanomaterials, substances normalized in the water and the air), which represent the basic and auxiliary methods of testing mutagens. Basic methods aimed to the evaluation of gene, chromosomal and genomic mutations include: assessment of gene mutations in bacteria, methods for estimating mutations in cell cultures of human and mammals in vitro, methods for inspecting mutations in somatic and germ cells of mammals in vivo. Analysis of Russian documents shows that the protocols of basic tests of assessment of the mutagenic activity are close to the protocols of the OECD. It is necessary to publish guidance documents on tests of assessment of the mutagenic activity of chemicals harmonized with the OECD documents.

[Role of repair gene polymorphism in estimating the sensitivity of human genome to radon in concentrations exceeding maximum permissible level].

The paper gives the results of investigating chromosome aberrations in human peripheral blood lymphocytes due to DNA repair genes, such as hOGG1, ADPRT, APE1, XRCC1, XpG, XpC, XpD, and NBS1, upon long-term exposure to excess indoor radon concentrations. The frequency of chromosome aberrations was found to be significantly lower in the carriers of the genotype hOGG1 326 Ser/Ser (versus the variant Ser/Cys), APE1 148 Asp/Asp (versus Val/Ala and Ala/Ala). The study polymorphic systems were shown to be of value in giving rise to individual types of chromosome aberrations (single fragments and chromosome exchanges).

[Taking into account the emotional tension of adults and children in the evaluation of the influence of environmental factors on genomic instability and sensitivity: results and prospects].

The paper summarizes the results of 8 genetic and psychological examinations in adults and children, which are aimed at evaluating the genotoxic effects of environmental factors on cultured lymphocytes. Human emotional tension was proved to be directly related to the level of genome damage, to genomic sensitivity to in vitro exposures, and to lymphocyte proliferative activity and to be inversely related to the level of apoptosis. There was an association of the degree of anxiety in children with their morbidity. High emotional tension in adult family members was found to negatively affect the degree of anxiety and the level of genomic instability in a child.

[Values of the micronucleus test on animal epithelial cells exposed to titanium dioxide].

The genetic safety of titanium dioxide (TD)-containing foods and cosmetic products has been little investigated. The study evaluated the mutagenic activity of TD in the micronucleus test with animal visceral mucosal epithelial cells. Two simethicone-coated anatase samples (mean size 160 and 33.2 nm) were inserted into the mouse stomach in doses of 40-200-1000 mg/kg seven times and applied as an ingredient of 10 and 25% cream (doses 250 and 625 mg/kg, respectively) to the hair-sheared rat skin once for 4 hours. Analysis of cytogenetic disorders (micronuclei, protrusions, and the atypical form of the nucleus) revealed no mutagenic properties of TD on the mucosal epithelium of the mouse and rat intestine, mouse prostomach, and rat uterine bladder. Enhanced mitotic activity was observed in all the study tissues after exposure of both samples to TD given in some or in all (in the rat urinary bladder mucosal epithelium) doses.

[Effect of titanium dioxide nano- and microparticles on the values of the micronucleus test using human blood lymphocytes in culture].

The activity of the nano- and microparticles of titanium dioxide (TD) given in doses of 1.6, 40.0, and 500 microg/ml was studied in the cytochalasin B block micronucleus test with blood cells from two donors. It was shown that nano-DT in doses of 1.6 and 40 microg/ml was more active than micro-DT in inducing micronuclei and nucleoplasmic bridges, asymmetric cell division, and accelerated cell proliferation. Some differences in individual sensitivity to TD between donor blood cultures were due to an inverse trend in the association between the indicators of genomic damage and apoptosis. The new nuclear morphometry test that had developed to screen genotoxic effects and used in this study for the first time revealed a nano-DT dose-depended increase in the asymmetry of nuclei in the binucleated cells in the cultures of both blood donors, the morphometric effects being directly correlated with the values of cytogenetic analysis.

[Morbidity among senior preschool children in Magnitogorsk].

The publication is the third fragment of the multiparameter study. The level and causes of genome instability and sensitivity are assessed in children living in Magnitogorsk, a city with one of the largest mills in Russia. The city is in the list of the world's 35 most polluted ones. A transverse retrospective analysis found no differences in primary morbidity among 5-7-year-old children who had been living in different districts of Magnitogorsk since birth and were going to municipal kindergartens located adjacent to their house. Contrary to the expectations, the prevalence of morbidity and diseases that were markers for an industrial town was significantly lower among the children residing in the settlements situated around the mills than that in the city's other districts. There were 9 organic compounds that had no hygienic standards, the content of which in the snow samples collected in the areas of the examined kindergartens correlated with the prevalence of the children's morbidity. Family social and living conditions were shown to affect the children's morbidity.

[Hygienic evaluation of the total mutagenic activity of snow samples from Magnitogorsk].

The paper gives the results of 4-year monitoring of the total mutagenic activity of snow samples from different Magnitogork areas in a test for induction of dominant lethal mutations (DLM) in the gametes of Drosophila melanogaster. An association was first found between the rate of DLM and the content of some chemical compounds in the ambient air and snow samples; moreover all the substances present in the samples, which had found genotoxic effects, showed a positive correlation with the rate of DLM. Furthermore, direct correlations were first established between the rate of DLM and the air pollution index and morbidity rates in 5-7-year-old children residing in the areas under study. The findings allow the test for induction of dominant lethal mutations (DLM) in the gametes of Drosophila melanogaster to be recommended due to its unique informative and prognostic value for monitoring ambient air pollution and for extensive use in the risk assessment system.

[Evaluation of epidemic risk from pathogenic and opportunistic bacteria isolated from water of its various use types].

The investigation was concerned with wild gram-positive and gram-negative microorganisms (E. coli spp., Klebsiella spp., Salmonella spp., and the nonfermentative bacteria Pseudomonas spp.) isolated from the waters of different types, as well as museum cultures (E. coli strain 1257, E. coli strain 675, Salmonella enteritidis ATCC 5765, Staphylococcus aureus 906, and Pseudomonas aeruginosa ATCC 10145). The wild strains were isolated from water when conducting experimental and field studies; these are able to survive in the waters disinfected by various procedures (a guanidine-containing disinfectant in non-toxic concentrations; photo-activated decontamination with sensitizers; exposure to magnetic and ultrasound waves). The cytotoxic, adhesive, and invasive activities of the bacteria isolated from environmental water objects increased on their cultivation on nutrient growth media, by simulating their possible effects in man. The developed experimental approach makes it possible to estimate the hazard of potentially pathogenic bacteria in one test trial, by applying the BGM cells and may be used to assess the microbial risk.

[Use of micronuclear test to the human buccal mucosal epithelium].

The paper presents microphotos of anomalies of the human buccal mucosal epitheliocytic nucleus and gives criteria for their identification. Two procedures for making a scrape from the buccal mucosa were compared. The smears prepared from the samples taken with a urogenital brush showed the lower frequency of cells with micronuclei, protrusions of the "broken egg" and "tongue" types, vacuolated cells, as well as cells with nuclear pyknosis and lysis than those prepared with a rough scrape spatula. The nuclear frequency of cells with condensed chromatin in such smears was higher than that in the rough scrape. In addition, the authors show a relationship of the frequency of cells with the binuclei, perinuclear vacuole, nuclear pyknosis, and condensed chromatin in the nucleus, and absorbed apoptotic (residual) bodies to the examinee's age.

[Use of micronuclear test to assess drinking waters].

The effect of drinking waters with their altered structure and charge state (a total of 9 samples) on the epitheliocytes of the proventriculus, liver, and kidney was studied in rats after 6- and 12-month water consumption. It was found that in the absence of changes in the animals' morphofunctional status, the degree of water structuredness was associated with the frequency of epitheliocytes with nuclear protrusion into the proventricular mucosa following 6-month water consumption and with the manifestations of adipose degeneration, hepatocytic alterations, and stromal overgrowth into the liver after 12-month water use. The biological implication of little studied (additional) types of anomalies of the proventricular epitheliocytic nucleus: the necrotic nature of a perinuclear vacuole, the predominant implication of nuclear pyknosis and rrhexis to apoptosis and the association of binucleated patterns with the restorative proliferation of hepatic and renal tissues, was specified.

[Use of morphofunctional and cytogenetic studies to analyze the influence of environmental factors].

Long-term studies of 2 (cytohistology and genetic monitoring) laboratories of the Research Institute of Human Ecology and Environmental Hygiene, Russian Academy of Medical Sciences, to investigate the influence of environmental factors in the experiments made it possible to develop a noninvasive procedure for evaluating their cytological and cytogenetic impacts on man. A concurrent study of morphofunctional (histological, cytological) and cytogenetic parameters in both experimental and field trials can substantially extend and refine the interpretation of responses to environmental factors, which generates a need for using these parameters in hygienic and epidemiological studies.

[Buccal epithelial micronuclear test in the comprehensive assessment of children's ecological well-being in Moscow].

In the buccal epithelial micronuclear test, only the higher frequency of cells with any nuclear degenerative changes is considered to be attributable to the adverse influence of environmental factors. Comprehensive examination of 223 children of 5-7 years of age, going to kindergartens and schools has indicated that the frequency of cells with nuclear chromatin condensation and incomplete nuclear lysis decreased when ambient air contamination was increased in the territories of children's establishments and when the child's throat was contaminated with Staphylococcus aureus or the pharyngeal resident microflora inhibited. Some poor conditions of the nasal and buccal mucosae were also associated with the increase or decrease of cell frequencies. It is suggested that nuclear chromatin condensation and nuclear lysis (rather than other signs of cell degeneration and death) reflect natural cell aging. A moderate toxic effect causes epitheliocytic physiological development retardation and a more intensive effect accelerates aging of cells and induces their death.

[A complex approach to evaluation of human genome instability].

In this study, evaluation of genome instability in individuals exposed to chemical compounds included detection of the genetic polymorphism of some xenobiotic metabolic enzymes (CYP1A1, CYP1E1, PON1, GSTM1, GSTT1), as well as measurement of oxidative state chemiluminescent variables and the level of cytogenetic damage. According to the study, the level of chromosomal aberrations in peripheral blood lymphocytes shows a strong correlation with PON54 left allele and GSTM1 null genotype, and can be described by the polynomial function of blood plasma luminol-dependent chemiluminescence. The frequencies of micronuclei in buccal epithelium displayed a weak association with GSTT1 null genotype.

[Proliferative activity parameters and their correlation with genetic damage of blood lymphocytes during cultivation under the conditions of cytokinetic block].

The subjects of the study were 15 volunteers aged 22 to 25 years, who underwent 25 air ionization sessions. The effects of genome instability were evaluated, and correlations between indicators of genome damage (lesions of micronuclei and nucleoplasmatic bridges) and parameters of proliferative and replicative activity (mitotic index, proliferative pool, the fraction of rapidly dividing cells, and replication index) of blood lymphocytes in the culture were studied. In order to establish the associations between the parameters, the parallel cultures were exposed to 0.07 mM of the standard mutagen MNNG during 5 hours. The study showed that the course of air ionization did not induce the micronuclei and nucleoplasmatic bridges in binuclear cells, but increased proliferative cell activity. This effect was accompanied by an increase in the fraction of rapidly dividing cells among all the dividing cells, and an increase in the dispersion of all proliferation parameters. MNNG induced a constant level of micronuclei in binuclear cells during the whole course, but not before the beginning of air ionization. The changes in the parameter "the fraction of dividing cells" (proliferative pool) were the most prominent manifestation of the suppression of proliferation by MNNG. MNNG loading inhibited the formation of binuclear cells most of all. The results demonstrate a non-random character of the correlation between the level of micronuclei in binuclear cells and proliferative activity parameters during cell cultivation under the conditions of cytokinetic block.

[Dioxins and medical-genetic indices of health of residents of the town of Chapayevsk]. / Dioksiny i mediko-geneticheskie pokazateli zdorov'ia naseleniia goroda Chapaevska.

The paper presents the results of an integrated medical genetic survey carried out in the town of Chapayevsk. The survey included an estimation of the incidence of congenital malformations (CMF), congenital morphogenetic options (CMGO), evaluation of the frequency of chromosomal mutations of various types and micronuclei in human somatic cells. The incidence of CMF among newborn infants corresponds to that in Russia, but such forms of CMF as congenital hydrocephalus and agenesia and disgenesis of the kidney were more common in the town. The study ascertained that the average number of CMGO per child was on the increase. Cytogenetic findings unambiguously demonstrate that there was a spatial gradient within the town (from the plant to remote districts), higher rates of chromosomal aberrations. Further studies of the effects of dioxins on genetic health are required to assess the actual genetic risk due to its human contact.

[Procedure for complex toxico-genetical investigations]. / Metodologiia provedeniia kompleksnykh genetiko-toksikologicheskikh issledovanií.

A biomonitoring system is proposed, which involves measurement of environmental genetoxicants, determination of mutagenic accumulation in biological substrates of human beings and the severity of genetic abnormalities in their somatic cells. The toxicogenetical monitoring system includes the assessment of the examinees mental status. The results of application of the system are given by using as an example two Yaroslavl (machine-building and oil-processing) plants.