Direct Photocontrol of Peptidomimetics: An Alternative to Oxygen-Dependent Photodynamic Cancer Therapy.

Conventional photodynamic treatment strategies are based on the principle of activating molecular oxygen in situ by light, mediated by a photosensitizer, which leads to the generation of reactive oxygen species and thereby causes cell death. A diarylethene-derived peptidomimetic is presented that is suitable for photodynamic cancer therapy without any involvement of oxygen. This light-sensitive molecule is not a mediator but is itself the cytotoxic agent.

[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.

[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.

Potent, orally available, selective COX-2 inhibitors based on 2-imidazoline core.

A novel series of compounds containing a polar, non-flat 2-imidazoline core was designed based on the SAR information available for aromatic azole cyclooxygenase-2 inhibitors. While the majority of the compounds prepared using an earlier developed imidazoline N-arylation methodology turned out to be inferior to the known COX-2 inhibitors, one lead compound displayed potency (300 nM) comparable to clinically used Celecoxib and was shown to be more selective. The series represents the first example of selective COX-2 inhibitors built around a distinctly polar core, contradicting an earlier accepted view that a lipophilic scaffold is required for high inhibitor potency.

[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.

[Experience of treatment of pancreatonecrosis in hospital in the extreme north].

Criteria of pancreatonecrosis are described in the article. Clinical and ultrasonic signs, the applied ways of treatment of acute pancreatitis are considered in 715 patients. The methods of treatment of complications of pancreatonecrosis are described.

[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.

[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.

[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.

[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).

UPLC-MS/MS method for bioequivalence study of oral drugs of meldonium.

A rapid and simple method based on ultra-performance liquid chromatography on a hydrophilic interaction chromatography column with tandem mass-selective detection (UPLC-MS/MS) to determine meldonium in human plasma was developed. The calibration curve acquired in the range of 10-6000 ng/mL had quadratic form. Method validation proved the conformity of its properties (selectivity, matrix effect, lower limit of quantification, accuracy, precision and recovery) with the established requirements.

[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.

Investigation of genotoxic and cytotoxic effects of micro- and nanosized titanium dioxide in six organs of mice in vivo.

Titanium dioxide is manufactured worldwide in large quantities for use in a wide range of applications including as food additives, in cosmetics and pigments for coloring ingested and externally applied drugs. Although TiO(2) is chemically inert it can cause negative health effects, such as lung cancer in rats. However, the mechanisms involved in TiO(2)-induced genotoxicity and carcinogenicity have not been clearly defined and are poorly studied in vivo.

[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.

[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.

[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.

[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.

[Tumor necrosis factor gene polymorphisms in breast cancer patients].

Analysis of microsatellite TNFalpha marker and (-308(G/A) polymorphisms in promoter of TNFalpha gene was conducted in 167 patients with various types of sporadic breast cancer (BC) as well as in 139 healthy Russian donors. It was shown that frequency of allele 7 in TNFalpha microsatellite marker was significantly higher in BC patients than in healthy donors (17.9% versus 10.

[Polymorphisms of tumor necrosis factor genes in sporadic and hereditary breast cancer].

A first attempt at investigating polymorphism of microsatellite TNFa and SNP-308 (G/A) in promoter of TNFalpha was made in patients with sporadic and hereditary breast cancer. 308 (A) TNFalpha and TNFa 12 alleles frequencies were significantly higher while that of TNFa10--significantly lower in the hereditary cancer group as compared with donors as well as sporadic cancer patients. That was contributed by cases of infiltrative-lobular tumors.

[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.

[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.

[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.

[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.