Search NEL Online

Comparative Study 2006; 27(Suppl 2): 74-77 PubMed PMID: 17159784 Citation  Keywords:  Anticonvulsants:adverse effects, Congenital Abnormalities:epidemiology, Czech Republic, Developmental Disabilities:chemically induced, Epilepsy:complications, Female, Fetal Death:chemically induced, Humans, Infant, Newborn, Information Services, Pregnancy.   

OBJECTIVES: Care, treatment and follow-up in psychiatric and epileptic pregnant women were compared with women inquiring Czech Teratology Information Service (CZTIS) due to other exposure to drugs during pregnancy.

METHODS: Data were collected by CZTIS, member of European Network of Teratology Information Services from 1996. Exposed groups were compared with pregnant women exposed to drugs which were not classified as major teratogens or hyperthermia. Groups do not vary in age, reproductive history and other parameters.

RESULTS: We observed higher frequency of miscarriage and voluntary termination of pregnancy in the group of psychiatric patients. The number of malformation in prospective follow-up cases was lower than in control group.

CONCLUSIONS: Chronic diseases as epilepsy or psychiatric disorders have to be treated during pregnancy. Women should obtain accurate information about possible risk before pregnancy. Co-operation is needed in these cases. Physicians should keep in mind that appropriate information is to be given to the patient according to her disease, education and comprehension of the problem. If there is any doubt they should organize help for their patients....

Read abstract

Comparative Study 2006; 27(Suppl 2): 65-68 PubMed PMID: 17159782 Citation  Keywords:  Asphyxia Neonatorum:blood, Delivery, Obstetric, Glutathione Peroxidase:blood, Humans, Infant, Newborn, Malondialdehyde:blood, Oxidative Stress, Stress, Physiological:blood, Superoxide Dismutase:blood, Term Birth:blood,.   

OBJECTIVES: In healthy term newborns (HTN) to determine on the 1st and 5th day of life the activity of total antioxidant capacity (TAS), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPX) and to compare the values with the group of asphyxiated term newborns (ATN).

PATIENTS/METHODS: The series consisted of 15 HTN and 24 ATN. In both groups TAS, MDA, GPX and SOD were investigated.

RESULTS: Reference values in HTN (1st/5th day of life) for TAS were 0.52+/-0.03/0.49+/-0.04 mmol/l, for MDA 0.72+/-0.07/1.08+/-0.09 micromol/l, for SOD 594.20+/-16.47/591.23+/-14.14 Ug/Hb and for GPX 25.48+/-1.32/25.98+/-1.20 Ug/Hb. In a group of ATN the obtained values were (1st/5th day of life): TAS 1.1+/-0.08/0.98+/-0.08 mmol/l, MDA 2.08+/-0.22/2.21+/-0.34 micromol/l, SOD 509.18+/-26.8/564.49+/-36.4 Ug/Hb and GPX 30.2+/-1.9/32.45+/-2.69 Ug/Hb.

CONCLUSIONS: Statistically significant differences were found on the 1st and 5th day of life between the two groups investigated in values of MDA (**p<0.01) and TAS (**p<0.01). Increased values of MDA in the group of ATN on the 1st and 5th day of life confirmed the presence of lipoperoxidation. The obtained values of TAS on the 1st and 5th day of life in the group of ATN were surprisingly higher than in HTN. The increase of TAS in ATN could point to a certain ability of ATN to prevent the damage of balance between overproduction of MDA and antioxidants. The results of SOD and GPX activity were not statistically significant, yet they are indicative of the biochemical reaction of the organism of term newborns to asphyxia....

Read abstract

Journal Article 2006; 27(Suppl 2): 57-60 PubMed PMID: 17159780 Citation  Keywords:  Adult, Antineoplastic Agents:toxicity, Chromosomes, Human, DNA Damage, DNA-Binding Proteins:genetics, Female, Gene Frequency, Genetic Predisposition to Disease, Humans, Male, Medical Staff, Hospital, Middle Aged, Occupational Diseases:chemically induced, .   

OBJECTIVES: Medical workers in oncological units have chronically been exposed to low doses of cytostatics (C) with potential consequences on DNA and chromosomal integrity. Our study addresses relationships between chromosomal aberrations (CAs), chromosome (CSA), and chromatid (CTA) types and polymorphisms in DNA repair genes XRCC1 and XRCC3.

METHODS: The study was conducted on 72 exposed individuals from hospitals in Martin (HMT; 28 individuals), Ruzomberok (HRK; 31 medical workers) and in Trstená (HTS; 13 individuals), and on 34 unexposed individuals. Conventional cytogenetic analysis was employed for the detection of CAs. XRCC1 and XRCC3 polymorphisms were assayed for by Taqman SNP genotyping assays ("Assay-by-Demand") using Real-Time allelic discrimination on AB 7 500 equipment (all from Applied Biosystems, Foster City, USA).

RESULTS: Higher frequencies of CAs were detected in exposed individuals than in controls (1.78% versus 1.32%, respectively). The frequency of aberrant cells (Ab.c.) was highest among workers from HRK (1.97%), followed by those from HMT and HTS (1.54% and 1.85 %, respectively). In the exposed group a moderately higher frequency of CTA (0.93%) in comparison with CSA (0.85%) was detected. Higher CAs were detected in individuals with homozygous variant polymorphism in XRCC1 exon 10 gene than in those with wild-type genotype (1.87% versus 1.60%). Variant T allele in XRCC3 exon 7 was also associated with higher CAs (1.71% and 1.74%) as compared to the wild-type C allele (1.45%).

CONCLUSIONS: The detection of individuals with increased susceptibility to genotoxic agents enables to take preventive measures during the working process....

Read abstract

Journal Article 2006; 27(Suppl 2): 40-43 PubMed PMID: 17159776 Citation  Keywords:  Animals, Antioxidants:analysis, Asbestos:toxicity, Cell Survival:drug effects, Chemokine CCL2:metabolism, Chemokine CCL4, Chemokines:metabolism, Glutathione Peroxidase:analysis, Glutathione Reductase:analysis, Inhalation Exposure, Lung:chemistry, Macropha.   

OBJECTIVES: Activity of cytoplasmatic superoxide dismutase, glutathione peroxidase,- and reductase, gamma-glutamyl transpeptidase and expression of macrophage chemoattractant protein-1 and macrophage inhibitory protein-1alpha was determined in primary culture of rat alveolar macrophages and type II pneumocytes after exposure to stone-wool, wollastonite and crocidolite (blue asbestos).

METHODS: The activity of redox enzymes was examined by RANDOX kits, chemokines were studied by ELISA.

RESULTS: The UICC crocidolite (positive control) decreased the activity of all redox enzymes and increased the expression of chemokines, whereas the two asbestos substituents did not alter the activity of redox enzymes either in the alveolar macrophages or pneumocytes. Stone-wool and wollastonite moderately increased the expression of chemokines in both cells.

CONCLUSIONS: The redox status and production of chemokines changed in the opposite direction, presumably owing to stronger toxic effect of asbestos. These data suggest that stone-wool and wollastonite, as potential substituents for asbestos, are less toxic than the human carcinogenic and fibrogenic crocidolite....

Read abstract

Journal Article 2006; 27(Suppl 2): 35-39 PubMed PMID: 17159775 Citation  Keywords:  Animals, Coloring Agents:pharmacokinetics, Cytochrome P-450 CYP1A1:metabolism, Cytochromes b5:physiology, DNA:metabolism, DNA Adducts:metabolism, Humans, Male, Metabolic Detoxication, Phase I, Models, Biological, Naphthols:metabolism, Rabbits, Rats, Rats,.   

OBJECTIVES: Modulation of the cytochrome P450 (CYP) 1A1-mediated oxidative activation and detoxication of carcinogenic Sudan I by the heme-protein cytochrome b(5) (b(5)) was investigated. Another aim of the study was to examine the formation of Sudan I-DNA adducts in vivo.

METHODS: High performance liquid chromatography (HPLC) with ultraviolet (UV) detection was employed for the separation of Sudan I metabolites formed by human recombinant CYPs and rat CYP1A1. The (32)P-postlabeling technique was utilized to determine Sudan I-DNA adducts.

RESULTS: The capabilities of the most efficient CYP enzymes oxidizing Sudan I, human and rat recombinant CYP1A1, as well as of human recombinant CYP1A2, 2A6 and 3A4 were significantly increased by b(5), while reactions catalyzed by human CYP1B1, 2C8, 2C9 and 2E1 were insensitive to this heme protein. Sudan I oxidation catalyzed by CYP2B6, 2C19 and 2D6 was even decreased by b(5). The stimulation of the CYP1A1-mediated Sudan I oxidation was dependent on concentration of b(5). Likewise, the increase in CYP1A1-mediated formation of Sudan I-DNA adducts by b(5) was concentration dependent. Other proteins containing heme such as cytochrome c or myoglobin were without this effect. The major Sudan I-DNA adducts formed in vitro are also generated in vivo, in livers of rats treated with Sudan I.

CONCLUSIONS: The data are the first report on the stimulation of CYP1A1-mediated oxidative reactions by b(5). In addition, the results demonstrating covalent binding of Sudan I to rat liver DNA in vivo indicate a genotoxic mechanism of Sudan I carcinogenicity in rats....

Read abstract

Comparative Study 2006; 27(Suppl 2): 31-34 PubMed PMID: 17159774 Citation  Keywords:  Hyaluronic Acid:chemistry, Hydrogen Peroxide:pharmacology, Manganese Compounds:pharmacology, Models, Biological, Molecular Weight, Oxides:pharmacology, Peroxynitrous Acid:chemical synthesis, Viscosity,.   

OBJECTIVES: This contribution presents the results of the kinetics of HA degradation by peroxynitrite, which represents one of the main reactive oxygen species degrading various biomacromolecules under inflammatory conditions.

METHODS: Two simple procedures have been adapted to prepare sodium peroxynitrite: the first containing an excess of H(2)O(2), and the second in which the H(2)O(2) excess had been decomposed by MnO(2) treatment. The kinetics of hyaluronan degradation by action of peroxynitrite was monitored by rotational viscometry.

RESULTS: High-molecular-weight hyaluronan was degraded by peroxynitrite. The degradation was increased in the presence of ONOO(-) previously treated by MnO(2) in order to remove residual hydrogen peroxide. One of the reasons of this finding could be that by the action of the residual metal the pathway of ONOO(-) decomposition starts to be manifested immediately on mixing traces of metals originally present in the HA sample with the ions of manganese.

CONCLUSIONS: Trace amounts of transition metal(s) should be taken into consideration on evaluating the experimental results. Purchase of the marketed peroxynitrite product appears to be the appropriate approach to simplify and standardize the quality of ONOONa....

Read abstract

Journal Article 2006; 27(Suppl 2): 27-30 PubMed PMID: 17159773 Citation  Keywords:  Adenine:analogs & derivatives, Bacteria:ultrastructure, Cell Membrane:metabolism, Cytochrome P-450 Enzyme System:genetics, Drug Interactions, Humans, Liver:drug effects, Metabolic Detoxication, Phase I, Models, Biological, NADPH-Ferrihemoprotein Reductase.   

OBJECTIVES: To determine a possible influence of acyclic nucleoside phosphonates on FMO3 and CYP activity at molecular level in vitro.

METHODS: Inhibition of individual CYP and FMO3 activities in the reconstituted system and in artificial membranes (bactosomes) was studied.

RESULTS: Activity of FMO3 was inhibited by PMPA and bisPOC-PMPA even at low levels of these drugs (below 100 microM). In reconstituted system with CYP2C9, no inhibition of CYP2C9 activity was observed. On the other hand, experiments based on membrane coexpressed system showed a modest extent of inhibition (for PMEA, PMPA, bisPOM-PMEA and bisPOC-PMPA the level of inhibition was 77.8%; 74.1%; 64.2% and 68.6%, respectively at 400 microM).

CONCLUSIONS: PMPA and bisPOC-PMPA are able to inhibit FMO3 activity at relatively low levels (10-100 microM) indicating a relatively specific interaction. Activity of CYP2C9 was affected when using the membranes coexpressed with NADPHcytochrome P450 reductase. This is probably due to more natural conditions for maintaining the CYP activity in bacterial membranes. As the inhibitor concentration in the systemic circulation does not exceed 2 microM, the probability of a significant in vivo effect of adefovir, tenofovir and the respective prodrugs on the microsomal system of cytochromes P450 and FMO3 is relatively low....

Read abstract

Evaluation Studies 2006; 27(Suppl 2): 23-26 PubMed PMID: 17159772 Citation  Keywords:  Animals, Antioxidants:analysis, Body Weight:drug effects, Bronchoalveolar Lavage Fluid:chemistry, Ceramics:toxicity, Glutathione Peroxidase:analysis, Inhalation Exposure:analysis, Lung:chemistry, Lung Diseases:chemically induced, Male, Mineral Fibers:toxi.   

OBJECTIVES: The programmes of asbestos replacement brought the need to use other fibres for insulation or reinforcement of material. The aim of the presented study was to follow the effect of refractory ceramic fibres (RCF3) alone or in combination with cigarette smoke (CS) on antioxidant status of the lung in experiment on animals. As free radicals are supposed to play a role in pathogenesis of lung diseases and the toxicity of particles has been associated with production of reactive oxygen species, the antioxidant status may serve as marker of lung injury. Our hypothesis was that the effect of combined exposure to RCF3 and CS will be additive or synergic.

DESIGN: Scheme of experiment: Wistar rats were randomly divided into 4 groups per 6 animals: control, intratracheal exposure to 4 mg of RCF3, inhalatory exposure to mainstream of cigarette smoke from 8 standard research 1R1 cigarettes per day, and both intratracheal exposure to RCF3 and inhalatory to CS. The exposure lasted 6 months, the inhalatory exposure was performed 5 times per week. After finishing the exposure bronchoalveolar lavage of lungs was performed and ascorbic acid, superoxide dismutase, glutathione and glutathione peroxidase were determined in lung tissue and cell free fraction of bronchoalveolar lavage fluid (BALF).

RESULTS: The results showed that the most sensitive indicator of changes in antioxidant status was glutathione, which was changed in all groups both in BALF and lung tissue homogenate....

Read abstract