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Comparative Study 2013; 34(Suppl 2): 74-78 PubMed PMID: 24362096 Citation  Keywords:  Absorption, Animals, Biological Availability, Chlorides:administration & dosage, Cholinesterase Reactivators:administration & dosage, Female, Injections, Intramuscular, Injections, Intravenous, Oximes:administration & dosage, Pyridinium Compounds:administ.   

OBJECTIVES: Oxime HI-6 is an acetylcholinesterase reactivator therapeutically efficient against nerve agents. Because of their physico-chemical properties, oximes are typically applied intramuscularly (i.m.). This route of administration has also some disadvantages, and alternative strategies ought to be examined. We evaluated the pharmacokinetic profiles of two HI-6 salts after their intravenous (i.v.) administration, and compare the results with the known pharmacokinetics after i.m. administration.r />r /> METHODS: Pigs were administered with HI-6 salts (i.v), either HI-6 dichloride (10.71 mg/kg) or molar equivalent HI-6 dimethansulphonate (13.59 mg/kg). Doses of the HI-6 salts corresponded with a standard HI-6 dichloride dose in one autoinjector (500 mg) and were recalculated for one kilogram of body weight.r />r /> RESULTS: The main pharmacokinetic parameters are comparable after i.v. and i.m. HI-6 administration. The compared pharmacokinetic parameters were half-life, terminal rate constant, mean residence time of the molecule in the body, clearance, and the apparent volume in the terminal phase. The bioavailability after i.m. administration was comparable with that of i.v.; these results suggest that the oxime is well released from the muscle depot. Significant differences were found in parameters Cmax and Tmax which are important in cases of emergency when rapidity and bioavailability are paramount for the success of treatment.r />r /> CONCLUSIONS: I.v. administration should solve the problem of rapid clearance. Infusion or bolus administration may be considered as a logical subsequent step in oxime treatment strategy. The main advantage is in maintenance of an effective therapeutic plasma concentration, a more easily achievable effective therapeutic concentration, and fewer local adverse reactions....

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Comparative Study 2013; 34(Suppl 2): 71-73 PubMed PMID: 24362095 Citation  Keywords:  Antioxidants:metabolism, Gestational Age, Glutathione Peroxidase:blood, Humans, Infant, Newborn:blood, Infant, Premature:blood, Malondialdehyde:blood, Oxidative Stress, Superoxide Dismutase:blood, Twins,.   

OBJECTIVES: The aim of the study was to determine the value of the total antioxidant system (TAS) and level of malondialdehyde (MDA), and the activity of glutathione peroxidase, superoxide dismutase in the case of premature twins - identical twins, monozygotic, on the 1st and 5th day of life and to compare the values between the first-born twin A and the second-born twin B.r />r /> RESULTS: We confirmed the difference between A and B twins in values of TAS and MDA, as well as the difference between the 1st and 5th day of life.r />r /> CONCLUSION: The values of TAS, which show the total activity of antioxidant enzymes in a newborn's organism, reflect the ability of protection against oxidative stress before and during delivery. In the case of twin pregnancy, the value of TAS is crucial and determines the degree and severity of consequences of asphyxia. MDA values indicate the presence of lipoperoxidation....

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Journal Article 2013; 34(Suppl 2): 64-70 PubMed PMID: 24362094 Citation  Keywords:  Adult, Blood Flow Velocity, Case-Control Studies, Diastole, Echocardiography, Doppler, Female, Humans, Liver Cirrhosis, Alcoholic:diagnostic imaging, Male, Middle Aged, Risk Factors, Ventricular Dysfunction, Left:diagnostic imaging,.   

OBJECTIVES: The aim of this study was to prove that the incidence of the more unusual and largely under-researched cardiac dysfunction, i.e. diastolic, is more frequent in patients with alcoholic cirrhosis. Comparison of the incidence of left ventricular diastolic dysfunction in medical-ward patients with no prior history of cardiovascular disease to that of the patients with hepatic cirrhosis caused by alcohol abuse was carried out. The study is original from the point of view of examination of patients with cirrhosis of solely alcoholic aetiology in one Central-European university hospital.r />r /> METHODS: Three methods of echocardiographic examination were used: (i) pulse Doppler echocardiography to assess blood flow through the mitral valve and in the pulmonary veins, (ii) tissue Doppler imaging (TDI) to assess mitral annular motion, and (iii) colour M-mode Doppler echocardiography to assess blood flow from the left atrium into the left ventricle.r />r /> RESULTS: The results found confirmed that the incidence of left ventricular diastolic dysfunction in patients with alcohol-related liver cirrhosis, classified as Child-Pugh grade A and B, was significantly higher than in the controls without any prior liver disease. Furthermore, our research team has newly noticed how the severity of diastolic dysfunction affects the morbidity and mortality of patients undergoing such treatments as the transjugular intrahepatic portosystemic shunt (TIPS), liver transplantation and other surgical interventions resulting from different indications.r />r /> CONCLUSION: The high incidence of diastolic dysfunction in cirrhotic alcoholics should not be underestimated. Examination of diastolic dysfunction should be a standard procedure for making clinical decisions about these patients....

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Comparative Study 2013; 34(Suppl 2): 55-63 PubMed PMID: 24362093 Citation  Keywords:  Animals, Benzo(a)pyrene:metabolism, Carcinogens:metabolism, Cytochrome P-450 CYP1A1:metabolism, Cytochromes b5:pharmacology, Humans, Inactivation, Metabolic, Male, Microsomes, Liver:drug effects, Oxidation-Reduction, Rats,.   

OBJECTIVES: Cytochrome P450 (CYP) 1A1 is the most important enzyme in both activation and detoxification of carcinogenic benzo[a]pyrene (BaP), in combination with microsomal epoxide hydrolase (mEH). To evaluate metabolism of BaP in human, identification of a suitable animal model that mimics the metabolic fate of BaP in human is of great importance. The aim of this work was to compare BaP oxidation by human CYP1A1 and CYP1A1 of one animal model, rat. Investigation of the effect of cytochrome b5 on BaP oxidation by CYP1A1 was another target of this study.r />r /> METHODS: High performance liquid chromatography (HPLC) was employed for separation of BaP metabolites formed by enzymatic systems. Their structures were identified by mass- and NMR-spectrometry.r />r /> RESULTS: Human hepatic microsomes oxidized BaP to BaP-9,10-dihydrodiol, BaP-4,5-dihydrodiol, BaP-7,8-dihydrodiol, BaP-1,6-dione, BaP-3,6-dione and BaP-3-ol. The same metabolites were generated by rat liver microsomes, but BaP-9-ol and a metabolite Mx, the structure of which has not been identified as yet, were also formed in these microsomes. Human CYP1A1 expressed with NADPH:CYP reductase (POR) in Supersomes™ oxidized BaP to the same metabolites as microsomes, but BaP-4,5-dihydrodiol has not been detected. Rat recombinant CYP1A1 in this SupersomesTM system oxidized BaP to BaP-9,10-dihydrodiol, a metabolite Mx, BaP-4,5-dihydrodiol, BaP-7,8-dihydrodiol, BaP-1,6-dione, BaP-3,6-dione, BaP-9-ol and BaP-3-ol. Addition of cytochrome b5 to rat and human recombinant CYP1A1 systems led to a more than 2-fold increase in BaP oxidation.r />r /> CONCLUSION: The results show similarities between human and rat CYP1A1 in BaP oxidation and demonstrate rats as a suitable model mimicking BaP oxidation in human....

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Journal Article 2013; 34(Suppl 2): 43-54 PubMed PMID: 24362092 Citation  Keywords:  Animals, Antineoplastic Agents:pharmacokinetics, Benzo(a)pyrene:pharmacology, Biotransformation:drug effects, Cytochrome P-450 CYP1A1:metabolism, Cytochrome P-450 CYP1A2:metabolism, Cytochrome P-450 Enzyme System:metabolism, Drug Evaluation, Preclinical, .   

OBJECTIVES: The aim of this study was to investigate a role of cytochrome P450 (CYP) and peroxidase in ellipticine oxidative activation in two mouse strains differing in expression of NADPH:CYP reductase (POR) [the HRN (Hepatic Cytochrome P450 Reductase Null) mice, in which POR is deleted in hepatocytes and its wild-type (WT) counterpart], and in levels of CYP1A1/2 and cytochrome b5 that were modulated by treatment of these mouse models with a CYP1A inducer, benzo[a]pyrene (BaP).r />r /> METHODS: Ellipticine-DNA adducts were detected by 32P-postlabeling. HPLC was employed for the separation and characterization of ellipticine metabolites.r />r /> RESULTS: Hepatic microsomes of HRN and WT mice activate ellipticine to form ellipticine-derived DNA adducts. A 2.2- and 10.4-fold increase in amounts of ellipticine-derived DNA adducts formed by liver microsomes was caused by exposure of HRN and WT mice to BaP, respectively. The results found and utilization of NADPH and arachidonic acid, cofactors of CYP- and cyclooxygenase (COX)-dependent enzyme systems, respectively, as well as inhibitors of CYP1A1/2 and 3A, demonstrate that the CYP1A and 3A enzymes play a major role in ellipticine activation in liver microsomes. In addition, the COX enzyme is important in ellipticine activation in liver of HRN mice.r />r /> CONCLUSION: The CYP1A and 3A enzymes activate ellipticine mainly in liver of WT mice, whereas peroxidase COX plays this role in liver of HRN mice. Treatment of mice with BaP increases an impact of CYP1A on ellipticine activation. A pattern of expression levels of these enzymes plays a crucial role in their impact on this process....

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Journal Article 2013; 34(Suppl 2): 37-42 PubMed PMID: 24362091 Citation  Keywords:  Animals, Antioxidants:metabolism, Carps:physiology, Catalase:metabolism, Glutathione Reductase:metabolism, Insecticides:toxicity, Oxidative Stress:drug effects, Pyrethrins:toxicity, Superoxide Dismutase:metabolism, Toxicity Tests, Acute,.   

OBJECTIVES: The aim of this study was to assess the effect of pesticide Fury 10 EW, containing zeta-cypermethrin 100 g.l-1, on common carp (Cyprinus carpio L.).r />r /> DESIGN: The toxicity tests were performed on common carp according to OECD 203 methodologies. The common carp were exposed to Fury 10 EW at concentrations, 5, 7, 10, 50 and 100 μg.l-1 for 96 h and compared to common carp in a non-treated control group. Acute toxicity tests were detected value 96hLC50=13.8 µg.l-1. On the basis of the results was assessed the effect on the hematological profile, oxidative stress parameters, and antioxidants biomarkers in tissues, in another acute test.r />r /> RESULTS: The observed 96hLC50 value of Fury 10 EW was 13.8 μg.l-1. A significantly lower large lymphocyte and monocyte count, and a significantly greater number of segmented eosinophil granulocyte and higher hematocrit was found in the pesticide-exposed common carp compared to controls. Oxidative damage was not detected in the experimental common carp, however there were significant differences from control in superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR) in tissue after acute exposure to 13.8 μg.l-1 Fury 10 EW.r />r /> CONCLUSIONS: Zeta-cypermethrin as Fury 10 EW was classified as a substance highly toxic to fish. The hematological profile well oxidative stress parameters and antioxidant defensive systems provide important information about the internal environment of organisms. There is a lack of experimental results about the effects of zeta-cypermethrin on fish in the literature....

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Journal Article 2013; 34(Suppl 2): 31-36 PubMed PMID: 24362090 Citation  Keywords:  Animals, Astacoidea:drug effects, Behavior, Animal:drug effects, Dose-Response Relationship, Drug, Motor Activity:drug effects, Pesticides:toxicity, Toxicity Tests, Acute, Triazines:toxicity,.   

OBJECTIVES: Crustacea are at high risk of toxic effects of agricultural pesticides. Currently, many questions regarding the toxicity of triazine herbicides to crayfish remain unresolved. The aim of this research was to evaluate the acute toxicity of atrazine, hexazinone, metribuzine, prometryne, simazine, and terbutryne to juvenile signal crayfish (Pacifastacus leniusculus).r />r /> DESIGN: Acute toxicity tests were performed in accordance with standardized guidelines for testing of chemicals, OECD no. 203, using a semistatic test system. Signal crayfish juveniles (n=672) of 49.0-81.5 mg weight and 12.8-16.0 mm total length were used for the bioassay. Mortalities were recorded daily to 96 h. Each pesticide was tested at concentrations of 1, 10, 40, 70, and 100 mg.l-1. Percent mortalities were analyzed by linear regression, and median lethal concentration (LC50) values were computed using probit analysis EKO-TOX 5.2 software.r />r /> RESULTS: 96hLC50 values for juvenile signal crayfish were 12.1 mg.l-1 for atrazine, 13.9 mg.l-1 for terbutryne, 14.4 mg.l-1 for prometryne, 19.5 mg.l-1 for hexazinone, 30.6 mg.l-1 for metribuzine, and 77.9 mg.l-1 for simazine. Atrazine showed the greatest toxicity to signal crayfish.r />r /> CONCLUSIONS: The present study demonstrated that triazines are toxic to signal crayfish. Signal crayfish is more sensitive than the fish for atrazine, hexazine, metribuzine, and for these triazines signal crayfish can be used as a bio-indicator of environmental contamination....

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Journal Article 2013; 34(Suppl 2): 25-30 PubMed PMID: 24362089 Citation  Keywords:  Adolescent, Adult, Central Nervous System Agents:poisoning, Czech Republic:epidemiology, Databases, Factual, Drug Overdose:epidemiology, Drug-Related Side Effects and Adverse Reactions:diagnosis, Female, Humans, Information Centers:statistics & numerical .   

OBJECTIVES: To analyze the number and trends in calls to the Toxicological Information Center (TIC) concerning pharmaceutical poisoning retrospectively during the past 15 years and to compare selected characteristics of the poisonings.r />r /> DESIGN: Inquiries arising from drug poisonings in the years 1997-2012 were extracted and evaluated from the Czech database recording the consultations of TIC specialists. In addition, their cause, severity and dose evaluation (data electronically collected after 2005) were compared in the years 2005-2012 using standard statistical methods.r />r /> RESULTS: During 15 years total 152,649 calls due to all types of potentially toxic agents were recorded in the TIC database. Central nervous system (CNS) affecting drugs represented 39.8% of calls due to all pharmaceutical poisonings. The proportion of adults was 72.2% and women comprised 64.4% of all patients. Whereas the number of calls caused by poisoning with tricyclic antidepressants (TCAs) and barbiturates decreased (by 366.7% and 340%, respectively), the calls due to selective serotonin reuptake inhibitors (SSRIs) and benzodiazepines overdose increased (by 1347.4% and 359.8%). The dose of CNS affecting drugs in 2005-2012 was considered lethal in 14.6% of the inquiries due to barbiturates and 8.6% due to TCAs, but only in 1.6% calls due to SSRIs and 0.5% of benzodiazepines. The highest percentage of medications errors was found during the treatment with barbiturates (16.4%).r />r /> CONCLUSIONS: The current drugs prescription with improved safety profiles brings the beneficial effect of lowering the severity of poisonings and better prognosis of intoxications as observed in the TIC statistics....

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