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Journal Article 2015; 36(Suppl 1): 150-155 PubMed PMID: 26757120 Citation  Keywords:  Animals, Cholinesterase Inhibitors:pharmacology, Electromyography, Female, Muscle, Smooth:drug effects, Stomach:drug effects, Sus scrofa, Tacrine:analogs & derivatives,.   

OBJECTIVES: Tacrine was the first acetylcholinesterase inhibitor approved for therapy of Alzheimer's disease. It has currently been withdrawn in some countries mostly due to the risk of hepatotoxicity and might be replaced by its derivate 7-methoxytacrine (7-MEOTA). The aim of this study was to assess the impact of these two compounds on gastric myoelectrical activity by means of surface cutaneous electrogastrography (EGG).r />r /> METHODS: Twelve pigs (Sus scrofa f. domestica, weighing 30-35 kg) entered the study. A single dose of tacrine (200 mg i.m., n=6) or 7-MEOTA (200 mg i.m., n=6) was administrated. All EGG recordings were performed under general anaesthesia in the morning after 24 hours of fasting. Basal (30 minutes) and study recordings (150 minutes) were accomplished using an EGG stand (MMS, Enschede, the Netherlands). Results were expressed as dominant frequency of gastric slow waves, power analysis (areas of amplitudes) and power ratio assessment (ratio of the areas of amplitudes after and before study drug administration).r />r /> RESULTS: Tacrine decreased EGG dominant frequency 10 minutes after its administration (from basal 3.1±0.6 to 2.8±0.6 cycles per minute; p=0.014). Tacrine induced a non-significant 60-minute increase of the power (with maximal value 493±533 μV2 at 20 minutes) and power ratio (with maximal value 2.04±3.4 at 10 minutes). Tacrine caused substantial gastric arrhythmia. 7-MEOTA did not influence dominant frequency of gastric slow waves significantly. 7-MEOTA caused a short-term late increase of the power ratio at 60 minutes (6.3±11.2; p=0.003). Blood cholinesterase activity did not correlate with any EGG parameter either after tacrine or 7-MEOTA at any time.r />r /> CONCLUSIONS: Tacrine and 7-MEOTA have different impacts on EGG. Tacrine decreased dominant frequency and induced long-lasting gastric arrhythmia. 7-MEOTA caused a short-term late increase of the EGG power in experimental pigs....

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Journal Article 2015; 36(Suppl 1): 29-37 PubMed PMID: 26757119 Citation  Keywords:  Aryl Hydrocarbon Hydroxylases:metabolism, Cytochrome P-450 CYP1A1:metabolism, Cytochrome P-450 CYP1A2:metabolism, Cytochrome P-450 CYP2A6:metabolism, Cytochrome P-450 CYP2B6:metabolism, Cytochrome P-450 CYP2C8:metabolism, Cytochrome P-450 CYP2C9:metabolis.   

OBJECTIVES: Cytochromes P450 (CYPs) are heme enzymes oxygenating a broad range of substrates. Their activity is dependent on the presence of a suitable electron donor (eukaryotic NADPH:CYP oxidoreductase or cytochrome b5). The Escherichia naturally contain no CYPs and no NADPH:CYP oxidoreductase, however it was reported that some CYPs heterologously expressed in E. coli may exist in the ferrous form. A small bacterial flavoprotein, flavodoxin is considered to be responsible for reduction some of these CYPs.r />r /> METHODS: The reduction state of several human CYPs expressed in the intact living E. coli cells was examined. In addition, molecular dynamics and steered molecular dynamics simulations were performed to predict and compare affinity of flavodoxin toward selected CYPs.r />r /> RESULTS: We determined the reduction state of five human CYPs heterologously expressed in E. coli. The computationally predicted stabilities of CYP-flavodoxin complexes correlate with the percentage of reduced CYPs in bacterial cells. The mean electron transfer distance within optimized complexes was also related to the percentage of reduced CYPs.r />r /> CONCLUSION: Depending on the resting state, the CYPs heterologously expressed in E. coli could be divided into two groups; CYP2C8, 2C9, 3A4 are in E. coli present mainly in the oxidized form; while CYP1A1, 1A2, 2A6, 2A13, 2B6, 2D6 are found predominantly in the reduced form. We found a significant correlation between the stability of CYP-flavodoxin complexes and the percentage of reduced CYPs in bacteria. Hence, the naturally expressed flavodoxin is probably responsible for reduction of a larger group of human CYPs in bacterial cells....

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Journal Article 2015; 36(Suppl 1): 68-72 PubMed PMID: 26757118 Citation  Keywords:  Animal Feed:analysis, Animals, Dogs, Food Contamination:analysis, Hair:chemistry, Mercury:analysis,.   

OBJECTIVES: The present work is aimed at assessing the mercury contamination of dogs through the analysis of hair. For the determination of the total mercury in dogs, we chose skin derivatives--hair. The content of total mercury was also measured in the pelleted feed.r />r /> METHODS: Dogs were divided into two groups. The first group (group A) was fed granular feed containing fish and the second group (group B) granular feed free of fish. A total of 131 hair and granular feed samples were collected. The total mercury in hair and granular feed samples was measured using atomic absorption spectrophotometry on AMA 254.r />r /> RESULTS: The values of the total mercury content in the hair of dogs had a median value of 0.0375 mg.kg(-1) in group A and of 0.0336 mg.kg(-1) in group B. No statistically significant difference was found between the groups (p>0.05). The median values of the total mercury were 0.0048 mg.kg(-1) in group A and 0.0017 mg.kg(-1) in group B, respectively. A highly statistically significant difference between the groups was found (p<0.01).r />r /> CONCLUSIONS: No correlation was obtained between the total mercury content in the hair of dogs and granulated feed (rs=0.2069, p>0.05). The reason may be a content of various mercury species in feed samples or a human failure (nonobservance of the prescribed diet)....

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Journal Article 2015; 36(Suppl 1): 120-125 PubMed PMID: 26757117 Citation  Keywords:  Animals, Carps:embryology, Embryo, Nonmammalian:drug effects, Kidney:drug effects, Pesticides:toxicity, Toxicity Tests, Chronic, Triazines:toxicity, Water Pollutants, Chemical:toxicity, Zygote:drug effects,.   

OBJECTIVES: The aim of this study was to assess the toxicity of terbuthylazine in different developmental stages of common carp (Cyprinus carpio) on the basis of mortality, early ontogeny, occurrence of morphological anomalies, growth rate, and Fulton's condition factor during and at the conclusion of the test.r />r /> DESIGN: The toxicity tests were performed on carp according to OECD 210 methodology. The developmental stages of carp were exposed to terbuthylazine at four concentrations, 2.9 (reported environmental concentration in Czech rivers); 70; 1,400; and 3,500 µg.L(-1) for 35 days and compared to carps in a non-treated control group.r />r /> RESULTS: Terbuthylazine in concentration 1,400 and 3,000 µg.L(-1) caused significant (p<0.01) decrease of mass, total length and delayed in development of carp. Fish exposed to terbuthylazine showed alteration of tubular system of caudal kidney. On the basis of histopathological changes the values of LOEC=2.9 µg.L(-1) terbuthylazine were estimated.r />r /> CONCLUSIONS: Chronic terbuthylazine exposure of early-life stages of common carp affected their growth rate, early ontogeny and histology. Some of the changes were observed only at higher exposures, but change founded in caudal kidney was affected in fish exposed to the real environmental concentration tested (i.e., 2.9 µg.L(-1))....

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Journal Article 2015; 36(Suppl 1): 133-140 PubMed PMID: 26757116 Citation  Keywords:  Animals, Carps:blood, Catalase:drug effects, Gills:drug effects, Glutathione Reductase:drug effects, Hematocrit, Hemoglobins:drug effects, Insecticides:toxicity, Kidney:drug effects, Liver:drug effects, Nitriles:toxicity, Oxidative Stress:drug effects, Py.   

OBJECTIVES: The aim of this study is to evaluate effects of the insecticide Decis Mega (DM; active substance deltamethrin 50 g.L(-1)) on common carp on the basis of haematological profile, oxidative stress, antioxidant enzymes and histopathology.r />r /> DESIGN: Fish were exposed two concentrations of DM 6.56 μg.L(-1) (1DM) and 65.6 μg.L(-1) (2DM) for 96 h. Then the remaining fish were transferred into DM-free water for depuration for another period of 96 h.r />r /> RESULTS: Exposure to 1DM and 2DM proved effect on enzymatic activity of superoxide dismutase, catalase, glutathione reductase and on oxidative damage of cells in gills, liver and kidney (p<0.05, p<0.01). Exposure to 1DM showed differences (p<0.05, p<0.01) in hematocrit and hemoglobin in blood. Histopathological changes were observed after acute exposure to DM as well as to DM-free water in gills, liver and kidney.r />r /> CONCLUSION: This study concludes that deltamethrin has influence on the haematological parameters, activity of antioxidant enzymes and caused oxidative damage, and histopathological changes in the fish. However, antioxidant balance in the body was restored after placing the fish in clean water for 4 days, however, this time was not sufficient complete regeneration....

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Journal Article 2015; 36(Suppl 1): 88-94 PubMed PMID: 26757115 Citation  Keywords:  Animals, Animals, Newborn, Diethylstilbestrol:toxicity, Estrogens, Non-Steroidal:toxicity, Female, Gonadotrophs:drug effects, Gonadotropin-Releasing Hormone:pharmacology, In Vitro Techniques, Lactates:toxicity, Luteinizing Hormone:drug effects, Nanopartic.   

OBJECTIVES: Polymeric PEG-b-PLA nanoparticles (NPs) were developed for delivery of poorly water-soluble drugs via blood brain barrier into brain parenchyma. We analyzed neuroendocrine disrupting effects of neonatal exposure of female rats to PEG-b-PLA NPs and diethylstilbestrol (DES) on the function of adenohypophyseal gonadotrophs of infantile or adult rats by examining in vitro luteinizing hormone releasing hormone (LHRH)-induced luteinizing hormone (LH) release.r />r /> METHODS: Neonatal female Wistar rats were injected intraperitoneally, daily, from postnatal day (PND) 4 to PND7 with PEG-b-PLA NPs (20 mg.kg b.w.(-1)), DES (4 µg.kg b.w.(-1)) or vehicle. At the necropsy day (PND15 in infantile and the first estrus day after PND176 in adult rats), adenohypophyseal cells were isolated by enzymatic digestion, plated in 96-well plates (5×10(4) cells.well(-1)) in serum-supplemented medium and left to recover for 96 h. LHRH (10-7 mol.L(-1)) treatment was performed in serum-free medium for 60 min and LH levels in culture media were determined by radioimmunoassay.r />r /> RESULTS: In all experimental groups, in vitro LHRH treatment significantly stimulated LH release from pituitary cells of infantile but not adult female rats. Neonatal DES treatment increased basal LH secretion from cultured pituitary cells of adult but not infantile rats. In both, infantile and adult rats, neonatal treatment with PEG-b-PLA significantly increased basal and LHRH-induced LH release from pituitary cells compared to corresponding controls and DES-treated group.r />r /> CONCLUSIONS: Data indicate that neonatal exposure to PEG-b-PLA NPs may alter pituitary LH release, and thereby modify reproductive system development in infantile female rats leading to reproductive dysfunctions in adult age....

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Journal Article 2015; 36(Suppl 1): 57-63 PubMed PMID: 26757114 Citation  Keywords:  Animals, Arsenic:pharmacology, Bacterial Infections:blood, Carcinogens:pharmacology, Cyanobacteria, Erythrocyte Indices:drug effects, Iron:blood, Leukocyte Count, Microcystins:pharmacology, Microcystis, Neutrophils:drug effects, Oncorhynchus mykiss:blood,.   

OBJECTIVES: Under environmental conditions, fish are simultaneously exposed to multiple stressors. This study provides new knowledge on the effects of controlled exposure to multiple stressors, namely cyanobacterial biomass and food contaminated with arsenic.r />r /> METHODS: Rainbow trout were divided into six groups of 25 fish and exposed to different contaminant combinations for 30 days: 1) control group, 2) cyanobacterial biomass, 3 & 4) two groups exposed to arsenic at concentrations of 5 mg.kg(-1) and 50 mg.kg(-1) fish feed, and 5 & 6) two groups exposed to cyanobacterial biomass and arsenic combined. We then evaluated pathological, haematological and immunological parameters at 10, 20 and 30 days after exposure.r />r /> RESULTS: Marked gross pathological findings were present in groups exposed to arsenic and arsenic/cyanobacteria after 30 days. A strong decrease in haemoglobin concentration was observed in all experimental groups receiving arsenic after 10 days exposure. Total leukocyte count increased markedly in fish exposed to cyanobacterial biomass, and to higher arsenic concentrations by the end of the experiment. Neutrophils decreased significantly at the end of exposure. Similarly, exposure to cyanobacteria and/or arsenic led to suppression of opsonised zymosan particle-induced neutrophil respiratory bursts.r />r /> CONCLUSIONS: Our results demonstrate that the effects of exposure to toxic cyanobacterial biomass and arsenic on fish are enhanced when the contaminants are combined. In particular, long-term exposure led to disturbances in the white blood-cell count. Modulation of phagocytosis, which is the first line of defence against invading pathogens, suggests that the combined action leads to a decreased ability to control infection....

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Journal Article 2015; 36(Suppl 1): 64-67 PubMed PMID: 26757113 Citation  Keywords:  Administration, Oral, Animals, Anthelmintics:pharmacokinetics, Antinematodal Agents:pharmacokinetics, Chromatography, Liquid, Fenbendazole:pharmacokinetics, Oncorhynchus mykiss:metabolism, Praziquantel:pharmacokinetics,.   

OBJECTIVES: The aim of this study was to evaluate and compare the rate of degradation and elimination of praziquantel and fenbendazole antiparasitics following oral administration to salmonids. In addition, we determine whether the length of the legal withdrawal period is sufficient for complete elimination of antiparasitic residue from the body. The use of these drugs in fish is currently considered off-label and data on degradation are not available for rainbow trout.r />r /> METHODS: The model species for this experiment was the rainbow trout (Oncorhynchus mykiss) and praziquantel and fenbendazole were chosen for experimental therapy. Both drugs were administered into the gastrointestinal tract using a stomach tube. Concentrations of fenbendazole and praziquantel were established through high performance liquid chromatography-tandem mass spectrometry.r />r /> RESULTS: Our results show that concentrations of praziquantel and fenbendazole reach their maximum in the body within 24 hours of administration, with concentrations dropping sharply over the following 24 hours. With one exception, when trace amounts of both substances were found in blood plasma, the drugs were completely degraded and eliminated from the body by the end of the experiment (corresponding to 497.6 degree days).r />r /> CONCLUSIONS: Praziquantel and fenbendazole both show a high rate of degradation and elimination from fish. As both substances were eliminated from the body within the required withdrawal period (i.e. within 500 degree days) they can be safely used based on current knowledge of their therapeutic effect for treating helminth infections....

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