The validity of behavioral and neurophysiological models can only be assessed with respect to the type of the modelled effect: for acute changes in activation level as well as for chronic motor or sensory deficits both approaches are equally prone to misinterpretation. Validation of behavioral criteria supported by neurophysiological correlates and vice versa is the best protection. In the cognitive and emotional sphere, a shift to testing of the readiness ("fluidity") dimension seems to be promising both in human and animal studies, permitting also more reliable extrapolations and efficient cooperation of behavioral and neurophysiological approaches.

• MeSH
• chování zvířat účinky léků   MeSH
• lidé MeSH
• nervový systém - fyziologické jevy MeSH
• nervový systém účinky léků   MeSH
• pohybová aktivita účinky léků   MeSH
• toxikologie metody   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Living organisms interact with various chemical compounds via receptors, which is described by the receptor theory. The affinity of the biologically active compounds toward receptors and their ability to trigger a biological or toxic signal vary substantially. In this work, we describe a new insight into understanding of the mode of action of receptor partial agonists and the receptor theory using a Full Logistic Model (FLM) of mixture toxicology. We describe the hypothesis that the effect of a partial agonist can be mathematically described via separation of agonistic and antagonistic behavior of the partial agonist where the antagonistic effect is described as an action of the compound producing zero effect. In this way, a competitive antagonist can be considered as an agonist with zero effect. This idea is also placed into a context with classical concepts, e.g., Gaddum's equation. Using the assumption that competitive antagonists are agonists with no effect, equations describing the microscopic and macroscopic equilibrium constants have been derived. Accordingly, we show that the constants could be calculated from the measured partial agonistic dose-response curve. As a consequence, we provide a simple mathematical tool for comparison of dose-response curves of drugs according to their affinities and efficacies.

• Klíčová slova
• Drug potency, Efficacy, Equilibrium dissociation constant, Mixture toxicology, Partial agonist, Receptor theory,
• MeSH
• biologické modely * MeSH
• lékové interakce * MeSH
• logistické modely * MeSH
• receptory buněčného povrchu metabolismus   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• receptory buněčného povrchu MeSH

The following topics are covered in this brief review on the environmental and occupational toxicology of chromium: occurrence, production and uses of chromium and chromium compounds; experimental toxicology; chromium toxicity for man; hygienic and ecologic aspects of chromium contamination of the environment. The review provides a conclusive evidence which suggests that chromium, especially its hexavalent form, is both toxic and carcinogenic, but its trivalent form is physiologically essential in the metabolism of insulin. It is also emphasized that among the major sources of environmental chromium today are the cement industry and the increasingly widespread use of chromium compounds added as an anticorrosion admixture to a variety of cooling systems, e.g. in large power plants, which may greatly contribute to the overall pollution of outdoor air at the sites.

• MeSH
• chrom škodlivé účinky   metabolismus   toxicita   MeSH
• dermatitida z povolání chemicky indukované   MeSH
• ekologie MeSH
• erytrocyty účinky léků   metabolismus   MeSH
• kouření MeSH
• látky znečišťující vzduch v pracovním prostředí škodlivé účinky   toxicita   MeSH
• látky znečišťující životní prostředí škodlivé účinky   toxicita   MeSH
• lidé MeSH
• mutageny MeSH
• nádory plic chemicky indukované   MeSH
• nemoci z povolání chemicky indukované   MeSH
• plíce účinky léků   metabolismus   MeSH
• plicní nemoci chemicky indukované   MeSH
• prach škodlivé účinky   MeSH
• riziko MeSH
• stárnutí účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• chrom MeSH
• látky znečišťující vzduch v pracovním prostředí MeSH
• látky znečišťující životní prostředí MeSH
• mutageny MeSH
• prach MeSH

This study was focused on gaining insights into the mechanism by which the herbicide- Spectracide®, induces oxidative stress and alters behavior in Drosophila melanogaster. Exposure to Spectracide® (50%) significantly (p < 0.05) reduced the negative geotaxis response, jumping behavior and dampened locomotor activity rhythm in adult flies compared to non-exposed flies. Protein carbonyl levels indicative of oxidative damage increased significantly coupled with down-regulation of Sniffer gene expression encoding carbonyl reductase (CR) and its activity in Spectracide®-exposed flies. In silico modeling analysis revealed that the active ingredients of Spectracide® (atrazine, diquat dibromide, fluazifop-p-butyl, and dicamba) have significant binding affinity to the active site of CR enzyme, with atrazine having comparatively greater affinity. Our results suggest a mechanism by which ingredients in Spectracide® induce oxidative damage by competitive binding to the active site of a protective enzyme and impair its ability to prevent damage to proteins thereby leading to deficits in locomotor behavior in Drosophila.

• Klíčová slova
• Behavioral toxicology, Carbonyl reductase, Drosophila melanogaster, Ecotoxicology, In silico modeling, Spectracide®,
• MeSH
• alkoholoxidoreduktasy metabolismus   MeSH
• atrazin toxicita   MeSH
• chování zvířat účinky léků   MeSH
• Drosophila melanogaster genetika   MeSH
• exprese genu MeSH
• herbicidy toxicita   MeSH
• lokomoce účinky léků   MeSH
• molekulární modely * MeSH
• oxidace-redukce MeSH
• oxidační stres genetika   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alcohol dehydrogenase (NADP+) MeSH Prohlížeč
• alkoholoxidoreduktasy MeSH
• atrazin MeSH
• herbicidy MeSH

Pharmaceuticals are emerging contaminants as their worldwide consumption increases. Fibrates such as gemfibrozil (GEM) are used in human medicine to reduce blood concentrations of cholesterol and triacylglycerol and also are some of the most frequently reported pharmaceuticals in waste waters and surface waters. Despite some studies have already demonstrated the negative impact in physiological and/or reproductive endpoints in adult fish, data on survival and behavioral effects in fish larvae are lacking. This study aimed to assess the effects of GEM on zebrafish eleutheroembryo development and locomotor behavior. A fish embryo toxicity (FET) test was undertaken to evaluate GEM acute toxicity by exposing embryos to 0, 6.58, 9.87, 14.81, 22.22, 33.33 and 50mg/L. Developmental endpoints such as hatching success, edemas and malformations were recorded. A second test was undertaken by exposing embryos to 0, 1.5, 3 and 6mg/L in order to evaluate the effects of GEM on 120 and 144h post fertilization (hpf) larvae locomotor activity by video tracking, using a Zebrabox(®) (Viewpoint, France) device. From the data recorded, several parameters such as total swimming distance (TSD) and total swimming time (TST) in each 120s integration time were calculated. Data showed that this compound has a moderate toxic effect on fish embryo development, affecting both survival and hatching success with a calculated 96h LC50 of 11.01mg/L and no effects at the developmental level at 6mg/L. GEM seems to impair locomotor activity, even at concentrations where developmental abnormalities were unperceived, at concentrations as low as 1.5mg/L. Both TSD and TST were sensitive to GEM exposure. These effects do not seem to be independent of the developmental stage as 120hpf larvae seem to present a development bias with repercussions in locomotor behavior. This study highlights the need to include behavioral endpoints in ecotoxicological assays as this seems to be a more sensitive endpoint often disregarded.

• Klíčová slova
• Developmental abnormalities, Gemfibrozil, Lipid regulator, Sub-lethal, Swimming behavior, Zebrafish,
• MeSH
• chemické látky znečišťující vodu toxicita   MeSH
• dánio pruhované růst a vývoj   fyziologie   MeSH
• embryonální vývoj účinky léků   MeSH
• gemfibrozil toxicita   MeSH
• larva účinky léků   MeSH
• plavání MeSH
• pohybová aktivita účinky léků   MeSH
• testy akutní toxicity MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• chemické látky znečišťující vodu MeSH
• gemfibrozil MeSH

Nickel and nickel compounds belong to the classic noxious agents encountered in industry, but is also known to affect non-occupationally exposed individuals, especially those handling stainless-steel and nickel plated articles of everyday use. For plants and some vertebrates, specifically for mammals, nickel is indispensable as one of the essential trace elements. The most important health problems due to exposure to nickel and nickel compounds are allergic dermatitis (nickel itch) and increased incidence of cancers of the lungs and nasal mucosa encountered among the workers after a long-term over-exposure to nickel. In this respect the most hazardous nickel compounds appear to be nickel sulfide and nickel oxide. The monitoring of nickel exposure levels can be based on blood serum and urine analyses, but also on nickel determinations in hair which have proved promising even in groups of non-occupationally exposed individuals. Nickel carbonyl is the most toxic of all of the nickel compounds encountered, but because of its relatively short half-life it does not seem to represent any actual biohazard from the standpoint of environmental pollution. To prevent incidence of malignancies it is recommended to include in the routine plan of the preventive medical examinations also the cytologic analysis supplemented, in the case of cytologic positivity, with the bioptic examination for epithelial dysplasia. A systematic medical surveillance of workers with known long-term exposure to nickel is, of course, essential. At present, a major attention is centered on biochemical interactions of nickel with copper, cadmium, iron, iodine and particularly with manganese known to significantly reduce the experimental carcinogenicity of nickel and nickel compounds.

• MeSH
• dermatitida z povolání MeSH
• kontaktní dermatitida MeSH
• kouření MeSH
• lidé MeSH
• maximální přípustná koncentrace MeSH
• nádory nosu chemicky indukované   MeSH
• nádory plic chemicky indukované   MeSH
• nikl analýza   metabolismus   otrava   MeSH
• nosní sliznice MeSH
• organokovové sloučeniny otrava   MeSH
• pneumokonióza etiologie   MeSH
• stopové prvky MeSH
• voda analýza   MeSH
• vystavení vlivu životního prostředí MeSH
• vzduch analýza   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• nickel carbonyl MeSH Prohlížeč
• nickel monoxide MeSH Prohlížeč
• nickel sulfide MeSH Prohlížeč
• nikl MeSH
• organokovové sloučeniny MeSH
• stopové prvky MeSH
• voda MeSH

Soman belongs to the most dangerous nerve agents because of the low effectiveness of the presently available antidotes. Soman acts by inhibiting acetylcholinesterase (AChE) both peripherally and centrally, with a subsequent accumulation of neuromediator acetylcholine and other metabolic changes. From the data published in literature it can be concluded that exposure to nerve agents leading to acute effects or chronic exposure to nerve agents may lead to delayed and persistent adverse effects. The aim of this study was to demonstrate changes in AChE and butyrylcholinesterase (BuChE) activities, stressogenic markers (i.e., tyrosine aminotransferase [TAT] activity, and plasma corticosterone level), and neuroexcitability and behavior 24 h and 4 wk following a single soman inhalation exposure at low level. AChE activity in erythrocytes and BuChE activity in plasma was decreased (dependent on the dose of soman) 24 h and 4 wk after the exposure. A similar decrease in AChE activity in different brain parts was observed. One of the stressogenic parameters, TAT, was changed 24 h after exposure only. Behavior of experimental animals was changed 24 h after the exposure, and 4 behavioral parameters persisted 4 wk after the exposure. Neuroexcitability was increased at 24 h after the exposure and had become about normal 4 wk after the exposure. Summarizing, long-term effects (4 wk) were observed after inhalation exposure of guinea pigs to sublethal concentrations of soman.

• MeSH
• acetylcholinesterasa krev   MeSH
• aplikace inhalační MeSH
• butyrylcholinesterasa krev   MeSH
• chemické bojové látky toxicita   MeSH
• cholinesterasové inhibitory aplikace a dávkování   toxicita   MeSH
• cholinesterasy krev   MeSH
• chování zvířat účinky léků   MeSH
• enzymy krev   MeSH
• erytrocyty účinky léků   enzymologie   MeSH
• inhalační expozice MeSH
• kortikosteron krev   MeSH
• morčata MeSH
• mozek účinky léků   enzymologie   MeSH
• soman aplikace a dávkování   toxicita   MeSH
• tyrosinaminotransferasa krev   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• morčata MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acetylcholinesterasa MeSH
• butyrylcholinesterasa MeSH
• chemické bojové látky MeSH
• cholinesterasové inhibitory MeSH
• cholinesterasy MeSH
• enzymy MeSH
• kortikosteron MeSH
• soman MeSH
• tyrosinaminotransferasa MeSH

Despite poisoning with the ecstasy substitute para-methoxymethamphetamine (PMMA) being typically associated with severe hyperthermia and death, behavioral and toxicological data on this drug are missing. Herein we present the behavioral profile of PMMA, its hyperthermic potency and pharmacokinetic profile in rats. The effects of PMMA 5 and 20 mg/kg on locomotion, on prepulse inhibition (PPI) of acoustic startle reaction (ASR), on body temperature under isolated and crowded conditions and on the pharmacokinetics analyzed with gas chromatography mass spectrometry (GC-MS) were evaluated. PMMA increased overall locomotion with the higher dose showing a biphasic effect. PPI was decreased dose-dependently. The hyperthermic response was present only with PMMA 20 mg/kg and was accompanied by extensive perspiration under crowded conditions. Serum levels of PMMA peaked at approximately 30 min after both treatments; on the contrary the maximum brain concentrations of PMMA at 20 mg/kg peaked approximately 1h after the administration, which was rather delayed compared to maximum after 5mg/kg dose. These data indicate that PMMA has a similar behavioral profile to stimulants and hallucinogens and that the toxicity might be increased in a crowded environment. High doses of PMMA have a gradual penetration to the brain which might lead to the delayed peak concentrations and prolonged effects of the drug.

• MeSH
• chování zvířat účinky léků   MeSH
• horečka chemicky indukované   MeSH
• krysa rodu Rattus MeSH
• methamfetamin aplikace a dávkování   analogy a deriváty   farmakokinetika   toxicita   MeSH
• modely u zvířat MeSH
• mozek účinky léků   metabolismus   MeSH
• pohybová aktivita účinky léků   MeSH
• potkani Wistar MeSH
• psychotropní léky aplikace a dávkování   farmakokinetika   toxicita   MeSH
• tělesná teplota účinky léků   MeSH
• úleková reakce účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• 4-methoxymethamphetamine MeSH Prohlížeč
• methamfetamin MeSH
• psychotropní léky MeSH

The activity of human cholinesterases, erythrocyte acetylcholinesterase (AChE; EC 3.1.1.7) and plasma butyrylcholinesterase (BChE; EC 3.1.1.8) represents an important marker when monitoring exposure to pesticides/nerve agents, and may also be used in occupational medicine in diagnosis and prognosis of some diseases. In this study "normal/baseline" AChE and BChE activity has been investigated in a young and healthy population, with subsequent evaluation of several intra-population factors including sex, age (categories 18-25, 26-35 and 36-45 years old) and smoker status. The modified Ellman's method was used for enzyme activity assessment in 387 young and healthy individuals (201 males and 186 females aged 18-45). A significant inter-sexual difference in AChE and BChE activity was found (AChE: 351±67 for males and 377±65 for females, (μmol/min)/(μmol of hemoglobin), p<0.001; BChE: 140±33 for males and 109±29 for females, μkat/l, p<0.001; mean±SD). Despite the finding that mean AChE activity somewhat decreased whereas BChE activity grew within the age categories of the tested subjects, no significant effect of age on cholinesterase activity was found (p>0.05). Smoking influenced cholinesterase activity - AChE activity in smokers was elevated (approx. 3% in males; 8% in females) relative to that in non-smokers (p<0.05). Smoking was found not to have any effect on BChE activity. Reference values based on confidence intervals for AChE and BChE activity were established. The presented results might be useful in routine clinical practice where the monitoring of blood AChE and plasma BChE activity is crucial for prognosis and diagnosis of organophosphate poisoning, in occupational medicine and in relevant mass casualty scenarios.

• Klíčová slova
• Acetylcholinesterase, Butyrylcholinesterase, Clinical study, Intra-population factors, Organophosphates,
• MeSH
• acetylcholinesterasa krev   MeSH
• biologické markery krev   MeSH
• butyrylcholinesterasa metabolismus   MeSH
• dospělí MeSH
• GPI-vázané proteiny krev   MeSH
• hemoglobiny analýza   MeSH
• hromadné neštěstí MeSH
• hygiena práce MeSH
• kouření krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• otrava organofosfáty krev   enzymologie   MeSH
• referenční hodnoty MeSH
• sexuální faktory MeSH
• věkové faktory MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• acetylcholinesterasa MeSH
• ACHE protein, human MeSH Prohlížeč
• biologické markery MeSH
• butyrylcholinesterasa MeSH
• GPI-vázané proteiny MeSH
• hemoglobiny MeSH

• Klíčová slova
• HYPERSENSITIVITY *, MENTAL DISORDERS *, PLASMA SUBSTITUTES *, TOXICOLOGIC REPORT *,
• MeSH
• alergie * MeSH
• duševní poruchy * MeSH
• náhražky plazmy * MeSH
• toxikologie * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• náhražky plazmy * MeSH