Oxidation of the carcinogenic non-aminoazo dye 1-phenylazo-2-hydroxy-naphthalene (Sudan I) by cytochromes P450 and peroxidases: a comparative study

Sudan I [1-(phenylazo)-2-hydroxynaphthalene, C.I. Solvent Yellow 14, CAS No: 842-07-9] is used as the compound employed in chemical industry and to color materials such as hydrocarbon solvents, oils, fats, waxes, plastics, printing inks, shoe and floor polishes and gasoline. Such a wide used could result in a considerable human exposure. Sudan I is known to cause developments of tumors in the liver or urinary bladder in rats, mice, and rabbits, and is considered a possible weak human carcinogen and mutagen. This carcinogen is also a potent contact allergen and sensitizer. Here, we compare the data concerning the Sudan I oxidative metabolism catalyzed by cytochrome P450 (CYP) and peroxidase enzymes, which has been investigated in our laboratory during the last two decades. These two types of enzymes are responsible both for Sudan I detoxication and activation. Among the Sudan I metabolites, C-hydroxylated derivatives and a dimer of Sudan I are suggested to be the detoxication metabolites formed by CYPs and peroxidases, respectively. Metabolic activation of Sudan I by both types of enzymes leads to formation of reactive species (the benzenediazonium ion by CYP and Sudan I radicals by peroxidase) that bind to DNA and RNA, generating covalent adducts in vitro and in vivo. Whereas the structure of the major adduct formed by the benzenediazonium ion in DNA has already been identified to be the 8-(phenylazo)guanine adduct, the structures of adducts formed by peroxidase, have not been characterized as yet. Biological significance of the DNA adducts of Sudan I activated with CYP and peroxidase enzymes and further aims of investigations in this field are discussed in this study

Ellipticine and benzo(a)pyrene increase their own metabolic activation via modulation of expression and enzymatic activity of cytochromes P450 1A1 and 1A2

Two compounds known to covalently bind to DNA after their activation with cytochromes P450 (CYPs), carcinogenic benzo(a)pyrene (BaP) and an antineoplastic agent ellipticine, were investigated for their potential to induce CYP and NADPH:CYP reductase (POR) enzymes in rodent livers, the main target organ for DNA adduct formation. Two animal models were used in the study: (i) rats as animals mimicking the fate of ellipticine in humans and (ii) mice, especially wild-type (WT) and hepatic POR null (HRN™) mouse lines. Ellipticine and BaP induce expression of CYP1A enzymes in livers of experimental models, which leads to increase in their enzymatic activity. In addition, both compounds are capable of generating DNA adducts, predominantly in livers of studied organisms. As determined by 32P postlabelling analysis, levels of ellipticine-derived DNA adducts formed in vivo in the livers of HRN™ mice were reduced (by up to 65%) relative to levels in WT mice, indicating that POR mediated CYP enzyme activity is important for the activation of ellipticine. In contrast to these results, 6.4 fold higher DNA binding of BaP was observed in the livers of HRN™ mice than in WT mice. This finding suggests a detoxication role of CYP1A in BaP metabolism in vivo. In in vitro experiments, DNA adduct formation in calf thymus DNA was up to 25 fold higher in incubations of ellipticine or BaP with microsomes from pretreated animals than with controls. This stimulation effect was attributed to induction of CYP1A1/2 enzymes, which are responsible for oxidative activation of both compounds to the metabolites generating major DNA adducts in vitro. Taken together, these results demonstrate that by inducing CYP1A1/2, ellipticine and BaP modulate their own enzymatic metabolic activation and detoxication, thereby modulating their either pharmacological (ellipticine) and/or genotoxic potential (both compounds)

Bacterially induced calcite formation at the surface of recycled concrete

The construction industry is one of the main sources of greenhouse gas emissions, and portland cement production is responsible for approximately 8 % of anthropogenic CO2 emissions. Microbially induced calcium precipitation (MICP) has the potential to partially replace cement or modify the properties of materials that would otherwise not find use in construction, for example, in concrete recycling. MICP might be an environmentally friendly method to improve the properties of recycled aggregates and form conglomerates from the finest fractions. In this paper, factors influencing MICP’s ability to solidify recycled concrete fines are thoroughly investigated. Calcium carbonate precipitate crystals produced by the bacterium Sporosarcina pasteurii were analyzed using scanning electron microscopy and energy dispersive spectroscopy

Stucture of phosphoenolpyruvate carboxylase from maize leaves

AbstractPhosphoenolpyruvate carboxylase (PEPC) from maize leaves has an Mr of 400000. The native enzyme molecule is a homotetramer. The amino acid composition of PEPC is determined. The enzyme contains 8 half-cystine residues per subunit. The role of half-cystine residues and the steric arrangement of the enzyme protein molecule are discussed

Ellipticine cytotoxicity to cancer cell lines — a comparative study

Ellipticine is a potent antineoplastic agent exhibiting multiple mechanisms of action. This anticancer agent should be considered a pro-drug, whose pharmacological efficiency and/or genotoxic side effects are dependent on its cytochrome P450 (CYP)- and/or peroxidase-mediated activation to species forming covalent DNA adducts. Ellipticine can also act as an inhibitor or inducer of biotransformation enzymes, thereby modulating its own metabolism leading to its genotoxic and pharmacological effects. Here, a comparison of the toxicity of ellipticine to human breast adenocarcinoma MCF-7 cells, leukemia HL-60 and CCRF-CEM cells, neuroblastoma IMR-32, UKF-NB-3 and UKF-NB-4 cells and U87MG glioblastoma cells and mechanisms of its action to these cells were evaluated. Treatment of all cells tested with ellipticine resulted in inhibition of cell growth and proliferation. This effect was associated with formation of two covalent ellipticine-derived DNA adducts, identical to those formed by 13-hydroxy- and 12-hydroxyellipticine, the ellipticine metabolites generated by CYP and peroxidase enzymes, in MCF-7, HL-60, CCRF-CEM, UKF-NB-3, UKF-NB-4 and U87MG cells, but not in neuroblastoma UKF-NB-3 cells. Therefore, DNA adduct formation in most cancer cell lines tested in this comparative study might be the predominant cause of their sensitivity to ellipticine treatment, whereas other mechanisms of ellipticine action also contribute to its cytotoxicity to neuroblastoma UKF-NB-3 cells

The comparison of cytotoxicity of the anticancer drugs doxorubicin and ellipticine to human neuroblastoma cells

Ellipticine is an antineoplastic agent, whose mode of action is based mainly on DNA intercalation, inhibition of topoisomerase II and formation of covalent DNA adducts mediated by cytochromes P450 and peroxidases. Here, the cytotoxicity of ellipticine to human neuroblastoma derived cell lines IMR-32 and UKF-NB-4 was investigated. Treatment of neuroblastoma cells with ellipticine was compared with that of these cancer cells with doxorubicin. The toxicity of ellipticine was essentially the same as that of doxorubicin to UKF-NB-4 cells, but doxorubicin is much more effective to inhibit the growth of the IMR-32 cell line than ellipticine. Hypoxic conditions used for the cell cultivation resulted in a decrease in ellipticine and/or doxorubicin toxicity to IMR-32 and UKF-NB-4 neuroblastoma cells

Genotoxic mechanisms for the carcinogenicity of the environmental pollutants and carcinogens o-anisidine and 2-nitroanisole follow from adducts generated by their metabolite N-(2-methoxyphenyl)-hydroxylamine with deoxyguanosine in DNA

An aromatic amine, o-anisidine (2-methoxyaniline) and its oxidative counterpart, 2-nitroanisole (2-methoxynitrobenzene), are the industrial and environmental pollutants causing tumors of the urinary bladder in rats and mice. Both carcinogens are activated to the same proximate carcinogenic metabolite, N-(2-methoxyphenyl)hydroxylamine, which spontaneously decomposes to nitrenium and/or carbenium ions responsible for formation of deoxyguanosine adducts in DNA in vitro and in vivo. In other words, generation of N-(2-methoxyphenyl)hydroxylamine is responsible for the genotoxic mechanisms of the o-anisidine and 2-nitroanisole carcinogenicity. Analogous enzymes of human and rat livers are capable of activating these carcinogens. Namely, human and rat cytochorme P4502E1 is the major enzyme oxidizing o-anisidine to N-(2-methoxyphenyl)hydroxylamine, while xanthine oxidase of both species reduces 2-nitroanisole to this metabolite. Likewise, O-demethylation of 2-nitroanisole, which is the detoxication pathway of its metabolism, is also catalyzed by the same human and rat enzyme, cytochorme P450 2E1. The results demonstrate that the rat is a suitable animal model mimicking the fate of both carcinogens in humans and suggest that both compounds are potential carcinogens also for humans

Quality of life of patients with Hodgkin's lymphoma

Autor práce: Markéta Stiborová Název práce: Kvalita života pacientů s Hodgkinovým lymfomem Vznik práce: Univerzita Karlova, Lékařská fakulta v Hradci Králové (Oddělení ošetřovatelství) Studijní program: Ošetřovatelství Bakalářský studijní obor: Všeobecná sestra Vedoucí práce: prof. PhDr. Jiří Mareš, CSc Počet stran: 85 Počet příloh: 1 Rok obhajoby: 2019 Cílem bakalářské práce je zjistit, jakou mají kvalitu života lidé po vyléčení Hodgkinova lymfomu. Teoretická část práce se nejdříve zabývá lymfatickým systémem. Hlavně anatomií lymfatického systému. Dále pak problematikou Hodgkinova lymfomu. V části práce se zajímám o ošetřovatelskou péči pacientů. Zvláštní kapitola se soustředí na kvalitu života pacientů. Obsah kapitol teoretické části je východiskem pro realizovaný výzkum. Ve výzkumné části byla zkoumána kvalita života 40 pacientů. Respondenti prodělali Hodgkinův lymfom. Kvalita života byla prozkoumána pomocí specifického dotazníku. Můžeme říci, že léčbu hodnotí zkoumaní pacientů příznivě. Dotázaní pacienti by souhlasili se stejnou léčbou, kdyby se znovu rozhodovali. Pacienti by doporučili stejnou léčbu svému příbuznému nebo příteli. V bakalářské práci byly také zkoumány vztahy mezi vybranými proměnnými. Byl studován vztah pohlaví pacienta k dalším proměnným. Pohlaví ovlivňuje rodinný stav našich...Author of the work: Markéta Stiborová Title: Quality of life of patients with Hodgkin's lymphoma Work originated: Charles University, Faculty of Medicine in Hradec králové (Department of Nursing) Study program: Nursing care Bachelor Degree: General Nurse Leader: prof. PhDr. Jiří Mareš, CSc. Nmber of pages: 85 Number of attachments: 1 Year of defense: 2019 The aim of this bachelor's essay is to find out what the quality of life is like for people who were cured of Hodgkin's Lymfoma. Quantitative research was used to examine the quality of the patients' lives. The theoretical part of this essay deals with the lymphatic system, especially its anatomy, followed by the specifics of the Hodgkin's Lymfoma. A part of this essay was dedicated to patients' nursing care. A separate chapter is focused on the patients' quality of life. The contents of the chapters in the theoretical part is the basis of the implemented research. The quality of life of 40 patients was investigated in the research part. The respondents suffered Hodgkin's lymphoma. The quality of life was examined using questionnaires. We can say that the treatment is evaluated favorably by patients. The interviewed patients would agree to the same treatment if they decided again. Patients would recommend the same treatment to their relative or...Ústav sociálního lékařstvíDepartment of Social MedicineFaculty of Medicine in Hradec KrálovéLékařská fakulta v Hradci Králov

Residential Building - Lesná

Stavba bytového domu se nachází v městské čtvrti Lesná, na ulici Dřínová. Budova tvoří přechod mezi dvoupodlažními řadovými domy a šestipodlažními terasovými bytovými domy umístěnými výš na terénu. Tvar stavby je definován zejména postavením okolních budov a sklonitým terénem, na kterém je budova umístěna. Je rozdělena příčně na dva bloky, mezi kterými vzniká prostor pro odpočinek a relaxaci. Tyto bloky jsou pak mezi sebou spojeny betonovými mostky. Zadáním bylo koncipovat budovu jako luxusní bytový dům s velice prostornými byty, proto lze na této stavbě pozorovat nejen tyto prostorově velkorysé plochy, ale jsou zde znát i technické a materiálové možnosti dnešní doby. Například ve formě velkoplošných oken, tmavých, hliníkových, fasádních panelů ALUCOBOND nebo vjezdu do garáží prostřednictvím auto-výtahu.The block of flats is located at the Lesná distrikt, on the Dřínová street. This building forms transition between two-storey row houses and six story terraced houses, which are situated up on the terrain. Form of the building is defined especially by positions of surrounding houses and by the hill, which is placed on. Building is dividend transversely to two blocks, which are connected by concrete bridges. Between these blocks is a space for repose and relaxation. The task was to design the building as a luxury apartment building with very spacious flats, therefore it is possible to observe not only the these generous areas, but there are technical and material possibilities of these times too. For example large windows, dark, aluminum, facade, profiles ALUCOBOND or entrance to the garage via car-lift.

Class actions

Class actions Abstract This thesis deals with the regulation of collective proceedings in the Czech Republic, first focusing on the current forms of collective proceedings and then moving on to the draft of the Act on Collective Civil Judicial Proceedings. The aim of the thesis is to contribute to the professional debate on the emerging form of collective proceedings with a mostly practical view of setting specific parameters of the law, to point out some shortcomings of the current proposed bill and to offer its own solutions. From the methodological point of view, the analytical, normative, comparative and synthetic approaches were used. However, a descriptive approach is also evident in the beginnig of the thesis. The analysis was mainly used in the examination of the current draft of the Act on Collective Civil Judicial Proceedings and the Polish legislation. The normative approach is most evident in the critical commentary on the current proposed bill. The thesis offers a comparative examination when comparing the proposed Czech and Polish legislation. The synthesis of the recorded findings is then most influenced by the section dealing with considerations on the future appropriate form of class actions. From the content point of view, the thesis first offers a theoretical excursus in which it deals...Hromadné žaloby Abstrakt Diplomová práce se zabývá úpravou hromadného řízení na území České republiky, kdy se nejdříve zaměřuje na současné podoby hromadného řízení a následně přechází k návrhu zákona o hromadném občanském řízení soudním. Cílem práce je přispět do odborné debaty o utvářející se podobě hromadného řízení převážně praktickým náhledem na nastavení konkrétních parametrů zákona, poukázat na některé nedostatky současného návrhu zákona a nabídnout vlastní řešení. Z metodologického hlediska byly při tvorbě užity zejména analytický, normativní, komparativní a syntetický přístup. V úvodu práce se však projevuje i přístup deskriptivní. Analýza byla užita především při zkoumání současného návrhu zákona o hromadném občanském řízení soudním a polské právní úpravy. Normativní přístup se nejvíce projevuje v kritickém komentáři k současnému návrhu. Komparativní zkoumání práce nabízí při porovnání navrhované české a současné polské právní úpravy. Syntézou zaznamenaných poznatků je pak nejvíce ovlivněna část věnující se úvahám o budoucí vhodné podobě hromadných žalob. Z obsahového hlediska práce nejprve nabízí teoretický exkurz, v němž se vypořádává s terminologií a obecnými otázkami hromadného řízení. Následně přechází ke zkoumání současných nástrojů, v nichž lze spatřovat prvky kolektivního řízení. Těžiště...Department of Civil LawKatedra občanského právaFaculty of LawPrávnická fakult