RESUMO
We studied effects of nutrient quercetin on cytochromes' Ð 450 1Ð (CYP1A) activities (measured spectrofluorimetrically using 7-ethoxy-resorufin for CYP1A1 and 7-methoxy-resorufin for CYP1A2 as substrates), on mRNA levels (measured by RT-PCR), and on DNA-binding activities (evaluated by an electrophoretic mobility shift assay) of proteins regulating CYP1A expression in untreated and benzo(α)pyrene (BaP)-treated rats. Wistar rats received quercetin, BaP, or both once daily for 1-3 days. Quercetin did not influence CYP1A1 in untreated rats but inhibited BaP-mediated CYP1A induction on the transcriptional level decreasing positive input (AhR functional activity) and increasing negative input (AhRR/ARNT expression and Oct-1 and C/EBP functional activities).
Assuntos
Antioxidantes/farmacologia , Hidrocarboneto de Aril Hidroxilases/genética , Benzo(a)pireno/toxicidade , Carcinógenos/toxicidade , Mutagênicos/toxicidade , Quercetina/farmacologia , Animais , Poluentes Ambientais/toxicidade , Regulação da Expressão Gênica , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos WistarRESUMO
For treatment of patients with diseases of lower limb arteries and prevention of cardiovascular complications in high-risk patients (those with diabetes mellitus, arterial hypertension, dyslipidemia, obesity) permanent antiplatelet therapy is indicated. A problem is variable individual sensitivity to therapeutic agents. For antiplatelet therapy in patients with atherosclerosis of lower limb arteries there has been obtained an evidence-supported base concerning efficacy of long-term administration of clopidogrel preparations, unlike patients with acute coronary syndrome, for whom there has been accumulated an evidence-confirmed base of administering clopidogrel preparations, as well as ticagrelor and prasugrel in various clinical situations. Clopidogrel is currently the best known representative from the group of thienopyridines. It is a pro-drug and has complicated metabolism: two-stage oxidation under the effect of isoforms of cytochrome 2C19. Its active form irreversibly inhibits binding of ADP with P2Y12 receptors of thrombocytes. This is followed by inhibition of binding of fibrinogen with the glycoprotein IIb/IIIa receptor and a decrease of aggregation. Determining blood platelet aggregation with ADP, collagen and arachidonic acid forms the basis of clinical assessment of the functional state of thrombocytic activity and may be a marker of efficacy of treatment with antiaggregants. A complicated mechanism of action of clopidogrel implies individual policy of the attending physician in making a decision concerning the duration of therapy and selection of the dose. These prerequisites resulted in working out a recommended algorithm of individual dosing of clopidogrel (based on the analysis of case histories of patients with atherosclerosis of lower limb arteries by the level of platelet aggregation to a series of inducers) and correction of the dose of the drug based on the results of molecular-genetic testing of the cytochrome CYPC19 gene. The algorithm makes it possible to achieve a maximum level of efficacy and safety of treatment with antiaggregants.
Assuntos
Arteriopatias Oclusivas , Ticlopidina/análogos & derivados , Algoritmos , Arteriopatias Oclusivas/sangue , Arteriopatias Oclusivas/tratamento farmacológico , Clopidogrel , Relação Dose-Resposta a Droga , Humanos , Extremidade Inferior/irrigação sanguínea , Seleção de Pacientes , Ativação Plaquetária/efeitos dos fármacos , Ativação Plaquetária/fisiologia , Inibidores da Agregação Plaquetária/farmacocinética , Inibidores da Agregação Plaquetária/uso terapêutico , Medicina de Precisão/métodos , Fatores de Risco , Ticlopidina/farmacocinética , Ticlopidina/uso terapêuticoRESUMO
The helminths Opisthorchis felineus, Opisthorchis viverrini, Clonorchis sinensis, Metorchis bilis are the agents of opisthorchiasis. The actual diagnostic of parasitic diseases based on microscope analysis of samples of human feces to detect presence of ova of parasites suffers of many shortcomings, in particular low sensitivity especially at earlier stages. The purpose of this study was to compare results of detection of parasites using both classical technique and technique of specific differentiation based on extraction of nucleic acids from samples of human feces and implementation of reaction of amplification of the chosen fragment of DNA with detection of products of polymerase chain reaction in the real time. The study detected 150 out of 165 positive samples and also 6 out of 37 negative samples both validated by coproovoscopy.
Assuntos
Clonorchis sinensis/isolamento & purificação , DNA Mitocondrial/isolamento & purificação , Opistorquíase/diagnóstico , Opisthorchis/isolamento & purificação , Kit de Reagentes para Diagnóstico , Adulto , Idoso , Animais , Criança , Clonorchis sinensis/genética , Clonorchis sinensis/patogenicidade , DNA Mitocondrial/genética , Fezes/parasitologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Opistorquíase/genética , Opistorquíase/parasitologia , Opisthorchis/genética , Opisthorchis/patogenicidadeRESUMO
Substrate properties of various morpholinonucleoside triphosphates in the reaction of DNA elongation catalyzed by DNA polymerase beta, reverse transcriptase of human immunodeficiency virus (HIV-1 RT), and reverse transcriptase of Moloney murine leukemia virus (M-MuLV RT) were compared. Morpholinonucleoside triphosphates were utilized by DNA polymerase beta and HIV-1 reverse transcriptase as substrates, which terminated further synthesis of DNA, but were virtually not utilized by M-MuLV reverse transcriptase. The kinetic parameters of morpholinoderivatives of cytosine (MorC) and uridine (MorU) were determined in the reaction of primer elongation catalyzed by DNA polymerase beta and HIV-1 reverse transcriptase. MorC was a more effective substrate of HIV-1 reverse transcriptase and significantly less effective substrate of DNA polymerase beta than MorU. The possible use of morpholinonucleoside triphosphates as selective inhibitors of HIV-1 reverse transcriptase is discussed.
Assuntos
DNA Polimerase beta/antagonistas & inibidores , Desoxirribonucleotídeos/farmacologia , Transcriptase Reversa do HIV/antagonistas & inibidores , Inibidores da Transcriptase Reversa/farmacologia , Catálise , DNA Polimerase beta/metabolismo , Reparo do DNA/efeitos dos fármacos , DNA Viral/biossíntese , Desoxirribonucleotídeos/metabolismo , Transcriptase Reversa do HIV/metabolismo , HIV-1/enzimologia , Cinética , Vírus da Leucemia Murina de Moloney/enzimologia , Morfolinas/metabolismo , Morfolinas/farmacologia , DNA Polimerase Dirigida por RNA/metabolismo , Proteínas Recombinantes , Inibidores da Transcriptase Reversa/metabolismo , Relação Estrutura-AtividadeRESUMO
The article covers data on methodic approaches to evaluation and control of sanitary and epidemiologic supervision activities, systemizes terminology of the problem.
Assuntos
Controle de Doenças Transmissíveis/normas , Eficiência Organizacional/normas , Órgãos Governamentais/normas , Serviços de Saúde/normas , Administração em Saúde Pública/normas , Controle de Doenças Transmissíveis/organização & administração , Órgãos Governamentais/organização & administração , Administração de Serviços de Saúde , Humanos , Controle de Qualidade , Federação RussaRESUMO
Circulating immune complexes (CIC) and immunoglobulins A, M, and G were measured in the maternal peripheral blood, mixed umbilical blood, and amniotic fluid in women with normal pregnancy and gestosis. CIC concentrations in the examined fluids did not surpass the levels typical of healthy donors. Maternal blood CIC levels were higher in gestosis than in normal pregnancy, and CIC levels in the umbilical blood and amniotic fluid were always lower than in maternal blood serum. IgG levels were found the most shifted. These data evidence changes of the humoral immunity in normal pregnancy, this being, probably, one of the mechanisms providing its favorable course.
Assuntos
Líquido Amniótico/imunologia , Complexo Antígeno-Anticorpo/análise , Sangue Fetal/imunologia , Imunoglobulina A/análise , Imunoglobulina G/análise , Imunoglobulina M/análise , Pré-Eclâmpsia/imunologia , Adolescente , Adulto , Feminino , Humanos , Gravidez , PrognósticoRESUMO
Immunologic analysis of the amniotic fluid included measurements of immunoglobulins A and M, circulating immune complexes, rheumatoid and antinuclear factors, immunophoresis and electrophoresis, and tests for the presence of donor lymphocytes, Changed immunologic parameters of the amniotic fluid indicate a complicated course of pregnancy, development of gestosis among other things. Basing on their findings, the authors suggest that gestosis involve dysfunction of the adaptive mechanisms, that may result from disordered interactions of the immunity system components.