Sample records for guanine
from WorldWideScience.org

Sample records 1 - 9 shown.



1

Tumores endócrinos associados às mutações das proteínas Gsalfa e Gi2alfa/ Endocrine tumors associated to protein Gsalpha/Gi2alpha mutations

Bezerra, Milena Gurgel Teles; Latronico, Ana Claudia; Fragoso, Maria Candida B.V.
2005-10-01

Resumo em português Diversas mutações em oncogenes promovem o crescimento tumoral através da indução de atividade de proteínas que normalmente transmitem sinais proliferativos a partir de fatores extracelulares. As proteínas G são uma família de proteínas ligadas ao nucleotídeo guanina que apresentam homologia estrutural e estão amplamente distribuídas em células eucariotas. Elas são constituídas por três sub-unidades (alfa, beta e gama). A sub-unidade alfa apresenta o síti (mais) o de ligação ao nucleotídeo guanina e é única para cada proteína G. A proteínas G estão acopladas aos receptores de superfície celular com sete hélices transmembrana com uma grande variedade de efetores intracelulares e segundos mensageiros. Um subgrupo de tumores endócrinos, incluindo os tumores hipofisários secretores de GH e ACTH, nódulos tireoideanos autônomos, tumores adrenocorticais e gonadais, foram associados a mutações somáticas ativadoras em códons altamente conservados das proteínas Gs (Arg201 e Gln227) e Gi (Arg179, Gln205). Estes achados moleculares indicaram que as proteínas G atuam como oncogenes, contribuindo no processo da tumorigênese endócrina em humanos. Resumo em inglês Many oncogenic mutations promote tumor growth by inducing autonomous activity of proteins that normally transmit proliferative signal initiated by extracelular factors. G proteins are a family of guanine nucleotide binding proteins, which are structurally homologous and widely distributed in eukaryotic cells. They are composed of three different subunits (alpha, beta e gamma). The alpha subunit, which contains the guanine nucleotide-binding site, is unique to each G prote (mais) in. The G proteins couple an array of seven transmembrane receptors at the cell surface with a variety of intracellular effectors, which produce second messenger molecules. A subset of endocrine tumors, such as GH- or ACTH-secreting pituitary adenomas, functioning thyroid adenomas, adrenocortical and gonadal tumors were associated with somatic activating mutations in the highly conserved codons of the Gs (Arg201 and Gln227) and Gi (Arg179 and Gln205) proteins. These findings indicated that the G proteins play a role as oncogenes, contributing with the human endocrine tumorigenesis.

Scientific Electronic Library Online (Portuguese)

2

Otimização de metodologia PCR-SSP para identificação de polimorfismos genéticos de TNF e IL2/ Optimization of the PCR-SSP methodology in the identification of TNF and IL2 genetic polymorphisms

Franceschi, Danilo A. S.; Viel, Dangelo O.; Sell, Ana Maria; Tsuneto, Luiza T.; Visentainer, Jeane E. L.
2009-08-01

Resumo em português A análise de polimorfismos únicos de nucleotídeos (SNPs) de citocinas pode ser útil em estudos de frequências alélicas e genotípicas em populações saudáveis de diversas regiões, em estudos de associação com doenças infecciosas ou autoimunes, em estudos antropológicos e na evolução pós-transplante. Estes SNPs podem ser avaliados por diferentes métodos moleculares. O objetivo deste estudo foi aperfeiçoar uma metodologia PCR-SSP simples e rápida para a g (mais) enotipagem de três SNPs de citocinas usando um único teste laboratorial. Para a identificação de IL2-330T/G e IL2+166G/T foram utilizados dois procedimentos na mesma genotipagem, cada um baseado no uso de quatro iniciadores. Para a detecção de TNF-238G/A foram utilizados dois iniciadores que amplificam a guanina e adenina na posição -238. Este estudo permitiu aperfeiçoar um método simples e rápido para identificar três SNPs de citocinas num único teste, podendo ser utilizado em qualquer laboratório de biologia molecular, como alternativa ao uso de kits de alto custo. Resumo em inglês The analysis of cytokine single nucleotide polymorphisms (SNPs) can be useful in studies of allelic and genotypic frequencies in healthy populations from different regions of Brazil, in association studies of infectious or auto-immune diseases, in anthropological studies and in studies on post-transplant evolution. These SNPs can be assessed by different molecular methods. The objective of this study was to improve a simple and fast methodology, PCR-SSP, for the genotypin (mais) g of three cytokine SNPs using a single laboratorial test. To identify IL2-330T/G and IL2+166G/T, two procedures were used in the same genotyping assay, each one based on the use of 4 primers. To detect TNF-238G/A, two primers were used that amplify guanine and adenine at position -238. This study enabled the improvement of a simple and fast method for identifying three cytokine SNPs in a single test, which can be adopted in any Molecular Biology laboratory as an alternative to the use of expensive kits.

Scientific Electronic Library Online (Portuguese)

3

Aflatoxinas: conceitos sobre mecanismos de toxicidade e seu envolvimento na etiologia do câncer hepático celular/ Aflatoxins in foodstuffs: current concepts on mechanisms of toxicity and its involvement in the etiology of hepatocellular carcinoma

Oliveira, Carlos Augusto Fernandes de; Germano, Pedro Manuel Leal
1997-08-01

Resumo em português Foram revistos os conceitos de maior relevância sobre mecanismos de toxicidade e evidências do envolvimento das aflatoxinas na etiologia do câncer hepático humano. A aflatoxina B1 (AFB1), principal metabólito produzido por fungos do gênero Aspergillus, manifesta seus efeitos tóxicos após conversão hepática em AFB1-epóxido, o qual reage com macromoléculas celulares, incluindo proteínas, RNA (ácido ribonucléico) e DNA (ácido desoxirribonucléico). A reação (mais) com o DNA ocorre através da ligação com guaninas, ao nível do códon 249, do gene supressor de tumores p53. Em seres humanos, estudos de biomonitoramento individual de derivados AFB1-N7-guanina tem demonstrado que as aflatoxinas constituem importantes fatores de risco, com uma provável interação sinergística com o vírus da hepatite B, para o desenvolvimento do carcinoma hepatocelular em populações expostas. Considerando-se a ocorrência freqüente das aflatoxinas em produtos alimentícios, no Brasil, ressalta-se a necessidade de estudos que avaliem criteriosamente o impacto dos níveis de exposição a estas toxinas sobre a saúde humana. Resumo em inglês Current concepts derived from intensive research over the last decade, on biotransformation, mechanisms of toxicity and evidences for the involvement of aflatoxins in the etiolgy of human liver cancer are summarily presented. Aflatoxin B1(AFB1), the main metabolite produced by moulds of genus Aspergillus, exerts its effects after conversion to the reactive compound AFB1-epoxide, by the action of cytochrome P450-dependent enzymes. This epoxide can form derivatives with cel (mais) lular macromolecules, including proteins, RNA and DNA. The reaction with DNA occurs with guanines in the códon 249 of tumor suppressor gene p53. Primary biotransformation of AFB1 also produces hydroxylated and less toxic derivatives, such as aflatoxins Q1 and P1. Differences intra and interspecies in the pathways of activation/detoxification are directly related to the susceptibility of animals to aflatoxin effects. In humans, studies of individual biomonitoring of AFB1 metabolites such as AFB1-N7-guanine have demonstrated that aflatoxins constitute an important risk factor for hepatocellular carcinoma (HCC) in exposed populations. Some of these studies also show a synergistic action between aflatoxins and the hepatitis B virus in the development of human HCC. In view of these concepts, and taking into account the frequent detection of aflatoxins in Brazilian foodstuffs, the need for investigation into the level of exposure to these toxins and its impact on human health is stressed.

Scientific Electronic Library Online (Portuguese)

4

Aflatoxinas: conceitos sobre mecanismos de toxicidade e seu envolvimento na etiologia do câncer hepático celular/ Aflatoxins in foodstuffs: current concepts on mechanisms of toxicity and its involvement in the etiology of hepatocellular carcinoma

Oliveira, Carlos Augusto Fernandes de; Germano, Pedro Manuel Leal
1997-08-01

Resumo em português Foram revistos os conceitos de maior relevância sobre mecanismos de toxicidade e evidências do envolvimento das aflatoxinas na etiologia do câncer hepático humano. A aflatoxina B1 (AFB1), principal metabólito produzido por fungos do gênero Aspergillus, manifesta seus efeitos tóxicos após conversão hepática em AFB1-epóxido, o qual reage com macromoléculas celulares, incluindo proteínas, RNA (ácido ribonucléico) e DNA (ácido desoxirribonucléico). A reação (mais) com o DNA ocorre através da ligação com guaninas, ao nível do códon 249, do gene supressor de tumores p53. Em seres humanos, estudos de biomonitoramento individual de derivados AFB1-N7-guanina tem demonstrado que as aflatoxinas constituem importantes fatores de risco, com uma provável interação sinergística com o vírus da hepatite B, para o desenvolvimento do carcinoma hepatocelular em populações expostas. Considerando-se a ocorrência freqüente das aflatoxinas em produtos alimentícios, no Brasil, ressalta-se a necessidade de estudos que avaliem criteriosamente o impacto dos níveis de exposição a estas toxinas sobre a saúde humana. Resumo em inglês Current concepts derived from intensive research over the last decade, on biotransformation, mechanisms of toxicity and evidences for the involvement of aflatoxins in the etiolgy of human liver cancer are summarily presented. Aflatoxin B1(AFB1), the main metabolite produced by moulds of genus Aspergillus, exerts its effects after conversion to the reactive compound AFB1-epoxide, by the action of cytochrome P450-dependent enzymes. This epoxide can form derivatives with cel (mais) lular macromolecules, including proteins, RNA and DNA. The reaction with DNA occurs with guanines in the códon 249 of tumor suppressor gene p53. Primary biotransformation of AFB1 also produces hydroxylated and less toxic derivatives, such as aflatoxins Q1 and P1. Differences intra and interspecies in the pathways of activation/detoxification are directly related to the susceptibility of animals to aflatoxin effects. In humans, studies of individual biomonitoring of AFB1 metabolites such as AFB1-N7-guanine have demonstrated that aflatoxins constitute an important risk factor for hepatocellular carcinoma (HCC) in exposed populations. Some of these studies also show a synergistic action between aflatoxins and the hepatitis B virus in the development of human HCC. In view of these concepts, and taking into account the frequent detection of aflatoxins in Brazilian foodstuffs, the need for investigation into the level of exposure to these toxins and its impact on human health is stressed.

Scientific Electronic Library Online (Portuguese)

5

Biomarcadores para avaliação da exposição humana às micotoxinas/ Biomarkers for assessment of human exposure to mycotoxins

Bando, Érika; Gonçales, Leandro Nishikawa; Tamura, Nathalie Kira; Machinski Junior, Miguel
2007-06-01

Resumo em português Atualmente, as micotoxinas representam um risco de contaminação ambiental, acarretando sérios prejuízos à saúde humana. Essas toxinas podem estar presentes em diferentes tipos de alimentos, que constituem a principal fonte de exposição para o homem. As exposições podem ser monitoradas através do uso de biomarcadores, que elucidam a relação causa/efeito e dose/efeito na avaliação de risco à saúde para fins de diagnóstico clínico e laboratorial. Realizou- (mais) se uma revisão bibliográfica do período de 1981-2005, no MEDLINE, sobre utilização e propostas de biomarcadores para a exposição a aflatoxinas, fumonisinas, desoxinivalenol e ocratoxina A. Os possíveis biomarcadores para avaliar a exposição humana às aflatoxinas foram os metabólitos urinários de aflatoxina B1, como aflatoxina M1, aflatoxina P1, aflatoxina Q1, aflatoxina livre em soro ou plasma, os adutos de AFB-N7-guanina, os adutos de albumina ou mutação no gene supressor de tumor p53, presentes em fluidos biológicos. Para as fumonisinas, os biomarcadores foram os níveis de fumonisina B1 e fumonisina B2 livres, ou de esfinganina e esfingosina em sangue e urina. O desoxinivalenol tem como biomarcadores de exposição os produtos de seu metabolismo e adutos macromoleculares (proteína/DNA) presentes nos fluidos biológicos. Para a exposição à ocratoxina A (OA) os biomarcadores se restringem à quantificação da própria toxina nos fluidos biológicos. A avaliação da exposição às micotoxinas constitui um importante aspecto para a saúde pública, tendo em vista a possibilidade de prevenir ou minimizar a incidência de doenças decorrentes da sua interação com o organismo. Resumo em inglês Currently, mycotoxins represent a risk of environmental contamination, causing serious damages to human health. Those toxins can be found in different kinds of foods, and they constitute the main source of human exposure. The evaluation of such exposures can be monitored through the use of biomarkers, which elucidates the cause/effect and dose/effect relation in the evaluation of health risks for clinical and laboratory diagnostic purposes. The MEDLINE review about the us (mais) e of biomarkers for assessment of aflatoxins, fumonisins, deoxynivalenol and ochratoxin A was carried out from 1981 to 2005. The biomarkers for assessment of human exposure to aflatoxins were the urinary metabolites of aflatoxin B1: aflatoxin M1, aflatoxin P1, aflatoxin Q1, the free aflatoxin in serum or plasma, the AFB-N7-guanine adducts and the albumin adducts or mutation in the tumour suppressor gene p53 present in human biological fluids. As far as fumonisins are concerned, levels of free fumonisin B1 and fumonisin B2, or levels of sphinganine and sphingosin, were quantified in blood and urine. As exposure biomarkers, deoxynivalenol has its own metabolism products and adducts (protein/DNA) present in human fluids. As to ochratoxin A exposure, we measure it in biological fluids, once it enables us to prevent or minimize the incidence of deaths or illnesses provoked by chemical exposure.

Scientific Electronic Library Online (Portuguese)

6

Lesões em DNA induzidas pela autoxidação de S(IV) na presença de íons metálicos de transição/ DNA damage induced by the autoxidation of S(IV) in the presence of transition metal ions

Moreno, Ruben G. M.; Alipázaga, María V.; Medeiros, Marisa H. G.; Coichev, Nina
2006-10-01

Resumo em inglês The oxidation of sulfite catalyzed by transition metal ions produces reactive oxysulfur species that can damage plasmid and isolated DNA in vitro. Among the four DNA bases, guanine is the most sensitive to one-electron oxidation promoted by the species formed in the autoxidation of sulfite (HSO5-, HO•, SO3•-, SO4•- and SO5•-) due to its low reduction potential and ability to bind transition metal ions capable to catalyze oxidative processes. Some oxidative DNA lesions (mais) are promutagenic and oxidative DNA damage is proposed to play a crucial role in certain human pathologies, including cancer.

Scientific Electronic Library Online (Portuguese)

7

Danos ao DNA promovidos por ácido 5-aminolevulínico: possível associação com o desenvolvimento de carcinoma hepatocelular em portadores de porfiria aguda intermitente/ DNA damage induced by 5-aminolevulinic acid: a possible association with the development of hepatocellular carcinoma in acute intermittent porphyria patients

Onuki, Janice; Teixeira, Priscila C.; Medeiros, Marisa H.G.; Di Mascio, Paolo
2002-07-01

Resumo em inglês 5-Aminolevulinic acid (ALA) is a heme precursor accumulated in acute intermittent porphyria (AIP), which might be associated with hepatocellular carcinoma (HCC) in symptomatic patients. Under metal catalyzed oxidation, ALA and its cyclic dimerization product, 3,6-dihydropyrazine-2,5-dipropanoic acid, produce reactive oxygen species that damage plasmid and calf thymus DNA bases, increase the steady state level of 8-oxo-7,8-dihydro-2´-deoxyguanosine in liver DNA and promot (mais) e mitochondrial DNA damage. The final product of ALA, 4,5-dioxovaleric acid (DOVA), is able to alkylate guanine moieties, producing adducts. ALA and DOVA are mutagenic in bacteria. This review shows an up-to-date literature data that reinforce the hypothesis that the DNA damage induced by ALA may be associated with the development of HCC in AIP patients.

Scientific Electronic Library Online (Portuguese)

8

Bioquímica e ação citotóxica de alfa-aminocetonas endógenas/ Biochemistry and cytotoxicity of alpha-aminoketones

Dutra, Fernando; Bechara, Etelvino J. H.
2005-06-01

Resumo em inglês alpha-Aminoketones are expected to undergo enolization and subsequent aerobic oxidation yielding oxyradicals and highly toxic a-oxoaldehydes. Our interest has been focused on two endogenous a-aminoketones: 5-aminolevulinic acid (ALA) and aminoacetone (AA), accumulated in porphyrias and diabetes mellitus, respectively, and recently implicated as contributing sources of oxyradicals in these diseases. The final oxidation product of ALA, 4,5-dioxovaleric acid (DOVA), is able (mais) to alkylate DNA guanine moieties and expected to promote protein cross-linking. Methylglyoxal (MG), the final oxidation product of AA, is also highly cytotoxic and able to aggregate protein molecules. This review covers chemical and biochemical aspects of these alpha-aminoketones and their putative roles in the oxidative stress associated with porphyric disorders and diabetes.

Scientific Electronic Library Online (Portuguese)

9

Associação entre polimorfismo Gln27Glu do receptor beta2-adrenérgico e hipertensão arterial sistêmica em obesos mórbidos

Villares, Sandra M.; Mancini, Marcio C.; Gomez, Sérgio; Charf, Ana M.; Frazzatto, Eliana; Halpern, Alfredo
2000-02-01

Resumo em português Há alguns relatos na literatura sugerindo associação entre polimorfismos do receptor beta2-adrenérgico com obesidade e outros com hipertensão arterial. O objetivo do nosso estudo foi estudar a freqüência de um polimorfismo do receptor beta2 adrenérgico (Gln27Glu) em pacientes obesos (BMI 48 ± 8,2kg/m²) e relacioná-lo com hipertensão arterial, e níveis de triglicérides, colesterol, insulina e glicose no sangue. Encontramos associação deste polimorfismo em obesos com hipertensão arterial. Resumo em inglês beta2-adrenergic receptors (beta2AR) are membrane-bound receptors, which upon binding the endogenous cathecolamines epinephrine and nore-pinephrine signal to the interior of cells via stimulatory guanine nucleotide-binding protein Gs. The sympathetic nervous system activation stimulates energy mobilization and utilization in the adipose tissue that is a favored target for high-energy substrate storage, mobilization and utilization. Adrenergic responsiveness may be altered (mais) in obesity and could be an important factor in the pathogenesis and maintenance of obesity state. In the hypertensive state there is physiological and biochemical evidence that b-adrenergic responsiveness is diminished in the face of increased sympathetic tone. Recently, several different polymorphic forms of the human beta2AR have been identified in general population, including N-terminal substitutions of glutamine (Gln) for glutamic acid (Glu) at position 27. The aim of this study was to investigate the potential interaction between the beta2AR (Gln27Glu) polymorphism and obesity accumulation and hypertension in morbidly obese subjects. The Ita I genotypes of beta2AR were established using RFLP methods in 135 individuals with BMI 48 ± 8.02kg/m². The frequency of Gln/Glu was 31.9% and in the homozygous Glu/Glu was 12.6%. No association was found between BMI, weight gain during the past years and the Ita I genotypes and neither was associated with levels of triglycerides, cholesterol, insulin and glucose. Positive association was found between blood pressure (systolic and diastolic) and presence of polymorphism. The results indicate at the first time that presence of polymorphism 27Glu may provide a mechanism for enhanced vascular reactivity and identify a candidate gene for hypertension in this obesity group.

Scientific Electronic Library Online (Portuguese)