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1.
Data Brief ; 21: 1315-1320, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30456250

RESUMO

This article describes data set of the profile of patients diagnosed with Diabetic Nephropathy (DN) undergoing hemodialysis and followed-up by Hemodialysis Service in medical centers in Goiânia, Go, Brazil. These data describe specifically the demographic, clinical, and lifestyle variables of 101 patients. In addition, these data provide detailed clinical associations about the profile of patients diagnosed with DN and which are made publicly available to enable critical or extended analyzes. For further interpretation of the data presented in this article, see the research article: Do GST polymorphisms influence in the pathogenesis of diabetic nephropathy? (Lima et al., 2018).

2.
Mol Cell Endocrinol ; 478: 10-16, 2018 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-29981844

RESUMO

Diabetic patients often develop Diabetic Nephropathy (DN) despite severe long-lasting hyperglycemia, while others develop DN even under intensive insulin therapy. This indicates that factors other than chronic hyperglycemia may also contribute to the susceptibility to the development of DN. The purpose of this case-control study was to investigate the possible role of GSTM1 and GSTT1 deletion polymorphisms, and Single Nucleotide Polymorphism (SNP), GSTP1 313 A > G (Ile105Val), in DN susceptibility. Multiple logistic regression analysis revealed that the occurrence of GST polymorphisms in the Central Brazilian population was not associated with increased risk of DN. However, the presence GSTT1 null genotype suggest an increase trend in systolic blood pressure and opposite inference was observed for the GSTP1 genotype (Ile/Val or Val/Val). On the order hand, other studies may clarify the relationship of these polymorphisms with DN and help in the prevention of this disease.


Assuntos
Nefropatias Diabéticas/enzimologia , Nefropatias Diabéticas/genética , Predisposição Genética para Doença , Glutationa S-Transferase pi/genética , Glutationa Transferase/genética , Polimorfismo Genético , Feminino , Humanos , Masculino , Polimorfismo de Nucleotídeo Único/genética
4.
Biochim Biophys Acta ; 1801(10): 1163-74, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20624480

RESUMO

The first committed step in the formation of 24-alkylsterols in the ascomycetous fungus Paracoccidiodes brasiliensis (Pb) has been shown to involve C24-methylation of lanosterol to eburicol (24(28)-methylene-24,25-dihydro-lanosterol) on the basis of metabolite co-occurrence. A similarity-based cloning strategy was employed to obtain the cDNA clone corresponding to the sterol C24-methyltransferase (SMT) implicated in the C24-methylation reaction. The resulting catalyst, prepared as a recombinant fusion protein (His/Trx/S), was expressed in Escherichia coli BL21(C43) and shown to possess a substrate specificity for lanosterol and to generate a single exocyclic methylene product. The full-length cDNA has an open reading frame of 1131 base pairs and encodes a protein of 377 residues with a calculated molecular mass of 42,502Da. The enzymatic C24-methylation gave a K(mapp) of 38microM and k(catapp) of 0.14min(-1). Quite unexpectedly, "plant" cycloartenol was catalyzed in high yield to 24(28)-methylene cycloartanol consistent with conformational arguments that favor that both cycloartenol and lanosterol are bound pseudoplanar in the ternary complex. Incubation of [27-(13)C]- or [24-(2)H]cycloartenol with PbSMT and analysis of the enzyme-generated product by a combination of (1)H and (13)CNMR and mass spectroscopy established the regiospecific conversion of the pro-Z methyl group of the Delta(24(25))-substrate to the pro-R isopropyl methyl group of the product and the migration of H24 to C25 on the Re-face of the original substrate double bond undergoing C24-methylation. Inhibition kinetics and products formed from the substrate analogs 25-azalanosterol (K(i) 14nM) and 26,27-dehydrolanosterol (K(i) 54muM and k(inact) of 0.24min(-1)) provide direct evidence for distinct reaction channeling capitalized by structural differences in the C24- and C26-sterol acceptors. 25-Azalanosterol was a potent inhibitor of cell growth (IC(50), 30nM) promoting lanosterol accumulation and 24-alkyl sterol depletion. Phylogenetic analysis of PbSMT with related SMTs of diverse origin together with the results of the present study indicate that the enzyme may have a similar complement of active-site amino acid residues compared to related yeast SMTs affording monofunctional C(1)-transfer behavior, yet there are sufficient differences in its overall amino acid composition and substrate-dependent partitioning pathways to group PbSMT into a fourth and new class of SMT.


Assuntos
Metiltransferases/genética , Metiltransferases/metabolismo , Paracoccidioides/enzimologia , Fitosteróis/biossíntese , Alquilação , Sequência de Aminoácidos , Biocatálise , Colestadienóis/química , Cromatografia Gasosa , Cromatografia Líquida de Alta Pressão , Clonagem Molecular , Eletroforese em Gel de Poliacrilamida , Ativação Enzimática , Lanosterol/química , Lanosterol/isolamento & purificação , Redes e Vias Metabólicas , Metiltransferases/antagonistas & inibidores , Metiltransferases/química , Dados de Sequência Molecular , Mutagênese Sítio-Dirigida , Filogenia , Fitosteróis/química , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo , Reprodutibilidade dos Testes , Alinhamento de Sequência , Análise de Sequência de DNA , Especificidade por Substrato , Tirosina/genética
5.
Cell Biol Toxicol ; 26(2): 165-76, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19444624

RESUMO

Morphological alterations, by means of histological and ultrastructural analysis, have been used to determine the effects of boric acid and fipronil on midgut tissues of honeybee worker, Apis mellifera L. larvae. In order to observe possible morphological alterations in the midgut, two groups of bioassays were performed. In the first one, the larvae were chronically treated with different concentrations of boric acid added to the food (1.0, 2.5 and 7.5 mg/g). In the second group, the larvae were fed with diets containing different concentrations of fipronil (0.1 and 1 microg/g) and compared with control groups without these chemical compounds. In the first bioassay, the larvae were collected on day 3 and in the second bioassay on day 4, when the mortality rate obtained in the toxicological bioassay was not very high. The larval midguts were removed and processed for morphological analyses using a light and transmission electron microscopy. We observed cytoplasmic vacuolizations, with the absence of autophagic vacuoles, and chromatinic compacting in most of the cells in the groups treated with pesticides. The morphological alterations were far greater in the larvae treated with boric acid than in the larvae treated with fipronil. Our data suggest that the midgut cell death observed was in response to boric acid and fipronil action. This study significantly improves the understanding of the toxicological effect of these insecticides from the ecotoxicological perspective.


Assuntos
Abelhas , Ácidos Bóricos/toxicidade , Inseticidas/toxicidade , Pirazóis/toxicidade , Estômago/efeitos dos fármacos , Administração Oral , Ração Animal , Animais , Morte Celular/efeitos dos fármacos , Quimioterapia Combinada , Enterócitos/efeitos dos fármacos , Enterócitos/ultraestrutura , Larva/efeitos dos fármacos , Longevidade/efeitos dos fármacos , Microscopia Eletrônica de Transmissão , Estômago/patologia
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