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Saudi J Kidney Dis Transpl ; 19(5): 761-6, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18711292


Angiotensin-converting enzyme (ACE) plays an important role in the development of systemic lupus erythematosus (SLE) because its end-product, angiotensin II, plays an integral role in the regulatory system responsible for endothelial control and vascular tone, systems that are commonly affected in patients with SLE. Additionally, ACE inhibitors have been shown to retard the progression of SLE and lupus nephritis. Our goal was to investigate whether ACE gene polymorphisms are associated with increasing severity of SLE. We genotyped 39 SLE patients of varying disease severity from a homogenous Asian population and 79 control subjects for ACE I/D and 2350 G > A dimorphisms. All patients met the American College of Rheumatology (ACR) criteria for SLE and their disease severity was measured using Systemic Lupus Activity Measure (SLAM). The "A" allele was found to be associated with increase in severity of SLE with the AA genotype present only in severe disease. No association with SLE in general, compared to healthy subjects, was found with either dimorphism. We also examined the transmission of haplotypes as defined by these polymorphisms. The D and A alleles were found in strong linkage disequilibrium especially in severe SLE. The DA-haplotype was more frequent in severe SLE, than mild to moderate disease. Our findings suggest that DNA sequence variation in the ACE gene influences disease progression and severity of SLE.

Lúpus Eritematoso Sistêmico/enzimologia , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/fisiopatologia , Peptidil Dipeptidase A/genética , DNA/sangue , DNA/genética , Feminino , Variação Genética , Genótipo , Humanos , Masculino , Paquistão , Polimorfismo de Nucleotídeo Único , Valores de Referência , Estudos Retrospectivos , Índice de Gravidade de Doença
Med Sci Monit ; 11(1): CR6-9, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15614196


BACKGROUND: The human G-protein beta 3 subunit gene (GNB3) and some of its variants are known to be important genetic influences involved in essential hypertension (EH). Left ventricular hypertrophy (LVH) has long been thought to be an end point of EH, rather than a separate entity, though it is influenced by a unique set of hormonal, vascular and genetic factors. METHODS/MATERIALS: We carried out a retrospective, case-control study of a GNB3 825 C>T dimorphism among nationals from the United Arab Emirates (Emirati), an ethnic group characterized by no alcohol intake and no cigarette smoking, for putative correlations with EH and LVH. We investigated a sample population of 454 Emirati (231 men, 223 women) comprising groups of controls and patients with clinical diagnoses of LVH, based on echocardiographic and ECG criteria, and EH, based on blood pressure values. The GNB3 825 C>T genotypes were determined by PCR and restriction digestion. RESULTS: The distribution of genotypes was in Hardy-Weinberg equilibrium in all three subject groups. GNB3 T825 alleles demonstrated a strong association with LVH (OR = 2.22; 95% CI: 1.29-3.83 and P = 0.0002), but not with EH. CONCLUSIONS: GNB3 825 C>T is likely to be a significant risk factor for LVH but not for EH in the Emirati population, thereby strengthening the view that LVH is genetically a separate clinical entity.

Proteínas Heterotriméricas de Ligação ao GTP/genética , Hipertensão/genética , Hipertrofia Ventricular Esquerda/genética , Polimorfismo Genético , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Subunidades Proteicas/genética , Estudos Retrospectivos , Emirados Árabes Unidos
Phytother Res ; 17(8): 921-4, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-13680825


The in vitro effect of aqueous extract of Nigella sativa seeds on nitric oxide (NO) production by murine macrophages was studied. Murine peritoneal macrophages were pre-incubated with the extract and then activated with Escherichia coli lipopolysaccharride. NO production was measured after 24 hours by spectrophotometry. The plant extract caused a dose-dependent decrease in NO production. Dialyzed preparation of the extract did not affect NO production. However, the boiled fraction of the extract resulted in a dose-dependent inhibition of NO apparently comparable to that of the whole extract. These results indicate that the aqueous extract of N. sativa seeds exhibits an inhibitory effect on nitric oxide production by murine macrophages and the active component(s) is/are non-protein in nature. In view of the fact that nitric oxide is a pro-inflammatory mediator, this study validates the traditional use of the Nigella sativa seeds for the treatment of rheumatism.

Macrófagos/efeitos dos fármacos , Nigella sativa , Óxido Nítrico/biossíntese , Fitoterapia , Extratos Vegetais/farmacologia , Animais , Relação Dose-Resposta a Droga , Humanos , Macrófagos/metabolismo , Camundongos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/uso terapêutico , Sementes