RESUMO
Inter-individual variability in drug metabolism may result in adverse drug responses. Pharmacogenetic studies have shown that polymorphisms in drug metabolizing enzymes may contribute to this variability. Among these enzymes, CYP3A4 is responsible for metabolizing over 50% of the clinically used drugs. The Brazilian population is composed of people with Native American, European, and African ancestries, and is therefore considered as one of the most intermixed populations in the world. A thorough knowledge of the genetic frequencies of CYP3A4 allelic variants is useful for the establishment of better pharmacological therapies; therefore, the aim of this study was to describe the polymorphic frequencies for CYP3A4 -392A>G (rs2740574) in a sample population from Maranhão, Brazil. Our results showed that 75.1, 21.9, and 3.0% of the individuals expressed the -392AA, -392AG, and -392GG genotypes, respectively. The -392A and -392G alleles were observed in 86.1 and 13.9% of the population, respectively. Our results reiterate the need for a better understanding of the variations in the genotype and allele frequencies of CYP3A4 -392A>G polymorphisms in various Brazilian regions, in order to elucidate the variability in drug response.
Assuntos
Citocromo P-450 CYP3A/genética , Inativação Metabólica/genética , Farmacogenética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , População Negra , Brasil , Feminino , Expressão Gênica , Frequência do Gene , Genótipo , Humanos , Indígenas Sul-Americanos , Masculino , Pessoa de Meia-Idade , População BrancaRESUMO
We examined the prevalence of human papillomavirus (HPV) infection in Brazilian women with cervical intraepithelial neoplasia. Our goal was to identify the types of HPV and their association with risk factors. This prospective cross-sectional study included 97 samples collected from women aged 14-79 years at the public health units of gynecological care in São Luís, MA, Brazil. HPV detection was performed by nested polymerase chain reaction and sequence analysis. The study patients completed a structured questionnaire to provide information regarding their socio-demographic, clinical, and behavioral status. HPV prevalence was found to be 80.4%, with 17 virus types detected, including HPV 16, 18, 58, 6, and 11. Significant associations between HPV infection and age and frequency of doctor visits were identified. The study findings indicate the significance of age and low frequency of visits to the gynecologist as risk factors for genital HPV infection, suggesting that HPV infection-derived cervical cancer could be prevented through orientation programs for women, which include sex education and information regarding screening tests. We also found an increased prevalence of high-risk HPV serotypes in cervical lesions, which reveals an association between cervical lesions and high-risk HPV.
Assuntos
Papillomaviridae/fisiologia , Infecções por Papillomavirus/virologia , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/virologia , Adolescente , Adulto , Fatores Etários , Idoso , Brasil/epidemiologia , Estudos Transversais , DNA Viral/química , DNA Viral/genética , Feminino , Interações Hospedeiro-Patógeno , Humanos , Pessoa de Meia-Idade , Papillomaviridae/classificação , Papillomaviridae/genética , Infecções por Papillomavirus/diagnóstico , Infecções por Papillomavirus/epidemiologia , Reação em Cadeia da Polimerase , Prevalência , Estudos Prospectivos , Fatores de Risco , Análise de Sequência de DNA , Especificidade da Espécie , Inquéritos e Questionários , Adulto JovemRESUMO
The treatment of neurological disorders and neurodegenerative diseases is related to the levels of acetylcholine (ACh) through the inhibition of acetylcholinesterase (AChE). Galanthamine, an important alkaloid isolated from the Amaryllidaceae family, is approved for the pharmacological treatment of Alzheimer's disease (AD) and acts by inhibiting the acetylcholinesterase (AChE) activity. In the present study, Ellman's method was used to verify the inhibition of AChE activity of some isoquinolines alkaloids such as galanthamine, montanine, hippeastrine and pretazettine. At the concentrations 1mM, 500 microm and 100 microm, galanthamine presented an AChE inhibition higher than 90%. Montanine inhibited, in a dose-dependent manner, more than 50% of the enzyme at 1mM concentration. With the concentrations 500 microm and 100 microm, 30-45% of AChE activity inhibition was detected. The alkaloids hippeastrine and pretazettine presented no significant inhibition of the AChE activity. The results demonstrate that montanine significantly inhibits AChE activity at the tested concentrations, suggesting the necessity of further investigations on this alkaloid use in treating neurological disorders.