Genetic variability of CYP3A4 in a heterogeneous Brazilian population from Maranhão.

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.

Molecular detection of human papillomavirus in Brazilian women with cervical intraepithelial neoplasia in a northeast Brazilian city.

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.

Exploiting monitoring data in environmental exposure modelling and risk assessment of pharmaceuticals.

In order to establish the environmental impact of an active pharmaceutical ingredient (API), good information on the level of exposure in surface waters is needed. Exposure concentrations are typically estimated using information on the usage of an API as well as removal rates in the patient, the wastewater system and in surface waters. These input data are often highly variable and difficult to obtain, so model estimates often do not agree with measurements made in the field. In this paper we present an approach which uses inverse modelling to estimate overall removal rates of pharmaceuticals at the catchment scale using a hydrological model as well as prescription and monitoring data for a few representative sites for a country or region. These overall removal rates are then used to model exposure across the broader landscape. Evaluation of this approach for APIs in surface waters across England and Wales showed good agreement between modelled exposure distributions and available monitoring data. The use of the approach, alongside estimates of predicted no-effect concentrations for the 12 study compounds, to assess risk of the APIs across the UK landscape, indicated that, for most of the compounds, risks to aquatic life were low. However, ibuprofen was predicted to pose an unacceptable risk in 49.5% of the river reaches studied. For diclofenac, predicted exposure concentrations were also compared to the Environmental Quality Standard previously proposed by the European Commission and 4.5% of river reaches were predicted to exceed this concentration. While the current study focused on pharmaceuticals, the approach could also be valuable in assessing the risks of other 'down the drain' chemicals and could help inform our understanding of the important dissipation processes for pharmaceuticals in the pathway from the patient to ecological receptors.

Effect of isoquinoline alkaloids from two Hippeastrum species on in vitro acetylcholinesterase activity.

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.