Structure of an Odorant-Binding protein from the Mosquito Aedes aegypti suggests a binding pocket covered by a pH-sensitive “Lid”

Background The yellow fever mosquito, Aedes aegypti, is the primary vector for the viruses that cause yellow fever, mostly in tropical regions of Africa and in parts of South America, and human dengue, which infects 100 million people yearly in the tropics and subtropics. A better understanding of the structural biology of olfactory proteins may pave the way for the development of environmentally-friendly mosquito attractants and repellents, which may ultimately contribute to reduction of mosquito biting and disease transmission. Methodology Previously, we isolated and cloned a major, female-enriched odorant-binding protein (OBP) from the yellow fever mosquito, AaegOBP1, which was later inadvertently renamed AaegOBP39. We prepared recombinant samples of AaegOBP1 by using an expression system that allows proper formation of disulfide bridges and generates functional OBPs, which are indistinguishable from native OBPs. We crystallized AaegOBP1 and determined its three-dimensional structure at 1.85 Å resolution by molecular replacement based on the structure of the malaria mosquito OBP, AgamOBP1, the only mosquito OBP structure known to date. Conclusion The structure of AaegOBP1 ( = AaegOBP39) shares the common fold of insect OBPs with six α-helices knitted by three disulfide bonds. A long molecule of polyethylene glycol (PEG) was built into the electron-density maps identified in a long tunnel formed by a crystallographic dimer of AaegOBP1. Circular dichroism analysis indicated that delipidated AaegOBP1 undergoes a pH-dependent conformational change, which may lead to release of odorant at low pH (as in the environment in the vicinity of odorant receptors). A C-terminal loop covers the binding cavity and this “lid” may be opened by disruption of an array of acid-labile hydrogen bonds thus explaining reduced or no binding affinity at low pH

Quality of life of HIV+ patients undergoing pharmacotherapeutic follow-up

The influence of pharmacotherapeutic follow-up (PTF) on quality of life was evaluated in 45 HIV+ patients, who were undergoing initial antiretroviral therapy at a specialized care center in northeast Brazil. PTF lasted nine months and quality of life was analyzed at the 1st and 9th meetings using a questionnaire validated for Brazil. The study identified 643 problems related to antiretrovirals and there were 590 pharmaceutical interventions during the PTF. The comparative analysis between the results of the 1st and the 9th meeting was statistically significant for all domains of the questionnaire. For asymptomatic patients, only one domain was statistically significant. For symptomatic patients, six domains were significant. Patients with one year of HIV/AIDS diagnosis had statistically significant differences in five domains. The results suggest that the PTF contributed to improving quality of life, particularly for symptomatic patients and those diagnosed for at least one year - important target groups for Pharmaceutical Treatment.A influência do seguimento farmacoterapêutico (SFT) sobre a qualidade de vida foi avaliada em 45 pacientes HIV+ assistidos em serviço de atendimento especializado do nordeste brasileiro. O SFT teve duração de 9 meses e a qualidade de vida foi analisada no 1º e 9º encontros através de questionário validado no País. Identificaram-se 643 problemas relacionados aos antirretrovirais e realizaram-se 590 intervenções farmacêuticas durante o SFT. A análise comparativa entre os resultados de qualidade de vida do 1º e 9º encontro foi estatisticamente significativa em todos os domínios do questionário. Quando analisados somente os pacientes assintomáticos, apenas um domínio apresentou significância estatística. Entre os sintomáticos, seis domínios foram significativos. Pacientes com até um ano de diagnóstico de HIV/AIDS apresentaram validade estatística em cinco domínios. Os resultados sugerem que o SFT contribuiu para a melhoria da qualidade de vida dos pacientes, sobretudo dos sintomáticos e/ou com até um ano de diagnóstico, representando grupos-alvo para a prática da Atenção Farmacêutica

Human toxocariasis: contribution by Brazilian researchers

In the present paper the main aspects of the natural history of human infection by Toxocara larvae that occasionally result in the occurrence of visceral and/or ocular larva migrans syndrome were reviewed. The contribution by Brazilian researchers was emphasized, especially the staff of the Tropical Medicine Institute of São Paulo (IMT)