Is the ADP ribose site of the Chikungunya virus NSP3 Macro domain a target for antiviral approaches?

Chikungunya virus (CHIKV) is a mosquito-transmitted virus of special concern as it causes Chikungunya fever, characterized by an acute febrile illness, rash, and arthralgia that can progress to chronic and debilitating arthritic symptoms. The effects of climate change on the geographic distribution of the mosquito vector has the potential to expose more of the globe to this virus. No antiviral agents or vaccines are currently available against CHIKV infection and the development of novel therapies that may lead to a future treatment is therefore necessary. In this context, the ADP-ribose binding site of the CHIKV nsP3 macro domain has been reported as a potential target for the development of antivirals. Mutations in the ADP-ribose binding site demonstrated decreased viral replication in cell culture and reduced virulence. In this study, 48,750 small molecules were screened in silico for their ability to bind to the ADP-ribose binding site of the CHIKV nsP3 macro domain. From this in silico analysis, 12 molecules were selected for in vitro analysis using a CHIKV subgenomic replicon in Huh-7 cells. Cell viability and CHIKV replication were evaluated and molecules C5 and C13 demonstrated 53 and 66% inhibition of CHIKV replication, respectively. By using a CHIKV-Dual luciferase replicon contain two reporter genes, we also demonstrated that the treatment with either compounds are probably interfering in the early replication rather than after RNA replication has occurred

The use of zootherapeutics in folk veterinary medicine in the district of Cubati, Paraíba State, Brazil

<p>Abstract</p> <p>Background</p> <p>The present work addresses the use of zootherapy in folk veterinary medicine (ethnoveterinary) by the residents of the municipal district of Cubati, microregion of Seridó, Paraíba State, Brazil. It sought to identify the principal animals used as medicinal sources for zootherapeutics and to contribute to the preservation and sustainability of this traditional knowledge.</p> <p>Methods</p> <p>Field research was undertaken on a weekly or biweekly basis during the period November, 2006, to January, 2007. Free, semi-structured, and open interviews were made with local residents of the municipal district of Cubati (in both urban and rural settings) as well as with venders in public markets. A total of 25 individuals of both sexes were interviewed (with ages varying from 26 to 78 years) although only 16 were finally chosen as informants as these people demonstrated the greatest degree of knowledge concerning zootherapeutics. Graphs and percentages were generated using Microsoft^©Excel 2007 software, and the species were identified by photographic registration and subsequent bibliographical surveys.</p> <p>Results</p> <p>Mammals constitute the main medicinal zootherapeutic source for folk veterinary medicines in the studied area, both in terms of the total number of species used and the frequency of their citation. Sheep (<it>Ovis aries</it>), pigs (<it>Sus scrofa</it>), cattle (<it>Bos taurus</it>), and foxes (<it>Cerdocyon thous</it>) were mentioned by 62.5, 43.75, 37.5, and 31.25% of the informants, respectively, as being used in folk veterinary medicine. Additionally, chameleons (<it>Iguana iguana</it>), chickens (<it>Gallus domesticus</it>), and rattlesnakes (<it>Crotalus durissus</it>) were mentioned by 75, 43.75, and 31.25% of the informants, respectively. Relatively simple animal illnesses, such as furuncles, or injuries resulting from embedded thorns or skin eruptions are responsible for the largest number of zootherapeutic treatment, while, diseases of greater complexity, such as rabies and brucellosis, were not even mentioned. Fat from various animals constituted the most frequently cited resource used for its medicinal-veterinary properties.</p> <p>Conclusion</p> <p>The examination of folk knowledge and health practices allows a better understanding of human interactions with their local environment, and aids in the formulation of appropriate strategies for natural resource conservation.</p

Induction of CD4+CD25+FOXP3+ Regulatory T Cells during Human Hookworm Infection Modulates Antigen-Mediated Lymphocyte Proliferation

Hookworm infection is considered one of the most important poverty-promoting neglected tropical diseases, infecting 576 to 740 million people worldwide, especially in the tropics and subtropics. These blood-feeding nematodes have a remarkable ability to downmodulate the host immune response, protecting themselves from elimination and minimizing severe host pathology. While several mechanisms may be involved in the immunomodulation by parasitic infection, experimental evidences have pointed toward the possible involvement of regulatory T cells (Tregs) in downregulating effector T-cell responses upon chronic infection. However, the role of Tregs cells in human hookworm infection is still poorly understood and has not been addressed yet. In the current study we observed an augmentation of circulating CD4+CD25+FOXP3+ regulatory T cells in hookworm-infected individuals compared with healthy non-infected donors. We have also demonstrated that infected individuals present higher levels of circulating Treg cells expressing CTLA-4, GITR, IL-10, TGF-β and IL-17. Moreover, we showed that hookworm crude antigen stimulation reduces the number of CD4+CD25+FOXP3+ T regulatory cells co-expressing IL-17 in infected individuals. Finally, PBMCs from infected individuals pulsed with excreted/secreted products or hookworm crude antigens presented an impaired cellular proliferation, which was partially augmented by the depletion of Treg cells. Our results suggest that Treg cells may play an important role in hookworm-induced immunosuppression, contributing to the longevity of hookworm survival in infected people

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

A simple hollow fiber renewal liquid membrane extraction method for analysis of sulfonamides in honey samples with determination by liquid chromatography-tandem mass spectrometry

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)A sensitive and precise analysis using hollow fiber renewal liquid membrane (HFRLM) extraction followed by high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) is described for determination of five sulfonamides in honey samples. In this procedure, the organic solvent introduced directly into the sample matrix extracts the sulfonamides and carries them over the polypropylene porous membrane. An organic solvent is immobilized inside the polypropylene porous membrane, leading to a homogeneous phase. The stripping phase at higher pH in the lumen of the membrane promotes the ionization of the target compounds releasing them to this phase. The most important parameters affecting the extraction efficiency were optimized by multivariable designs (pH and sample mass, pH and buffer for stripping phase, extraction temperature and time, type and volume of extractor solvent and use of salt to saturate the sample). Detection limits in the range of 5.1-27.4 mu g kg(-1) and linearity coefficient of correlation higher than 0.987 were obtained for the target analytes. The results obtained for the proposed method show that HFRLM-LC-MS/MS can be used for determination of the five sulfonamides studied in honey samples with excellent precision, accuracy, practicality and short analysis time. (C) 2010 Elsevier B.V. All rights reserved.12174264496454Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Multiresidue determination of pesticides in industrial and fresh orange juice by hollow fiber microporous membrane liquid-liquid extraction and detection by liquid chromatography-electrospray-tandem mass spectrometry

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)A procedure involving hollow fiber microporous membrane liquid-liquid extraction (HF-MMLLE) and detection by liquid chromatography with tandem mass spectrometry was developed and applied. The extraction is based on liquid-liquid microextraction with a polypropylene porous membrane as a solid support for the solvent. On the membrane walls the solvent forms a renewable liquid membrane which improves the trueness of the method and promotes the sample clean-up. The applicability of this method was evaluated through the simultaneous extraction of 18 pesticides of different classes: polar organophosphates, carbamates, neonicotinoids, amides, pyrimidines, benzimidazoles and triazoles in industrial and fresh orange juice. The parameters affecting the extraction efficiency were optimized by multivariable designs. Under optimized conditions, analytes were concentrated onto 1.5 cm long microporous membranes placed directly into the sample containing 9 mL of juice at pH 7.0, 4g of ammonium sulfate and 400 mu L of toluene:ethyl acetate (85:15, v/v). The best extraction conditions were achieved at 25 degrees C with 35 min of extraction time. The analyte desorption was carried out using 50 mu L of methanol:acetone (50:50, v/v) for 2 min in an ultrasonic bath. Limits of detection ranging between 0.003-0.33 mg L-1, 0.003-0.35 mg L-1 and 0.003-0.15 mg L-1 were obtained for the carton orange juice, carton light orange juice and fresh orange juice samples, respectively. Good repeatability (lower than 7.6%) was obtained for all three sample types. The method was applied to five different juice samples containing soybean extract, orange pulp, nectar, light juice and fresh orange juice. The results suggest that the proposed method represents a very simple and low-cost alternative microextraction procedure rendering adequate limits of quantification for the determination of these pesticides in juice samples. (C) 2011 Elsevier B.V. All rights reserved.88573580Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Transtorno de estresse pós-traumático como acidente de trabalho em um bancário: relato de um caso Trastorno por estrés postraumático como accidente laboral en un bancario: relato de caso Post-traumatic stress disorder as a result of occupational injury: the case of a bank employee

Este artigo relata o caso de um gerente de banco atendido por uma equipe multidisciplinar através de anamnese psiquiátrica e ocupacional e aplicação de entrevista psiquiátrica semi-estruturada (SCID) para transtorno de estresse pós-traumático (TEPT). O objetivo do artigo é exemplificar, com um caso clínico, as relações entre o TEPT e eventos traumáticos ocorridos no trabalho, demonstrando que o TEPT pode ser uma conseqüência de acidente de trabalho bancário. A visão do TEPT como doença ocupacional é um conceito novo e relevante devido aos índices elevados de violência no Brasil. O reconhecimento do TEPT no contexto do trabalho bancário é importante para orientar serviços de saúde, administradores e profissionais de recursos humanos na prevenção de TEPT (treinamento adequado, suporte psicológico, emissão de Comunicação de Acidente de Trabalho, intervenções na organização do trabalho), visando à melhoria da qualidade de vida.<br>Este artículo relata el caso de un gerente de banco atendido por un equipo multidisciplinar a través de anamnesia psiquiátrica y ocupacional, y aplicación de entrevista psiquiátrica semi-estructurada (SCID) para trastorno por estrés postraumático (TEPT). El objetivo del artículo es ejemplificar, con un caso clínico, las relaciones entre TEPT y eventos traumáticos ocurridos en el trabajo, demostrando que el TEPT puede ser una consecuencia de accidente de trabajo bancario. La visión del TEPT como enfermedad ocupacional es un concepto nuevo y relevante, debido a los índices elevados de violencia en Brasil. El reconocimiento del TEPT en el contexto del trabajo bancario es importante para orientar los servicios de salud, administradores y profesionales de recursos humanos en la prevención del TEPT (entrenamiento adecuado, soporte psicológico, emisión de comunicación de accidente de trabajo, intervenciones en el ordenamiento del trabajo), visando a la mejoría de la calidad de vida.<br>This article reports the case of a bank manager assessed by a multidisciplinary team using psychiatric and occupational history taking and a semi-structured interview (SCID) for post-traumatic stress disorder (PTSD). The aim of this article is to use a clinical case to illustrate the relationship between PTSD and traumatic events in the workplace, showing that PTSD may result from an occupational injury. The notion of PTSD as an occupational disease is a new and relevant concept due to high levels of violence in Brazil. Acknowledging PTSD in the context of bank workers is important to guide health services, administrators, and human resource professionals in applying preventive measures (appropriate training, psychological support, filling out of Work Injury Reports and interventions in the organization of work) that will provide improved quality of life