Screening method of mildronate and over 300 doping agents by reversed-phase liquid chromatography-high resolution mass spectrometry.

Considering the huge amount of substances associated with athletic performance improvement, current doping control analysis requires a comprehensive screening method, which leads to the detection of prohibited substances of different physico-chemical properties. This comprehensiveness associated with instrumental approaches based on high resolution mass spectrometry has allowed the development of extremely sensitive and selective detection methods. Furthermore, it is desirable the method to be simple, fast and straightforward. Mildronate is a highly polar quaternary amine, classified as metabolic modulator by the World Anti-Doping Agency (WADA). The inclusion of mildronate in the screening strategy is a challenge considering its singular physicochemical properties, compared to numerous doping agents of low and medium polarity. For this purpose, a method combining solid-phase extraction (SPE) and dilute-and-shoot approach has been developed and validated, allowing the detection of mildronate and other 332 prohibited substances. In the sample preparation protocol, the enzymatic deconjugation step and SPE conditions were stressed to enable the recovery of mildronate without jeopardizing the detection of other doping agents. The C18/18% SPE cartridge without any type of ionic interaction, associated with the dilute-and-shoot approach proved to be effective for all monitored substances. The instrumental method employed was based on liquid chromatography using a reversed-phase column in a 12-minute gradient coupled to a high-resolution mass spectrometry in full scan with positive and negative switching and fragmentation in the positive mode, for the most critical detection compounds. The performance of the method was evaluated regarding selectivity, precision, recovery, carry-over, limit of detection and stability, following the recommendations of WADA.

Saúde mental e trabalho na saúde da família: relato de experiência / Mental health and work in a family health: an experience report / Salud mental y trabajo en la salud de la familia: relato de experiencia

Este é um relato sobre uma experiência em saúde mental e trabalho no contexto de uma unidade da Saúde da Família, principal política para viabilizar a atenção básica no Sistema Único de Saúde. Foi desenvolvida durante um estágio de Psicologia. O objetivo foi relatar uma experiência numa unidade de Saúde da Família, com base em um diagnóstico organizacional com ênfase no trabalho do agente comunitário de saúde. O método foi a observação participante, seguida de dois encontros os quais possibilitaram reflexão sobre as dificuldades da equipe bem como a ampliação da discussão no âmbito da gestão. Os resultados mais relevantes foram proporcionados pelas reflexões sobre a potência da escuta qualificada nos atendimentos e no trabalho em equipe, possibilidades de apoio por meio do matriciamento e a importância da comunicação na relação com a gestão. A intervenção foi considerada positiva, pois abriu possibilidades favoráveis no trabalho, mesmo que de forma preliminar, com solicitações de continuidade do trabalho.

This is a report about an experience engaging both mental health and work in the context of a Family Health Unit, which is the main policy to enable basic health care in the Unified Health System. It was developed during a psychology internship. The objective was to report an experience in a Family Health unit, based on an organizational diagnosis with emphasis on the work of the community health agent. The method used was the participant observation, followed by two meetings, which allowed the reflection on the difficulties of the team, as well as the expansion of the discussion within the scope of management. The reflections on the power of qualified listening in the attendance and teamwork, along with the possibilities of support through the Matrix Support, and the importance of communication in relation to management provided the most relevant results. The intervention was considered positive, since it opened favorable possibilities at work, even preliminarily, with requests for the continuity of the work.

Este es un relato sobre una experiencia en salud mental y trabajo en el contexto de una unidad de Salud de la Familia, principal política para viabilizar la atención básica en el Sistema Único de Salud. Fue desarrollada durante una pasantía en psicología. El objetivo fue relatar una experiencia en una unidad de Salud de la Familia, a partir de un diagnóstico organizacional con énfasis en el trabajo del agente comunitario de salud. El método fue la observación participante, seguida de dos encuentros, que posibilitaron una reflexión sobre las dificultades del equipo, así como la ampliación de la discusión en el ámbito de la gestión. Los resultados más relevantes fueron proporcionados por las reflexiones sobre la potencia de la escucha calificada en las atenciones y en el trabajo en equipo, posibilidades de apoyo por medio del matriciamiento y la importancia de la comunicación en la relación con la gestión. La intervención fue considerada positiva, pues abrió posibilidades favorables en el trabajo, aunque de forma preliminar, con solicitudes de continuidad del trabajo.

Zebrafish (Danio rerio) water tank model for the investigation of drug metabolism: Progress, outlook, and challenges.

Zebrafish (Danio rerio) water tank (ZWT) approach was investigated as an alternative model for metabolism studies based on six different experiments with four model compounds. Sibutramine was applied for the multivariate optimization of ZWT conditions, also for the comparison of the metabolism among ZWT, humans and mice, beyond for the role of CYP2B6 in ZWT. After the optimization, 18 fish and 168 hours of experiments is the minimum requirement for a relevant panel of biotransformation products. A comparison among the species resulted in the observation of the same hydroxylated metabolites, with differences in metabolites concentration ratio. However, the ZWT allowed tuning of the conditions to obtain a specific metabolic profile, depending on the need. In addition, by utilizing CYP2B6 inhibition, a relevant ZWT pathway for the demethylation of drugs was determined. The stereospecificity of the ZWT metabolism was investigated using selegiline and no racemization or inversion transformations were observed. Moreover, the investigation of metabolism of cannabimimetics was performed using JWH-073 and the metabolites observed are the same described for humans, except for the hydroxylation at the indol group, which was explained by the absence of CYP2C9 orthologs in zebrafish. Finally, hexarelin was used as a model to evaluate studies by ZWT for drugs with low stability. As a result, hexarelin displays a very fast metabolization in ZWT conditions and all the metabolites described for human were observed in ZWT. Therefore, the appropriate conditions, merits, and relevant limitations to conduct ZWT experiments for the investigation of drug metabolism are described.

Ultrasound progression of prenatally detected multicystic dysplastic kidney.

OBJECTIVES: To evaluate the sonographic involution of prenatally detected multicystic dysplastic kidney (MCDK). METHODS: A total of 53 children with unilateral MCDK detected by prenatal ultrasonography between 1989 and 2004 were included in this analysis. All children received conservative management with follow-up visits every 6 months. Follow-up ultrasound examinations were performed at 6-month intervals during the first 2 years after birth and yearly thereafter. A linear mixed effect model was constructed, including MCDK length as the dependent variable and body size parameters and contralateral renal dimensions as independent variables. RESULTS: The mean follow-up time was 68 months. A total of 334 ultrasound scans were analyzed. The ultrasound scan demonstrated partial or total involution of the MCDK in 48 cases (91%). A consistent negative correlation was found among MCDK length, patient age, and body size parameters. As a whole, the MCDK length reduction was estimated to be 0.29 mm/mo. The rate of reduction was not constant over time and was intense during the first 30 months of age. According to the regression model, MCKD reduced in length by 0.80 mm/mo during the first 30 months of age, 0.26 mm between 30 and 84 months old, and 0.30 mm in children older than 84 months. CONCLUSIONS: Our results suggest a clear tendency of MCDK to decrease in size, with the rate of the involution greater during the first 30 months than the rate in older children.