Analgesic-like activity of perillyl acetate: In vivo and in silico studies

Objective: To evaluate the antinociceptive activity of perillyl acetate in mice and in silico simulations. Methods: The vehicle, perillyl acetate (100, 150 and/or 200 mg/kg, i.p.), diazepam (2 mg/kg, i.p.) or morphine (6 mg/kg, i.p.) was administered to mice, respectively. Rotarod test, acetic acid-induced abdominal writhing, formalin-induced nociception, hot plate test, and tail-flick test were performed. Opioid receptors-involvement in perillyl acetate antinociceptive effect was also investigated. Results: Perillyl acetate did not affect the motor coordination of mice. However, it reduced the number of acetic acid-induced abdominal twitches and licking times in the formalin test. There was an increase of latency time in the tail-flick test of 30 and 60 minutes. Pretreatment with naloxone reversed the antinociceptive effect of perillyl acetate (200 mg/kg). In silico analysis demonstrated that perillyl acetate could bind to μ-opioid receptors. Conclusions: Perillyl acetate has antinociceptive effect at the spinal level in animal nociception models, without affecting the locomotor integrity and possibly through μ-opioid receptors. In silico studies have suggested that perillyl acetate can act as a μ-opioid receptor agonist.

Analgesic-like activity of perillyl acetate: In vivo and in silico studies

Objective: To evaluate the antinociceptive activity of perillyl acetate in mice and in silico simulations. Methods: The vehicle, perillyl acetate (100, 150 and/or 200 mg/kg, i.p.), diazepam (2 mg/kg, i.p.) or morphine (6 mg/kg, i.p.) was administered to mice, respectively. Rotarod test, acetic acid-induced abdominal writhing, formalin-induced nociception, hot plate test, and tail-flick test were performed. Opioid receptors-involvement in perillyl acetate antinociceptive effect was also investigated. Results: Perillyl acetate did not affect the motor coordination of mice. However, it reduced the number of acetic acid-induced abdominal twitches and licking times in the formalin test. There was an increase of latency time in the tail-flick test of 30 and 60 minutes. Pretreatment with naloxone reversed the antinociceptive effect of perillyl acetate (200 mg/kg). In silico analysis demonstrated that perillyl acetate could bind to μ-opioid receptors. Conclusions: Perillyl acetate has antinociceptive effect at the spinal level in animal nociception models, without affecting the locomotor integrity and possibly through μ-opioid receptors. In silico studies have suggested that perillyl acetate can act as a μ-opioid receptor agonist.

Estratificação de territórios prioritários para vigilância da doença de Chagas crônica: análise multicritério para tomada de decisão em saúde / Stratification of priority territories for surveillance of chronic Chagas disease: multicriteria analysis for decision-making in health / Estratificación de territorios prioritarios para la vigilancia de la enfermedad de Chagas crónica: análisis multicriterio para la toma de decisión en salud

Para o reconhecimento da magnitude da doença de Chagas crônica no Brasil, é necessário rearticular as ações de vigilância em saúde, buscando o desenvolvimento de uma ampla rede hierarquizada de serviços distribuída geograficamente, para prover atendimento aos milhares de cidadãos acometidos pela infecção por Trypanosoma cruzi. O objetivo do trabalho foi elaborar um modelo de priorização de municípios para a vigilância da doença de Chagas crônica, a fim de ofertar cuidado integral às pessoas afetadas pela enfermidade. Para isso, foi realizada uma análise multicritério utilizando o algoritmo PROMETHEÉ II implementado no software Pradin. Os critérios de avaliação do modelo foram compostos de três índices construídos a partir de indicadores (a) epidemiológicos diretamente relacionados à doença de Chagas crônica, (b) decorrentes da evolução da doença de Chagas crônica, e (c) relacionados ao acesso aos serviços de saúde. A Escala Fundamental de Saaty foi utilizada para definição dos pesos dos indicadores, com maior importância aos diretamente relacionados à doença de Chagas crônica e àqueles com maior confiabilidade e respectiva qualidade de informação. A avaliação da consistência dos modelos se deu em comparação com dados disponíveis das áreas historicamente endêmicas, com a distribuição de casos agudos, e outras análises de sensibilidade. O modelo mais adequado foi definido por 1.345 municípios de média prioridade, 1.003 de alta e 601 como muito alta prioridade para doença de Chagas crônica, com maiores proporções nas regiões Sudeste e Nordeste. A priorização permite à gestão racionalizar e direcionar recursos, sendo essencial para identificar os territórios onde as pessoas infectadas estão vivendo, a fim de promover a assistência integral e melhorar a qualidade de vida.

The identification of the magnitude of chronic Chagas disease in Brazil requires linking activities in health surveillance, seeking to develop a wide, hierarchically organized and geographically distributed network of services to provide care to thousands of individuals with Trypanosoma cruzi infection. The study aimed to elaborate a model for prioritization of municipalities for chronic Chagas disease, to offer comprehensive care for persons with the disease. A multicriteria analysis was thus performed using the PROMETHEÉ II algorithm, implemented in the Pradin software. The criteria for assessing the model consisted of three indices built from the following indicators: (a) epidemiological, directly related to chronic Chagas disease, (b) related to the evolution in chronic Chagas disease, and (c) related to access to health services. Saaty's Fundamental Scale was used to define the indicators' weights, with greater importance assigned to those directly related to chronic Chagas disease and to those with greater reliability and respective quality of information. Assessment of the models' consistency was based on comparison of the available data in historically endemic areas with the distribution of acute cases, besides other sensitivity analyses. The best model was defined by 1,345 municipalities with medium priority, 1,003 high priority, and 601 with very high priority for chronic Chagas disease, with the highest proportions in the Southeast and Northeast regions. Prioritization allows the administration to rationalize and channel resources, and it is essential to identify the territories where persons with chronic Chagas disease are living, to promote comprehensive care and improve quality of life.

Para el reconocimiento de la magnitud de la enfermedad de Chagas crónica en Brasil, es necesario rearticular las acciones de vigilancia en salud, buscando el desarrollo de una amplia red jerarquizada de servicios distribuida geográficamente, para proveer atención a los millares de ciudadanos afectados por la infección por Trypanosoma cruzi. El objetivo del trabajo fue elaborar un modelo de priorización de municipios para la vigilancia de la enfermedad de Chagas crónica, con el fin de ofertar cuidado integral a las personas afectadas por la enfermedad. Para eso, se realizó un análisis multicriterio, utilizando el algoritmo PROMETHEÉ II, implementado en el software Pradin. Los criterios de evaluación del modelo estuvieron compuestos por tres índices construidos a partir de indicadores (a) epidemiológicos directamente relacionados con la enfermedad de Chagas crónica, (b) derivados de la evolución de la enfermedad de Chagas crónica y, (c) relacionados con el acceso a los servicios de salud. La Escala Fundamental de Saaty se utilizó para la definición de los pesos de los indicadores, con mayor importancia a los directamente relacionados con la enfermedad de Chagas crónica y aquellos con mayor confiabilidad, así como su respectiva calidad de información. La evaluación de la consistencia de los modelos se consiguió en comparación con los datos disponibles de las áreas históricamente endémicas, con la distribución de casos agudos, y otros análisis de sensibilidad. El modelo más adecuado se definió por 1.345 municipios de media prioridad, 1.003 de alta y 601 como mucho alta prioridad para enfermedad de Chagas crónica, con mayores proporciones en las regiones Sudeste y Nordeste. La priorización permite a las áreas de gestión racionalizar y dirigir recursos, y es esencial para identificar los territorios donde estas personas están viviendo, con el fin de promover la asistencia integral y mejorar la calidad de vida.

Identification of the sentinel lymph node using hemosiderin in locally advanced breast cancer / Identificação do linfonodo sentinela utilizando hemossiderina em casos de câncer de mama localmente avançado

ABSTRACT Objective: to verify the agreement rate in the identification of sentinel lymph node using an autologous marker rich in hemosiderin and 99 Technetium (Tc99) in patients with locally advanced breast cancer. Methods: clinical trial phase 1, prospective, non-randomized, of 18 patients with breast cancer and clinically negative axilla stages T2=4cm, T3 and T4. Patients were submitted to sub-areolar injection of hemosiderin 48 hours prior to sentinel biopsy surgery, and the identification rate was compared at intraoperative period to the gold standard marker Tc99. Agreement between methods was determined by Kappa index. Results: identification rate of sentinel lymph node was 88.9%, with a medium of two sentinel lymph nodes per patients. The study identified sentinel lymph nodes stained by hemosiderin in 83.3% patients (n=15), and, compared to Tc99 identification, the agreement rate was 94.4%. Conclusion: autologous marker rich in hemosiderin was effective to identify sentinel lymph nodes in locally advanced breast cancer patients.

RESUMO Objetivo: verificar a taxa de concordância na identificação do linfonodo sentinela utilizando um marcador autólogo rico em hemossiderina e o Tecnécio 99 (Tc99) em casos de câncer de mama localmente avançados. Métodos: ensaio clínico fase 1, do tipo prospectivo, não randomizado, em 18 pacientes portadoras de câncer de mama com axila clinicamente negativa em estádio T2=4cm, T3 e T4. As pacientes foram submetidas à injeção subareolar de um marcador autólogo rico em hemossiderina 48 horas antes do procedimento cirúrgico para biópsia do linfonodo sentinela, e sua taxa de identificação foi comparada, no intraoperatório, com o marcador radioativo Tc99 (padrão-ouro). A concordância entre os métodos foi estabelecida pelo índice de Kappa. Resultados: a taxa de identificação do linfonodo sentinela foi de 88,9%, com uma média de dois linfonodos sentinelas por paciente. O estudo identificou os linfonodos sentinelas corados com hemossiderina em 83,3% dos casos (n=15), quando comparados com a taxa de identificação do Tc99, tendo sido observada concordância em 94,4% dos casos estudados. Conclusão: o marcador autólogo rico em hemossiderina se mostrou eficaz na identificação do linfonodo sentinela em casos de câncer de mama localmente avançado.

II Consenso Brasileiro em Doença de Chagas, 2015 / Brazilian Consensus on Chagas Disease, 2015

A doença de Chagas é uma condição crônica negligenciada com elevada carga de morbimortalidade e impacto dos pontos de vista psicológico, social e econômico. Representa um importante problema de saúde pública no Brasil, com diferentes cenários regionais. Este documento traduz a sistematização das evidências que compõe o Consenso Brasileiro de Doença de Chagas. O objetivo foi sistematizar estratégias de diagnóstico, tratamento, prevenção e controle da doença de Chagas no país, de modo a refletir as evidências científicas disponíveis. Sua construção fundamentou-se na articulação e contribuição estratégica de especialistas brasileiros com conhecimento, experiência e atualização sobre diferentes aspectos da doença. Representa o resultado da estreita colaboração entre a Sociedade Brasileira de Medicina Tropical e o Ministério da Saúde. Espera-se com este documento fortalecer o desenvolvimento de ações integradas para enfrentamento da doença no país com foco em epidemiologia, gestão, atenção integral (incluindo famílias e comunidades), comunicação, informação, educação e pesquisas.

Chagas disease is a neglected chronic condition that presents high morbidity and mortality burden, with considerable psychological, social, and economic impact. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on collaboration and contribution of renowned Brazilian experts with vast knowledge and experience on various aspects of the disease. It is the result of close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. This document shall strengthen the development of integrated control measures against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research.

Comparison between hemosiderin and Technetium-99 in sentinel lymph node biopsy in human breast cancer

PURPOSE: To assess the safety and potential equivalence of the use of hemosiderin compared to the Technetium-99 in sentinel lymph node biopsy in human breast cancer. METHODS: Non-random sample of 14 volunteer women diagnosed with breast cancer with primary tumors (T1/T2) and clinically tumor-free axilla were submitted to the identification of sentinel lymph node using hemosiderin obtained from autologous blood injected in the periareolar region 24h before surgery on an outpatient basis. Patients received preoperative subareolar intradermal injection of Technetium-99 in the immediate preoperative period. Patients were submitted to sentinel lymph node biopsy, with incision in the axillary fold guided by Gamma-Probe, dissection by planes until the identification of the point of maximum uptake of Technetium-99, identifying the marked nodes and their colors. All surgical specimens were sent for pathological and immunohistochemical study. RESULTS: The results showed no evidence of side effects and/or allergic and non-allergic reactions in patients submitted to SLNB with hemosiderin. The SLN identification rate per patient was 100%. SLNB identification rate per patient with hemosiderin was the same as that of Technetium, with a concordance rate of 100% between the methods. CONCLUSION: Hemosiderin is a safe dye that is equivalent to Technetium in breast sentinel lymph node biopsy.