Permitted daily exposure from preclinical studies of Ginkgo biloba L. dry extract

Abstract Resolution 658/2022 of the Brazilian Regulatory Agency requires the determination of the permitted daily exposure (PDE) of pharmaceutical agents. Ginkgo biloba L. is used therapeutically to treat memory deficits and other brain diseases. However, published results indicate that more studies are needed to confirm the safety of Ginkgo biloba. This study aimed to evaluate the dry extract of Ginkgo biloba L. leaves PDE as an ingredient in an oral pharmaceutical product in preclinical studies using mice. Acute oral toxicity and repeated dose experiments were performed based on OECD guidelines, as well as genotoxicity tests. The results indicate that Ginkgo biloba L. has low acute toxicity, no liver toxicity, and does not alter blood glucose levels. No changes in weight gain were observed, but food intake decreased in males during the first week of treatment at the highest dose. Hematological parameters were not altered in males, whereas females presented lower leukocyte and lymphocyte counts and higher neutrophil counts at the highest dose. The lipid profile was not altered in males, whereas total cholesterol was increased in females. The estimated PDE was 0.1 mg/day and, when related to the maximum residual concentration, indicates that the cleaning process used is safe and does not require reassessment.

Cytotoxicity evaluation of haloperidol, clozapine and a new molecule with antipsychotic potential, PT-31, in NIH-3T3 cells

Abstract Schizophrenia is an illness that affects 26 million people worldwide. However, conventional antipsychotics present side effects and toxicity, highlighting the need for new antipsychotics. We aimed to evaluate the cytotoxicity of haloperidol (HAL), clozapine (CLO), and a new molecule with antipsychotic potential, PT-31, in NIH-3T3 cells. The neutral red uptake assay and the MTT assay were performed to evaluate cell viability and mitochondrial activity, morphological changes were assessed, and intracellular reactive oxygen species (ROS) detection was performed. HAL and CLO (0.1 µM) showed a decrease in cell viability in the neutral red uptake assay and in the MTT assay. In addition, cell detachment, content decrease, rounding and cell death were also observed at 0.1 µM for both antipsychotics. An increase in ROS was observed for HAL (0.001, 0.01 and 1 µM) and CLO (0.01 and 1 µM). PT-31 did not alter cell viability in any of the assays, although it increased ROS at 0.01 and 1 µM. HAL and CLO present cytotoxicity at 0.1 µM, possibly through apoptosis and necrosis. In contrast, PT-31 does not present cytotoxicity to NIH-3T3 cells. Further studies must be performed for a better understanding of these mechanisms and the potential risk of conventional antipsychotics

Analysis of Adherence to Fluoxetine Treatment through its Plasma Concentration

Abstract Depression plays an important role in non-adherence to medical recommendations. Fluoxetine is a first line of depression treatment. This study aimed to evaluate adherence to drug therapy in fluoxetine users by different methods. A cross-section study was conducted with 53 depressed patients on fluoxetine for at least six months. Drug therapy adherence was assessed by validated questionnaires [Brief Medication Questionnaire (BMQ) and Morisky-Green test (MG)] and by the blood concentration of fluoxetine and its active metabolite norfluoxetine. Blood samples were taken before the daily first dose of fluoxetine. The plasmatic concentration of fluoxetine and norfluoxetine indicated that 58.5% volunteers were within the recommended therapeutic range and thus considered adherent to drug therapy. However, questionnaires indicated a non-adherent majority: 41.5% patients had a high degree of adherence in MG and only 13.2% were adherent to pharmacological treatment in BMQ. Most fluoxetine users showed a plasma concentration of fluoxetine and norfluoxetine within the therapeutic range, despite the low adherence to the drug therapy evaluated by the questionnaires. Thus, we suggest that plasma levels of fluoxetine and norfluoxetine could be used as the main method to check adherence to treatment.

Abreviação do jejum: aspectos clínicos perioperatórios de pacientes submetidos à cirurgia cardíaca / Reduced preoperative fasting time: the perioperative clinical aspects related to cardiac surgical patients

Introdução: A cirurgia cardíaca é realizada quando a probabilidade de uma vida útil de um paciente é maior com o tratamento cirúrgico do que com o clínico. Na cirurgia ocorre a resposta metabólica ao trauma, que é potencializada pelo jejum pré-operatório prolongado. O objetivo deste estudo foi analisar o comportamento dos pacientes submetidos à cirurgia cardíaca com abreviação do jejum pré-operatório a partir da administração de suplemento nutricional oral com carboidratos e proteínas. Método: Realizada uma pesquisa do tipo estudo de caso na Unidade de Terapia Intensiva Adulta de um Hospital Público da região metropolitana de Porto Alegre, Rio Grande do Sul. Os casos analisados foram de pacientes que realizaram abreviação de jejum pré-operatório de cirurgia cardíaca, no período de outubro a novembro de 2015. Resultados: Avaliados três pacientes, do sexo masculino, com idade entre 47 e 73 anos, que realizaram cirurgia cardíaca com abreviação do jejum pré-operatório três horas antes da cirurgia com suplemento nutricional com carboidrato e proteína, isento de lipídeos e fibras. Dois pacientes apresentaram complicações pós-operatórias, não relacionadas à abreviação do jejum. A média da glicemia capilar pós-operatória foi de 112 mg/dl. Não houve casos de broncoaspiração, náuseas ou vômitos. O tempo médio de internação hospitalar foi de 7,8 dias. Conclusão: A abreviação do jejum pré-operatório em cirurgia cardíaca é relevante para melhorar o desfecho do paciente cirúrgico, em função da melhoria do perfil glicêmico, redução da resposta metabólica ao trauma, maior satisfação do paciente, menor tempo de internação hospitalar e consequente redução dos custos.(AU)

Introduction: Cardiac surgery is performed when the likelihood of life span of a patient is higher with surgery than with medical treatment. During surgery, the metabolic response to trauma takes place, which is enhanced by prolonged preoperative fasting. The objective of this study was to analyze the behavior of patients undergoing cardiac surgery with abbreviation of preoperative fasting from oral nutritional supplement administration with carbohydrates and protein. Methods: We conducted a case study research at the Adult Intensive Care Unit (ICU) of a public hospital located in the metropolitan area of Porto Alegre, Rio Grande do Sul, Brazil. We analyzed cases from patients undergoing reduced preoperative fasting time prior to cardiac surgery during the months of October and November 2015. Results: We evaluated three male patients, aged 47 to 73 years old. Three hours prior to surgery they were given a carbohydrate and protein enriched nutritional supplement, which was lipid and fiber free. Two of the patients had postoperative complications unrelated to the reduced fasting time. The average postoperative blood glucose was 112 mg/dl. There were no cases of pulmonary aspiration, nausea, or vomiting. The average hospital stay was 7.8 days. Conclusion: The reduction of preoperative fasting time in cardiac surgery appears to improve the outcome of surgical patients. This is shown here by the improved glucose profiles; reduced metabolic response to trauma; patient satisfaction; shorter hospital stay; and cost reduction observed.(AU)

Plantas utilizadas na medicina popular brasileira com potencial atividade antifúngica / Plants with potencial antifungal activity employed in Brazilian folk medicine

Neste trabalho foi realizado um levantamento bibliográfico etnobotânico sobre plantas utilizadas pela população brasileira no tratamento de sinais e sintomas relacionados às infecções fúngicas. Foram citadas 409 espécies, distribuídas em 98 famílias, com maior concentração em Fabaceae e Asteraceae. Para as dez espécies mais citadas, foi realizada uma busca relativa a estudos de atividade antifúngica na base de dados MEDLINE-PubMed. Somente foram encontrados estudos para Phytolacca americana L., Rosmarinus officinalis L., Mirabilis jalapa L., Schinus molle L. Entre as dez espécies mais utilizadas, seis correspondem a espécies nativas: Anacardium occidentale L., Cecropia peltata L., Schinus molle L., Schinus terebinthinfolius Raddi, Stryphnodendron adstringens (Mart.) Coville e Tabebuia heptaphylla (Vell.) Toledo.

The aim of this work was to draw up a list of plants used by Brazilian population for the treatment of signs and symptoms related to fungal infections and to verify the existence of scientific data related to the antifungal activity in the databasis MEDLINE-PubMed. Four hundread and nine species were listed, which are distributed in ninety eight families, mainly Fabaceae and Asteraceae. Among the more frequently mentioned species (10), only four were evaluated regarding to the antifungal activity: Phytolacca americana L., Rosmarinus officinalis L., Mirabilis jalapa L. and Schinus molle L. From those ten species, six are native (Anacardium occidentale L., Cecropia peltata L., Schinus molle L., Schinus terebinthifolius Raddi, Stryphnodendron adstringens (Mart.) Coville e Tabebuia heptaphylla (Vell.) Toledo.