Impacto da administração de medicamento psicoestimulante e de doença negligenciada na saúde: efeitos cardiovasculares do dimesilato de lisdexanfetamina e da dinâmica espaço temporal da mortalidade por Leishmaniose Visceral no Brasil

Abstract

Human health is influenced by various factors that can affect disease development and population quality of life. Among these, the administration of pharmacological substances during critical periods of development and the persistence of infectious diseases associated with contexts of vulnerability are particularly noteworthy. In this context, the present thesis brought together evidence on two important health conditions: the cardiovascular effects associated with the administration of lisdexamfetamine dimesylate during the juvenile-pubertal period and the spatiotemporal patterns of visceral leishmaniasis mortality in Brazil. The first study investigated the cardiac effects of lisdexamfetamine dimesylate administration during the juvenile and peripubertal periods in Wistar rats. Components of the NADPH oxidase complex, oxidative stress biomarkers, MAPK pathway proteins, and histological parameters of the left ventricle were evaluated. Reduced gene expression of NOX4, p22phox, and p47phox was observed, with no changes in oxidative stress biomarkers. Additionally, increased p38-MAPK protein expression, greater deposition of type I and type III collagen, and increased nuclear fractal dimension of cardiomyocytes were detected. These findings demonstrate that juvenile-pubertal lisdexamfetamine dimesylate administration promotes molecular and structural cardiac remodeling associated with modulation of redox signaling pathways and extracellular matrix remodeling. The second study analyzed the temporal and spatial distribution of visceral leishmaniasis mortality in Brazil between 2015 and 2024 using data from the Mortality Information System (SIM/DATASUS). A total of 816 deaths were recorded during the study period, with a significant downward trend in mortality rates. Despite this decline, mortality remained heterogeneously distributed across the country, with persistent high-risk areas concentrated in the North and Northeast regions. Mortality was more frequent among males and individuals aged 20 to 59 years. Spatial analyses identified persistent clusters in historically vulnerable states, highlighting regional inequalities associated with the occurrence of the disease. Although they address different health problems, both studies contribute to understanding factors that may influence the health–disease process, either through biological changes resulting from the administration of pharmacological substances during development or through the persistence of infectious diseases associated with contexts of population vulnerability. The findings provide evidence that may support health decision-making, contributing to the monitoring of pharmacological therapy safety, the guidance of epidemiological surveillance actions, and the development of public policies aimed at disease prevention, health promotion, and the reduction of regional health inequalities.