Fluvoxamine alters the activity of energy metabolism enzymes in the brain

Objective: Several studies support the hypothesis that metabolism impairment is involved in the pathophysiology of depression and that some antidepressants act by modulating brain energy metabolism. Thus, we evaluated the activity of Krebs cycle enzymes, the mitochondrial respiratory chain, and creatine kinase in the brain of rats subjected to prolonged administration of fluvoxamine. Methods: Wistar rats received daily administration of fluvoxamine in saline (10, 30, and 60 mg/kg) for 14 days. Twelve hours after the last administration, rats were killed by decapitation and the prefrontal cortex, cerebral cortex, hippocampus, striatum, and cerebellum were rapidly isolated. Results: The activities of citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV were decreased after prolonged administration of fluvoxamine in rats. However, the activities of complex II, succinate dehydrogenase, and creatine kinase were increased. Conclusions: Alterations in activity of energy metabolism enzymes were observed in most brain areas analyzed. Thus, we suggest that the decrease in citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV can be related to adverse effects of pharmacotherapy, but long-term molecular adaptations cannot be ruled out. In addition, we demonstrated that these changes varied according to brain structure or biochemical analysis and were not dose-dependent

Molecular epidemiological investigation of Mayaro virus in febrile patients from Goiania City, 2017-2018.

Mayaro virus (MAYV) has historically been associated with sylvatic transmission; however, urban outbreaks have been reported in Brazil, including cases of co-detection with dengue virus (DENV). Therefore, we performed a molecular survey to investigate MAYV circulation and cocirculation with DENV within Goiania, a major city in Central-West Brazil. Among 375 subjects with arbovirus-like symptoms, 259 were positive for DENV and 26 for MAYV. Of these, 17 were coinfected with DENV-2, suggesting co-transmission of the viruses. The most common complaints at the time of inclusion were myalgia, headache, fever, arthralgia, retro-orbital pain, and skin rash. No specific symptoms were associated with MAYV when either detected alone or co-detected with DENV, compared to that when DENV was detected alone. Most MAYV-infected subjects were women with no recent travel history to rural/sylvatic areas. Phylogenetic reconstruction indicated that the MAYV identified in this study is closely related with a lineage observed in Peru, belonging to genotype D. Our results corroborate the growing circulation of MAYV in urban environments in Brazil and reinforce the need to implement laboratory diagnosis in the Unified Health System, considering that the clinical manifestations of Mayaro fever are similar to those of other arboviruses, particularly dengue. Furthermore, most cases occurred in association with DENV-2. Further phylogenetic studies are needed to evaluate MAYV, which has not been widely examined

Genomic history of coastal societies from eastern South America

Sambaqui (shellmound) societies are among the most intriguing archaeological phenomena in pre-colonial South America, extending from approximately 8,000 to 1,000 years before present (yr bp) across 3,000 km on the Atlantic coast. However, little is known about their connection to early Holocene hunter-gatherers, how this may have contributed to different historical pathways and the processes through which late Holocene ceramists came to rule the coast shortly before European contact. To contribute to our understanding of the population history of indigenous societies on the eastern coast of South America, we produced genome-wide data from 34 ancient individuals as early as 10,000 yr bp from four different regions in Brazil. Early Holocene hunter-gatherers were found to lack shared genetic drift among themselves and with later populations from eastern South America, suggesting that they derived from a common radiation and did not contribute substantially to later coastal groups. Our analyses show genetic heterogeneity among contemporaneous Sambaqui groups from the southeastern and southern Brazilian coast, contrary to the similarity expressed in the archaeological record. The complex history of intercultural contact between inland horticulturists and coastal populations becomes genetically evident during the final horizon of Sambaqui societies, from around 2,200 yr bp, corroborating evidence of cultural change

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Fluvoxamine alters the activity of energy metabolism enzymes in the brain

Objective: Several studies support the hypothesis that metabolism impairment is involved in the pathophysiology of depression and that some antidepressants act by modulating brain energy metabolism. Thus, we evaluated the activity of Krebs cycle enzymes, the mitochondrial respiratory chain, and creatine kinase in the brain of rats subjected to prolonged administration of fluvoxamine. Methods: Wistar rats received daily administration of fluvoxamine in saline (10, 30, and 60 mg/kg) for 14 days. Twelve hours after the last administration, rats were killed by decapitation and the prefrontal cortex, cerebral cortex, hippocampus, striatum, and cerebellum were rapidly isolated. Results: The activities of citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV were decreased after prolonged administration of fluvoxamine in rats. However, the activities of complex II, succinate dehydrogenase, and creatine kinase were increased. Conclusions: Alterations in activity of energy metabolism enzymes were observed in most brain areas analyzed. Thus, we suggest that the decrease in citrate synthase, malate dehydrogenase, and complexes I, II-III, and IV can be related to adverse effects of pharmacotherapy, but long-term molecular adaptations cannot be ruled out. In addition, we demonstrated that these changes varied according to brain structure or biochemical analysis and were not dose-dependent

Sports Stars Brazil in children with autism spectrum disorder: A feasibility randomized controlled trial protocol.

BackgroundAutism Spectrum Disorder (ASD) children have lower levels of participation in recreational and sporting activities when compared to their peers. Participation has been defined based on the Family of Participation-Related Constructs (fPRC) which defines participation as including both attendance and involvement, with sense of self, preferences and activity competence related to a child's participation. Modified sports interventions such as Sports Stars can act on physical literacy and some of the fPRCs components. This study aims to assess the feasibility of the Sports Stars Brazil intervention for children with ASD.MethodsThis study will be conducted with 36 participants with ASD aged 6 to 12 years old following the CONSORT for pilot and feasibility recommendation. Participants will be randomly allocated into two groups. Intervention group will receive eight, weekly Sports Stars sessions. Each session will include of sports-focused gross motor activity training, confidence building, sports-education and teamwork development. Study assessments will occur at baseline, immediately post-intervention and 20-weeks post-randomization. First, we will assess process feasibility measures: recruitment, assessment completion, adherence, adverse events and satisfaction. Second, we will investigate the scientific feasibility of the intervention by estimating the effect size and variance at the level of achievement sports-related activity and physical activity participation goals (Goal Attainment Scaling), activity competence (Ignite Challenge, Test of Gross Motor Development-second edition, Physical Literacy Profile Questionnaire, Pediatric Disability Assessment Inventory-Computer Adaptive Test-PEDI-CAT-mobility, 10×5 Sprint Test and Muscle Power Sprint Test), sense of self (PEDI-CAT-responsibility), and overall participation at home, school and community, (Participation and Environment Measure for children and young people, PEM-CY).DiscussionThe results of this feasibility study will inform which components are critical to planning and preparing a future RCT study, aiming to ensure that the RCT will be feasible, rigorous and justifiable.Trial registrationThe trial was registered with the Brazilian Registry of Clinical Trials database (ID: RBR-9d5kyq4) on June 15, 2022

Evaluation of Na+, K+-ATPase activity in the brain of young rats after acute administration of fenproporex

Objectives: Fenproporex is an amphetamine-based anorectic which is rapidly converted into amphetamine in vivo. Na+, K+-ATPase is a membrane-bound enzyme necessary to maintain neuronal excitability. Considering that the effects of fenproporex on brain metabolism are poorly known and that Na+, K+-ATPase is essential for normal brain function, this study sought to evaluate the effect of this drug on Na+, K+-ATPase activity in the hippocampus, hypothalamus, prefrontal cortex, and striatum of young rats. Methods: Young male Wistar rats received a single injection of fenproporex (6.25, 12.5, or 25 mg/kg intraperitoneally) or polysorbate 80 (control group). Two hours after the last injection, the rats were killed by decapitation and the brain was removed for evaluation of Na+, K+-ATPase activity. Results: Fenproporex decreased Na+, K+-ATPase activity in the striatum of young rats at doses of 6.25, 12.5, and 25 mg/kg and increased enzyme activity in the hypothalamus at the same doses. Na+, K+-ATPase activity was not affected in the hippocampus or prefrontal cortex. Conclusion: Fenproporex administration decreased Na+, K+-ATPase activity in the striatum even in low doses. However, in the hypothalamus, Na+, K+-ATPase activity was increased. Changes in this enzyme might be the result of the effects of fenproporex on neuronal excitability