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This study aimed to evaluate the safety and tolerability of STP1, a combination of ibudilast and bumetanide, tailored for the treatment of a clinically and biologically defined subgroup of patients with Autism Spectrum Disorder (ASD), namely ASD Phenotype 1 (ASD-Phen1). We conducted a randomized, double-blind, placebo-controlled, parallel-group phase 1b study with two 14-day treatment phases (registered at clinicaltrials.gov as NCT04644003). Nine ASD-Phen1 patients were administered STP1, while three received a placebo. We assessed safety and tolerability, along with electrophysiological markers, such as EEG, Auditory Habituation, and Auditory Chirp Synchronization, to better understand STP1's mechanism of action. Additionally, we used several clinical scales to measure treatment outcomes. The results showed that STP1 was well-tolerated, with electrophysiological markers indicating a significant and dose-related reduction of gamma power in the whole brain and in brain areas associated with executive function and memory. Treatment with STP1 also increased alpha 2 power in frontal and occipital regions and improved habituation and neural synchronization to auditory chirps. Although numerical improvements were observed in several clinical scales, they did not reach statistical significance. Overall, this study suggests that STP1 is well-tolerated in ASD-Phen1 patients and shows indirect target engagement in ASD brain regions of interest. [ABSTRACT FROM AUTHOR]

RESUMO: A espécie Leopardus pardalis, conhecida popularmente como jaguatirica, é um felino de médio porte com ampla distribuição em território nacional e está incluída na lista de espécies da fauna brasileira ameaçadas de extinção. Este estudo teve como objetivo caracterizar os aspectos macroscópicos e microscópico da traqueia e lobos pulmonares em L. pardalis. As análises foram feitas utilizando cinco exemplares de jaguatirica, sendo dois machos e três fêmeas, adultos, três desses exemplares foram a óbito por atropelamento em rodovias próximas ao município de Alta Floresta, e dois doados após a morte pelo IBAMA ao o Laboratório de Zoologia e Morfologia Animal. Nos espécimes a traqueia era um tubo flexível formado por pares de arcos cartilaginosos, apresentando epitélio pseudo-estratificado não ciliado no seu revestimento interno, e outros estruturas básicas deste órgão. O pulmão se mostrou como um órgão constituído por lobos separados por fissuras com um parênquima usual aos demais mamíferos descritos. No que diz respeito às caraterísticas anatômicas da traqueia e pulmão se mostraram semelhantes à de outros mamíferos, já nos aspectos microscópicos da traqueia apresentou certas peculiaridades diferindo dos demais trabalhos encontrados. No que tange o aspecto do parênquima pulmonar as características histológicas não variaram com as que estão descritas.

The Coordination for the Improvement of High Education Personnel (CAPES), the Brazilian federal agency for graduate programs, plays a fundamental role for the expansion and consolidation of the National Postgraduate System (SNPG) and the execution of the National Graduate Plan (PNPG) 2011-2020. In this paper, we discuss the evolution of the Brazilian graduate program in chemistry and its role in the formation of highly qualified professionals in chemistry (academic master’s degree, professional master’s degree and doctoral degree) for the academy, teachers and lecturers for all levels of the education system, as well for the non-academic market.

OBJECTIVES: The present study was designed to evaluate the bone phenotypes and mechanisms involved in bone disorders associated with hepatic osteodystrophy. Hepatocellular disease was induced by carbon tetrachloride (CCl4). In addition, the effects of disodium pamidronate on bone tissue were evaluated. METHODS: The study included 4 groups of 15 mice: a) C = mice subjected to vehicle injections; b) C+P = mice subjected to vehicle and pamidronate injections; c) CCl4+V = mice subjected to CCl4 and vehicle injections; and d) CCl4+P = mice subjected to CCl4 and pamidronate injections. CCl4 or vehicle was administered for 8 weeks, while pamidronate or vehicle was injected at the end of the fourth week. Bone histomorphometry and biomechanical analysis were performed in tibiae, while femora were used for micro-computed tomography and gene expression. RESULTS: CCl4 mice exhibited decreased bone volume/trabecular volume and trabecular numbers, as well as increased trabecular separation, as determined by bone histomorphometry and micro-computed tomography, but these changes were not detected in the group treated with pamidronate. CCl4 mice showed increased numbers of osteoclasts and resorption surface. High serum levels of receptor activator of nuclear factor-κB ligand and the increased expression of tartrate-resistant acid phosphatase in the bones of CCl4 mice supported the enhancement of bone resorption in these mice. CONCLUSION: Taken together, these results suggest that bone resorption is the main mechanism of bone loss in chronic hepatocellular disease in mice.