Malnutrition during central nervous system growth and development impairs permanently the subcortical auditory pathway.

The brain that grows and develops under the continued influence of malnutrition presents permanent impairment on functioning and neurotransmitter release. The aim of this study was to investigate the chronic effects of neonatal food restriction on neurochemical and neurodynamical aspects within the primary auditory sensory pathway. Our working hypothesis is that neonatal malnutrition may affect the flow of primary sensory information both at a neurochemical and neurodynamical level. To test this hypothesis, three groups of rats were assigned, from birth to 370 days of life, to the following dietary scheme: a wellnourished (WN) group fed ad libitum lab chow diet; an undernourished (UN) group fed 60% of diet consumed by WN group; and a rehabilitated group, undergoing same dietary restriction as undernourished until 42 days of age and thereafter fed ad libitum until the end of the experiment. At 370 days of age, the animals were submitted to brainstem auditory-evoked potentials (BAEPs) recordings and sacrificed for neurochemical evaluation of glutamate release. Undernutrition decreased glutamate release in the cortex, hippocampus, midbrain and brainstem, and significantly increased the latency of BAEP wave V. In addition; the re-establishment of the dietary conditions was not sufficient to reverse the neurochemical and electrophysiological alterations observed in the UN group. Taken altogether, our results suggest that malnutrition imposed at a critical development period caused an irreversible effect within the auditory primary sensory pathway

Randomized, phase 1/2, double-blind pioglitazone repositioning trial combined with antifungals for the treatment of cryptococcal meningitis – PIO study

Background: Cryptococcosis affects more than 220,000 patients/year, with high mortality even when the standard treatment [amphotericin B (AMB), 5-flucytosin (5-FC) and fluconazole] is used. AMB presents high toxicity and 5-FC is not currently available in Brazil. In a pre-clinical study, pioglitazone (PIO - an antidiabetic drug) decreased AMB toxicity and lead to an increased mice survival, reduced morbidity and fungal burden in brain and lungs. The aim of this trial is to evaluate the efficacy and safety of PIO combined with standard antifungal treatment for human cryptococcosis. Methods: A phase 1/2, randomized, double blind, placebo-controlled trial will be performed with patients from Belo Horizonte, Brazil. They will be divided into three groups (placebo, PIO 15 mg/day or PIO 45 mg/day) and will receive an additional pill during the induction phase of cryptococcosis’ treatment. Our hypothesis is that treated patients will have increased survival, so the primary outcome will be the mortality rate. Patients will be monitored for survival, side effects, fungal burden and inflammatory mediators in blood and cerebrospinal fluid. The follow up will occur for up 60 days. Conclusions: We expect that PIO will be an adequate adjuvant to the standard cryptococcosis’ treatment. Trial registration: ICTRP/WHO (and International Clinical Trial Registry Plataform (ICTRP/WHO) (http://apps.who.int/trialsearch/Trial2.aspx?TrialID=RBR-9fv3f4), RBR-9fv3f4 (http://www.ensaiosclinicos.gov.br/rg/RBR-9fv3f4). UTN Number: U1111-1226-1535. Ethical approvement number: CAAE 17377019.0.0000.5149

Immunostimulatory property of a synthetic peptide belonging to the soluble ATP diphosphohydro-lase isoform (SmATPDase 2) and immunolocalisation of this protein in the Schistosoma mansoni egg

A peptide (SmB2LJ; r175-194) that belongs to a conserved domain from Schistosoma mansoni SmATPDase 2 and is shared with potato apyrase, as predicted by in silico analysis as antigenic, was synthesised and its immunostimulatory property was analysed. When inoculated in BALB/c mice, this peptide induced high levels of SmB2LJ-specific IgG1 and IgG2a subtypes, as detected by enzyme linked immunosorbent assay. In addition, dot blots were found to be positive for immune sera against potato apyrase and SmB2LJ. These results suggest that the conserved domain r175-194 from the S. mansoni SmATPDase 2 is antigenic. Western blots were performed and the anti-SmB2LJ antibody recognised in adult worm (soluble worm antigen preparation) or soluble egg antigen antigenic preparations two bands of approximately 63 and 55 kDa, molecular masses similar to those predicted for adult worm SmATPDase 2. This finding strongly suggests the expression of this same isoform in S. mansoni eggs. To assess localisation of SmATPDase 2, confocal fluorescence microscopy was performed using cryostat sections of infected mouse liver and polyclonal antiserum against SmB2LJ. Positive reactions were identified on the external surface from the miracidium in von Lichtenberg's envelope and, in the outer side of the egg-shell, showing that this soluble isoform is secreted from the S. mansoni eggs

Uma história de conceitos na saúde pública: integralidade, coordenação, descentralização, regionalização e universalidade A history of public health concepts: integrity, coordination, decentralization, regionalization, and universality

O Sistema Único de Saúde conferiu visibilidade a uma série de conceitos próprios da organização de sistemas de saúde. Entre eles a integralidade, que delimita fronteiras comuns com quase todos os demais princípios do Sistema, tem sido objeto de ampla literatura no Brasil. Com base em extensa revisão de fontes primárias e secundárias, este artigo apresenta uma recuperação histórica dos conceitos de integralidade, descentralização, regionalização e universalidade - ideias e conceitos que em grande parte se conformam e se interligam no ideário da organização dos serviços sanitários pelo modelo dos Centros de Saúde distritais.<br>Brazil's Unified Health System (Sistema Único de Saúde) has highlighted a series of concepts specific to the organization of healthcare systems. Among these, integrity - which shares boundaries with almost all other System principles - has been the object of much academic production in Brazil. Based on an extensive review of primary and secondary sources, the article offers a historical recovery of the concepts of integrity, decentralization, regionalization, and universality - ideas and concepts that in good measure are shaped by and interlinked with the set of ideals of the organization of sanitary services according to the district health centers model