Adolescent Stress-Induced Ventral Hippocampus Redox Dysregulation Underlies Behavioral Deficits and Excitatory/Inhibitory Imbalance Related to Schizophrenia.

BACKGROUND AND HYPOTHESIS: Redox dysregulation has been proposed as a convergent point of childhood trauma and the emergence of psychiatric disorders, such as schizophrenia (SCZ). A critical region particularly vulnerable to environmental insults during adolescence is the ventral hippocampus (vHip). However, the impact of severe stress on vHip redox states and their functional consequences, including behavioral and electrophysiological changes related to SCZ, are not entirely understood. STUDY DESIGN: After exposing adolescent animals to physical stress (postnatal day, PND31-40), we explored social and cognitive behaviors (PND47-49), the basal activity of pyramidal glutamate neurons, the number of parvalbumin (PV) interneurons, and the transcriptomic signature of the vHip (PND51). We also evaluated the impact of stress on the redox system, including mitochondrial respiratory function, reactive oxygen species (ROS) production, and glutathione (GSH) levels in the vHip and serum. STUDY RESULTS: Adolescent-stressed animals exhibited loss of sociability, cognitive impairment, and vHip excitatory/inhibitory (E/I) imbalance. Genome-wide transcriptional profiling unveiled the impact of stress on redox system- and synaptic-related genes. Stress impacted mitochondrial respiratory function and changes in ROS levels in the vHip. GSH and glutathione disulfide (GSSG) levels were elevated in the serum of stressed animals, while GSSG was also increased in the vHip and negatively correlated with sociability. Additionally, PV interneuron deficits in the vHip caused by adolescent stress were associated with oxidative stress. CONCLUSIONS: Our results highlight the negative impact of adolescent stress on vHip redox regulation and mitochondrial function, which are partially associated with E/I imbalance and behavioral abnormalities related to SCZ.

Impact of diabetic neuropathy on quality of life and postural balance in brazilian older adults / O impacto da neuropatia diabética na qualidade de vida e equilíbrio postural em idosos brasileiros

ABSTRACT Objective: To analyze the impact of the Peripheral Diabetic Neuropathy (PDN) on the postural and functional balance and quality of life of Brazilian older adults. Methods: A cross-sectional study. Sixty older men and women (60-79 years) were divided into three groups: control, DM without and with PDN. The following parameters were evaluated: anthropometry; quality of life; postural balance (BESTest); functional balance in force plate (NeuroCom Balance). Results: PDN group presented significant differences compared with the other groups, with the worst performance in quality of life than DM2 without PDN in: sensory functioning (p = 0.030); past and future (p = 0.036); death and dying (p = 0.035). Postural balance deficit in the total score (p = 0.025) and biomedical constraints section (p = 0.043) of the BESTest, compared with DM2 without PDN (p = 0.007). In the functional balance (Neurocom), PDN group presented a worse performance in the time spent on the left side (p = 0.030) than the control group. During step up over test, the control group performed the task faster than the group with PDN (p = 0.004). Conclusion: This study showed that neuropaths presented worse physical performance and postural balance deficits, sensorial limitations, affecting the daily tasks and, as a consequence, decreasing the quality of life in Brazilian older adults. Level of Evidence II, Cross-sectional observational study.

RESUMO Objetivo: Analisar a influência da neuropatia diabética periférica (NDP) no equilíbrio postural, atividades funcionais e na qualidade de vida em idosos. Métodos: Estudo transversal. Avaliamos 60 homens e mulheres idosos (60-79 anos) divididos em três grupos: controle, DM sem e com NDP. Foram avaliados: antropometria; qualidade de vida; equilíbrio postural (BESTest); atividades funcionais pelo equilíbrio funcional na placa de força (NeuroCom Balance). Resultados: Grupo NDP apresentou diferenças comparado a outros grupos, pior desempenho na qualidade de vida que o DM2 sem NDP em: funcionamento sensorial (p = 0,030); passado e futuro (p = 0,036); morte e morrer (p = 0,035). Déficit de equilíbrio postural no escore total (p = 0,025) e seção de restrições biomédicas (p = 0,043) do BESTest comparado ao DM2 sem NDP (p = 0,007). No equilíbrio funcional (Neurocom), o grupo NDP apresentou pior desempenho no tempo gasto no lado esquerdo (p = 0,030) comparado ao grupo controle. Durante a etapa de teste, o grupo controle executou a tarefa mais rapidamente que o grupo NDP (p = 0,004). Conclusão: Neuropatas apresentaram pior desempenho físico e déficits no equilíbrio postural, limitações sensoriais, afetando as tarefas diárias da doença e, consequentemente, diminuição da qualidade de vida em idosos brasileiros. Nível de Evidência II, Estudo observacional transversal.

Inibição de metaloproteinases da matriz extracelular: uma possível estratégia terapêutica na hipertensão arterial? / Inhibition of matrix metalloproteinases: a possible therapeutic strategy in arterial hypertension?

A hipertensão é um importante problema de saúde pública associado ao aumento do risco de doenças cardiovasculares. Dentre outros modelos utilizados experimentalmente para estudar a hipertensão arterial, o modelo de hipertensão 2 rins-1clipe (2R1C) está associado à significativa ativação do sistema renina-angiotensina, produzindo alterações vasculares possivelmente decorrentes do aumento do estresse oxidativo e da ativação excessiva de metaloproteinases da matriz extracelular (MMPs). As MMPs são reguladas por vários processos, e a ativação dessas proteases promove degradação excessiva dos componentes da matriz extracelular e desse modo provoca um remodelamento vascular patológico. Entre várias dessas enzimas proteolíticas, asgelatinases (MMP-2 e MMP-9) têm merecido destaque por terem um importante papel nas doenças cardiovasculares. Estudos demonstram que o aumento na atividade e nos níveis de MMP-2 pode prejudicar o relaxamento vascular dependente do endotélio e causar hipertrofia arterial, especialmente da camada média, deposição excessiva decolágeno e elastina e, desse modo, contribuir para disfunção e remodelamento vascular hipertensivo. Portanto, como as MMPs desempenham importante papel no desenvolvimento e progressão de diversas doenças cardiovasculares, a inibição dessas proteases tem sido muito estudada e valorizada como uma importante estratégia terapêutica para o tratamento dessas doenças, inclusive das consequências deletérias da hipertensão arterial.

Hypertension is an important public health problem associated with increased risk of cardiovascular disease. The experimental model of hypertension-2 kidney 1clipe (2K1C) promotes significant activation of the renin-angiotensin system, and produces vascular changes associated with increased oxidative stress and upregulation of extracellular matrix metalloproteinases (MMPs). MMPs can be regulated by several processes, and increased activation of these proteases promotes excessive degradation of extracellular matrix components, thereby causing pathological vascular remodeling. Among these proteolytic enzymes,the gelatinases (MMP-2 and MMP-9), have shown an important role in cardiovascular disease. Studies show that increased activity and levels of MMP-2 may impair the endothelium-dependent vasorelaxation and cause artery wall hypertrophy, excessive deposition of collagen and elastin, thus contributing to dysfunction and hypertensive vascular remodeling. Therefore, as the MMPs play an important role in the development and progression of various cardiovascular diseases, inhibiting these proteases has been valued as a possible therapeutic strategy in the treatment of cardiovascular diseases, including the complications associated with hypertension.

Distribution, detection of enterotoxigenic strains and antimicrobial drug susceptibility patterns of Bacteroides fragilis group in diarrheic and non-diarrheic feces from Brazilian infants

Despite the importance of gastrointestinal diseases and their global distribution, affecting millions of individuals around the world, the role and antimicrobial susceptibility patterns of anaerobic bacteria such as those in the Bacteroides fragilis group (BFG) are still unclear in young children. This study investigated the occurrence and distribution of species in the BFG and enterotoxigenic strains in the fecal microbiota of children and their antimicrobial susceptibility patterns. Diarrheic (n=110) and non-diarrheic (n=65) fecal samples from children aged 0-5 years old were evaluated. BFG strains were isolated and identified by conventional biochemical, physiological and molecular approaches. Alternatively, bacteria and enterotoxigenic strains were detected directly from feces by molecular biology. Antimicrobial drug susceptibility patterns were determined by the agar dilution method according to the guidelines for isolated bacteria. BFG was detected in 64.3 percent of the fecal samples (55 percent diarrheic and 80.4 percent non-diarrheic), and 4.6 percent were enterotoxigenic. Antimicrobial resistance was observed against ampicillin, ampicillin/sulbactam, piperacillin/tazobactam, meropenem, ceftriaxone, clindamycin and chloramphenicol. The data show that these bacteria are prevalent in fecal microbiota at higher levels in healthy children. The molecular methodology was more effective in identifying the B. fragilis group when compared to the biochemical and physiological techniques. The observation of high resistance levels stimulates thoughts about the indiscriminate use of antimicrobial drugs in early infancy. Further quantitative studies are needed to gain a better understanding of the role of these bacteria in acute diarrhea in children.

Importância do Fator Antinuclear (FAN) em pacientes com Artrite Reumatóide Juvenil (ARJ) / Significance of Antinuclear Antibodies (ANA) in Juvenile Rheumatoid Arthritis (JRA)

Amostras de soro de 24 pacientes com Artrite Reumatoíde Juvenil (ARJ) foram utilizadas para avaliar a presença do fator antinuclear pela técnica de imunofluorescência indireta-Help-2. A presença ou näo desse auto-anticorpo foi associada com as classificaçöes existentes (pauciarticular, poliarticular ou sistêmica) contribuindo par melhor seguimento da fisiopatologia.