O papel da oxitocina no hipocampo dorsal na memória de medo

A formação de memórias é fundamental para nossa adaptação ao ambiente, mas dependendo do grau de aversão que uma determinada experiência simboliza, pode se tornar inconveniente e prejudicar gravemente a qualidade de vida do indivíduo, o que pode dar origem a transtornos psiquiátricos relacionados a traumas e estressores, como transtorno de estresse pós-traumático. A ocitocina é um neuropeptídeo envolvido na interação social, memória de reconhecimento social e, mais recentemente, na modulação da memória do medo. Esse hormônio tem sido estudado em memórias de medo em diferentes estruturas cerebrais, como córtex pré-frontal medial e amígdala basolateral, porém, ainda não foi estudado no hipocampo, apesar de ser uma estrutura central na consolidação de experiências aversivas. Diante disso, nosso objetivo é investigar o papel da ocitocina no hipocampo dorsal, na região CA1, nas diferentes fases da memória do medo, em ratos machos e fêmeas. Em nossos resultados, descobrimos que a ocitocina infundida no hipocampo após uma breve sessão de reativação da memória de medo atenua sua expressão em uma sessão de teste posterior. Além disso, encontramos um prejuízo na aquisição da memória de medo sob o efeito da ocitocina em machos, mas não em fêmeas, e nenhum efeito na memória de extinção.The formation of memories is fundamental for our adaptation to the environment, but depending on the degree of aversion that a given experience symbolizes, it can become inconvenient and seriously impair the individual's quality of life, which can give rise to psychiatric disorders related to trauma and stressors such as post-traumatic stress disorder. Oxytocin is a neuropeptide involved in social interaction, social recognition memory, and more recently in the modulation of fear memory. This hormone has been studied in fear memories in different brain structures, such as the medial prefrontal cortex and basolateral amygdala, however, it has not yet been studied in the hippocampus, despite being a central structure in the consolidation of aversive experiences. Considering this, our objective is to investigate the role of oxytocin in the dorsal hippocampus, in the CA1 region, in the different phases of fear memory, in male and female rats. In our results, we found that oxytocin infused into the hippocampus after a brief fear memory reactivation session attenuates its expression in a later testing session. Furthermore, we found animpairment in the acquisition of fear memory under the effect of oxytocin in males, but not in females, and no effect on extinction memory

Amikacin for the treatment of carbapenem-resistant Klebsiella pneumoniae infections : clinical efficacy and toxicity

Infections by carbapenem-resistant Klebsiella pneumoniae (CRKp) are an increasing global threat with limited therapeutic options. Our objective was to evaluate clinical and microbiological outcomes of patients treated with amikacin for CRKp infections. We did a retrospective cohort of patients>18 years old, with CRKp infections treated with amikacin in two tertiary care hospitals in Porto Alegre, Brazil. The impact of clinical factors, antibiotic treatment, and amikacin minimum inhibitory concentration (MIC) on patients’ 30-day mortality was assessed. Microbiological clearance and nephrotoxicity (assessed by RIFLE score) were evaluated as secondary outcomes. A Cox regression analysis was done for mortality. We included 84 patients for analysis. Twenty-nine (34.5%) patients died in 30 days. Amikacin MIC values ranged from 0.125 to 8 μg/mL and did not infuence on mortality, regardless of the prescribed dose of this antibiotic (P=0.24). Bacterial clearance occurred in 17 (58.6%) of 29 patients who collected subsequent cultures. Two (16.6%) of the 12 persistently positive cultures changed the amikacin susceptibility profle from susceptible to intermediate. Twenty-nine (37.2%) patients developed acute kidney injury (AKI): risk 13, injury 11, and failure 5. Risk factors for AKI were higher baseline eGFR (P<0.01) and combination therapy with colistin (P=0.02). Comparing patients who received combination with colistin vs polymyxin B, AKI occurred in 60.0% vs 20.6%, respectively, P<0.01. Fifteen of the 16 (16.6%) patients who developed renal injury or failure were receiving colistin. In conclusion, amikacin was an efective treatment for CRKp infections. Within susceptible range, amikacin MIC values did not infuence on clinical outcomes. Combination therapy of amikacin and colistin was highly nephrotoxic and should be used with caution