Phosphodiesterase Inhibition in the Treatment of Preeclampsia: What Is New?

PURPOSE OF REVIEW: The present study intends to review the possibility of using phosphodiesterase inhibitors as a treatment option for preeclampsia, addressing potential risks and benefits. RECENT FINDINGS: Preeclampsia is the most common hypertensive disorder of pregnancy, often responsible for severe maternal and fetal complications, which can lead to early pregnancy termination and death. Despite the numerous studies, its pathophysiology is still unclear, although it seems to involve a multiplicity of complex factors related to angiogenesis, ineffective vasodilation, oxidative stress, inflammatory cytokines, and endothelial dysfunction. It has been hypothetically suggested that the use of phosphodiesterase inhibitors is capable of improving placental and fetal perfusion, contributing to gestational scenario, by decreasing the symptomatology and severity of this syndrome. In this literature review, it has been found that most of the studies were conducted in animal models, and there is still lack of evidence supporting its use in clinical practice. Research in human indicates conflicting findings; randomized controlled trials were scarce and did not demonstrate any benefit in morbidity or mortality. Data regarding to pathophysiological and interventional research are described and commented in this review. The use of phosphodiesterase inhibitors in the treatment of preeclampsia is controversial and should not be encouraged taking into account recent data.

Using the Reduced Uterine Perfusion Pressure model of preeclampsia to study the blood brain barrier permeability / Uso do modelo de Redução da Pressão de Perfusão Uterina de pré-eclâmpsia para estudar a permeabilidade da barreira hematoencefálica

AIMS: To use the Reduced Uterine Perfusion Pressure (RUPP) model for preeclampsia to describe and evaluate the blood brain barrier permeability in pregnant rats. METHODS: Forty-one pregnant Wistar rats were divided into different intervention groups between 13 to 15 days of gestation: PregnantControl (PC; n=12), Reduced Uterine Perfusion Pressure (RUPP; n=15), Invasive Blood Pressure-Control (IBP; n=7) and Reduced Uterine Perfusion Pressure and Invasive Blood Pressure (RUPP-IBP; n=7). The 14 rats of groups IBP and RUPP-IBP had their mean arterial pressure measured at day 21. All animals were then sacrificed, administered Evans Blue dye through the tail vein and perfused with paraformaldehyde 4%. Brains were removed and evaluated by a blinded pathologist. Results are presented as means and standard errors. Comparisons between the groups were performed using Student's t-test for continuous variables and Fisher's exact test for categorical variables. Statistical significance was set as a p value less than 0.05. RESULTS: Mean arterial pressure averaged 85.4±2.2 mmHg in the IPB group and 102.5±8.3 mmHg in the RUPP-IPB group (p=0.002). Among all the RUPP rats (RUPP and RUPP-IBP groups), 82% had a positive staining with Evans Blue dye for at least one of the brain hemispheres, while none of the pregnant control rats (PC and IBP groups) had brain staining (p<0.001). CONCLUSIONS: In this study, altered permeability of the blood brain barrier was successfully reproduced in pregnant rats exposed to the RUPP protocol. Therefore, we concluded that the RUPP model is a valid surrogate to study blood brain barrier abnormalities.

OBJETIVOS: Usar o modelo de Redução da Pressão de Perfusão Uterina / Reduced Uterine Perfusion Pressure (RUPP) de pré-eclâmpsia para descrever e avaliar a permeabilidade da barreira hematoencefálica. MÉTODOS: Quarenta e uma ratas Wistar prenhes foram estratificadas em diferentes grupos de intervenção entre 13 a 15 dias de gestação: grupo controle (PC; n=12), grupo modelo de redução da pressão de perfusão uterina (RUPP; n=15), grupo monitorização invasiva da pressão arterial (IBP; n=7) e grupo redução da pressão de perfusão uterina e monitorização invasiva da pressão arterial (RUPP-IBP; n=7). As 14 ratas dos grupos IBP e RUPP-IBP tiveram sua pressão arterial média aferida no dia 21. Logo após todos os animais foram sacrificados e foi administrado o corante Azul de Evans pela veia da cauda, seguido de formaldeído 4%. Os cérebros foram removidos e avaliados por um patologista cegado para os grupos. Os resultados são apresentados em médias e erros padrão. As comparações entre os grupos foram realizadas utilizando o teste t de Student para variáveis contínuas e o teste exato de Fisher para variáveis categóricas. A significância estatística foi definida como um valor de p inferior a 0,05. RESULTADOS: As médias e desvios padrões da pressão arterial média foram 85,4±2,2 mmHg no grupo IPB e 102,5±8,3 mmHg no grupo RUPP-IPB (p=0,002). Entre todas as ratas RUPP (grupos RUPP e RUPP-IBP), 82% tiveram marcação positiva pelo corante em pelo menos um dos hemisférios cerebrais, enquanto nenhuma das ratas controle (grupos PC e IBP) teve marcação cerebral positiva (p<0,001). CONCLUSÕES: Neste estudo, a permeabilidade alterada da barreira hematoencefálica foi reproduzida com sucesso em ratas prenhes expostas ao protocolo RUPP. Portanto, concluímos que o modelo RUPP é um substituto válido para estudar anormalidades da barreira hematoencefálica.

Rastreamento, diagnóstico e estadiamento do adenocarcinoma de cólon / Screening, diagnosis and staging of the colon adenocarcinoma

Introdução: O Câncer de Cólon (CC) é uma doença extremamente prevalente e letal quando não diagnosticada em tempo hábil para tratamento, o que justifica a necessidade de programas de rastreio na população. Métodos: Foram selecionados dezessete artigos das bases de dados Pubmed, Medline, Lilacs e Embase para compor uma revisão de literatura. Resultados: O objetivo do rastreamento do CC é detectar lesões precursoras (pólipos adenomatosos) ou câncer em estágio inicial, enquanto ainda são passíveis de tratamento. Pode-se utilizar diversos métodos para realizar este rastreamento, sendo a colonoscopia o exame padrão-ouro devido a capacidade de estabelecer diagnóstico histopatológico da doença e fornecer oportunidade de tratamento no mesmo procedimento em casos de lesão precursoras. O estadiamento é clínico e envolve exame físico, radiografia torácica e tomografia computadorizada (TC) de abdome e pelve. Conclusão: O CC é uma das neoplasias mais frequentes em adultos no mundo inteiro e é possivelmente curável se diagnosticado precocemente. O método padrão-ouro para rastreamento e diagnóstico é a colonoscopia, uma vez que ela permite biópsia para análise histopatológica na presença de lesão. O estadiamento deve ser feito para avaliar a extensão local e sistêmica da doença por meio do exame físico e exames complementares.

Introduction: The colorectal cancer (CC) is an extremely common disease that is lethal if not diagnosed in early stages, which justifies the need for screening in the general population. Methods: Seventeen publications from Pubmed, Medline, Embase and Lilacs databases were selected to compose a literature review. Results: The goal of screening for CC is to detect precursor lesions (polyps) or early stage cancer. There is a variety of methods available in order to perform this screening, being colonoscopy the gold standard due to the possibility of establishing both histopathological diagnosis of the disease and offering treatment in case of precursor lesions. The staging is clinical and includes physical examination, chest imaging and abdominal and pelvic CT scans. Conclusion: The CC is one of the most common cancers in adults and possibly treatable if early diagnosed. The gold standard method for screening is colonoscopy, since it allows biopsy for histopathological analysis. The staging needs to be done to assess the local and systemic extent of the disease through physical examination and complementary tests.

Could BDNF be involved in compensatory mechanisms to maintain cognitive performance despite acute sleep deprivation? An exploratory study.

BACKGROUND: Neuroimaging studies suggest that acute sleep deprivation can lead to adaptations, such as compensatory recruitment of cerebral structures, to maintain cognitive performance despite sleep loss. However, the understanding of the neurochemical alterations related to these adaptations remains incomplete. OBJECTIVE: Investigate BDNF levels, cognitive performance and their relations in healthy subjects after acute sleep deprivation. METHODS: Nineteen sleep deprived (22.11±3.21years) and twenty control (25.10±4.42years) subjects completed depression, anxiety and sleep quality questionnaires. Sleep deprived group spent a full night awake performing different playful activities to keep themselves from sleeping. Attention, response inhibition capacity and working memory (prefrontal cortex-dependent) were assessed with Stroop and Digit Span tests. Declarative memory (hippocampus-dependent) was assessed with Logical Memory test. Serum BDNF was measured by sandwich ELISA. Data were analyzed with independent samples T-test, ANOVA, ANCOVA and curve estimation regressions. p<0.05 was deemed statistically significant. RESULTS: The sleep deprived group showed higher BDNF levels and normal performance on attention, response inhibition capacity and working memory. However, declarative memory was impaired. A sigmoidal relation between BDNF and Stroop Test scores was found. CONCLUSIONS: Increased BDNF could be related, at least in part, to the maintenance of normal prefrontal cognitive functions after sleep deprivation. This potential relation should be further investigated.