Synaptic Homeostasis and Restructuring across the Sleep-Wake Cycle.

Sleep is critical for hippocampus-dependent memory consolidation. However, the underlying mechanisms of synaptic plasticity are poorly understood. The central controversy is on whether long-term potentiation (LTP) takes a role during sleep and which would be its specific effect on memory. To address this question, we used immunohistochemistry to measure phosphorylation of Ca2+/calmodulin-dependent protein kinase II (pCaMKIIα) in the rat hippocampus immediately after specific sleep-wake states were interrupted. Control animals not exposed to novel objects during waking (WK) showed stable pCaMKIIα levels across the sleep-wake cycle, but animals exposed to novel objects showed a decrease during subsequent slow-wave sleep (SWS) followed by a rebound during rapid-eye-movement sleep (REM). The levels of pCaMKIIα during REM were proportional to cortical spindles near SWS/REM transitions. Based on these results, we modeled sleep-dependent LTP on a network of fully connected excitatory neurons fed with spikes recorded from the rat hippocampus across WK, SWS and REM. Sleep without LTP orderly rescaled synaptic weights to a narrow range of intermediate values. In contrast, LTP triggered near the SWS/REM transition led to marked swaps in synaptic weight ranking. To better understand the interaction between rescaling and restructuring during sleep, we implemented synaptic homeostasis and embossing in a detailed hippocampal-cortical model with both excitatory and inhibitory neurons. Synaptic homeostasis was implemented by weakening potentiation and strengthening depression, while synaptic embossing was simulated by evoking LTP on selected synapses. We observed that synaptic homeostasis facilitates controlled synaptic restructuring. The results imply a mechanism for a cognitive synergy between SWS and REM, and suggest that LTP at the SWS/REM transition critically influences the effect of sleep: Its lack determines synaptic homeostasis, its presence causes synaptic restructuring.

Hypersensitivity to dipyrone in aspirin-exacerbated respiratory disease patients is associated with urticaria.

OBJECTIVE: To phenotype patients with aspirin-exacerbated respiratory disease (AERD) according to the presence of atopy, urticaria and level of peripheral eosinophils. METHODS: This study included adult asthmatic patients with AERD followed up at a tertiary hospital. They were classified according to atopy and/or urticaria, assessing clinical and laboratorial differences among the groups in order to identify possible aggravating factors of the disease. RESULTS: We included 73 patients, 78.1% being female with a mean age of 54.0 years. Severe asthma was observed in 68.5% and respiratory exacerbation with dipyrone in 67.1% of these patients. They had median total serum IgE of 191.6 IU/mL, mean peripheral eosinophils of 718.5 cells/mm3, and 50.7% were atopic. Urticaria was observed in 32.9% of them, and exacerbations were more often triggered by dipyrone (p = .016). Atopic patients were younger than nonatopic patients (p = .023), and had, on average, higher total serum IgE levels (p = .022). We observed a good correlation between asthma severity and peripheral eosinophils count (r2 = 026; p = .021). CONCLUSIONS: In this study, severe asthma was highly prevalent in AERD patients. Likewise, urticaria was quite prevalent and its presence was associated with dipyrone induced hypersensitivity reaction. Atopy was found in half of the patients, with no association with asthma severity. Patients with higher levels of peripheral eosinophils had more severe asthma. Dypirone hypersensitivity may be a marker for concomitant respiratory and cutaneous hypersensitivity reactions.

Hérnias internas após bypass gástrico laparoscópico em Y-de-Roux: espaços intermesentéricos, sintomas e diagnóstico / Internal hernias after laparoscopic Roux-Y gastric bypass: intermesenteric spaces, symptoms and diagnosis

Introdução: Com o aumento da prevalência mundial de obesidade, operações para redução de peso vêm sendo cada vez mais frequentes, sendo o bypass gástrico laparoscópico a principal delas. Entretanto, existem complicações associadas, dentre elas, a formação de hérnias internas. Objetivos: Revisar o bypass gástrico e o desenvolvimento de hérnias internas, e discorrer sobre a importância do uso de tomografia no diagnóstico dessa complicação. Métodos: Revisão integrativa, envolvendo 646 artigos pesquisados nas bases de dados BVS e PubMed; deles, apenas 10 respeitaram os critérios de inclusão. Resultados: Atualmente o bypass gástrico é um dos principais métodos cirúrgicos utilizados em procedimentos que visam a redução de peso em obesos. Entretanto, a formação de hérnias internas em espaços mesentéricos criados durante o procedimento é uma possibilidade e resulta em sintomas inespecíficos, podendo levar a consequências graves. Nesse contexto, a tomografia computadorizada é instrumento diagnóstico muito útil. Conclusão: Em pronto-socorro, tomografia abdominal deve ser realizada em pacientes com queixa de dor abdominal inespecífica e com histórico de bypass gástrico, pois é útil no diagnóstico precoce das hérnias internas, diminuindo sua morbimortalidade.

Introduction: With the increase in the worldwide prevalence of obesity, operations to reduce weight are becoming more frequent, with laparoscopic gastric bypass being the main one. However, there are associated complications, among them, the formation of internal hernias. Objectives: To review gastric bypass and the development of internal hernias and discuss the importance of using tomography in the diagnosis of this complication. Methods: Integrative review, involving 646 articles searched in the BVS and PubMed databases; of them, only 10 met the inclusion criteria. Results: Currently, gastric bypass is one of the main surgical methods used in procedures aimed at reducing weight in obese people. However, the formation of internal hernias in mesenteric spaces created during the procedure is a possibility and results in nonspecific symptoms, which can lead to serious consequences. In this context, computed tomography is a very useful diagnostic tool. Conclusion: In an emergency room, abdominal tomography should be performed in patients complaining of nonspecific abdominal pain and with a history of gastric bypass, as it is useful in the early diagnosis of internal hernias, reducing their morbidity and mortality.

Qual é a influência da microbiota na obesidade e em seu quadro inflamatório? / What is the influence of microbiota on obesity and its inflammatory involvement?

A obesidade tem causa multifatorial que atinge atualmente mais da metade da população brasileira. Mais recentemente, a microbiota intestinal foi considerada um fator que contribui para essa condição. Os objetivos deste estudo foram revisar a influência da microbiota intestinal na obesidade e no processo inflamatório, e analisar os efeitos da utilização dos pré e probióticos. Foi realizada revisão sistemática sobre o assunto. Dos mais de 27.000 artigos, apenas 16 respeitaram os critérios de inclusão. Em conclusão, o desequilíbrio da microbiota aparece como fator favorável ao desenvolvimento da obesidade e do quadro inflamatório decorrente dela. Tanto o uso de prebióticos quanto probióticos são recursos válidos no tratamento da obesidade, porém os primeiros parecem proporcionar melhor qualidade de vida.

Obesity has a multifactorial etiological condition that involves more than half of the Brazilian population. More recently, the intestinal microbiota was considered a factor that contributes to this condition. The aims of this study were to review the intestinal microbiota influence in the obesity and in the inflammatory response, and to analyze the effects of using prebiotic and probiotic medications. A systematic review was firstly done. More than 27,000 articles were found, but only 16 contained the proper criteria. In conclusion, the microbiota imbalance seems to increase the obesity development and its inflammatory aspects. Both the use of pre and probiotics are good options in the obesity treatment, though the first ones seem to enhance bettere quality of life.

Síndrome PFAPA (febre periódica, aftas orais, faringite e adenite cervical) em crianças e adultos / PFAPA (periodic fevers with aphthous stomatitis, pharyngitis, and adenitis) syndrome in children and adults

A síndrome PFAPA (febre periódica, aftas orais, faringite e adenite cervical) é a forma mais comum das doenças autoinflamatórias. Trata-se de uma doença rara, não genética, bimodal, usualmente com início dos sintomas antes dos 5 anos de vida, que também pode prolongar-se ou iniciar-se na vida adulta. A prevalência é variável em todo o mundo, e não há dados estatísticos da doença no Brasil. Diversos pontos da doença são discutíveis, como os critérios diagnósticos, as avaliações laboratoriais, a ausência de mutações genéticas específicas e a abordagem terapêutica e prognóstica. Este trabalho tem como objetivo rever, de forma narrativa e crítica, aspectos relacionados ao diagnóstico e tratamento da síndrome PFAPA em adultos e crianças. Foram feitas buscas nas redes de dados PubMed, Bireme e Cochrane, utilizando o acrônimo PFAPA sem auxílio de qualquer filtro. Quanto ao diagnóstico, os critérios pediátricos foram adaptados para os adultos, com análises variadas e divergentes. Há a necessidade pujante de desenvolver um consenso com diretrizes de diagnóstico de pacientes em populações bem caracterizadas para melhor diagnosticar a doença. Já em relação ao tratamento, a cirurgia com remoção das tonsilas é considerada curativa, com necessidade de se manter acompanhamento após o procedimento para confirmação da remissão da doença. As drogas poupadoras de corticoide ainda são incertas, e o uso de imunobiológicos deve ser reservado somente para pacientes refratários ao tratamento cirúrgico e com grande impacto na qualidade de vida.

PFAPA (periodic fevers with aphthous stomatitis, pharyngitis, and adenitis) syndrome is the most common form of autoinflammatory disease. It is a rare, non-genetic, bi-modal disease, usually with onset of symptoms before the age of 5 years, which may also be prolonged or start in adult life. The prevalence varies worldwide and there are no specific statistical data in Brazil. Several aspects of the disease are debatable, such as diagnostic criteria, laboratory evaluations, absence of specific genetic mutations, and therapeutic and prognostic approach. This paper aims to review in a narrative and critical manner aspects related to diagnosis and treatment of PFAPA syndrome in adults and children. PubMed, Bireme and Cochrane databases were searched using the acronym PFAPA without any filter. Regarding diagnosis, pediatric criteria were adapted for use in adults, with varied and divergent analyses. There is a strong need to develop consensus diagnostic guidelines for patients in well-characterized populations to better diagnose the disease. Regarding treatment, tonsillectomy is considered curative, requiring follow-up after the procedure to confirm remission of the disease. Corticosteroid-sparing agents remain uncertain, and the use of immunobiological agents should be reserved only for patients who are refractory to surgical treatment and experience a great impact on quality of life.

Diagnóstico e tratamento da DREA: realidades da prática clínica / Diagnosis and treatment of AERD: clinical practice reality

Introdução: A doença respiratória exacerbada por aspirina (DREA), caracterizada por asma, rinossinusite, polipose nasal e hipersensibilidade à aspirina, pode ser sugerida pela história, porém, o teste de provocação oral com a aspirina é o padrão ouro para o diagnóstico, e a dessensibilização com aspirina, uma boa opção terapêutica. O objetivo do trabalho foi avaliar as características clínicas e os resultados dos procedimentos de provocação e/ou de dessensibilização com aspirina nos pacientes com suspeita de DREA, bem como observar se houve correlação com a literatura. Métodos: Neste estudo retrospectivo, foram avaliados prontuários de pacientes adultos com suspeita de DREA, em acompanhamento em um hospital terciário e que foram submetidos à provocação e/ ou dessensibilização com aspirina. Dois protocolos foram utilizados para o teste de provocação: (a) cetorolaco nasal/aspirina oral, e (b) apenas aspirina oral. Foram avaliados: características clínicas, a positividade do teste e da dessensibilização e a comparação deste resultado com a história prévia. Resultados: Participaram do estudo 24 pacientes, com média de idade de 50,8 anos, sendo 54,2% do sexo feminino. Treze pacientes (54,2%) tinham asma grave, e seis (25%), asma alérgica. Média do volume expiratório forçado no primeiro segundo (VEF1) foi de 81,5% do valor predito. Dezenove pacientes (79,2%) referiam broncoespasmo e/ou urticária com anti-inflamatórios não esteroidais. Cinco pacientes não faziam associação com essas medicações. Independente do protocolo usado, onze pacientes (45,8%) apresentaram teste positivo, confirmando a DREA, sendo que seis pacientes (25%) foram submetidos à dessensibilização com aspirina. Oito pacientes (33,3%) apresentaram provocação negativa, e cinco (20,8%) não conseguiram completar a investigação devido à presença de urticária. Conclusões: Pacientes com suspeita de DREA deveriam ser submetidos à provocação com aspirina para confirmar o diagnóstico. Um quarto dos pacientes foi submetido à dessensibilização, entretanto, para a maioria dos pacientes não foi possível confirmar o diagnóstico ou o teste foi negativo.

Introduction: Aspirin-exacerbated respiratory disease (AERD) is characterized by asthma, rhinosinusitis, nasal polyps, and aspirin hypersensitivity. The condition may be suggested by the patient's medical history; however, oral provocation test with aspirin is the gold standard for diagnosis, and desensitization with aspirin, a good therapeutic option. The aim of this study was to evaluate the clinical characteristics and results obtained with aspirin provocation tests and/or desensitization in patients with suspected AERD, as well as to correlate these data with the literature available. Methods: In this retrospective study, the medical records of adult patients with suspected AERD followed at a tertiary hospital who underwent aspirin challenge and/or desensitization were evaluated. Two protocols were used for the challenge test: (a) nasal ketorolac/ oral aspirin; and (b) oral aspirin alone. Clinical characteristics and both test and desensitization positivity were evaluated, and the results were compared with data from the patient's history. Results: Twenty-four patients participated in the study, with a mean age of 50.8 years; 54.2% were female. Thirteen patients (54.2%) had severe asthma, and six (25%) had allergic asthma. Mean forced expiratory volume in 1 second (FEV1) was 81.5% of the predicted value. Nineteen patients (79.2%) reported bronchospasm and/or urticaria with nonsteroidal anti-inflammatory drugs. Five patients had no association with these medications. Regardless of the protocol used, eleven patients (45.8%) presented positive tests, confirming the diagnosis of AERD, and six patients (25%) underwent aspirin desensitization. Eight patients (33.3%) had negative results in the provocation test, and five (20.8%) failed to complete the investigation due to the presence of urticaria. Conclusions: Patients with suspected AERD should undergo aspirin challenge to confirm the diagnosis. One-fourth of our patients underwent desensitization, but for most patients, either it was not possible to confirm the diagnosis or the test resulted negative.

Características de pacientes asmáticos com bronquiectasias / Characteristics of asthmatic patients with bronchiectasis

Introdução: A bronquiectasia é uma enfermidade caracterizada por dilatações anormais e irreversíveis de um ou mais brônquios. Pode estar associada a diversas outras comorbidades respiratórias, entre elas, a asma. Objetivo: Caracterizar os pacientes asmáticos com bronquiectasias acompanhados em um serviço terciário de alergia. Métodos: Análise retrospectiva de prontuários de pacientes asmáticos que apresentavam bronquiectasias nos exames de tomografia computadorizada de tórax. Os portadores de aspergilose broncopulmonar alérgica (ABPA) foram excluídos. Foram analisados os dados demográficos e exames complementares (espirometria, eosinófilos periféricos, IgE total e IgE específica). A caracterização das bronquiectasias foi avaliada conforme sua localização nos campos pulmonares. Resultados: Quarenta e nove pacientes foram selecionados, sendo 88% do sexo feminino. A média de idade do grupo era de 63 anos, e de tempo de doença de 43 anos. O tratamento prévio de tuberculose (TB), em algum momento da vida, foi relatado por 31% dos pacientes. Doença do refluxo gastroesofágico (DRGE) estava presente em 76% dos pacientes, e a história de tabagismo ativo ou passivo, em 65% dos pacientes. Mais de 80% dos pacientes estavam no step 4 de tratamento da asma, e apresentavam VEF1 reduzido. A média de eosinófilos periféricos foi de 253,4 cel/mm3, de IgE total foi de 458,8 UI/mL, e 69% dos pacientes eram sensibilizados para algum aeroalérgeno. Em relação à localização das bronquiectasias, o lobo superior direito foi o mais acometido, seguido pelo lobo superior esquerdo e lobo inferior direito, respectivamente. Conclusão: Neste estudo, 88% dos pacientes asmáticos com bronquiectasias apresentavam asma grave e função pulmonar alterada, apesar do tratamento otimizado. A bronquiectasia pode estar associada à dificuldade no controle da asma e, embora a história de TB prévia estivesse presente em 31% dos pacientes, a frequência elevada de comprometimento dos lobos superiores (49%) sugere uma frequência maior de doença pulmonar associada à TB.

Introduction: Bronchiectasis is a disease characterized by abnormal and irreversible dilatation of one or more bronchi. It may be associated with several other respiratory comorbidities including asthma. Objective: To characterize asthmatic patients with bronchiectasis seen at a tertiary allergy service. Methods: Retrospective analysis of medical records of asthmatic patients showing bronchiectasis on chest computed tomography scans was conducted. Patients with allergic bronchopulmonary aspergillosis (ABPA) were excluded. Demographic data and complementary tests (spirometry, peripheral eosinophils, total IgE and specific IgE) were analyzed. Bronchiectasis characterization was evaluated according to its location in the lung fields. Results: Forty-nine patients were selected, and 88% were female. Mean age in the group was 63 years, and disease time was 43 years. Previous treatment of tuberculosis (TB) at some point in life was reported by 31% of the patients. Gastroesophageal reflux disease (GERD) was present in 76% of the patients, and history of active or passive smoking in 65%. More than 80% of the patients were on step 4 of asthma treatment and showed reduced FEV1. Mean peripheral eosinophils was 253.4 cell/mm3, total IgE was 458.8 IU/mL, and 69% of the patients were sensitized to some aeroallergen. Regarding the location of bronchiectasis, the right upper lobe was most commonly affected, followed by the left upper lobe and the right lower lobe, respectively. Conclusion: In this study, 88% of asthmatic patients with bronchiectasis had severe asthma and altered pulmonary function despite optimized treatment. Bronchiectasis may be associated with difficulty in controlling asthma. Although previous history of TB was present in 31% of the patients, the high frequency of involvement of the upper lobes (49%) suggests a higher frequency of TB-associated lung disease.