Weight-drop model as a valuable tool to study potential neurobiological processes underlying behavioral and cognitive changes secondary to mild traumatic brain injury.

The pathophysiology of post-traumatic brain injury (TBI) behavioral and cognitive changes is not fully understood, especially in its mild presentation. We designed a weight drop TBI model in mice to investigate the role of neuroinflammation in behavioral and cognitive sequelae following mild TBI. C57BL/6 mice displayed depressive-like behavior at 72 h after mild TBI compared with controls, as indicated by a decrease in the latency to first immobility and climbing time in the forced swim test. Additionally, anxiety-like behavior and hippocampal-associated spatial learning and memory impairment were found in the elevated plus maze and in the Barnes maze, respectively. Levels of a set of inflammatory mediators and neurotrophic factors were analyzed at 6 h, 24 h, 72 h, and 30 days after injury in ipsilateral and contralateral hemispheres of the prefrontal cortex and hippocampus. Principal components analysis revealed two principal components (PC), which represented 59.1% of data variability. PC1 (cytokines and chemokines) expression varied between both hemispheres, while PC2 (neurotrophic factors) expression varied only across the investigated brain areas. Our model reproduces mild TBI-associated clinical signs and pathological features and might be a valuable tool to broaden the knowledge regarding mild TBI pathophysiology as well as to test potential therapeutic targets.

Traumatic brain injury in Brazil: an epidemiological study and systematic review of the literature.

BACKGROUND: Traumatic brain injury (TBI) is a serious public health problem worldwide. Although TBI is common in developing countries, there are few epidemiological studies. OBJECTIVE: To investigate the sociodemographic and clinical features of patients with TBI at the Hospital João XXIII, a public reference center for trauma in Belo Horizonte, Brazil, and to systematically review the available literature on TBI in Brazil. METHODS: Clinical and sociodemographic data were collected from electronic medical records for the entire month of July 2016. The literature on epidemiology of TBI in Brazil was systematically reviewed using MeSH/DeCS descriptors in the PubMed and Lilacs databases. RESULTS: Most patients admitted with TBI were male and under 60 years of age. Mild TBI was the most prevalent form and the most common cause of TBI was falls. A Glasgow Coma Scale score below 12, neuroimaging changes on computer tomography, and presence of any medical conditions were significantly associated with longer hospital stay. Brazilian studies showed that TBI affected mainly men and young adults. In addition, mild TBI was the most common TBI severity reported and the most common causes were motor vehicle accidents and falls. CONCLUSIONS: Overall, the profile of TBI in this center reflects the data from other Brazilian studies.

Traumatic brain injury in Brazil: an epidemiological study and systematic review of the literature / Traumatismo cranioencefálico no Brasil: um estudo epidemiológico e uma revisão sistemática da literatura

ABSTRACT Background: Traumatic brain injury (TBI) is a serious public health problem worldwide. Although TBI is common in developing countries, there are few epidemiological studies. Objective: To investigate the sociodemographic and clinical features of patients with TBI at the Hospital João XXIII, a public reference center for trauma in Belo Horizonte, Brazil, and to systematically review the available literature on TBI in Brazil. Methods: Clinical and sociodemographic data were collected from electronic medical records for the entire month of July 2016. The literature on epidemiology of TBI in Brazil was systematically reviewed using MeSH/DeCS descriptors in the PubMed and Lilacs databases. Results: Most patients admitted with TBI were male and under 60 years of age. Mild TBI was the most prevalent form and the most common cause of TBI was falls. A Glasgow Coma Scale score below 12, neuroimaging changes on computer tomography, and presence of any medical conditions were significantly associated with longer hospital stay. Brazilian studies showed that TBI affected mainly men and young adults. In addition, mild TBI was the most common TBI severity reported and the most common causes were motor vehicle accidents and falls. Conclusions: Overall, the profile of TBI in this center reflects the data from other Brazilian studies.

RESUMO Antecedentes: O traumatismo cranioencefálico (TCE) representa, mundialmente, um problema sério de saúde pública. Apesar de o TCE ser prevalente em países em desenvolvimento, estudos epidemiológicos permanecem escassos. Objetivo: Investigar as características sociodemográficas e clínicas de pacientes acometidos por TCE no Hospital João XXIII - centro de referência em trauma situado em Belo Horizonte, Brasil - e revisar sistematicamente toda a literatura disponível sobre o TCE no Brasil. Métodos: Os dados clínicos e sociodemográficos foram coletados apenas para o mês de julho, 2016, por meio de prontuários eletrônicos. A literatura sobre a epidemiologia do TCE no Brasil foi sistematicamente revisada usando descritores Medical Subject Headings (MeSH)/Descritores em Ciências da Saúde (DeCS) nos bancos de dados PubMed e Literatura Latino-Americana e do Caribe em Ciências da Saúde (Lilacs). Resultados: Os pacientes acometidos por TCE eram em sua maioria homens com menos de 60 anos. O TCE leve foi a gravidade mais prevalente entre os casos. O TCE foi causado principalmente por quedas. Escores menores que 12 na escala de Coma de Glasgow mais alterações de neuroimagem em tomografia computadorizada e a presença de qualquer comorbidade médica estão significativamente associados à maior estadia hospitalar. Estudos brasileiros demonstraram que o TCE acomete principalmente homens e adultos jovens. Além disso, o TCE leve foi a gravidade mais comum reportada, e os mecanismos de TCE mais comuns foram acidentes automobilísticos e quedas. Conclusões: O perfil de pacientes acometidos por TCE no centro de referência em questão reflete os dados de outros estudos brasileiros.

Brain-derived neurotrophic factor is down regulated after bovine alpha-herpesvirus 5 infection in both wild-type and TLR3/7/9 deficient mice.

Neurotrophic factors have been implicated in the control of neuronal survival and plasticity in different brain diseases. Meningoencephalitis caused by bovine alpha-herpesvirus 5 (BoHV-5) infection is a frequent neurological disease of young cattle, being the involvement of apoptosis in the development of neuropathological changes frequently discussed in the literature. It's well known that Toll-like receptors (TLRs) can activate neuroinflammatory response and consequently lead to neuronal loss. However, there are no studies evaluating the expression of neurotrophic factors and their association with brain pathology and TLRs during the infection by BoHV-5. The current study aimed to analyze brain levels of neurotrophic factors along with neuropathological changes during acute infection by BoHV-5 in wild-type (WT) and TLR3/7/9 (TLR3/7/9-/-) deficiency mice. The infection was induced by intracranial inoculation of 1 × 104 TCID50 of BoHV-5. Infected animals presented similar degrees of clinical signs and neuropathological changes. Both infected groups had meningoencephalitis and neuronal damage in CA regions from hippocampus. BoHV-5 infection promoted the proliferation of Iba-1 positive cells throughout the neuropil, mainly located in the frontal cortex. Moreover, significant lower levels of brain-derived neurotrophic factor (BDNF) were detected in both BoHV-5 infected WT and TLR3/7/9 deficient mice, compared with non-infected animals. Our study showed that BDNF down regulation was associated with brain inflammation, reactive microgliosis and neuronal loss after bovine alpha-herpesvirus 5 infection in mice. Moreover, we demonstrated that combined TLR3/7/9 deficiency does not alter those parameters.

Clinical and molecular correlates of the ASPECTS in the acute phase of stroke.

BACKGROUND: The Alberta Stroke Program Early CT Score (ASPECTS) scale was developed for monitoring early ischemic changes on CT, being associated with clinical outcomes. The ASPECTS can also associate with peripheral biomarkers that reflect the pathophysiological response of the brain to the ischemic stroke. OBJECTIVE: To investigate the association between peripheral biomarkers with the Alberta Stroke Program Early CT Score (ASPECTS) in individuals after ischemic stroke. METHODS: Patients over 18 years old with acute ischemic stroke were enrolled in this study. No patient was eligible for thrombolysis. The patients were submitted to non-contrast CT in the first 24 hours of admission, being the Alberta Stroke Program Early CT Score and clinical and molecular evaluations applied on the same day. The National Institutes of Health Stroke Scale (NIHSS), modified Rankin scale and the Mini-Mental State Examination for clinical evaluation were also applied to all subjects. Plasma levels of BDNF, VCAM-1, VEGF, IL-1ß, sTNFRs and adiponectin were determined by ELISA. RESULTS: Worse neurological impairment (NIHSS), cognitive (MEEM) and functional (Rankin) performance was observed in the group with changes in the NCTT. Patients with NCTT changes also exhibited higher levels of IL-1ß and adiponectin. In the linear multivariate regression, an adjusted R coefficient of 0.515 was found, indicating adiponectin and NIHSS as independent predictors of ASPECTS. CONCLUSION: Plasma levels of adiponectin are associated with the ASPECTS scores.

Clinical and molecular correlates of the ASPECTS in the acute phase of stroke / Correlação clínica e molecular com a ASPECTS na fase aguda do acidente vascular cerebral

ABSTRACT Background: The Alberta Stroke Program Early CT Score (ASPECTS) scale was developed for monitoring early ischemic changes on CT, being associated with clinical outcomes. The ASPECTS can also associate with peripheral biomarkers that reflect the pathophysiological response of the brain to the ischemic stroke. Objective: To investigate the association between peripheral biomarkers with the Alberta Stroke Program Early CT Score (ASPECTS) in individuals after ischemic stroke. Methods: Patients over 18 years old with acute ischemic stroke were enrolled in this study. No patient was eligible for thrombolysis. The patients were submitted to non-contrast CT in the first 24 hours of admission, being the Alberta Stroke Program Early CT Score and clinical and molecular evaluations applied on the same day. The National Institutes of Health Stroke Scale (NIHSS), modified Rankin scale and the Mini-Mental State Examination for clinical evaluation were also applied to all subjects. Plasma levels of BDNF, VCAM-1, VEGF, IL-1β, sTNFRs and adiponectin were determined by ELISA. Results: Worse neurological impairment (NIHSS), cognitive (MEEM) and functional (Rankin) performance was observed in the group with changes in the NCTT. Patients with NCTT changes also exhibited higher levels of IL-1β and adiponectin. In the linear multivariate regression, an adjusted R coefficient of 0.515 was found, indicating adiponectin and NIHSS as independent predictors of ASPECTS. Conclusion: Plasma levels of adiponectin are associated with the ASPECTS scores.

RESUMO Introdução: A Alberta Stroke Early Score (ASPECTS) foi desenvolvida para monitorização de alterações isquêmicas precoces na tomografia computadorizada de crânio, estando associada a desfechos clínicos. A ASPECTS também pode se associar aos biomarcadores periféricos que refletem a resposta fisiopatológica do cérebro ao AVC isquêmico. Objetivo: Investigar à associação entre os parâmetros periféricos com a Alberta Stroke Early Score (ASPECTS) em indivíduos após acidente vascular cerebral isquêmico. Métodos: Pacientes acima de 18 anos com AVC isquêmico agudo foram incluídos neste estudo. Nenhum paciente foi elegível para trombólise. Os pacientes foram submetidos à tomografia computadorizada sem contraste nas primeiras 24 horas da admissão, a ASPECTS e as avaliações clínicas e moleculares aplicadas no mesmo dia. O National Institutes of Health Stroke Scale (NIHSS), a escala de Rankin modificada e o Mini Exame do Estado Mental para avaliação clínica também foram aplicados a todos os indivíduos. Os níveis plasmáticos de BDNF, VCAM-1, VEGF, IL-1β, sTNFRs e adiponectina foram determinados por ELISA. Resultados: Pior desempenho neurológico (NIHSS), cognitivo (MEEM) e funcional (Rankin) foram observados no grupo com alterações na ASPECTS. Pacientes com alterações na ASPECTS também exibiram níveis mais altos de IL-1β e adiponectina. Na regressão multivariada linear, foi encontrado um coeficiente R ajustado de 0,515, indicando adiponectina e NIHSS como preditores independentes para a ASPECTS. Conclusão: Os níveis plasmáticos de adiponectina estão associados aos escores da ASPECTS.

Lamotrigine as a mood stabilizer: insights from the pre-clinical evidence.

INTRODUCTION: Lamotrigine (LTG) is a well-established anticonvulsant that is also approved for the prevention of mood relapses in bipolar disorder. However, the mechanisms underlying LTG mood stabilizing effects remain unclear. Areas covered: Herein, the pre-clinical evidence concerning LTG's' mode of action in depression and mania is reviewed. Bottlenecks and future perspectives for this expanding and promising field are also discussed. Pre-clinical studies have indicated that neurotransmitter systems, especially serotoninergic, noradrenergic and glutamatergic, as well as non-neurotransmitter pathways such as inflammation and oxidative processes might play a role in LTG's antidepressant effects. The mechanisms underlying LTG's anti-manic properties remain to be fully explored, but the available pre-clinical evidence points out to the role of glutamatergic neurotransmission, possibly through AMPA-receptors. Expert opinion: A major limitation of current pre-clinical investigations is that there are no experimental models that recapitulate the complexity of bipolar disorder. Significant methodological differences concerning time and dose of LTG treatment, administration route, animal strains, and behavioral paradigms also hamper the reproducibility of the findings, leading to contradictory conclusions. Moreover, the role of other mechanisms (e.g. inositol phosphate and GSK3ß pathways) implicated in the mode of action of different mood-stabilizers must also be consolidated with LTG.

Association between executive and food functions in the acute phase after stroke.

Purpose To investigate potential associations among executive, physical and food functions in the acute phase after stroke. Methods This is a cross-sectional study that evaluated 63 patients admitted to the stroke unit of a public hospital. The exclusion criteria were other neurological and/or psychiatric diagnoses. The tools for evaluation were: Mini-Mental State Examination and Frontal Assessment Battery for cognitive functions; Alberta Stroke Program Early CT Score for quantification of brain injury; National Institutes of Health Stroke Scale for neurological impairment; Modified Rankin Scale for functionality, and the Functional Oral Intake Scale for food function. Results The sample comprised 34 men (54%) and 29 women with a mean age of 63.6 years. The Frontal Assessment Battery was significantly associated with the other scales. In multivariate analysis, executive function was independently associated with the Functional Oral Intake Scale. Conclusion Most patients exhibited executive dysfunction that significantly compromised oral intake.

Association between executive and food functions in the acute phase after stroke / Associações entre função executiva e habilidade de alimentação pós-AVC na fase aguda

ABSTRACT Purpose To investigate potential associations among executive, physical and food functions in the acute phase after stroke. Methods This is a cross-sectional study that evaluated 63 patients admitted to the stroke unit of a public hospital. The exclusion criteria were other neurological and/or psychiatric diagnoses. The tools for evaluation were: Mini-Mental State Examination and Frontal Assessment Battery for cognitive functions; Alberta Stroke Program Early CT Score for quantification of brain injury; National Institutes of Health Stroke Scale for neurological impairment; Modified Rankin Scale for functionality, and the Functional Oral Intake Scale for food function. Results The sample comprised 34 men (54%) and 29 women with a mean age of 63.6 years. The Frontal Assessment Battery was significantly associated with the other scales. In multivariate analysis, executive function was independently associated with the Functional Oral Intake Scale. Conclusion Most patients exhibited executive dysfunction that significantly compromised oral intake.

RESUMO Objetivo Investigar potenciais associações entre funções executiva, física global e de alimentação na fase aguda do acidente vascular cerebral (AVC). Métodos Trata-se de estudo transversal envolvendo 63 pacientes admitidos em unidade de AVC de um hospital público. Os critérios de exclusão foram outros diagnósticos neurológicos e/ou psiquiátricos. Os instrumentos utilizados foram: Mini-Exame do Estado Mental e Bateria de Avaliação Frontal para avaliar funções cognitivas; Alberta Stroke Program Early CT Score para quantificação da lesão cerebral; National Institutes of Health Stroke Scale para comprometimento neurológico; Escala Modificada de Rankin para funcionalidade e Functional Oral Intake Scale para função alimentar. Resultados A amostra compreendeu 34 homens e 29 mulheres, sendo a idade média de 63,6 anos. A Bateria de Avaliação Frontal correlacionou significativamente com as demais escalas. Na análise multivariada, a variável independentemente associada com a função executiva foi a Functional Oral Intake Scale. Conclusão A maioria dos pacientes com AVC apresenta alterações das funções executivas que comprometem significativamente a alimentação oral.

Epidemiologia do traumatismo cranioencefálico no Brasil / Epidemiology of traumatic brain injury in Brazil

Introdução: O traumatismo cranioencefálico (TCE) é considerado a maior causa de morte e incapacidade em todo mundo, principalmente entre adultos jovens. No Brasil, estima-se que mais de um milhão de pessoas vivam com sequelas neurológicas decorrentes do TCE. Apesar da sua alta prevalência e taxas de incidência em constante elevação, estudos epidemiológicos permanecem escassos. Objetivo: Discutir as evidências disponíveis em relação ao perfil epidemiológico da população brasileira acometida por TCE. Métodos: Realizou- se uma revisão de literatura nas bases de dados SciELO, LILACS e PubMed. Os termos utilizados na busca foram traumatismo cranioencefálico, e/ou epidemiologia, e/ou Brasil. Para a busca no PubMed foram utilizados os termos em inglês traumatic brain injury, e/ou epidemiology, e/ou Brazil. Foram incluídos artigos originais, descritivos e de revisão que não restringiram a causa, a gravidade do TCE e a faixa etária estudada. Resultados: Foram encontrados oito estudos de 1993 a 2015, todos retrospectivos, sendo cinco deles realizados em hospitais de emergência e três baseados em bancos de dados. Indivíduos com menos de 40 anos, do sexo masculino foram os mais acometidos e as causas principais foram quedas e os acidentes de trânsito, destacando-se os motociclísticos. Conclusão: Estudos epidemiológicos robustos sobre o TCE no Brasil ainda são escassos. Todos os estudos foram retrospectivos e apenas dois apresentaram dados nacionais. Nesse contexto, estudos epidemiológicos de caráter prospectivo que investiguem de forma sistemática os fatores associados ao TCE, são urgentemente recomendados. (AU)

Introduction: Traumatic brain injury (TBI) is the leading cause of death and disability worldwide, especially among young adults. In Brazil, it is estimated that more than one million people live with disabilities due to TBI. Despite the high incidence of TBI and related socioeconomic burden, epidemiological studies are scarce. Objective: To discuss the available evidence regarding the epidemiological profile of Brazilian people victims of TBI. Methods: A literature review was conducted on the SciELO, LILACS and PubMed databases. The terms used were traumatic brain injury and/or epidemiology, and/or Brazil. Original, descriptive and review studies that investigated only one specific cause of TBI, only one level of severity or a specific age group were not included in the current review. Results: Eight retrospective articles published between 1993 and 2015 were included. Five studies were conducted in emergency hospitals and three studies were based on databases records. Men under 40 years old were the most affected group, and the main causes of TBI were falls and traffic accidents, especially involving motorcycle. Conclusion: Sound epidemiological studies on TBI are still rare. All studies included were retrospective and only two reported national data. In this scenario, prospective epidemiological studies that systematically investigate the profile of TBI victims in Brazil are urgently necessary. (AU)

The preclinical discovery and development of quetiapine for the treatment of mania and depression.

INTRODUCTION: Bipolar disorder is a chronic disabling condition characterized by alternating manic and depressive episodes. Bipolar disorder has been associated with functional impairment, poor quality of life, morbidity and mortality. Despite its significant clinical, social and economic burden, treatment options for bipolar disorder are still limited. Several clinical trials have shown efficacy of the atypical antipsychotic quetiapine (QTP) in the treatment of this condition. However, the mechanisms underlying the antidepressant and anti-manic effects of QTP remain poorly understood. Areas covered: The article provides the emerging evidence from pre-clinical studies regarding the antidepressant and anti-manic mechanisms of action of QTP. In combination with its primary active metabolite norquetiapine, QTP modulates several neurotransmitter systems, including serotonin, dopamine, noradrenaline and histamine. QTP also seems to influence mediators of the immune system. Expert opinion: Pre-clinical studies have provided valuable information on the potential antidepressant mechanisms of action of QTP, but pre-clinical studies on QTP's anti-manic effects are still scarce. A major problem refers to the lack of valid experimental models for bipolar disorder. Additionally, immune and genetic based studies are largely descriptive. The role of the QTP metabolite norquetiapine in modulating non-neurotransmitter systems also needs to be further addressed.

Platelet-activating factor receptor (PAFR) plays a crucial role in experimental global cerebral ischemia and reperfusion.

Stroke is one of the most frequent causes of death and disability worldwide leading to a significant clinical and socioeconomic burden. Although different mechanisms are involved in the pathogenesis of stroke, inflammatory response occurs after ischemia and contributes to the expansion of brain injury. Platelet-activating factor receptor (PAF) plays crucial roles in both physiological and pathological conditions in the brain. PAF receptor (PAFR) may be expressed on cellular and nuclear membranes of various cell types, especially leukocytes, platelets, endothelial cells, neuronal cells and microglia. Herein, using mice lacking the PAFR receptor (PAFR(-/-)), we investigate a potential role for this receptor during experimental transient global cerebral ischemia and reperfusion (BCCAo). In PAFR deficiency, we observed a significant improvement in the neurological deficits, which were associated with a reduction of brain infarcted area as evaluated by triphenyltetrazolium chloride (TTC). Moreover, a decrease in the percentage of necrotic cavities areas and in the frequency of ischemic neurons was also found by employing histometric analysis. In addition, in PAFR(-/-) mice there was prevention of caspase-3 activation and decreased vascular permeability and brain edema. Decreased brain levels of the cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and the chemokine (C-X-C motif) ligand 1 (CXCL1) by ELISA were also detected in PAFR(-/-) BCCAo animals. Taken together, our results suggest that PAFR activation might be crucial for the global brain ischemia and reperfusion injury.

Influence of Cytokines and Soluble Receptors in the Quality of Life and Functional Capacity of Workers Exposed to Silica.

OBJECTIVES: The aim of the study was to evaluate the plasma levels of inflammatory mediators in subjects exposed to silica, with and without silicosis compared with unexposed control group; and to check the association between inflammatory mediators with pulmonary function, quality of life, functional capacity, and dyspnea grade. METHODS: Inflammatory mediators were measured by enzyme-linked immunosorbent assay. There were 30 subjects exposed to silica and 24 control group. RESULTS: Interleukin-6 plasma levels were higher in subjects exposed to silica with and without silicosis than in the control group. There was a positive correlation between radiological severity and the quality of life, whereas there was a negative correlation between radiological severity and pulmonary function. A negative correlation between sTNFR1 plasma level and functional capacity was found. Interleukin-10 was negatively correlated with the quality of life total score and was positively correlated with the functional capacity and pulmonary function.

Increased BDNF levels in long-term bipolar disorder patients.

INTRODUCTION: Bipolar disorder (BD) is a prevalent, chronic and progressive illness. There is a growing body of evidence indicating that brain-derived neurotrophic factor (BDNF) plays an important role in the pathophysiology of BD. OBJECTIVE: The aim of this study was to evaluate BDNF plasma levels in BD patients with long term illness in comparison with controls. METHODS: 87 BD type I patients and 58 controls matched by age, gender and education level were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatric Interview and the patients by the Young Mania Rating Scale and the Hamilton Depression Rating Scale. The plasma levels of BDNF were measured by ELISA. RESULTS: On average, patients had suffered from BD for 23.4 years. In comparison with controls, BD patients with mania presented a 1.90-fold increase in BDNF plasma levels (p = .001), while BD patients in remission presented a 1.64-fold increase in BDNF plasma levels (p = .03). BDNF plasma levels were not influenced by age, length of illness or current medications. CONCLUSIONS: The present study suggests that long-term BD patients exhibit increased circulating levels of BDNF.

The behavior and diagnostic utility of procalcitonin and five other inflammatory molecules in critically ill patients with respiratory distress and suspected 2009 influenza a H1N1 infection.

OBJECTIVES: During the 2009 influenza A H1N1 pandemic, it became difficult to differentiate viral infections from other conditions in patients admitted to the intensive care unit. We sought to evaluate the behavior and diagnostic utility of procalcitonin, C-reactive protein and four other molecules in patients with suspected 2009 Influenza A H1N1 infection. METHODS: The serum levels of procalcitonin, C-reactive protein, tumor necrosis factor α, interferon γ, interleukin 1ß, and interleukin 10 were tested on admission and on days 3, 5, and 7 in 35 patients with suspected 2009 H1N1 infection who were admitted to two ICUs. RESULTS: Twelve patients had confirmed 2009 influenza A H1N1 infections, 6 had seasonal influenza infections, and 17 patients had negative swabs. The procalcitonin levels at inclusion and on day 3, and the C-reactive protein levels on day 3 were higher among subjects with 2009 influenza A H1N1 infections. The baseline levels of interleukin 1b were higher among the 2009 influenza A H1N1 patients compared with the other groups. The C-reactive protein levels on days 3, 5, and 7 and procalcitonin on days 5 and 7 were greater in non-surviving patients. CONCLUSION: Higher levels of procalcitonin, C-reactive protein and interleukin-1ß might occur in critically ill patients who had a 2009 H1N1 infection. Neither procalcitonin nor CRP were useful in discriminating severe 2009 H1N1 pneumonia. Higher levels of CRP and procalcitonin appeared to identify patients with worse outcomes.

The behavior and diagnostic utility of procalcitonin and five other inflammatory molecules in critically ill patients with respiratory distress and suspected 2009 influenza a H1N1 infection

OBJECTIVES: During the 2009 influenza A H1N1 pandemic, it became difficult to differentiate viral infections from other conditions in patients admitted to the intensive care unit. We sought to evaluate the behavior and diagnostic utility of procalcitonin, C-reactive protein and four other molecules in patients with suspected 2009 Influenza A H1N1 infection. METHODS: The serum levels of procalcitonin, C-reactive protein, tumor necrosis factor α, interferon γ, interleukin 1β, and interleukin 10 were tested on admission and on days 3, 5, and 7 in 35 patients with suspected 2009 H1N1 infection who were admitted to two ICUs. RESULTS: Twelve patients had confirmed 2009 influenza A H1N1 infections, 6 had seasonal influenza infections, and 17 patients had negative swabs. The procalcitonin levels at inclusion and on day 3, and the C-reactive protein levels on day 3 were higher among subjects with 2009 influenza A H1N1 infections. The baseline levels of interleukin 1b were higher among the 2009 influenza A H1N1 patients compared with the other groups. The C-reactive protein levels on days 3, 5, and 7 and procalcitonin on days 5 and 7 were greater in non-surviving patients. CONCLUSION: Higher levels of procalcitonin, C-reactive protein and interleukin-1β might occur in critically ill patients who had a 2009 H1N1 infection. Neither procalcitonin nor CRP were useful in discriminating severe 2009 H1N1 pneumonia. Higher levels of CRP and procalcitonin appeared to identify patients with worse outcomes.

Behavioral investigation of mice with experimental autoimmune encephalomyelitis / Investigação comportamental de camundongos com encefalomielite autoimune experimental

Multiple sclerosis is a neuroinflammatory disease that results in serious neurological disability. Besides physical impairment, behavioral symptoms are also common in patients with multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) is considered to be a model of multiple sclerosis and mimics the main features of the disease, such as demyelination and motor impairment. In this work, we aimed to study behavioral parameters in animals with EAE using the MOG35-55 model in C57BL/6 mice. We analyzed memory and anxiety in animals using the elevated plus maze, the step down inhibitory avoidance task and the memory recognition test. No differences in any tests were found when comparing controls and animals induced with EAE. Therefore, we conclude that behavioral changes in animals with EAE induced with MOG35-55 are probably subtle or absent.

Esclerose múltipla é uma doença neuroinflamatória que resulta em séria incapacidade neurológica. Além do comprometimento físico, sintomas comportamentais também são comuns em pacientes com esclerose múltipla. A encefalomielite autoimune experimental (EAE) é considerada um modelo de esclerose múltipla e mimetiza as principais caracte-rísticas da doença, como a desmielinização e a fraqueza motora. Neste trabalho, objetivamos estudar parâmetros comportamentais em animais com EAE usando o modelo de MOG35-55 em camundongos C57BL/6. Analisamos memória e ansiedade em animais utilizando o labirinto em cruz elevado, o teste da esquiva inibitória e o teste de memória de reconhecimento. Nenhuma diferença em quaisquer dos testes foi encontrada comparando animais controles e animais induzidos com EAE. Assim, concluímos que alterações comportamentais em animais com EAE induzidos com MOG35-55 são provavelmente sutis ou ausentes.

Behavioral investigation of mice with experimental autoimmune encephalomyelitis.

Multiple sclerosis is a neuroinflammatory disease that results in serious neurological disability. Besides physical impairment, behavioral symptoms are also common in patients with multiple sclerosis. Experimental autoimmune encephalomyelitis (EAE) is considered to be a model of multiple sclerosis and mimics the main features of the disease, such as demyelination and motor impairment. In this work, we aimed to study behavioral parameters in animals with EAE using the MOG(35-55) model in C57BL/6 mice. We analyzed memory and anxiety in animals using the elevated plus maze, the step down inhibitory avoidance task and the memory recognition test. No differences in any tests were found when comparing controls and animals induced with EAE. Therefore, we conclude that behavioral changes in animals with EAE induced with MOG(35-55) are probably subtle or absent.

Sintomas neurológicos agudos e residuais na malária / Acute and residual neurological symptoms in malaria

A malária é a principal e a mais grave doença parasitária no mundo. A infecção pelo Plasmodium falciparum é capaz de afetar diretamente o sistema nervoso central, causando déficits cognitivos e comportamentais que caracterizam a malária cerebral (MC). A MC é uma complicação decorrente da malária grave sendo responsável pela maioria dos casos de incapacidade e óbito. A ocorrência de seqüelas cognitivas e comportamentais após tratamento da MC tem sido descrita, principalmente em crianças. Adultos e crianças apresentam diferenças nas manifestações clínicas resultantes da MC. Geralmente, as crianças cursam com um espectro maior de alterações e apresentam déficits em vários domínios cognitivos após o tratamento da doença. Apesar da sua relevância clínica, os mecanismos patogênicos envolvidos no desenvolvimento das seqüelas resultantes da MC permanecem pouco elucidados. O entendimento desses mecanismos é fundamental para elaboração de intervenções terapêuticas adequadas que atuem na prevenção desses transtornos.

Malaria is the main and most serious parasitic disease in the world. Plasmodium falciparum infection can affect directly the central nervoussystem leading to cognitive and behavioral impairment which characterize cerebral malaria (CM). CM is a complication of severe malaria beingresponsible for almost all disability and death. The occurrence of cognitive and behavioral impairment after treatment has been reported, especially in children. Adults and children have differences in clinical manifestations related to CM. In general, children tend to present a greater spectrum of symptoms and impairment in almost all domains of cognition after infection treatment. Despite of its clinical relevance, pathogenic mechanisms involved in the development of CM sequelae remain poorly understood. A better understanding of these mechanisms is essential for the elaboration of appropriate therapeutic interventions which may contribute to the prevention of CM sequelae.