Extracellular vesicles in Alzheimer's disease.

Extracellular vesicles (EVs) are small vesicles released by cells that facilitate cell signaling. They are categorized based on their biogenesis and size. In the context of the central nervous system (CNS), EVs have been extensively studied for their role in both normal physiological functions and diseases like Alzheimer's disease (AD). AD is a neurodegenerative disorder characterized by cognitive decline and neuronal death. EVs have emerged as potential biomarkers for AD due to their involvement in disease progression. Specifically, EVs derived from neurons, astrocytes, and neuron precursor cells exhibit changes in quantity and composition in AD. Neuron-derived EVs have been found to contain key proteins associated with AD pathology, such as amyloid beta (Aß) and tau. Increased levels of Aß in neuron-derived EVs isolated from the plasma have been observed in individuals with AD and mild cognitive impairment, suggesting their potential as early biomarkers. However, the analysis of tau in neuron-derived EVs is still inconclusive. In addition to Aß and tau, neuron-derived EVs also carry other proteins linked to AD, including synaptic proteins. These findings indicate that EVs could serve as biomarkers for AD, particularly for early diagnosis and disease monitoring. However, further research is required to validate their use and explore potential therapeutic applications. To summarize, EVs are small vesicles involved in cell signaling within the CNS. They hold promise as biomarkers for AD, potentially enabling early diagnosis and monitoring of disease progression. Ongoing research aims to refine their use as biomarkers and uncover additional therapeutic applications.

As vesículas extracelulares (VEs) são pequenas estruturas liberadas pelas células que agem na sinalização celular. No sistema nervoso central (SNC), as VEs são estudadas em relação à doença de Alzheimer (DA), um distúrbio neurodegenerativo que cursa com declínio cognitivo e morte neuronal. As VEs podem ser biomarcadores potenciais para a DA devido ao seu papel na progressão da doença. As VEs derivadas de neurônios, astrócitos e células precursoras apresentam alterações na DA, contendo proteínas associadas à patologia da DA, como beta-amiloide (Aß) e tau. Níveis elevados de Aß foram observados nas VEs de neurônios de indivíduos com DA, sugerindo seu potencial como biomarcadores precoces. A análise de tau nas VEs de neurônios ainda é inconclusiva. Além disso, as VEs neurais carregam outras proteínas relacionadas à DA, incluindo proteínas sinápticas. As VEs podem ser promissoras como biomarcadores para o diagnóstico precoce e monitoramento da DA, porém mais pesquisas são necessárias para validar seu uso e explorar aplicações terapêuticas. Em resumo, as VEs são vesículas envolvidas na sinalização celular no SNC, com potencial como biomarcadores para a DA.

Extracellular vesicles in Alzheimer's disease / Vesículas extracelulares na doença de Alzheimer

Abstract Extracellular vesicles (EVs) are small vesicles released by cells that facilitate cell signaling. They are categorized based on their biogenesis and size. In the context of the central nervous system (CNS), EVs have been extensively studied for their role in both normal physiological functions and diseases like Alzheimer's disease (AD). AD is a neurodegenerative disorder characterized by cognitive decline and neuronal death. EVs have emerged as potential biomarkers for AD due to their involvement in disease progression. Specifically, EVs derived from neurons, astrocytes, and neuron precursor cells exhibit changes in quantity and composition in AD. Neuron-derived EVs have been found to contain key proteins associated with AD pathology, such as amyloid beta (Aß) and tau. Increased levels of Aß in neuron-derived EVs isolated from the plasma have been observed in individuals with AD and mild cognitive impairment, suggesting their potential as early biomarkers. However, the analysis of tau in neuron-derived EVs is still inconclusive. In addition to Aß and tau, neuron-derived EVs also carry other proteins linked to AD, including synaptic proteins. These findings indicate that EVs could serve as biomarkers for AD, particularly for early diagnosis and disease monitoring. However, further research is required to validate their use and explore potential therapeutic applications. To summarize, EVs are small vesicles involved in cell signaling within the CNS. They hold promise as biomarkers for AD, potentially enabling early diagnosis and monitoring of disease progression. Ongoing research aims to refine their use as biomarkers and uncover additional therapeutic applications.

Resumo As vesículas extracelulares (VEs) são pequenas estruturas liberadas pelas células que agem na sinalização celular. No sistema nervoso central (SNC), as VEs são estudadas em relação à doença de Alzheimer (DA), um distúrbio neurodegenerativo que cursa com declínio cognitivo e morte neuronal. As VEs podem ser biomarcadores potenciais para a DA devido ao seu papel na progressão da doença. As VEs derivadas de neurônios, astrócitos e células precursoras apresentam alterações na DA, contendo proteínas associadas à patologia da DA, como beta-amiloide (Aß) e tau. Níveis elevados de Aß foram observados nas VEs de neurônios de indivíduos com DA, sugerindo seu potencial como biomarcadores precoces. A análise de tau nas VEs de neurônios ainda é inconclusiva. Além disso, as VEs neurais carregam outras proteínas relacionadas à DA, incluindo proteínas sinápticas. As VEs podem ser promissoras como biomarcadores para o diagnóstico precoce e monitoramento da DA, porém mais pesquisas são necessárias para validar seu uso e explorar aplicações terapêuticas. Em resumo, as VEs são vesículas envolvidas na sinalização celular no SNC, com potencial como biomarcadores para a DA.

Effects of pre-analytical sample care and analysis methodology on measures of metabolic acidosis in hemodialysis patients.

INTRODUCTION: We evaluated the effects of pre-analytical care on total carbon dioxide (tCO2 ) in hemodialysis patients, as calculated by blood gas analysis (ctCO2 ) or measured by an enzymatic assay (mtCO2 ). METHODS: Blood samples were collected via vascular access before dialysis sessions. For blood gas analysis, eight aliquots were collected, refrigerated or non-refrigerated, and analyzed at 0, 4, 8, and 24 h after collection. A blood sample was then collected for the enzymatic method and distributed into 14 aliquots. Half of the aliquots were refrigerated. The samples analyzed at time point 0 were centrifuged immediately. The remaining aliquots of both the refrigerated and non-refrigerated clusters were centrifuged before storage. Samples were analyzed at 4, 8, and 24 h post-collection. FINDINGS: By blood gas analysis, no significant change was found in bicarbonate values over time, either in the non-refrigerated or refrigerated samples. ctCO2 values during the experiment showed a minor but statistically significant increase of questionable clinical relevance in both non-refrigerated and refrigerated aliquots. In the enzymatic assay, the reduction in mtCO2 levels during the experiment was negligible. The median absolute reductions at the end of the experiment were 1.77, 1.21, 1.04, and 1.12 mmol/L for the non-centrifuged/non-refrigerated, centrifuged/non-refrigerated, non-centrifuged/refrigerated, and centrifuged/refrigerated aliquots, respectively. DISCUSSION: Our results suggest that measured or calculated tCO2 levels of capped and cooled samples are adequate for analyzing the acid-base status of hemodialysis patients, even when such determination is not performed immediately after collection.

Worsening Renal Function and Congestion in Patients with Acute Heart Failure: A Study with Bioelectrical Impedance Vector Analysis (BIVA) and Neutrophil Gelatinase-Associated Lipocalin (NGAL). / Agravamento da Função Renal e Congestão em Pacientes com Insuficiência Cardíaca Aguda: Estudo com Análise Vetorial de Bioimpedância Elétrica (BIVA) e Lipocalina Associada à Gelatinase Neutrofílica (NGAL).

BACKGROUND: Worsening renal function (WRF) is frequently observed in the setting of aggressive diuresis for the treatment of acute decompensated heart failure (ADHF) and is associated with poor outcomes in some studies. OBJECTIVE: We sought to assess the relationship of WRF and congestion at discharge with events (cardiac death or heart failure hospitalization). METHODS: Eighty patients with ADHF were studied. WRF was defined by an absolute increase in serum creatinine of ≥0.5 mg/dL from the values measured at the time of admission. B-type natriuretic peptide (BNP) and plasma neutrophil gelatinase-associated lipocalin (NGAL) were measured at admission and at discharge. Congestive state at discharge was assessed using bioelectrical impedance vector analysis (BIVA). Primary endpoint was time to first event defined as a combination of cardiac death or heart failure hospitalization. Receiver operating characteristic (ROC) curve analysis was used to determine the best hydration index cutoff to predict events. Kaplan-Meier event-free survival curves were constructed and compared using the log-rank test. Cox proportional hazards models were used to investigate the association with events. The criterion for determining statistical significance was p<0.05. RESULTS: Mean age was 60.6±15 years, and 48 (60%) were male. Mean ejection fraction was 35.3±7.8%. WRF occurred in 37.5% of the sample. Baseline creatinine was associated with WRF (p<0.001), but neither admission BNP (p=0.35) nor admission NGAL (p=0.18) was predictor of WRF. Using Cox proportional hazard models, hydration index at discharge calculated with BIVA was significantly associated with events (HR 1.39, 95% CI 1.25-1.54, p<0.0001) but not WRF (HR 2.14, 95% CI 0.62-7.35, p=0.22). CONCLUSION: Persistent congestion at discharge was associated with worse outcomes. WRF seems to be related to hemodynamic changes during the decongestion process but not to kidney tubular injuries.

FUNDAMENTO: O agravamento da função renal (AFR) é frequentemente observado na terapia agressiva com diuréticos para o tratamento de insuficiência cardíaca aguda descompensada (ICAD) e está associado com piores desfechos em alguns estudos. OBJETIVO: Avaliar a relação de AFR e congestão na alta hospitalar com ocorrência de eventos (morte cardíaca ou internação por insuficiência cardíaca). MÉTODOS: Oitenta pacientes com ICAD foram estudados. O AFR foi definido por um aumento absoluto (≥0,5 mg/dL) nos níveis séricos de creatinina a partir dos valores obtidos na admissão. Concentrações de peptídeo natriurético do tipo B (BNP) e lipocalina associada à gelatinase neutrofílica (NGAL) foram medidas na admissão e na alta hospitalar. Congestão foi avaliada na alta utilizando a análise vetorial de bioimpedância elétrica (BIVA). O desfecho primário foi o tempo para o primeiro evento, definido como uma combinação de morte cardíaca ou hospitalização por insuficiência cardíaca. Análise de curva Característica de Operação do Receptor (curva ROC) foi realizada para determinar o ponto de corte de IH mais adequado para predição de eventos. Curvas Kaplan-Meier de sobrevida livre de eventos foram construídas e comparadas usando o teste de log-rank. Modelos de riscos proporcionais de Cox foram usados para investigar a associação com eventos. O critério para se estabelecer significância estatística foi um p<0.05. RESULTADOS: A idade média foi 60,6 ± 15,0 anos, e 48 (60%) pacientes eram do sexo masculino. A fração de ejeção média foi 35,3±7,8%. O AFR ocorreu em 37,5% da amostra. A creatinina basal associou-se com AFR (p<0,001), mas nem BNP (p=0,35) nem NGAL (p=0,18) na admissão foram preditores de AFR. Usando modelos de riscos proporcionais de Cox, o índice de hidratação na alta, estimado por BIVA, associou-se significativamente com ocorrência de eventos (HR 1,39; IC95% 1,25-1,54, p<0,0001), mas não com AFR (HR 2,14; IC95% 0,62-7,35, p=0,22). CONCLUSÃO: A congestão persistente na alta associou-se com piores desfechos. O AFR parece estar relacionado com alterações hemodinâmicas durante o processo de descongestionamento, mas não com lesões renais.

Agravamento da Função Renal e Congestão em Pacientes com Insuficiência Cardíaca Aguda: Estudo com Análise Vetorial de Bioimpedância Elétrica (BIVA) e Lipocalina Associada à Gelatinase Neutrofílica (NGAL) / Worsening Renal Function and Congestion in Patients with Acute Heart Failure: A Study with Bioelectrical Impedance Vector Analysis (BIVA) and Neutrophil Gelatinase-Associated Lipocalin (NGAL)

Resumo Fundamento: O agravamento da função renal (AFR) é frequentemente observado na terapia agressiva com diuréticos para o tratamento de insuficiência cardíaca aguda descompensada (ICAD) e está associado com piores desfechos em alguns estudos. Objetivo: Avaliar a relação de AFR e congestão na alta hospitalar com ocorrência de eventos (morte cardíaca ou internação por insuficiência cardíaca). Métodos: Oitenta pacientes com ICAD foram estudados. O AFR foi definido por um aumento absoluto (≥0,5 mg/dL) nos níveis séricos de creatinina a partir dos valores obtidos na admissão. Concentrações de peptídeo natriurético do tipo B (BNP) e lipocalina associada à gelatinase neutrofílica (NGAL) foram medidas na admissão e na alta hospitalar. Congestão foi avaliada na alta utilizando a análise vetorial de bioimpedância elétrica (BIVA). O desfecho primário foi o tempo para o primeiro evento, definido como uma combinação de morte cardíaca ou hospitalização por insuficiência cardíaca. Análise de curva Característica de Operação do Receptor (curva ROC) foi realizada para determinar o ponto de corte de IH mais adequado para predição de eventos. Curvas Kaplan-Meier de sobrevida livre de eventos foram construídas e comparadas usando o teste de log-rank. Modelos de riscos proporcionais de Cox foram usados para investigar a associação com eventos. O critério para se estabelecer significância estatística foi um p<0.05. Resultados: A idade média foi 60,6 ± 15,0 anos, e 48 (60%) pacientes eram do sexo masculino. A fração de ejeção média foi 35,3±7,8%. O AFR ocorreu em 37,5% da amostra. A creatinina basal associou-se com AFR (p<0,001), mas nem BNP (p=0,35) nem NGAL (p=0,18) na admissão foram preditores de AFR. Usando modelos de riscos proporcionais de Cox, o índice de hidratação na alta, estimado por BIVA, associou-se significativamente com ocorrência de eventos (HR 1,39; IC95% 1,25-1,54, p<0,0001), mas não com AFR (HR 2,14; IC95% 0,62-7,35, p=0,22). Conclusão: A congestão persistente na alta associou-se com piores desfechos. O AFR parece estar relacionado com alterações hemodinâmicas durante o processo de descongestionamento, mas não com lesões renais.

Abstract Background: Worsening renal function (WRF) is frequently observed in the setting of aggressive diuresis for the treatment of acute decompensated heart failure (ADHF) and is associated with poor outcomes in some studies. Objective: We sought to assess the relationship of WRF and congestion at discharge with events (cardiac death or heart failure hospitalization). Methods: Eighty patients with ADHF were studied. WRF was defined by an absolute increase in serum creatinine of ≥0.5 mg/dL from the values measured at the time of admission. B-type natriuretic peptide (BNP) and plasma neutrophil gelatinase-associated lipocalin (NGAL) were measured at admission and at discharge. Congestive state at discharge was assessed using bioelectrical impedance vector analysis (BIVA). Primary endpoint was time to first event defined as a combination of cardiac death or heart failure hospitalization. Receiver operating characteristic (ROC) curve analysis was used to determine the best hydration index cutoff to predict events. Kaplan-Meier event-free survival curves were constructed and compared using the log-rank test. Cox proportional hazards models were used to investigate the association with events. The criterion for determining statistical significance was p<0.05. Results: Mean age was 60.6±15 years, and 48 (60%) were male. Mean ejection fraction was 35.3±7.8%. WRF occurred in 37.5% of the sample. Baseline creatinine was associated with WRF (p<0.001), but neither admission BNP (p=0.35) nor admission NGAL (p=0.18) was predictor of WRF. Using Cox proportional hazard models, hydration index at discharge calculated with BIVA was significantly associated with events (HR 1.39, 95% CI 1.25-1.54, p<0.0001) but not WRF (HR 2.14, 95% CI 0.62-7.35, p=0.22). Conclusion: Persistent congestion at discharge was associated with worse outcomes. WRF seems to be related to hemodynamic changes during the decongestion process but not to kidney tubular injuries.

Laboratory findings in SARS-CoV-2 infections: State of the art.

OBJECTIVE: The scientific community is constantly assessing the clinical and laboratory manifestations of COVID-19 in the organism. In view of the fragmentation of the large amount of information, knowledge gaps in relation to laboratory markers, and scarcity of papers in Portuguese, we propose a Literature review on laboratory changes observed in patients infected with SARS-CoV-2. METHODS: Analysis of articles published between December 2019 and May 2020 on the PubMed and SciELO databases. The articles were identified, filtered, and evaluated based on the approach to the subject, language, and impact. Then, the articles were subjected to a thorough reading, in full, by 4 (four) independent researchers. RESULTS: Leukopenia and lymphopenia were included in most studies, even in case definitions. Platelet count and platelet-lymphocyte ratio, at peak platelet, were associated with advanced age and longer hospital stay. Eosinopenia showed a sensitivity of 74.7% and specificity of 68.7% and, together with increased CRP, these are one of the future prospects for screening for disease. A high level of procalcitonin may indicate bacterial co-infection, leading to a worse prognosis. COVID-19 manifests itself with increased levels of many inflammatory markers such as IL-1, IL-2, IL-6, IL-7, IL-12, IP10, IFN-γ, MIP1A, MCP1, GSCF, TNF-α, and MCP1/CCL2, as well as LDH, ESR, D-dimer, CK, ALT, and AST. CONCLUSION: There is a need for further studies on the new SARS-CoV-2. So far, there is no consensus regarding laboratory findings and their usefulness, whether as a prognostic marker, mortality, or disease severity.

Laboratory findings in SARS-CoV-2 infections: State of the art

SUMMARY OBJECTIVE The scientific community is constantly assessing the clinical and laboratory manifestations of COVID-19 in the organism. In view of the fragmentation of the large amount of information, knowledge gaps in relation to laboratory markers, and scarcity of papers in Portuguese, we propose a Literature review on laboratory changes observed in patients infected with SARS-CoV-2. METHODS Analysis of articles published between December 2019 and May 2020 on the PubMed and SciELO databases. The articles were identified, filtered, and evaluated based on the approach to the subject, language, and impact. Then, the articles were subjected to a thorough reading, in full, by 4 (four) independent researchers. RESULTS Leukopenia and lymphopenia were included in most studies, even in case definitions. Platelet count and platelet-lymphocyte ratio, at peak platelet, were associated with advanced age and longer hospital stay. Eosinopenia showed a sensitivity of 74.7% and specificity of 68.7% and, together with increased CRP, these are one of the future prospects for screening for disease. A high level of procalcitonin may indicate bacterial co-infection, leading to a worse prognosis. COVID-19 manifests itself with increased levels of many inflammatory markers such as IL-1, IL-2, IL-6, IL-7, IL-12, IP10, IFN-γ, MIP1A, MCP1, GSCF, TNF-α, and MCP1/CCL2, as well as LDH, ESR, D-dimer, CK, ALT, and AST. CONCLUSION There is a need for further studies on the new SARS-CoV-2. So far, there is no consensus regarding laboratory findings and their usefulness, whether as a prognostic marker, mortality, or disease severity.

RESUMO OBJETIVO A comunidade científica avalia a todo momento, as manifestações clínicas e laboratoriais da COVID-19 no organismo e, em vista da fragmentação da grande quantidade de informações, lacunas de conhecimento em relação aos marcadores laboratoriais e escassez de trabalhos em português, propomos uma revisão de Literatura sobre alterações laboratoriais observadas em pacientes infectados por SARS-CoV-2. MÉTODOS Análise de artigos publicados entre dezembro de 2019 a maio de 2020 nas plataformas PubMed e SciELO. Os artigos foram identificados, filtrados e avaliados com base na abordagem ao assunto, idioma e impacto. Depois, os artigos foram submetidos a uma minuciosa leitura, na íntegra, por 4 (quatro) pesquisadores independentes. RESULTADOS A leucopenia e a linfopenia constaram na maioria dos trabalhos, presente até em definições de caso. A contagem de plaquetas e a razão plaquetas-linfócitos, no pico plaquetário, foram associados à idade avançada e maior tempo de hospitalização. A eosinopenia apresentou sensibilidade de 74,7% e especificidade de 68,7% e, juntamente com aumento da PCR, são uma das perspectivas futuras de triagem para doença. O alto nível de procalcitonina pode indicar uma co-infecção bacteriana, levando a pior prognóstico. A COVID-19 se manifesta com níveis aumentados de muitos marcadores inflamatórios como IL-1, IL-2, IL-6, IL-7, IL-12, IP10, IFN-γ, MIP1A, MCP1, GSCF, TNF-α e MCP1/CCL2, bem como LDH, VHS, dímero-D, CK, ALT e AST. CONCLUSÃO Há necessidade de estudos adicionais sobre o novo SARS-CoV-2. Até agora, não há unanimidade em relação aos achados laboratoriais e sua utilidade, seja como marcador prognóstico, de mortalidade, ou de severidade de doença.

COVID-19: clinical and laboratory manifestations in novel coronavirus infection / COVID-19: manifestações clínicas e laboratoriais na infecção pelo novo coronavírus

ABSTRACT COVID-19 is a highly contagious disease caused by the coronavirus of severe acute respiratory syndrome 2 (SARS-CoV-2). In 2020, due to the outbreak, it was considered by the World Health Organization (WHO) as a pandemic. The infection caused by the novel coronavirus has high mortality in a small portion of the infected population, especially in elderly, immunosuppressed, diabetic, cardiac, and hypertensive individuals. Many infected are asymptomatic (and may be carriers) or present mild or moderate flu-like symptoms. The most severe clinical picture of COVID-19 is characterized by an inflammatory cytokine storm, with hematological changes and coagulation dysfunction, which can lead to tissue damage and death. Nonspecific laboratory biomarkers may be either increased or decreased as the course of the disease progresses and are often useful in predicting complications of the disease, such as the use of D-dimer and platelet/lymphocyte ratio. Specific laboratory diagnosis is based on the detection of viral ribonucleic acid (RNA) by real-time polymerase chain reaction (RT-PCR) of nasal and oropharyngeal swab samples; it is more effective when performed in the first days after symptom onset. Serological tests are useful in detecting the immune response, since both class M (IgM) and class G (IgG) immunoglobulin antibodies can be detected seven days after the onset of clinical symptoms, and may extend for more than 25 days, although not exempting the individual from remaining infectious, depending on their viral load and clinical presentation. The rational use of specific laboratory markers must respect the disease chronology, and the correct interpretation may provide subsidies for a better management of affected patients, as well as identifying asymptomatic carriers or those with mild symptoms.

RESUMEN La COVID-19 es una enfermedad altamente contagiosa causada por el coronavirus del síndrome respiratorio agudo grave (SARS-CoV-2). En 2002, a causa del brote, fue reconocida como una pandemia por la Organización Mundial de la Salud (OMS). La infección por el nuevo coronavirus provoca alta mortalidad en una pequeña parcela de la población infectada, especialmente en ancianos, pacientes inmunodeprimidos, diabéticos, cardiópatas e hipertensos. Muchos infectados son asintomáticos (y pueden ser portadores) o presentan síntomas leves a moderados, como en un estado gripal. El cuadro clínico de la COVID-19 en la forma más grave es caracterizado por una tormenta inflamatoria de citoquinas, con cambios hematológicos y de la coagulación que pueden llevar a daño tisular y muerte. Pruebas de laboratorio inespecíficas pueden presentar tasas más altas o bajas según el curso de la enfermedad, y muchas veces son útiles en la predicción de complicaciones, como el uso del dímero D y la ratio plaquetas/linfocitos. El diagnóstico de laboratorio específico se basa en la detección del ácido ribonucleico (ARN) viral por reacción en cadena de la polimerasa (PCR) en tiempo real de muestras de hisopado nasal y orofaríngeo; es más efectiva en los primeros días tras el inicio de los síntomas. Pruebas serológicas son útiles para detectar la respuesta inmune, pues tanto los anticuerpos de la inmunoglobulina M (IgM) como de la G (IgG) pueden se detectar siete días después del inicio de los síntomas clínicos, y pueden permanecer por más de 25 días, aunque no eximen al individuo de seguir infeccioso, dependiendo de su carga viral y presentación clínica. El uso racional de los marcadores de laboratorio específicos debe respetar la cronología de la enfermedad, y la interpretación correcta puede proporcionar recursos para un mejor manejo de los pacientes afectados, así como identificar portadores asintomáticos o con pocos síntomas.

RESUMO COVID-19 é uma doença altamente contagiosa provocada pelo coronavírus da síndrome respiratória aguda grave 2 (SARS-CoV-2). Em 2020, devido ao surto, foi caracterizada pela Organização Mundial da Saúde (OMS) como pandemia. A infecção causada pelo novo coronavírus tem alta mortalidade em uma pequena parcela da população infectada, especialmente em indivíduos idosos, imunodeprimidos, diabéticos, cardiopatas e hipertensos. Muitos infectados são assintomáticos (e podem ser portadores) ou apresentam sintomas leves a moderados, semelhantes ao estado gripal. O quadro clínico da COVID-19 na forma mais severa é caracterizado por uma tempestade inflamatória de citocinas, com alterações hematológicas e da coagulação que podem levar ao dano tecidual e morte. Exames laboratoriais inespecíficos podem apresentar-se mais elevados ou diminuídos conforme o curso da doença, e muitas vezes são úteis na predição de complicações, como o uso do D-dímero e a razão plaqueta/linfócitos. O diagnóstico laboratorial específico se baseia na detecção do ácido ribonucleico (RNA) viral por reação em cadeia da polimerase em tempo real (RT-PCR) de amostras de suabe nasal e orofaríngeo; é mais efetivo nos primeiros dias após o início dos sintomas. Testes sorológicos são úteis na detecção da resposta imune, pois tanto os anticorpos da imunoglobulina da classe M (IgM) quanto da classe G (IgG) podem ser detectados após sete dias do início dos sintomas clínicos, podendo se estender por mais de 25 dias, embora não isente o indivíduo de continuar infectante, dependendo de sua carga viral e apresentação clínica. O uso racional dos marcadores laboratoriais específicos deve respeitar a cronologia da doença, e a interpretação correta pode fornecer subsídios para um melhor manejo dos pacientes acometidos, bem como identificar portadores assintomáticos ou com pouco sintomas.

Clinical, laboratorial diagnosis and prophylaxis of measles in Brazil / Diagnóstico clínico, laboratorial e profilático do sarampo no Brasil

ABSTRACT Measles is an acute febrile exanthematic disease of viral etiology, highly contagious, being the cause of morbidity and mortality of children in developing countries, whereas it has become rarer in developed countries due to vaccination. Its differential diagnosis should be made with other childhood viral respiratory diseases such as influenza, rhinovirus and adenovirus, and exanthematic febrile diseases such as rubella, roseola and varicella. In tropical regions, it should be performed with dengue, zika and chikungunya. Its clinical picture presents the following phases: incubation, usually asymptomatic; a prodrome, in which fever, malaise, coryza can occur, besides Koplik's signs; exanthematic, with presence of maculopapular exanthema after the fever condition that progresses to a craniocaudal evolution, with clinical improvement in uncomplicated cases. Common complications are pneumonia, otitis media, keratitis; the rarest are acute disseminated encephalomyelitis and subacute sclerosing panencephalitis. Nonspecific laboratory alterations are seen in the blood count. The specific laboratory diagnosis is based on the detection of viral ribonucleic acid (RNA) [polymerase chain reaction (PCR) of nasal swab samples, oral mucosa or urine]. Immunoglobulin class M (IgM) can be detected during the exanthematous period by enzyme-linked immunosorbent assay (ELISA), and immunoglobulin class G (IgG) throughout the convalescence period, and the detection of specific IgG by the plaque reduction neutralization test may also be performed. The prophylaxis of the disease is based on vaccination in children from 15 months in order to reach about 85% to 95% of the population, what confers herd immunity. Thus, vaccination is the most effective measure in combating measles, since the treatment consists only of clinical and symptomatic support.

RESUMEN El sarampión es una enfermedad exantemática febril aguda de etiología viral altamente contagiosa. Causa morbilidad y mortalidad de niños en países en desarrollo, mientras que se hizo más raro en países desarrollados gracias a la vacunación. El diagnóstico diferencial se hace con otras enfermedades infantiles, como influenza, rinovirus, adenovirus, rubéola, roséola y varicela. En regiones tropicales, incluye dengue, zika y chikungunya. Su cuadro clínico presenta las siguientes fases: incubación - en general asintomática; pródromo - en la cual pueden ocurrir fiebre, malestar y coriza, además de manchas de Koplik; y la exantemática - con presencia de exantema máculo-papular después del cuadro febril, que se disemina desde la cara a tronco y extremidades, con mejora clínica en casos no complicados. Complicaciones comunes son neumonía, otitis media y queratoconjuntivitis; las más raras, encefalomielitis aguda diseminada y panencefalitis esclerosante subaguda. Alteraciones inespecíficas de laboratorio son vistas en el hemograma. El diagnóstico específico de laboratorio se basa en el aislamiento del ácido ribonucleico (ARN) viral (PCR de muestras nasales, mucosa oral u orina). La inmunoglobulina M (IgM) pude ser detectada durante el período exantemático por ensayo por inmunoadsorción ligado a enzimas (ELISA); la inmunoglobulina G (IgG), a lo largo del período de convalecencia, y la detección de IgG específica por la prueba de neutralización por reducción de placa. La profilaxis de la enfermedad se basa en vacunación en niños desde los 15 meses de edad, buscando alcanzar 85%-95% de la población, lo que confiere inmunidad de grupo. La vacunación es la medida más eficaz en el combate al sarampión, puesto que el tratamiento consiste sólo en soporte clínico.

RESUMO O sarampo é uma doença exantemática febril aguda de etiologia viral altamente contagiosa. É causa de morbidade e mortalidade de crianças em países em desenvolvimento, ao passo que se tornou mais rara em países desenvolvidos devido à vacinação. O diagnóstico diferencial deve ser realizado em relação a outras doenças da infância, como influenza, rinovírus, adenoviroses, rubéola, roséola e varicela. Já em regiões tropicais, inclui dengue, vírus da zika e chikungunya. Seu quadro clínico apresenta as seguintes fases: a de incubação - em geral assintomática; a prodrômica - na qual podem ocorrer febre, mal-estar e coriza, além de sinais de Koplik; e a exantemática - com presença de exantema maculopapular após o quadro febril, que progride de forma craniocaudal, com melhora clínica em casos não complicados. Complicações comuns são pneumonia, otite média e ceratoconjuntivite; as mais raras, encefalomielite disseminada aguda e panencefalite esclerosante subaguda. Alterações laboratoriais inespecíficas são vistas no hemograma. O diagnóstico laboratorial específico baseia-se na detecção do ácido ribonucleico (RNA) viral [reação em cadeia da polimerase (PCR) de amostras de swab nasal, mucosa oral ou urina]. Imunoglobulina da classe M (IgM) pode ser detectada durante o período exantemático por ensaio de imunoadsorção enzimática (ELISA) e imunoglobulina da classe G (IgG), ao longo do período de convalescença, podendo também ser realizada a detecção de IgG específica pelo teste de neutralização por redução de placas. A profilaxia da doença é baseada na vacinação em crianças a partir dos 15 meses de idade, visando atingir cerca de 85% a 95% da população, o que confere imunidade de rebanho. A vacinação é a medida mais eficaz no combate ao sarampo, visto que o tratamento consiste apenas em suporte clínico.

Evaluation of vitamin D plasma levels after mild exposure to the sun with photoprotection.

BACKGROUND: Most of the organism's vitamin D (VD) is obtained through the cutaneous synthesis after exposure to the sun's UVB radiation. Sunscreens are indicated for the prevention of actinic damage to the skin, however, there are few clinical trials assessing the synthesis of cutaneous VD in real-life situations of sun exposure with ordinary clothing and usual photoprotection. OBJECTIVES: To evaluate the synthesis of VD with suberythemal sun exposure in healthy adults using topical photoprotection (SPF 30). METHODS: Quasi-experimental study, conducted at Rio de Janeiro (Brazil), during winter, with 95 healthy adults who had 25-OH-VD checked twice, 24 hours apart, and were exposed to the sun (UVB=20 mJ/cm2), according to a randomized grouping: SC - use of SPF 30 on the face, neck and chest (n=64), NO - no sunscreens (n=10), CO - confined from sun exposure for 24h (n=21). The groups were matched according to the propensity score related to gender, age, phototype, body mass index, glycosylated hemoglobin and baseline levels of VD. The outcome evaluated was the variation (ΔVD) in serum level of 25-OH-VD (ng/ml) between the groups. RESULTS: A statistically significant difference was identified between CO and SC groups [median (p25-p75)]: ΔVD =1.4 (-0.3-3.6) vs. 5.5 (4.8-6.6); p<0.01. There was no difference between SC and NO groups: 5.4 (3.1-6.1) vs. 4.1 (2.5-6.0); p=0.17. STUDY LIMITATIONS: Laboratory analysis technique (chemiluminescence) with great variability, loss of food intake standardatization, unbalanced groups. CONCLUSIONS: Suberythemal sun exposure with sunscreen (SPF 30) provides similar vitamin D serum variation than without photoprotection in healthy adults.

Evaluation of vitamin D plasma levels after mild exposure to the sun with photoprotection

Abstract: Background: Most of the organism's vitamin D (VD) is obtained through the cutaneous synthesis after exposure to the sun's UVB radiation. Sunscreens are indicated for the prevention of actinic damage to the skin, however, there are few clinical trials assessing the synthesis of cutaneous VD in real-life situations of sun exposure with ordinary clothing and usual photoprotection. Objectives: To evaluate the synthesis of VD with suberythemal sun exposure in healthy adults using topical photoprotection (SPF 30). Methods: Quasi-experimental study, conducted at Rio de Janeiro (Brazil), during winter, with 95 healthy adults who had 25-OH-VD checked twice, 24 hours apart, and were exposed to the sun (UVB=20 mJ/cm2), according to a randomized grouping: SC - use of SPF 30 on the face, neck and chest (n=64), NO - no sunscreens (n=10), CO - confined from sun exposure for 24h (n=21). The groups were matched according to the propensity score related to gender, age, phototype, body mass index, glycosylated hemoglobin and baseline levels of VD. The outcome evaluated was the variation (ΔVD) in serum level of 25-OH-VD (ng/ml) between the groups. Results: A statistically significant difference was identified between CO and SC groups [median (p25-p75)]: ΔVD =1.4 (-0.3-3.6) vs. 5.5 (4.8-6.6); p<0.01. There was no difference between SC and NO groups: 5.4 (3.1-6.1) vs. 4.1 (2.5-6.0); p=0.17. Study limitations: Laboratory analysis technique (chemiluminescence) with great variability, loss of food intake standardatization, unbalanced groups. Conclusions: Suberythemal sun exposure with sunscreen (SPF 30) provides similar vitamin D serum variation than without photoprotection in healthy adults.

Effects of Heart Rate Reduction With Either Pyridostigmine or Ivabradine in Patients With Heart Failure: A Randomized, Double-Blind Study.

BACKGROUND: Heart rate (HR) reduction with ivabradine has been proved to reduce hospitalization and death from heart failure (HF). We sought to investigate whether pyridostigmine would effectively reduce HR in patients with chronic HF as compared with ivabradine. METHODS: Twenty-one patients with HF who were in sinus rhythm with a resting HR over 70 bpm, despite optimal medical treatment, were included in a randomized, double-blind study comparing pyridostigmine versus ivabradine. The initial dose of ivabradine was 5 mg twice daily to reach a target HR between 50 and 60 bpm and could be titrated to a maximum of 7.5 mg twice daily. Pyridostigmine was used in a fixed dose of 30 mg 3 times daily. RESULTS: The baseline HR for ivabradine and pyridostigmine groups was 89.1 (13.5) and 80.1 (7.2) bpm, respectively (P = .083). After 6 months of treatment, HR was significantly reduced to 64.8 (8.3) bpm in the ivabradine group (P = .0014) and 63.6 (5.9) bpm in the pyridostigmine group (P = .0001). The N-terminal pro-B-type natriuretic peptide was reduced in the ivabradine group (median: 1308.4 [interquartile range: 731-1896] vs 755.8 [134.5-1014] pg/mL; P = .027) and in the pyridostigmine group (132.8 [89.9-829] vs 100.7 [38-360] pg/mL; P = .002). Inflammatory markers interleukin-1, interleukin-6, and tumor necrosis factor were reduced in both groups. Exercise capacity was improved in both groups, with increments in volume of oxygen utilization (V˙O2; ivabradine: 13.1 vs 15.6, P = .048; pyridostigmine: 13.3 vs 16.7, P = .032). Heart rate recovery in the first minute postexercise was improved with pyridostigmine (11.8 [3.9] vs 18 [6.5]; P = .046), but not with ivabradine (13.3 [6.9] vs 14.1 [8.2]; P = .70). No differences in either group were observed in the myocardial scintigraphy with 123-iodine-metaiodobenzylguanidine. CONCLUSION: Both drugs significantly reduced HR, with improvements in exercise capacity and in neurohormonal and inflammatory profiles.

Yellow fever: laboratorial diagnosis and clinical manifestations / Febre amarela: diagnóstico laboratorial e manifestações clínicas

ABSTRACT Yellow fever is an infectious disease of acute evolution, initially non-contagious, transmitted by a ribonucleic acid (RNA) virus that belongs to the Flaviviridae family. In the period from December 2016 until March 17, 2017, 1, 561 suspected cases of wild yellow fever were reported to the Ministry of Health in Brazil. Among these cases, 850 (54.8%) remain under investigation, 448 (28.7%) were confirmed and 263 (16.9%) were discarded. Out of the total cases reported, 264 died, 144 (54.5%) were confirmed for the disease, 110 (41.7%) were investigated and 10 (3.8%) were discarded. The case fatality rate among confirmed cases was 32.2%. The specific diagnosis for determining the etiology of infection can be made by demonstrating the humoral response of the antibodies, virus isolation, or histopathological study of the liver. Only through early laboratory diagnosis and epidemiological data supply can government and cooperative organizations establish public policies to combat future disease epidemics, as well as social awareness campaigns.

RESUMO A febre amarela é uma doença infecciosa de evolução aguda, a princípio não contagiosa, transmitida por um vírus do ácido ribonucleico (RNA) que pertence à família Flaviviridae. No período de dezembro de 2016 a 17 de março de 2017, foram notificados ao Ministério da Saúde, 1.561 casos suspeitos de febre amarela silvestre no Brasil. Destes, 850 (54, 8%) permanecem em investigação; 448 (28, 7%) foram confirmados e 263 (16, 9%), descartados. Do total dos casos notificados, 264 evoluíram para óbito, sendo 144 (54, 5%) confirmados para a doença; 110 (41, 7%) em investigação e 10 (3, 8%), descartados. A taxa de letalidade entre os casos confirmados foi de 32, 2%. O diagnóstico específico para determinação da etiologia da infecção pode ser feito por meio da demonstração da resposta humoral dos anticorpos, do isolamento do vírus ou do estudo histopatológico do fígado. Apenas mediante o diagnóstico laboratorial precoce e o abastecimento de dados epidemiológicos é que governo e organizações cooperativas poderão estabelecer políticas públicas de combate a futuras epidemias da doença, bem como campanhas de conscientização social.

Increased Cytokeratin 19 Fragment Levels Are Positively Correlated with Adenosine Deaminase Activity in Malignant Pleural Effusions from Adenocarcinomas.

Adenosine deaminase (ADA) and cytokeratin 19 (CK19) are known pleural biomarkers. Although ADA in humans functions mainly in the immune system, it also appears to be associated with the differentiation of epithelial cells. Keratin filaments are important structural stabilizers of epithelial cells and potent biomarkers in epithelial differentiation. This study aimed to investigate the simultaneous presence of the ADA enzyme and CK19 fragments to assess epithelial differentiation in malignant and benign pleural fluids. Diagnosis of the cause of pleural effusion syndrome was confirmed by means of standard examinations and appropriate surgical procedures. An ADA assay, in which ADA irreversibly catalyzes the conversion of adenosine into inosine, was performed using a commercial kit. The CK19 assay was performed using a CYFRA 21-1 kit, developed to detect quantitative soluble fragments of CK19 using an electrochemiluminescence immunoassay. One hundred nineteen pleural fluid samples were collected from untreated individuals with pleural effusion syndrome due to several causes. ADA levels only correlated with CK19 fragments in adenocarcinomas, with high significance and good correlation (rho = 0.5145, P = 0.0036). However, further studies are required to understand this strong association on epithelial differentiation in metastatic pleural fluids from adenocarcinomas.

Clinical and laboratory diagnosis of Zika fever: an update / Diagnóstico clínico e laboratorial da febre pelo vírus da zika: uma atualização

ABSTRACT Zika fever can be defined as an acute febrile viral illness, mainly transmitted by the mosquito of the genus Aedes. It makes a differential diagnosis from diseases caused by other flaviviruses, such as chikungunya and dengue fever. Many people with Zika virus (ZIKV) infection will not have symptoms or will only have mild clinical symptoms. The clinical conditions are nonspecific and characterized by low-grade fever, pruritic erythematous maculopapular rash, non-purulent conjunctival hyperemia without pruritus, arthralgia, myalgia, and headache. It is a benign, self-limiting and short-duration condition. Complications such as Guillain-Barré syndrome (GBS), spontaneous abortion and fetal malformations, mainly microcephaly and retinal lesions, may occur. The laboratory investigation is more important in cases suspected of ZIKV infection that have evolved with neurological complications, in pregnant women, abortion or congenital malformations, and is a key part for diagnostic definition. Real-time polymerase chain reaction (RT-PCR) can detect the virus in blood samples about four to seven days after the onset of symptoms. In urine, it is possible to identify viral ribonucleic acid (RNA) up to 15 days after clinical onset, even if viremia has ceased, and it is an alternative for late diagnosis. Serological tests may also be performed, while there may be cross-reactivity with other flaviviruses. Immunoglobulin class M (IgM) can be screened between the 2nd and 12th week after clinical presentation. The immunoglobulin class G (IgG) can be identified after the 15th day, and is present even in the convalescence and cure phase. Non-specific laboratory abnormalities, in general, do not present significant alterations. Patients with GBS must have cerebrospinal fluid (CSF) collection for analysis.

RESUMO A febre zika pode ser definida como uma doença viral febril aguda, transmitida principalmente pelo mosquito do gênero Aedes, e faz diagnóstico diferencial com doenças causadas por outros flavivírus, como a dengue e a Chikungunya. Muitos indivíduos infectados pelo vírus da zika (ZIKV) não terão ou terão apenas leve sintomatologia clínica. O quadro clínico é inespecífico e caracterizado por febre baixa, exantema maculopapular pruriginoso, hiperemia conjuntival não purulenta e sem prurido, artralgia, mialgia e cefaleia. A doença é autolimitada, de curta duração e de evolução benigna, mas podem ocorrer complicações, como síndrome de Guillain-Barré (SGB), aborto espontâneo e malformações fetais, principalmente microcefalia e lesões retinianas. A investigação laboratorial apresenta maior importância nos casos suspeitos de infecção pelo ZIKV que evoluíram com complicações neurológicas, em gestantes, aborto ou malformações congênitas, sendo fundamental para definição diagnóstica. A reação em cadeia da polimerase em tempo real (RT-PCR) pode detectar o vírus em amostras de sangue por volta de quatro a sete dias após o início dos sintomas. Na urina, é possível identificar o ácido ribonucleico (RNA) viral até 15 dias após o início do quadro clínico, mesmo que a viremia tenha cessado, sendo uma alternativa para o diagnóstico tardio. Os testes sorológicos também podem ser realizados, embora haja possibilidade de reação cruzada com outros flavivírus. A imunoglobulina da classe M (IgM) pode ser pesquisada entre a 2ª e 12ª semana após o início do quadro clínico; a da classe G (IgG), após o 15º dia, estando presente mesmo na fase de convalescência e na cura. As alterações laboratoriais inespecíficas, em geral, não apresentam alterações significativas. Nos casos em que os pacientes apresentam SGB, é importante a coleta e a análise do liquor.

Role of advanced glycation end products in the onset of diabetic kidney disease complications

Advanced glycation end products are known to play an important role in diabetes complications, such as diabetic nephropathy. Most known pathways of diabetic complications involve oxidative stress, that have pivotal role in cell dysfunction onset and progression of angiopathies. This review will explore how AGEs cause endothelial dysfunction in diabetes and what current biochemical mechanisms have been proposed as an explanation for the development of diabetic nephropathy (AU)

Is the creatine kinase isoenzyme MB level a marker of myocardial ischemia in ventilated premature infants? / O nível sérico de creatinofosfoquinase fração MB serve como marcador de isquemia miocárdica em recém-nascidos prematuros ventilados?

ABSTRACT INTRODUCTION: It is not clear whether the levels of troponin I (TI) and creatine kinase isoenzyme MB (CK-MB) are changed in premature infants (PI) without evidence of myocardial ischemia (MI). OBJECTIVES: To investigate whether TI and CK-MB change their levels in newborns without MI while on mechanical ventilation (MV). METHODS: We conducted a prospective cohort study in which 165 PI were divided into control group ([CG]; n = 68), mechanical ventilated group ([VG]; n = 21) and a surfactant therapy group ([SG]; n = 76), and had their TI, creatine kinase (CK) and CK-MB levels were determined. After the division, within the first four hours after the introduction of the mechanical ventilation (MV) and one hour after the withdrawal of it, we performed a new measurement of TI, CK and CK-MB to all PI from VG and VS. We used the chi-square test to evaluate the association among qualitative variables and the Kruskall-Wallis test to compare the serum levels of TI, and CK-MB among the groups, before, during and after MV using the statistical package SPSS 16.0 software. RESULTS: TI, CK, and CK-MB serum values before the groups were divided were considered normal. The TI concentration among the groups before and after MV (p > 0.05) did not changed; however, the CK-MB levels were higher in VG when compared to the CG (p = 0.009). CONCLUSION: The increase of CK-MB serum levels in VG and SG seems to indicate an increased work of thoracic skeletal muscle and do not represent a MI signal, which invalidate its use as a marker.

RESUMO INTRODUÇÃO: Não está claro se os níveis séricos de troponina I (TI) e de creatinoquinase fração MB (CK-MB) estão alterados em recém-nascidos prematuros (RNP) sem indícios de isquemia miocárdica (IM). OBJETIVO: Investigar se os níveis de TI e CK-MB se alteram nos RNP sem IM quando em ventilação mecânica (VM). MÉTODOS: Coorte prospectiva com 165 RNP que, antes de serem divididos em grupo-controle ([CG]; n = 68), ventilado ([VG]; n = 21) e surfactante ([SG]; n = 76), tiveram seus níveis séricos de TI, creatinoquinase (CK) e CK-MB determinados. Após a divisão, dentro das primeiras 4 horas do início da VM e 1 hora após sua retirada, realizamos nova dosagem de TI, CK e CK-MB nos RNP dos VG e VS. Foram utilizados o teste do Qui-quadrado para avaliar a associação entre as variáveis qualitativas e o teste de Kruskall-Wallis para comparar os valores séricos de TI e CK-MB entre os grupos, antes, durante e depois da VM, usando o pacote estatístico SPSS 16.0. RESULTADOS: Os valores séricos de TI, CK e CK-MB antes dos grupos serem divididos foram considerados normais. As concentrações de TI entre os grupos antes e depois da VM não se alteraram (p > 0,05), entretanto as de CK-MB foram maiores nos ventilados em relação aos do CG (p = 0,009). CONCLUSÃO: A elevação dos níveis séricos de CK-MB nos VG e SG parece indicar aumento do trabalho da musculatura torácica e não um sinal de IM, o que inviabiliza o uso desta como um marcador.

Infecção do trato urinário em mulheres com vida sexual ativa / Urinary tract infection in women with active sex life

As infecções do trato urinário (ITUs) estão entre as queixas mais frequentes em consultas de atendimento primário, principalmente entre mulheres. As ITUs ocorrem em 1% a 3% das meninas em idade escolar, com aumento acentuado da incidência com o início da atividade sexual. Calcula-se uma incidência anual de 7% em mulheres de todas as idades, atingindo um pico máximo entre 15 e 24 anos de idade e entre mulheres com mais de 65 anos. Escherichia coli e Staphylococcus saprophyticus estão envolvidos em cerca de 80% das infecções urinárias não complicadas encontradas na população. O aumento da resistência aos antibióticos reforça a necessidade da escolha do medicamento com o auxílio de cultura e sensibilidade bacterianas. A profilaxia da ITU está recomendada em determinados casos, principalmente em mulheres que apresentam recorrência; dentre elas estão as sexualmente ativas.

Urinary tract infections (UTIs) are the most common complaint in primary care appointment, mainly for women. UTI occurs between 1% and 3% of school-age children with increasing incidence due to the beginning of sexual life. It is estimated an incidence of 7% in women of all ages reaching the highest peak between the ages of 15-24 and more than 65 years old. Escherichia coli and Staphylococcus are involved in about 80% of uncomplicated urinary infections in population. The increasing antibiotic resistance supports the necessity of medicament choice with bacterial culture and sensitivity assistance. Prophylaxis for urinary tract infections (UTIs) is recommended in some cases, mainly for women who show recurrence; among those that are sexually active.

Adenosina desaminase: uma enzima extraordinária e onipresente Adenosina desaminase: uma enzima extraordinária e onipresente / Adenosine deaminase: an extraordinary and omnipresent enzyme

Depois de introduzir os conceitos básicos da enzima adenosina desaminase (ADA), uma breve discussão sobre a estrutura, o mecanismo enzimático, terapia genética e potencial utilização terapêutica de inibidores de ADA são apresentados. O estudo da ADA é muito mais complexo do que simplesmente seu papel como biomarcador diagnóstico para tuberculose pleural que veio revolucionar o setor de diagnóstico na medicina clínica nos últimos anos. O aumento de sua atividade no líquido pleural, e em outros líquidos orgânicos, impede que o paciente na maioria dos casos com síndrome do derrame pleural por tuberculose seja submetido a procedimentos cirúrgicos invasivos com possíveis complicações potencialmente fatais AU.

After introducing the basic concepts of ADA, a brief discussion on the structure, enzymatic mechanism, gene therapy and potential therapeutic use of ADA inhibitors are presented. The study of the ADA is much more complex than simply its role as a biomarker for pleural tuberculosis that has revolutionized the diagnostic in clinical medicine in recent years. The increase in its activity in the pleural fluid, and other body fluids, prevents the patient in most cases with pleural effusion tuberculosis is subjected to invasive surgical procedures with possible life-threatening complications. AU

Prognostic value of plasma neutrophil gelatinase-associated lipocalin in patients with heart failure.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of kidney injury. We sought to assess the prognostic value of this biomarker in patients with stable chronic heart failure (HF). METHODS: We studied 61 patients with chronic systolic HF who had been receiving optimal medical treatment for at least six months. Biomarkers were measured at baseline and included plasma NGAL, microalbuminuria, serum creatinine, and B-type natriuretic peptide (BNP). Estimated glomerular filtration rate (eGFR) was also calculated. Mean follow-up was 10.6±6.6 months. The primary endpoint was time to first cardiovascular event, defined as a combination of cardiovascular death, HF hospitalization or emergency department visit due to HF. Variables independently related to events were determined using a Cox proportional hazards model. RESULTS: Fifteen (24.6%) patients reached the primary endpoint. Patients with events were more likely to have worse renal function at baseline and also higher NGAL levels (median 316 [interquartile range 122-705] vs. 107 [78-170]; p=0.006). NGAL correlated significantly with creatinine (r=0.50; p<0.0001), albuminuria (r=0.33; p=0.008), and eGFR (r=-0.47; p=0.0001) but not with BNP (r=0.003; p=0.97). The best NGAL cutoff as determined by ROC curve analysis was 179 ng/ml. Event-free survival was lower in patients with NGAL above this cutoff. Variables independently related to events were NGAL (HR 1.0035, 95% CI 1.0019-1.0052; p<0.0001) and male gender (HR 5.9, 95% CI 1.22-28.6; p=0.028). CONCLUSION: NGAL correlated with other biomarkers of renal function but not with BNP and was independently associated with outcomes.