What lessons can we learn? Clinical and epidemiological retrospective analysis of 267 patients with urticaria in a Brazilian tertiary center

Abstract Background: There are few epidemiological studies of urticaria, published in the indexed literature (PubMed/Medline). Objective: The study aimed to evaluate the epidemiological and clinical data among patients with urticaria/angioedema attending a reference clinic in Brazil. Methods: Two hundred sixty-seven patients were evaluated retrospectively considering demographic data, time course of the disease, triggering symptoms, the presence of angioedema, complementary laboratory tests including total blood count, reactive-C protein, erythrocyte sedimentation rate, IgE serum levels, and other, as necessary. Results: The most commonly diagnosed type of urticaria was chronic spontaneous urticaria (56.93%). Angioedema was associated with chronic urticaria in 108 patients (40.08%). Study limitations: Unicentered and retrospective. Conclusion: Some relevant findings in this study are the observation of a female prevalence of cases (4-females: 1-man), a result more elevated than demonstrated in previous studies in Europe and Asia, the median age was 43-years old and the delay of time between the diagnosis of urticaria and the admission for treatment in a specialized center was approximately 2-years. Other multicenter studies can better establish these differences in Brazilian patients.

What lessons can we learn? Clinical and epidemiological retrospective analysis of 267 patients with urticaria in a Brazilian tertiary center.

BACKGROUND: There are few epidemiological studies of urticaria, published in the indexed literature (PubMed/Medline). OBJECTIVE: The study aimed to evaluate the epidemiological and clinical data among patients with urticaria/angioedema attending a reference clinic in Brazil. METHODS: Two hundred sixty-seven patients were evaluated retrospectively considering demographic data, time course of the disease, triggering symptoms, the presence of angioedema, complementary laboratory tests including total blood count, reactive-C protein, erythrocyte sedimentation rate, IgE serum levels, and other, as necessary. RESULTS: The most commonly diagnosed type of urticaria was chronic spontaneous urticaria (56.93%). Angioedema was associated with chronic urticaria in 108 patients (40.08%). STUDY LIMITATIONS: Unicentered and retrospective. CONCLUSION: Some relevant findings in this study are the observation of a female prevalence of cases (4-females: 1-man), a result more elevated than demonstrated in previous studies in Europe and Asia, the median age was 43-years old and the delay of time between the diagnosis of urticaria and the admission for treatment in a specialized center was approximately 2-years. Other multicenter studies can better establish these differences in Brazilian patients.

BRAFV600E and KIT immunoexpression in early-stage melanoma

Abstract: Melanoma is widely known as the most lethal skin cancer. Specific tumor-related mortality can be significantly reduced if diagnosis and treatment are properly performed during initial phases of the disease. The current search for biomarkers in early-stage melanomas is a high-priority challenge for physicians and researchers. We aimed to assess the immunoexpression of BRAFV600E and KIT in a case series consisting of 44 early-stage melanomas. Formalin-fixed paraffin-embedded samples were systematically evaluated using a semi-quantitative method based on scores of percentage and intensity for immunostained tumor cells. We observed significant concordance between BRAFV600E and KIT immunoexpression in thin invasive melanomas. Our findings corroborate previous evidence showing abnormal expression of proteins associated with MAPK intracellular signaling pathway in early-stage melanomas.

Soluble ST2 Testing: A Promising Biomarker in the Management of Heart Failure / Teste com ST2 Solúvel: Um Biomarcador Promissor no Tratamento da Insuficiência Cardíaca

Abstract ST2 is a member of the interleukin-1 receptor family biomarker and circulating soluble ST2 concentrations are believed to reflect cardiovascular stress and fibrosis. Recent studies have demonstrated soluble ST2 to be a strong predictor of cardiovascular outcomes in both chronic and acute heart failure. It is a new biomarker that meets all required criteria for a useful biomarker. Of note, it adds information to natriuretic peptides (NPs) and some studies have shown it is even superior in terms of risk stratification. Since the introduction of NPs, this has been the most promising biomarker in the field of heart failure and might be particularly useful as therapy guide.

Resumo ST2 é um biomarcador pertencente à família dos receptores de interleucina-1 e concentrações do ST2 solúvel refletem fibrose e estresse cardiovascular. Estudos recentes demonstram que o ST2 solúvel é um forte preditor de desfechos cardiovasculares em pacientes com insuficiência cardíaca crônica e aguda. Trata-se de um novo biomarcador que preenche critérios necessários para uso na prática clínica. Ele acrescenta informação aos peptídeos natriuréticos (PNs) e em alguns estudos tem sido até superior a estes em relação à estratificação de risco. Desde a introdução dos PNs, este é o biomarcador mais promissor na área de insuficiência cardíaca e pode vir a ser particularmente útil para guiar a terapia.

Galectin-3: A Link between Myocardial and Arterial Stiffening in Patients with Acute Decompensated Heart Failure? / Galectina-3: Ligação entre Rigidez Miocárdica e Arterial em Pacientes com Insuficiência Cardíaca Descompensada?

Abstract Background: Heart failure is accompanied by abnormalities in ventricular-vascular interaction due to increased myocardial and arterial stiffness. Galectin-3 is a recently discovered biomarker that plays an important role in myocardial and vascular fibrosis and heart failure progression. Objectives: The aim of this study was to determine whether galectin-3 is correlated with arterial stiffening markers and impaired ventricular-arterial coupling in decompensated heart failure patients. Methods: A total of 79 inpatients with acute decompensated heart failure were evaluated. Serum galectin-3 was determined at baseline, and during admission, transthoracic echocardiography and measurements of vascular indices by Doppler ultrasonography were performed. Results: Elevated pulse wave velocity and low arterial carotid distensibility are associated with heart failure in patients with preserved ejection fraction (p = 0.04, p = 0.009). Pulse wave velocity, carotid distensibility and Young’s modulus did not correlate with serum galectin-3 levels. Conversely, raised galectin-3 levels correlated with an increased ventricular-arterial coupling ratio (Ea/Elv) p = 0.047, OR = 1.9, 95% CI (1.0‑3.6). Increased galectin-3 levels were associated with lower rates of left ventricular pressure rise in early systole (dp/dt) (p=0.018) and raised pulmonary artery pressure (p = 0.046). High galectin-3 levels (p = 0.038, HR = 3.07) and arterial pulmonary pressure (p = 0.007, HR = 1.06) were found to be independent risk factors for all-cause mortality and readmissions. Conclusions: This study showed no significant correlation between serum galectin-3 levels and arterial stiffening markers. Instead, high galectin-3 levels predicted impaired ventricular-arterial coupling. Galectin-3 may be predictive of raised pulmonary artery pressures. Elevated galectin-3 levels correlate with severe systolic dysfunction and together with pulmonary hypertension are independent markers of outcome.

Resumo Fundamento: A insuficiência cardíaca é acompanhada por anormalidades na interação ventrículo-vascular devido à rigidez miocárdica e arterial aumentada. A galectina-3 é um biomarcador recentemente descoberto que exerce um importante papel na fibrose miocárdica e vascular, e na progressão da insuficiência cardíaca. Objetivos: O objetivo deste estudo foi determinar se a galectina-3 está correlacionada com marcadores de rigidez arterial e acoplamento ventriculoarterial deficiente em pacientes com insuficiência cardíaca descompensada. Métodos: Um total de 79 pacientes internados com insuficiência cardíaca descompensada foi avaliado. Galectina-3 sérica basal foi determinada e, durante a admissão hospitalar, foram realizadas ecocardiografia transtorácica e medidas de índices vasculares por ultrassonografia Doppler. Resultados: Velocidade de onda de pulso elevada e baixa distensibilidade da artéria carótida estão associadas com insuficiência cardíaca em pacientes com fração de ejeção preservada (p = 0,04, p = 0,009). Velocidade de pulso, distensibilidade da artéria carótida e módulo de Young não se correlacionaram com níveis séricos de galectina-3. Por outro lado, níveis elevados de galectina-3 correlacionaram com razão de acoplamento ventriculoarterial aumentada (Ea/Elv) p = 0,047, OR = 1,9, IC 95% (1,0-3,6). Níveis aumentados de galectina-3 estavam associados com taxas mais baixas de pressão ventricular esquerda na fase inicial da sístole (dp/dt) (p = 0,018), e pressão arterial pulmonar aumentada (p = 0,046). Os resultados mostraram que níveis elevados de galectina-3 (p = 0,038, HR = 3,07) e pressão pulmonar arterial (p = 0,007, HR = 1,06) são fatores de risco independentes para mortalidade de todas as causas e reinternações hospitalares. Conclusões: O estudo mostrou que não houve correlação significativa entre níveis séricos de galectina-3 e marcadores de rigidez arterial. Altos níveis de galectina-3, por outro lado, foi um preditor de acoplamento ventriculoarterial deficiente. A galectina-3 pode ser um preditor de pressões arteriais pulmonares aumentadas. Níveis elevados de galectina-3 correlacionam-se com disfunção sistólica grave e, juntamente com hipertensão pulmonar, é um marcador independente de desfecho.

Renal biomarkers of male and female Wistar rats (Rattus norvegicus) undergoing renal ischemia and reperfusion

PURPOSE: To investigate biomarkers of acute renal injury in Wistar rats, subjected to left renal ischemia for 10 minutes, and then compare reperfusion at 24 hours, and at 5, 7, 14 and 21 days after the procedure. METHODS: Eight female and male rats between 60 and 81 days old were used in the Central Animal Facility of the UFMS. Assessed biomarkers included urine protein, urea, creatinine, glucose, sodium, potassium, urine alkaline phosphatase and gamma-glutamyl transferase activities, and protein-to-creatinine ratio; and in serum: urea, creatinine, sodium and potassium, fractional excretion of sodium, potassium, urine flow and creatinine clearance. RESULTS: Greater variance was observed in the parameters at 24 hours and at five days (p<0.05) after reperfusion. On the 21st day, these parameters approximated those obtained for the control group. CONCLUSIONS: Renal ischemia for 10 minutes was sufficient to raise urine levels of protein, glucose, fractional excretion of potassium, urea, creatinine clearance, urine activity of gamma-glutamyltransferase and alkaline phosphatase enzymes in the first 24 hours, up to five days after reperfusion, which may indicate risk of acute kidney injury, according to the RIFLE classification. .

Renal biomarkers of male and female Wistar rats (Rattus norvegicus) undergoing renal ischemia and reperfusion

PURPOSE: To investigate biomarkers of acute renal injury in Wistar rats, subjected to left renal ischemia for 10 minutes, and then compare reperfusion at 24 hours, and at 5, 7, 14 and 21 days after the procedure.METHODS: Eight female and male rats between 60 and 81 days old were used in the Central Animal Facility of the UFMS. Assessed biomarkers included urine protein, urea, creatinine, glucose, sodium, potassium, urine alkaline phosphatase and gamma-glutamyl transferase activities, and protein-to-creatinine ratio; and in serum: urea, creatinine, sodium and potassium, fractional excretion of sodium, potassium, urine flow and creatinine clearance.RESULTS:Greater variance was observed in the parameters at 24 hours and at five days (p 0.05) after reperfusion. On the 21st day, these parameters approximated those obtained for the control group.CONCLUSIONS:Renal ischemia for 10 minutes was sufficient to raise urine levels of protein, glucose, fractional excretion of potassium, urea, creatinine clearance, urine activity of gamma-glutamyltransferase and alkaline phosphatase enzymes in the first 24 hours, up to five days after reperfusion, which may indicate risk of acute kidney injury, according to the RIFLE classification.(AU)

Microparticles as Potential Biomarkers of Cardiovascular Disease / Micropartículas como Possíveis Biomarcadores da Doença Cardiovascular

Primary prevention of cardiovascular disease is a choice of great relevance because of its impact on health. Some biomarkers, such as microparticles derived from different cell populations, have been considered useful in the assessment of cardiovascular disease. Microparticles are released by the membrane structures of different cell types upon activation or apoptosis, and are present in the plasma of healthy individuals (in levels considered physiological) and in patients with different pathologies. Many studies have suggested an association between microparticles and different pathological conditions, mainly the relationship with the development of cardiovascular diseases. Moreover, the effects of different lipid-lowering therapies have been described in regard to measurement of microparticles. The studies are still controversial regarding the levels of microparticles that can be considered pathological. In addition, the methodologies used still vary, suggesting the need for standardization of the different protocols applied, aiming at using microparticles as biomarkers in clinical practice.

A prevenção primária da doença cardiovascular constitui uma opção de grande relevância pelos seus impactos na saúde. Alguns biomarcadores têm sido considerados úteis na avaliação da doença cardiovascular, dentre eles micropartículas originadas de diferentes populações de células. Micropartículas são estruturas liberadas pela membrana de diferentes tipos celulares após ativação ou apoptose, presentes tanto no plasma de indivíduos saudáveis (níveis considerados fisiológicos) quanto em portadores de diferentes doenças. Muitos estudos têm sugerido uma associação entre micropartículas e diferentes condições patológicas, destacando-se a relação com o desenvolvimento das doenças cardiovasculares. Além disso, têm sido descritos os efeitos de diferentes terapias hipolipemiantes na mensuração de micropartículas. Os estudos ainda são controversos quanto aos níveis de micropartículas que possam ser considerados patológicos, e os métodos utilizados ainda são variados, o que sugere a necessidade da padronização dos diferentes protocolos utilizados, visando à utilização de micropartículas como biomarcadores úteis na prática clínica.

Avaliação do tempo de início do tratamento, estadiamento histopatológico e positividade dos biomarcadores (RE, RP, HER-2) em 3.566 pacientes tratadas pelo SUS no período de 2012 a 2014, no Hospital Pérola Byington / Evaluation of starting treatment time, histopathological staging and positivity of biomarkers (ER, PR, HER-2) in 3,566 patients treated by SUS from 2012 to 2014, at Perola Byington Hospital

A finalidade do estudo foi avaliar o tempo para início de tratamento, idade, estadiamento cirúrgico e a positividade dos biomarcadores (ER, PR e HER-2) em 3.566 pacientes com carcinoma de mama atendidas pelo SUS no período de janeiro de 2012 a dezembro de 2014, no Hospital Pérola Byington (SP). O tempo mediano para o início da terapêutica foi de 32 dias. A idade das pacientes variou de 12 a 98 anos, sendo 49 pacientes (1,4%) com menos de 30 anos, 396 (11,1%) entre 30 e 39 anos, 1.002 (28,1%) entre 40 e 49 anos, 1.737 (48,7%) entre 50 e 69 anos e 382 (10,7%) acima de 70 anos. Quanto ao estadiamento, 8,1% dos tumores tratados foram ?in situ?, 17,2% encontravam-se no Estádio I, 43,1% no II, 28,6% no III e apenas 3% no Estádio IV. A positividade dos receptores de estrogênio e/ou progesterona foi de 72,9% e a de HER-2 de 17,4 %. Os tumores luminais A e B representaram, respectivamente, 23 e 46%; e os triplo-negativos, 17,5% dos casos. Os dados mostram um expressivo número de pacientes com tumores in situ e predomínio de pacientes nos Estádio I e II.

The purpose of the study was the time to start treatment, age, surgical staging and the positivity of biomarkers (ER, PR and HER-2) in 3,566 patients with breast carcinoma served by SUS from January 2012 to December 2014 in Perola Byington Hospital (SP), Brazil. The median time to initiation of therapy was 32 days. The age of patients ranged from 12 to 98 years with 49 patients (1.4%) with less than 30 years, 396 (11.1%) between 30 and 39 years, 1,002 (28.1%) between 40 and 49 years, 1,737 (48.7%) between 50 and 69 years and 382 (10.7%) over 70 years. As to staging, 8.1% of the tumors were treated ?in situ?, 17.2% were in stage I, 43.1% in II, III and 28.6% in only 3% in Stage IV. The positivity of the estrogen receptor and/or progesterone was 72.9% and the HER-2 17.4%. Tumors luminal A and B represented by 23 and 46% and triple-negative, 17.5% of cases. The data show a significant number of patients with tumors in situ and prevalence of patients in Stage I and II.

Effect of allopurinol on the kidney function, histology and injury biomarker (NGAL, IL 18) levels in uninephrectomised rats subjected to ischaemia-reperfusion injury

PURPOSE: To investigate whether allopurinol exerts a protective effect on kidneys by measuring new kidney injury biomarkers (NGALp, NGALu, KIM 1 and IL 18) and analysing the renal function and histology in uninephrectomised rats subjected to ischaemia-reperfusion injury. METHODS: Thirty two Wistar rats were randomly allocated to four groups: Sham (S): laparotomy; Control (C): laparotomy and ischaemia-reperfusion in the left kidney; Control Allopurinol (CA): laparotomy and allopurinol at a dose of 100mg·kg 1·d 1; and Allopurinol (A): laparotomy ischaemia-reperfusion in the left kidney and allopurinol at a dose of 100mg·kg 1·d 1. The NGALp, NGALu, KIM 1, IL 18 and creatinine levels and the kidney histology were analysed. The significance level was established as p<0.05. RESULTS: Creatinine level increased in all the groups, with A ≈ C > S ≈ CA. The NGALp, NGALu and IL 18 levels exhibited similar behaviour in all the groups. KIM 1 was higher in group A than C and showed intermediate values in groups S and CA. Severity of injury in the left kidney was greater in groups C and A compared to S and CA. CONCLUSION: Allopurinol did not exert protective or damaging effects on the kidneys of rats subjected to ischaemia-reperfusion injury. .

Effect of allopurinol on the kidney function, histology and injury biomarker (NGAL, IL 18) levels in uninephrectomised rats subjected to ischaemia-reperfusion injury

PURPOSE: To investigate whether allopurinol exerts a protective effect on kidneys by measuring new kidney injury biomarkers (NGALp, NGALu, KIM 1 and IL 18) and analysing the renal function and histology in uninephrectomised rats subjected to ischaemia-reperfusion injury. METHODS: Thirty two Wistar rats were randomly allocated to four groups: Sham (S): laparotomy; Control (C): laparotomy and ischaemia-reperfusion in the left kidney; Control Allopurinol (CA): laparotomy and allopurinol at a dose of 100mg·kg 1·d 1; and Allopurinol (A): laparotomy ischaemia-reperfusion in the left kidney and allopurinol at a dose of 100mg·kg 1·d 1. The NGALp, NGALu, KIM 1, IL 18 and creatinine levels and the kidney histology were analysed. The significance level was established as p<0.05. RESULTS: Creatinine level increased in all the groups, with A ≈ C > S ≈ CA. The NGALp, NGALu and IL 18 levels exhibited similar behaviour in all the groups. KIM 1 was higher in group A than C and showed intermediate values in groups S and CA. Severity of injury in the left kidney was greater in groups C and A compared to S and CA. CONCLUSION: Allopurinol did not exert protective or damaging effects on the kidneys of rats subjected to ischaemia-reperfusion injury.(AU)

Marcadores bioquímicos do infarto agudo do miocárdio / Biochemical markers of acute myocardial infarction

Introdução: Número crescente de biomarcadores tem sido usado para auxiliar no diagnóstico do infarto agudo do miocárdio (IAM), estratificação de risco dos pacientes e predição de eventos após a síndrome coronariana aguda (SCA). Alguns desses biomarcadores são amplamente usados na prática clínica, outros ainda não apresentam evidências científicas que sustentem seu uso clínico. Objetivos: analisar o significadoclínico dos diversos marcadores bioquímicos descritos para o IAM, isolados ou combinados, buscando-se a descrição de acordo com a origem, comportamento na evolução da doença, incluindo validação, limitação diagnóstica e significado clínico em diferentes contextos. Métodos: realizada pesquisa bibliográfica usando a base de dados PubMed, por intermédio de artigos originais e revisões sobre biomarcadores para o IAM. A busca limitou-se aos artigos escritos em inglês, publicados nos últimos cinco anos. Resultados: foram obtidos 90 artigos, dos quais 57 foram excluídos. Dos 32 estudos selecionados, 14 eram randomizados e controlados. Após análise judiciosa, foramdescritos vários biomarcadores: troponina, creatinoquinase fração MB, mioglobina, H-FABP, BNP e seu fragmento N-terminal inativo, ANP, copeptin, fator-15 de diferenciação e crescimento, proteína receptora da interleucina-1, cardiotrofina, mieloperoxidase, endotelina 1, entre outros. Conclusões: as troponinas T e I (na admissão e 6-9h após injúria) seguidas pela CK-MB massa são os biomarcadores sugeridos para avaliação de lesão miocárdica. O hs-TnI e hs-TnT são muito sensíveis nos estágios precoces e a CK-MB massa tem sido útil para diagnóstico de reinfarto, pelo seu curto período de meia-vida. Todos os demais biomarcadores estudados, seja na inclusão ou exclusão de hipóteses, foram importantes para o diagnóstico e/ou prognóstico do IAM. Entretanto, ainda são necessários novos estudos para confirmar os dados presentes.

Introduction: A number of biomarkers have been used to aid in the diagnosis of acute myocardial infarction (AMI), in the risk stratification of patients and for predicting events after acute coronary syndrome (ACS). Some of these biomarkers are widely used in clinical practice whileothers still have no scientific evidence to support their clinical use. Objectives: To analyze the clinical significance of the various biochemical markers for AMI, alone or in combined use, seeking a description according to the source, behavior in the evolution of the disease, including validation, diagnostic limitations, and clinical significance in different contexts. Methods: We performed a literature review using the PubMed database, including original articles and reviews on the use of biomarkers for AMI. The search was limited to articles written in English, published in the last five years. Results: 90 articles were accessed, 57 of which were excluded. Of the 32 selected studies, 14 were randomized and controlled. After judicious analysis, several biomarkers were described: troponin, creatine kinase-MB fraction, myoglobin, H-FABP, BNP and its inactive N-terminal fragment, ANP, copeptin, growth/differentiation factor-15, interleukin-1 receptor antagonis, cardiotrophin, myeloperoxidase, endothelin- 1, among others. Conclusions: troponins T and I (at baseline and 6-9h after event) followed by CK-MB mass are the suggested biomarkers for assessing myocardial injury. Hs-cTnI and hs-TnT are very sensitive in the early stages and CK-MB mass has been useful in reinfarction diagnoses given its short half-life. All other biomarkers studied, either for hypotheses inclusion or exclusion, were important for thediagnosis and/or prognosis of AMI. However, further studies are needed to confirm the present data.

Inflamação e aterosclerose: novos biomarcadores e perspectivas terapêutica / Inflammation and atherosclerosis: new biomakers and outlooks for treatment

Atualmente a aterosclerose é considerada uma doença inflamatória crônica, provavelmente iniciada por disfunção endotelial associada a fatores inerentes à ativação do sistema imunológico. A disfunção endotelial pode ser causada por diversos fatores, como colesterol alto, presença de radicais livres, associada a fatores externos, hipertensão, diabetes mellitus, alterações genéticas, dentre outros. No local onde o endotélio se torna disfuncional ocorre uma resposta inflamatória, que estimula a migração e a proliferação de células musculares lisas, que se agregam à área de inflamação, formando uma lesão mais complexa. Além disso, ocorre o recrutamento de leucócitos e adesão de plaquetas ao endotélio na região da placa de ateroma. Apesar da indubitável utilidade do perfil lipídico na avaliação do risco aterosclerótico, esse dado fornece um panorama incompleto do paciente, uma vez que vários eventos cardiovasculares ocorrem em indivíduos com concentrações plasmáticas de colesterol e LDL consideradas adequadas. Considerando o papel de destaque dado ao processo inflamatório no desenvolvimento da aterosclerose, se faz necessária a observação de novos biomarcadores para uma melhor previsão de risco cardiovascular. Este trabalho resume aspectos importantes relacionados às metaloproteinases (MMP), proteína C-reativa (PCR), moléculas de adesão, TNF-α, interleucinas (IL) e adiponectina. O conhecimento destes possíveis marcadores constitui-se de vital importância para o direcionamento eficiente de novas abordagens terapêuticas, representando um novo horizonte no tratamento da aterosclerose.

Atherosclerosis is currently considered as a chronic inflammatory disease, probably caused by an endothelial dysfunction associated with factors inherent to the activation of the immune system. Endothelial dysfunction may be caused by several factors such as high cholesterol, free radicals, associated with external factors, hypertension, diabetes mellitus, genetic disorders and others. An inflammatory response occurs at the location where the endothelium becomes dysfunctional, stimulating the migration and proliferation of smooth muscle cells, clumping in the inflammation area and forming a more complex lesion, together with the recruitment of leukocytes and platelet adhesion to the endothelium in the atheromatous plaque region. Despite the undoubted utility of the lipid profile in atherosclerotic risk assessment, these data provide an incomplete overview of the patient, as many cardiovascular events occur in patients with cholesterol and LDL plasma concentrations rated as adequate. Considering the prominent role assigned to the inflammatory process for the development of atherosclerosis, it is necessary to observe new biomarkers in order to predict cardiovascular risk more effectively. This paper summarizes important aspects related to matrix metalloproteinases (MMPs), C-reactive protein (CRP), adhesion molecules, TNF-α, interleukins (ILs) and adiponectin. Knowledge of these potential markers is of vital importance for efficiently targeting new therapeutic approaches, opening up a new horizon for atherosclerosis treatment.

Gliomas: marcadores tumorais e prognóstico / Gliomas: tumors biomarkers and prognosis

Os gliomas representam 30%-40% de todas as neoplasias intracranianas e aproximadamente 50% são glioblastomas. São classificados em graus pela OMS, de acordo com sua patologia. Apresentam altas taxas de mortalidade. Existem marcadores tumorais que podem auxiliar na detecção precoce e avaliar prognóstico. Realizada revisão sobre o tema marcadores tumorais por meio do site PubMed. MGMT é uma proteína que restaura o DNA, impedindo a sua alquilação. A metilação do MGMT por meio de fenômeno epigenético impede sua transcrição inibindo sua ação, tornando o tumor suscetível a fármacos. IDH e codeleção cromossômica 1p19q são marcadores tumorais e estão associados a melhor prognóstico. As neoplasias intracranianas apresentam altas taxas de mortalidade e sua detecção precoce por meio de marcadores e o conhecimento de alterações que conferem bom prognóstico podem auxiliar no tratamento dessa doença. A análise molecular auxilia na detecção e no tratamento de tumores.

Gliomas represent 30%-40% of all intracranial tumors and approximately 50% are glioblastomas. They are classified by the WHO in degrees, according to their pathology. Have high mortality rates. There are tumor markers may help in early detection and assess prognosis. Was performed a review about the topic tumor markers through PubMed. MGMT is a protein that restores the DNA, preventing its alkylation. Methylation of MGMT through epigenetic phenomenon prevents their transcription and inhibits its action, making the tumor susceptible to drugs. IDH and chromosomal deletion 1p19q are tumor markers and are associated with better prognosis. The intracranial tumors have high rates of mortality and early detection through biomarkers and knowledge of changes that confer a good prognosis can help in treating this disease. Molecular analysis allows the detection and treatment of tumors.

Procalcitonin in patients with influenza A (H1N1) infection and acute respiratory failure / Pró-calcitonina em pacientes com infecção por influenza A (H1N1) e insuficiência respiratória aguda

ABSTRACT Objective: To verify serum procalcitonin levels of patients with acute respiratory failure secondary to influenza A (H1N1) upon their admission to the Intensive Care Unit and to compare these results to values found in patients with sepsis and trauma admitted to the same unit. Methods: Analysis of records of patients infected with influenza A (H1N1) and respiratory failure admitted to the General Intensive Care Unit during in a period of 60 days. The values of serum procalcitonin and clinical and laboratory data were compared to those of all patients admitted with sepsis or trauma in the previous year. Results: Among patients with influenza A (H1N1) (n = 16), the median serum procalcitonin level upon admission was 0.11 ng/mL, lower than in the sepsis group (p < 0.001) and slightly lower than in trauma patients. Although the mean values were low, serum procalcitonin was a strong predictor of hospital mortality in patients with influenza A (H1N1). Conclusion: Patients with influenza A (H1N1) with severe acute respiratory failure presented with low serum procalcitonin values upon admission, although their serum levels are predictors of hospital mortality. The kinetics study of this biomarker may be a useful tool in the management of this group of patients.

RESUMO Objetivo: Verificar os níveis de pró-calcitonina sérica em pacientes com insuficiência respiratória aguda secundária à influenza A (H1N1) admitidos à Unidade de Terapia Intensiva, e comparar esses resultados com valores encontrados em pacientes com sepse e trauma admitidos na mesma unidade. Métodos: Análise de prontuários de pacientes infectados com influenza A (H1N1) e insuficiência respiratória aguda admitidos na Unidade de Terapia Intensiva Geral em um período de 60 dias. Os valores de pró-calcitonina sérica e os dados clínicos e laboratoriais foram comparados com todos pacientes admitidos com sepse ou trauma no ano anterior. Resultados: Entre os pacientes com influenza A (H1N1) (n = 16), a mediana de pró-calcitonina sérica na admissão foi 0,11 ng/mL, menor do que o grupo de sepse (p < 0,01) e levemente menor do que os com trauma. Embora os valores médios tenham sido baixos, o nível sérico de pró-calcitonina foi um poderoso preditor de mortalidade hospitalar em pacientes com influenza A (H1N1). Conclusão: Pacientes com influenza A (H1N1) com insuficiência respiratória aguda grave tiveram baixos níveis de pró-calcitonina à admissão, embora seu nível sérico seja preditor de mortalidade hospitalar. A cinética desse biomarcador poderia ser uma ferramenta útil para o manejo desses pacientes.

Temperatura do ar exalado, um novo biomarcador no controle da asma: um estudo piloto / Exhaled breath temperature, a new biomarker in asthma control: a pilot study

OBJETIVO: Avaliar se a temperatura do ar exalado (TAE), medida por um método não invasivo, é efetiva no monitoramento de pacientes com asma não controlada. MÉTODOS: Estudo piloto com nove pacientes (sete mulheres e dois homens; média de idade: 39 anos) com diagnóstico de asma por pelo menos um ano e sem uso de tratamento de manutenção por pelo menos três meses antes do início do estudo. Na primeira visita, os pacientes foram submetidos à espirometria e à medida da TAE. Todos os pacientes foram orientados a iniciar tratamento com budesonida/formoterol (200/6 µg) inalatório a cada 12 h por seis semanas. Além disso, os pacientes com asma grave (VEF1 < 60 por cento do previsto) foram orientados a utilizar prednisolona oral (40 mg/dia) por cinco dias. Após seis semanas, os pacientes foram submetidos aos mesmos testes. RESULTADOS: Todos os pacientes relataram melhora dos sintomas de asma; confirmada por um aumento significativo de VEF1 da primeira para a segunda visita (média de VEF1: 56,1 por cento vs. 88,7 por cento do previsto; p < 0,05). Cinco pacientes utilizaram prednisolona oral, mas somente nos cinco dias iniciais do tratamento. Seis pacientes utilizaram doses extras da medicação inalatória (média de tempo de uso de medicação adicional = 2,5 semanas). Houve uma diminuição significativa da TAE entre os momentos de avaliação (média de TAE: 35,1ºC vs. 34,1ºC; p < 0,05). CONCLUSÕES: A asma não controlada, sobretudo durante exacerbações, é acompanhada pela elevação da TAE, que se reduz após o controle adequado da asma, demonstrado pela melhora do VEF1 e dos sintomas referidos. Esses resultados preliminares apontam para o monitoramento da TAE como um parâmetro possível na avaliação do controle da asma.

OBJECTIVE: To evaluate whether the exhaled breath temperature (EBT), measured by a noninvasive method, is an effective means of monitoring patients with uncontrolled asthma. METHODS: A pilot study comprising nine patients (seven women and two men; mean age: 39 years) diagnosed with asthma at least one year prior to the beginning of the study and not having been under maintenance therapy for the last three months. In the first visit, the patients underwent spirometry and measurement of EBT. The patients were then instructed to use inhaled budesonide/formoterol (200/6 µg) every 12 h for six weeks. In addition, the patients with severe asthma (FEV1 < 60 percent of predicted) were instructed to use oral prednisolone (40 mg/day) for five days. After six weeks, the patients underwent the same tests. RESULTS: All of the patients reported an improvement in the symptoms of asthma, as confirmed by a statistically significant increase in FEV1 from the first to the second visit (mean, 56.1 percent vs. 88.7 percent of predicted; p < 0.05). Five patients used oral prednisolone for the first five days of the treatment period. Six patients used additional doses of inhaled budesonide/formoterol (mean duration, 2.5 weeks). The EBT decreased significantly from the first to the second visit (mean EBT: 35.1ºC vs. 34.1ºC; p < 0.05). CONCLUSIONS: Uncontrolled asthma, especially during exacerbations, is followed by an increase in EBT, which decreases after appropriate asthma control, as demonstrated by an increase in FEV1 and an improvement of the reported symptoms. These preliminary results suggest that EBT can be used as a parameter for the assessment of asthma control.

Instituto Nacional de Ciência e Tecnologia em Medicina Translacional (INCT-TM): abordagens metodológicas / National Science and Technology Institute for Translational Medicine (INCT-TM): advancing the field of translational medicine and mental health

OBJECTIVE: Translational medicine has been described as the integrated application of innovative pharmacology tools, biomarkers, clinical methods, clinical technologies and study designs to improve the understanding of medical disorders. In medicine, translational research offers an opportunity for applying the findings obtained from basic research to every-day clinical applications. The National Science and Technology Institute for Translational Medicine is comprised of six member institutions (Universidade Federal do Rio Grande do Sul, Universidade de São Paulo-Ribeirão Preto, Universidade Federal do Rio de Janeiro, Pontifícia Universidade Católica do Rio Grande do Sul, Universidade Estadual de Santa Catarina and a core facility that serves all centers). The objectives of the project are divided into four areas: Institutional, Research, Human Resources and Technology for the Community and Productive Sector. METHOD: In this manuscript, we describe some of the approaches used to attain the main objectives of the National Science and Technology Institute for Translational Medicine, which include the development of 1) animal models for bipolar disorder; 2) strategies to investigate neurobehavioral function and cognitive dysfunction associated with brain disorders; 3) experimental models of brain function and behavior, neuropsychiatric disorders, cell proliferation, and cancer; 4) Simulated Public Speaking and 5) Virtual reality simulation for inducing panic disorder and agoraphobia. CONCLUSION: The main focus of the National Science and Technology Institute for Translational Medicine is the development of more useful methods that allow for a better application of basic research-based knowledge to the medical field.

OBJETIVO: Medicina translacional pode ser descrita como a aplicação integrada de ferramentas farmacológicas inovadoras, biomarcadores, métodos e tecnologias clínicas e delineamentos de pesquisa para aumentar o conhecimento a respeito das doenças. A pesquisa translacional oferece uma oportunidade para aplicar os achados de pesquisa básica na clínica cotidiana. O Instituto Nacional de Ciência e Tecnologia - Medicina Translacional foi criado com seis centros (Universidade Federal do Rio Grande do Sul, Universidade de São Paulo-Ribeirão Preto, Universidade Federal do Rio de Janeiro, Pontifícia Universidade Católica do Rio Grande do Sul, Universidade Estadual de Santa Catarina e uma core facility que serve a todos os centros). Os objetivos deste projeto são divididos em quatro dimensões: institucional, pesquisa, formação de recursos humanos e transferência de tecnologia para a comunidade e setor produtivo. MÉTODO: Neste artigo, são apresentadas algumas das estratégias utilizadas para atingir os objetivos do Instituto Nacional de Ciência e Tecnologia - Medicina Translacional: 1) Desenvolvimento de modelos animais para o transtorno bipolar; 2) Estratégias de investigação neurocomportamental e disfunções cognitivas dos transtornos cerebrais; 3) Modelos experimentais de funcionamento cerebral e comportamento, proliferação celular e câncer; 4)Teste de Simulação de Falar em Público e 5) Realidade Virtual para indução de Pânico e Agorafobia. CONCLUSÃO: O Instituto Nacional de Ciência e Tecnologia - Medicina Translacional possui como foco principal o desenvolvimento de metodologias mais úteis para aumentar a aplicabilidade dos conhecimentos da pesquisa básica em medicina.