Amélia Feliciano

Overview of proteomics studies in obstructive sleep apnea.

Obstructive sleep apnea (OSA) is an underdiagnosed common public health concern causing deleterious effects on metabolic and cardiovascular health. Although much has been learned regarding the pathophysiology and consequences of OSA in the past decades, the molecular mechanisms associated with such processes remain poorly defined. The advanced high-throughput proteomics-based technologies have become a fundamental approach for identifying novel disease mediators as potential diagnostic and therapeutic targets for many diseases, including OSA. Here, we briefly review OSA pathophysiology and the technological advances in proteomics and the first results of its application to address critical issues in the OSA field.

Hemangioendotelioma epitelióide do pulmão – Raridade, dificuldades diagnósticas e terapêutica

Resumo Os autores apresentam um caso de hemangioendotelioma epitelioide (HEE) primario do pulmao num doente de 51 anos, sexo masculino, que iniciou queixas de tosse seca, seguida de sintomas constitucionais e dispneia. Apos realizacao de alguns exames complementares de diagnostico, que incluiram biopsia cirurgica, foi considerada a hipotese de tuberculose pulmonar e iniciou antibacilares, que manteve durante tres semanas. Por agravamento clinico e imagiologico, foi feita revisao do caso e estudo imunoistoquimico dos tecidos pulmonares biopsados e concluiu-se estar perante um HEE de alto grau/angiossarcoma do pulmao. Iniciou quimioterapia com carboplatina, etoposido e bevacizumab, com ligeira melhoria. Faleceu sete meses apos o aparecimento dos primeiros sintomas e sete semanas apos o diagnostico definitivo. Os autores pretendem realcar a raridade desta neoplasia pulmonar, a importância da suspeicao clinica e as dificuldades no diagnostico e tratamento, e salientar os potenciais beneficios da utilizacao de um farmaco antiangiogenico.

Hematological evaluation in males with obstructive sleep apnea before and after positive airway pressure

Obstructive sleep apnea syndrome (OSAS) is a systemic inflammatory disease associated with cardiovascular consequences. Red blood cell distribution width (RDW), mean platelet volume (MPV), and platelet distribution width (PDW) are recognized biomarkers of cardiovascular morbidity/mortality. Limited data is available on the association between these parameters and OSAS severity and the relationship with positive airway pressure therapy (PAP). In this prospective study of male OSAS patients we analyzed hematological data in order to evaluate their value in predicting OSAS severity, the relationship with sleep parameters, and their behavior under PAP. Seventy-three patients were included (mean age 46.5 years), of which 36 were mild (49.3%), 10 moderate (13.7%), and 27 severe (37%). The mean RDW increased significantly with OSAS severity and showed a positive correlation with respiratory disturbance index and hypoxemic burdens. Additionally, a group of 48 patients (mean age 47.2 years) were submitted to PAP. After six months, red blood cell count, hemoglobin, hematocrit, and platelet count showed a significant decrease (p<0.0001; p<0.0001; p=0.001; p<0.0001; respectively). Concerning OSAS severity, these parameters also significantly decreased in mild patients (p=0.003; p=0.043; p=0.020; p=0.014; respectively) but only hemoglobin, hematocrit, and platelet count decreased in severe cases (p<0.0001; p=0.008; p=0.018; respectively). This study demonstrated an association between RDW values and OSAS severity. Moreover, red cell and platelet parameters changed significantly after PAP, supporting its cardiovascular protective effect. RDW may become a simple/inexpensive blood biomarker, making it useful in prioritizing OSAS patients waiting for polysomnography, and red cell and platelet parameters could be useful in PAP follow up.

Evening and morning peroxiredoxin-2 redox/oligomeric state changes in obstructive sleep apnea red blood cells: Correlation with polysomnographic and metabolic parameters

We have examined the effects of Obstructive Sleep Apnea (OSA) on red blood cell (RBC) proteome variation at evening/morning day time to uncover new insights into OSA-induced RBC dysfunction that may lead to OSA manifestations. Dysregulated proteins mainly fall in the group of catalytic enzymes, stress response and redox regulators such as peroxiredoxin 2 (PRDX2). Validation assays confirmed that at morning the monomeric/dimeric forms of PRDX2 were more overoxidized in OSA RBC compared to evening samples. Six month of positive airway pressure (PAP) treatment decreased this overoxidation and generated multimeric overoxidized forms associated with chaperone/transduction signaling activity of PRDX2. Morning levels of overoxidized PRDX2 correlated with polysomnographic (PSG)-arousal index and metabolic parameters whereas the evening level of disulfide-linked dimer (associated with peroxidase activity of PRDX2) correlated with PSG parameters. After treatment, morning overoxidized multimer of PRDX2 negatively correlated with fasting glucose and dopamine levels. Overall, these data point toward severe oxidative stress and altered antioxidant homeostasis in OSA RBC occurring mainly at morning time but with consequences till evening. The beneficial effect of PAP involves modulation of the redox/oligomeric state of PRDX2, whose mechanism and associated chaperone/transduction signaling functions deserves further investigation. RBC PRDX2 is a promising candidate biomarker for OSA severity and treatment monitoring, warranting further investigation and validation.

Effects of positive airway pressure therapy on cardiovascular and metabolic markers in males with obstructive sleep apnea

INTRODUCTION Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular/metabolic complications. Some analytical parameters (homocysteine, glycemic and lipidic profiles) are recognized markers of these consequences. Limited data is available on the association of these markers and OSASs severity/response to positive airway pressure therapy (PAP). MATERIAL AND METHODS In this prospective study we analyzed polysomnographic and analytical data of male patients admitted to sleep laboratory. The aim was to evaluate metabolic/cardiovascular markers in snorers and OSAS patients, to relate with sleep parameters and PAP response. One-hundred and three patients were included, and 73 (71%) were OSAS patients. OSAS patients were similar to snorers except for higher body mass index (BMI) and dyslipidemia. Severe OSAS patients showed higher glycemia, HbA1c, insulin, and insulin resistance, and lower HDL cholesterol in comparison to mild-moderate (p<0.05, p<0.05, p<0.001, p<0.001, p<0.05, respectively). Glycemic profile and triglycerides were slightly correlated with OSAS severity. 46 OSAS patients were submitted to 6 months of PAP, with a statistical decrease in mean values of homocysteine, glycemia, total and LDL cholesterol (p<0.05, p<0.05, p<0.05, respectively), and in glycemia and LDL cholesterol in severe group only (p<0.05, p<0.05, respectively). RESULTS This study demonstrated an association between glucose metabolism parameters and triglycerides with OSAS severity underlying the complexity of the process leading to cardiovascular/metabolic complications in this disorder. Moreover, homocysteine, glycemic and lipidic profiles changed significantly after 6 months of PAP therapy in OSAS, supporting its cardiovascular and metabolic protective effect. CONCLUSION Our study has reinforced the importance of analytical cardiovascular/metabolic evaluation as complementary tool of diagnosis/treatment response in OSAS.

Evening and morning alterations in Obstructive Sleep Apnea red blood cell proteome

This article presents proteomics data referenced in [1] Using proteomics-based evaluation of red blood cells (RBCs), we have identified differentially abundant proteins associated with Obstructive Sleep Apnea Syndrome (OSA). RBCs were collected from peripheral blood of patients with moderate/severe OSA or snoring at pre- (evening) and post-night (morning) polysomnography, so that proteome variations between these time points could be assessed. RBC cytoplasmic fraction depleted of hemoglobin, using Hemovoid™ system, were analyzed by two-dimensional fluorescence difference gel electrophoresis (2D-DIGE), the 2D image software-based analyzed and relevant differentially abundant proteins identified by mass spectrometry (MS). MS identified 31 protein spots differentially abundant corresponding to 21 unique proteins possibly due to the existence of post-translational modification regulations. Functional analysis by bioinformatics tools indicated that most proteins are associated with catalytic, oxidoreductase, peroxidase, hydrolase, ATPase and anti-oxidant activity. At morning a larger numbers of differential proteins including response to chemical stimulus, oxidation reduction, regulation of catalytic activity and response to stress were observed in OSA. The data might support further research in OSA biomarker discovery and validation.

Anemia no doente oncológico

RESUMO No presente artigo de revisao os autores analisam os principais mecanismos da anemia no doente oncologico, a sua metodologia diagnostica e as opcoes terapeuticas, nomeadamente as indicacoes da transfusao de concentrado eritrocitario e da utilizacao da eritropoietina recombinante. E tambem discutido o impacto da anemia na qualidade de vida dos doentes, na evolucao e no tratamento da doenca oncologica. REV PORT PNEUMOL 2003; IX (2): 117-128