Variations in Inflammatory Markers in Acute Myocardial Infarction: a Longitudinal Study

Actualmente a inflamação é considerada uma componente importante na aterosclerose, desde o seu início até à ruptura da placa seguida de trombose e da progressiva obstrução do vaso. A ruptura da cápsula fibrótica da placa expõe factores de tecido presentes no seu núcleo necrótico que induzem o processo inflamatório, promovendo a adesão celular e a coagulação e que conduzem à formação do trombo. Por seu turno, várias citocinas e moléculas de adesão celular contribuem activamente para o desenvolvimento da placa. Em particular a citocina TNF-a e a molécula de adesão intercelular (ICAM-1) poderão ser indicadoras de inflamação enquanto que as formas solúveis de P-selectina e de CD40 ligando (sCD40L) poderão dar a magnitude da activação plaquetária. Neste trabalho foram estudados 17 doentes com enfarte de miocárdio submetidos a angioplastia (grupo AMI) e 16 doentes com confirmação angiográfica de ausência de doença coronária. Os doentes do grupo AMI foram seguidos nas primeiras 24h de evolução do enfarte agudo de miocárdio antes da administração de medicação e da intervenção angiográfica e ao longo do período de recuperação, 2 e 40 dias após enfarte. Foram medidas no soro por imunoensaio as concentrações de TNF-a e das formas solúveis de CD40L, ICAM-1 e P-selectina. Foram observadas variações significativas de sP-selectina relativamente aos controlos. Imediatamente após o enfarte de miocárdio verificou-se um aumento de sP-selectina, seguido de uma descida brusca dos seus níveis às 48h, e de um incremento para valores idênticos aos observados no grupo de controlo ao 40º dia. As variações observadas nas concentrações de sCD40L não foram significativas relativamente aos controlos. No entanto, verificou-se uma tendência de diminuição da concentração até 48h após o enfarte de miocárdio, seguindo-se um aumento que atingiu valores ligeiramente superiores ao do grupo controlo no 40º dia. As concentrações de TNF-a medidas foram sistematicamente superiores às verificadas no grupo controlo, tendo-se ainda observado uma subida gradual desde o enfarte de miocárdio até ao 40º dia, sendo este incremento significativo. Os valores de sICAM-1 não apresentaram quaisquer variações após o enfarte nem relativamente ao grupo controlo. As variações observadas sugerem um papel importante destes marcadores no processo inflamatório e na evolução do enfarte de miocárdio. O aumento brusco da concentração de sP-selectina após o enfarte de miocárdio evidencia a activação plaquetária e trombose. Na evolução do enfarte, e à medida que as variáveis hemodinâmicas retornam a valores estáveis, devido à medicação aplicada, o aumento de sCD40L e TNF-a em circulação pode reflectir o papel destas moléculas na recuperação endotelial e do miocárdio

Biomarkers of Thermal Adaptation: New Tools in Sustainable Livestock Production under Climate Change

Climate changes have been identified as one of the greatest environmental, social and economic threats to the planet and humanity. The increase of extreme weather events, such as prolonged droughts, extreme ambient temperatures or periods with high and intensive precipitation has effects on animal production systems. Crops, and consequently forage productivity and availability are compromised, the risk of new diseases increase, and animal production is impaired (growth, reproductive performance, metabolic and health status, and immune response can be affected). In this way the development of resilient and robust animal production systems, together with an improvement in the knowledge of the environmental impact in animal production and welfare are crucial to enhance innovation, sustainability and productivity in the animal sector. Ambient temperature and its abrupt extreme events have a major impact on the energy metabolism of livestock. This implies that animals presenting more physiological versatility can be best adapted, and therefore less susceptible to thermal stress and more productive. To achieve a production system where the detrimental effect of the climate change can be the minimum is necessary to improve the ability of the animal to cope with environmental stress by management and selection. The existence of biomarkers that allow to identify the levels of thermal stress and/or acclimation are valuable in the process of selecting the best well suited animals for each environmental condition, to propose selection programs based on that and for the herds management. Ideally biomarkers should be obtained from readily accessible samples, preferably non-invasively or minimally invasive, such as saliva, sweat and milk, hair and feces. Nowadays, the most commonly fluid used in biomarkers studies is the blood/plasma, but with growing tendency for being replaced. Blood cortisol has been one of the parameters more frequently used for assessing stressful conditions such as thermal stress. Nevertheless, it does not allow a full understanding of heat stress, due to its circadian cycle and because the confounding with other types of stress. Moreover, and taking the advantage of saliva as a non-invasive source of this corticosteroid, salivary cortisol has been also referred as potentially interesting. However, some of the limitations in taking conclusions from salivary cortisol results are the same reported for blood cortisol. Consequently, new and better non-invasive methods, than allow assessing stress, are necessary. The aim of this chapter is to present the state of the art on stress responses (climate, housing) and the principal effects of great temperature amplitudes in livestock production and the existing means to evaluate heat stress and acclimation capacity. Focus will be put on the importance of new reliable biomarkers. Saliva, hair, milk and feces will be discussed as potential sources of such non-invasive biomarkers

Variações Longitudinais de Lipoproteínas de Baixa Densidade Oxidadas Associadas à Artéria "Culpada" no Enfarte do Miocárdio com Elevação ST - um Marcador Promissor?

The aim of the present study was to investigate variations in oxidized LDL (oxLDL) at the onset of acute myocardial infarction (AMI) and over the recovery period, exploring their relationship with coronary disease severity. A follow-up of 50 AMI patients was evaluated against 25 healthy volunteers (reference group). The AMI patients were evaluated at three time points: at admission before the administration of IIb/IIIa inhibitors and angioplasty, and two and 40 days after intervention. Plasma oxLDL concentrations were measured by ELISA. oxLDL was found to be significantly higher in AMI patients in the acute phase relative to reference levels, decreasing progressively over the recovery period. The results also demonstrated that oxLDL levels were decreased in patients with the left circumflex artery (LCX) as culprit vessel compared to the left anterior descending coronary (LAD) or right coronary artery (RCA). The results highlight a significant increase in oxLDL concentration related to coronary artery disease severity, as conditions such as LCX lesions are usually associated with a favorable prognosis, contrasting with LAD-associated conditions that can compromise large areas of myocardium. The results thus suggest that oxLDL may constitute a promising marker in assessment of AMI evolution

The expression of monocarboxylate transporters in thyroid carcinoma can be associated with the morphological features of BRAF (V600E) mutation

BRAF (V600E) mutation, usually performed by DNA techniques, is one of the most common diagnostic markers in papillary thyroid carcinoma. Few papers have demonstrated that plump cells (eosinophilic cytoplasms and papillary thyroid carcinoma nuclei) and peculiar sickle-shaped nuclei represent morphological features of BRAF (V600E) on papillary thyroid carcinomas. These features seem to be linked to glycolytic phenotype whereby monocarboxylate transporters 1-4 are hypothesized to have a dominant role as lactate transporters. We investigated the association between these morphological features and monocarboxylate transporters 1 and 4 in 48 cyto-histological samples diagnosed as "positive for malignancy-favoring papillary thyroid carcinoma". These cases were processed with liquid-based cytology and underwent BRAF (V600E) mutational analysis (pyrosequencing) on liquid-based cytology and monocarboxylate transporters immunostaining on histology. The expression of monocarboxylate transporter 1, monocarboxylate transporter 4, glucose trasporter-1 and carbonic anhidrase were scored semi-quantitatively with expression from 0 to 3+ (strong positivity). The 33 mutated and 15 wild type cases showed 100 % cyto-histological concordance. The cytological evaluation revealed plump cells and sickle nuclear shape in 100 % mutated cases. Monocarboxylate transporter 1 yielded 76 % positivity in the mutated cases especially in both the plump cells and sickle-shaped nuclei, whereas the wild types showed 13.3 % positive monocarboxylate transporter 1 (p = 0.00013). Monocarboxylate transporter 4 resulted in 100 % positivity in mutated and 40 % in wild types (p 0.05). This is the first report analyzing the association between monocarboxylate transporter expression and the morphological features of BRAF (V600E) mutated papillary thyroid carcinomas suggesting the possible involvement of lactate in the morphological features.info:eu-repo/semantics/publishedVersio

Changes of Soluble CD40 Ligand in the Progression of Acute Myocardial Infarction Associate to Endothelial Nitric Oxide Synthase Polymorphisms and Vascular Endothelial Growth Factor But Not to Platelet CD62P Expression

Reported in vitro data implicated soluble CD40 ligand (sCD40L) in endothelial dysfunction and angiogenesis. However, whether sCD40L could exert that influence in endothelial dysfunction and angiogenesis after injury in acute myocardial infarction (AMI) patients remains unclear. In the present study, we evaluated the association of sCD40L with markers of platelet activation, endothelial, and vascular function during a recovery period early after AMI. To achieve this goal, the time changes of soluble, platelet-bound, and microparticle-bound CD40L levels over 1 month were assessed in AMI patients and correlated with endothelial nitric oxide synthase (eNOS) polymorphisms, vascular endothelial growth factor (VEGF) concentrations, and platelet expression of P-selectin (CD62P). The association of soluble form, platelet-bound, and microparticle-bound CD40L with CD62P expression on platelets, a marker of platelet activation, was also assessed to evaluate the role of CD40L in the thrombosis, whereas the association with eNOS and VEGF was to evaluate the role of CD40L in vascular dysfunction. This work shows for the first time that time changes of sCD40L over 1 month after myocardial infarct onset were associated with G894T eNOS polymorphism and with the VEGF concentrations, but not to the platelet CD62P expression. These results indicate that, in terms of AMI pathophysiology, the sCD40L cannot be consider just as being involved in thrombosis and inflammation but also as having a relevant role in vascular and endothelial dysfunction

Stratification of ST-Elevation Myocardial Infarction Patients Based on Soluble CD40L Longitudinal Changes

Involvement of soluble CD40 ligand (sCD40L) in thrombosis and inflammation on the context of coronary artery disease is currently being revised. In that perspective, we had studied the association of sCD40L with markers of platelet activation and markers of endothelial and vascular function. On that cohort, a stratification of patients with acute myocardial infarction (AMI) 1 month after percutaneous coronary intervention (PCI) was observed based on concentrations of sCD40L. The study intended to identify the groups of AMI patients with different profiles of sCD40L concentrations and verify how medication, clinical evolution, biochemical data, and markers of regulation of endothelial function at genetic (endothelial nitric oxide synthase polymorphisms) and post-transcriptional levels (circulating microRNAs) affect sCD40L serum levels. Lower quartiles of sCD40L (<2.3 ng/mL) were associated with higher concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), high frequency of G894T polymorphism, and altered expression of a set of microRNAs assumed to be involved in the regulation of endothelial and cardiac function and myocardium hypertrophy, relative to patients in sCD40L upper quartiles. A characteristic sCD40L variation pattern in STEMI patients was identified. Low levels of sCD40L 1 month after PCI distinguish STEMI patients with worse prognosis, a compromised cardiac healing, and a persistent endothelial dysfunction, as given by the association between sCD40L, NT-proBNP, G894T polymorphism, and specific profile of miRNA expression. These results suggest sCD40L could have a prognostic value in STEMI patients.info:eu-repo/semantics/publishedVersio

Consensus Recommendations of the Multiple Sclerosis Study Group and Portuguese Neuroradiological Society for the Use of the Magnetic Resonance Imaging in Multiple Sclerosis in Clinical Practice: Part 1

INTRODUCTION: Magnetic resonance imaging is established as a recognizable tool in the diagnosis and monitoring of multiple sclerosis patients. In the present, among multiple sclerosis centers, there are different magnetic resonance imaging sequences and protocols used to study multiple sclerosis that may hamper the optimal use of magnetic resonance imaging in multiple sclerosis. In this context, the Group of Studies of Multiple Sclerosis and the Portuguese Society of Neuroradiology, after a joint discussion, appointed a committee of experts to create recommendations adapted to the national reality on the use of magnetic resonance imaging in multiple sclerosis. The purpose of this document is to publish the first Portuguese consensus recommendations on the use of magnetic resonance imaging in multiple sclerosis in clinical practice. MATERIAL AND METHODS: The Group of Studies of Multiple Sclerosis and the Portuguese Society of Neuroradiology, after discussion of the topic in national meetings and after a working group meeting held in Figueira da Foz on May 2017, have appointed a committee of experts that have developed by consensus several standard protocols on the use of magnetic resonance imaging in the diagnosis and follow-up of multiple sclerosis. The document obtained was based on the best scientific evidence and expert opinion. Subsequently, the majority of Portuguese multiple sclerosis consultants and departments of neuroradiology scrutinized and reviewed the consensus paper; comments and suggestions were considered. Technical magnetic resonance imaging protocols regarding diagnostic, monitoring and the recommended information to be included in the magnetic resonance imaging report will be published in a separate paper. RESULTS: We provide some practical guidelines to promote standardized strategies to be applied in the clinical practice setting of Portuguese healthcare professionals regarding the use of magnetic resonance imaging in multiple sclerosis. CONCLUSION: We hope that these first Portuguese magnetic resonance imaging guidelines, based in the best available clinical evidence and practices, will serve to optimize multiple sclerosis management and improve multiple sclerosis patient care across Portugal.info:eu-repo/semantics/publishedVersio

Keratocystic odontogenic tumor overexpresses invadopodia-related proteins, suggesting invadopodia formation

OBJECTIVE: Keratocystic odontogenic tumor (KOT) is an odontogenic neoplasm that shows aggressive clinical behavior and local invasiveness. Invadopodia are actin-rich cellular protrusions exhibiting proteolytic pericellular activity, thereby inducing focal invasion in neoplastic cells and increasing neoplasms aggressiveness. Thus, this study aimed to evaluate immunoexpression of invadopodia-related proteins, cortactin, MT1-MMP, Tks4, and Tks5, in KOT. STUDY DESIGN: Immunohistochemistry of 16 cases of KOT, eight cases of calcifying cystic odontogenic tumor (CCOT), and eight samples of the oral mucosa (OM) was carried out to assess the expression of the above described invadopodia-related proteins in the basal and suprabasal layer. RESULTS: KOT samples showed higher and significant immunoexpression of cortactin, MT1-MMP, TKs4, and TKs5 compared with the CCOT and OM samples. Significant expression of all these proteins was observed in the basal layer compared with the suprabasal layer in KOT. CONCLUSIONS: Overexpression of cortactin, MT1-MMP, TKs4, and TKs5 was observed in KOT compared with samples of CCOT and OM. These proteins were also overexpressed in the basal over the suprabasal layer of KOT samples. Taken together, these results suggest the participation of invadopodia-related proteins on the pathogenesis of this lesion