An integrative approach based on GC-qMS and NMR metabolomics data as a comprehensive strategy to search potential breast cancer biomarkers.

INTRODUCTION: Globally, breast cancer (BC) is leading at the top of women's diseases and, as a multifactorial disease, there is the need for the development of new approaches to aid clinicians on monitoring BC treatments. In this sense, metabolomic studies have become an essential tool allowing the establishment of interdependency among metabolites in biological samples. OBJECTIVE: The combination of nuclear magnetic resonance (NMR) and gas chromatography-quadrupole mass spectrometry (GC-qMS) based metabolomic analyses of urine and breast tissue samples from BC patients and cancer-free individuals was used. METHODS: Multivariate statistical tools were used in order to obtain a panel of metabolites that could discriminate malignant from healthy status assisting in the diagnostic field. Urine samples (n = 30), cancer tissues (n = 30) were collected from BC patients, cancer-free tissues were resected outside the tumor margin from the same donors (n = 30) while cancer-free urine samples (n = 40) where obtained from healthy subjects and analysed by NMR and GC-qMS methodologies. RESULTS: The orthogonal partial least square discriminant analysis model showed a clear separation between BC patients and cancer-free subjects for both classes of samples. Specifically, for urine samples, the goodness of fit (R2Y) and predictive ability (Q2) was 0.946 and 0.910, respectively, whereas for tissue was 0.888 and 0.813, revealing a good predictable accuracy. The discrimination efficiency and accuracy of tissue and urine metabolites was ascertained by receiver operating characteristic curve analysis that allowed the identification of metabolites with high sensitivity and specificity. The metabolomic pathway analysis identified several dysregulated pathways in BC, including those related with lactate, valine, aspartate and glutamine metabolism. Additionally, correlations between urine and tissue metabolites were investigated and five metabolites (e.g. acetone, 3-hexanone, 4-heptanone, 2-methyl-5-(methylthio)-furan and acetate) were found to be significant using a dual platform approach. CONCLUSION: Overall, this study suggests that an improved metabolic profile combining NMR and GC-qMS may be useful to achieve more insights regarding the mechanisms underlying cancer.

Analytical Platforms for the Determination of Phospholipid Turnover in Breast Cancer Tissue: Role of Phospholipase Activity in Breast Cancer Development.

Altered lipid metabolism has been associated with the progression of various cancers, and aberrant expression of enzymes involved in the lipid metabolism has been detected in different stages of cancer. Breast cancer (BC) is one of the cancer types known to be associated with alterations in the lipid metabolism and overexpression of enzymes involved in this metabolism. It has been demonstrated that inhibition of the activity of certain enzymes, such as that of phospholipase A2 in BC cell lines sensitizes these cells and decreases the IC50 values for forthcoming therapy with traditional drugs, such as doxorubicin and tamoxifen. Moreover, other phospholipases, such as phospholipase C and D, are involved in intracellular signal transduction, which emphasizes their importance in cancer development. Finally, BC is assumed to be dependent on the diet and the composition of lipids in nutrients. Despite their importance, analytical approaches that can associate the activity of phospholipases with changes in the lipid composition and distribution in cancer tissues are not yet standardized. In this review, an overview of various analytical platforms that are applied on the study of lipids and phospholipase activity in BC tissues will be given, as well as their association with cancer diagnosis and tumor progression. The methods that are applied to tissues obtained from the BC patients will be emphasized and critically evaluated, regarding their applicability in oncology.

Síndrome de hemiconvulsión-hemiplejía-epilepsia: caso clínico y uso de dextrometorfano / Hemiconvulsion-hemiplegia-epilepsy syndrome: case report and use of dextromethorphan

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Comparative analysis of impacted upper canines: Panoramic radiograph Vs Cone Beam Computed Tomography.

BACKGROUND: The use of CBCT exam in the study of IMC is not new. However, it's still not known in what specific aspects CBCT exam shows a better result than then conventional exams. The aim of this study was to compare and conclude in what way the opinion regarding upper canine impaction differed when observing a panoramic image compared to the observation of a set of CBCT reconstructions. MATERIAL AND METHODS: Twenty patients (10 males and 10 females) with a total of 28 impacted maxillary canines were identified from the database of the Department of Dentistry, Faculty of Medicine, University of Coimbra. For each canine, two different images were available: a panoramic image and a set of CBCT reconstructions. After a random distribution of both groups images, nine orthodontists completed a questionnaire where they were asked to evaluate ten different questions regarding canine impaction. Statistic analysis was performed using Cronbach's alpha statistics, Kappa statistics and McNemar test, considering p<0,05 statistically significant. RESULTS: This study showed differences between the two images regarding tooth position. A statistical significant poor agreement was found between the two methods for the mesio-distal position of the apex (k=0,388, p<0,001) and for the labio-palatal tip cusp position (k=0,035, p=0,114). The adjacent root resorption showed a poor and very poor agreement between the two methods. Every other items were scored with an agreement between modalities ranging from moderate to strong. CONCLUSIONS: The analyses of panoramic images versus CBCT images reconstructions provided different information regarding tooth position (especially concerning the mesio-distal apex position and the labio-palatal cusp position) but also in the assessment of root resorption. Further investigation should be done to determine in what cases CBCT exam has a clear advantage over conventional 2D exams, justifying its use. Key words:Cone-Beam Computed Tomography, Orthodontics, Impacted Tooth, Root resorption.

Re-exploring the high-throughput potential of microextraction techniques, SPME and MEPS, as powerful strategies for medical diagnostic purposes. Innovative approaches, recent applications and future trends.

The human population continues to grow exponentially in the fast developing and most populated countries, whereas in Western Europe it is getting older and older each year. This inevitably raises the demand for better and more efficient medical services without increasing the economic burden in the same proportion. To meet these requirements, improvement of medical diagnosis is certainly a key aspect to consider. Therefore, we need powerful analytical methodologies able to go deeper and further in the characterization of human metabolism and identification of disease biomarkers and endogenous molecules in body fluids and tissues. The ultimate goal is to have a reliable and early medical diagnosis, mitigating the disease complications as much as possible. Microextraction techniques (METs) represent a key step in these analytical methodologies by providing samples in the suitable volumes and purification levels necessary for the characterization of the target analytes. In this aspect, solid-phase microextraction (SPME) and, more recently, microextraction by packed sorbent (MEPS), are powerful sample preparation techniques, characterized by their reduced time of analysis, low solvent consumption, and broad application. Moreover, as miniaturized techniques, they can be easily automatized to have a high-throughput performance in the clinical environment. In this review, we explore some of the most interesting MEPS and SPME applications, focusing on recent trends and applications to medical diagnostic, particularly the in vivo and near real time applications.

Drugs that may provoke Kounis syndrome.

Kounis Syndrome (KS) is the contemporary occurrence of Acute Coronary Syndromes (ACS) with an allergic or hypersensitivity reaction. This syndrome has been reported in association with a variety of drugs, food, insect stings, environmental exposures and medical conditions. Cases of KS seem to be more often encountered in everyday clinical practice than anticipated. It is believed that the lack of awareness of this association may lead to underreporting. We report a case of KS secondary to diclofenac intake.

Fármacos que podem provocar Síndrome de Kounis / Drugs that may provoke Kounis Syndrome / Fármacos que pueden provocar Síndrome de Kounis

A Síndrome de Kounis (SK) corresponde ao aparecimento simultâneo de síndromes coronárias agudas (SCA) com reações alérgicas ou de hipersensibilidade. Na literatura têm sido reportados vários casos associados a fármacos, picadas de inseto, alimentos, exposições ambientais e doenças médicas. Essa síndrome é encontrada na prática médica diária mais frequentemente do que antecipada. Por isso, o desconhecimento dessa síndrome poderá contribuir para a falha no diagnóstico. Apresentamos um caso clínico de Síndrome de Kounis secundária à ingestão de diclofenaco.

Kounis Syndrome (KS) is the contemporary occurrence of Acute Coronary Syndromes (ACS) with an allergic or hypersensitivity reaction. This syndrome has been reported in association with a variety of drugs, food, insect stings, environmental exposures and medical conditions. Cases of KS seem to be more often encountered in everyday clinical practice than anticipated. It is believed that the lack of awareness of this association may lead to underreporting. We report a case of KS secondary to diclofenac intake.

El Síndrome de Kounis (SK) es el surgimiento simultáneo de síndromes coronarios agudos (SCA) con reacciones alérgicas o de hipersensibilidad. En la literatura han sido reportados varios casos asociados con fármacos, picadas de insecto, alimentos, exposiciones ambientales y enfermedades médicas. Ese síndrome se encuentra en la práctica médica diaria con más frecuencia de lo que se cree. Por eso, su descubrimiento podrá contribuir a la mejoría en los fallos de diagnóstico. Presentamos un caso clínico del Síndrome de Kounis secundario a la ingestión de diclofenaco.