Biomarcadores em gliomas : conhecimento atual e perspetivas futuras

Monografia realizada no âmbito da unidade de Estágio Curricular do Mestrado Integrado em Ciências Farmacêuticas, apresentada à Faculdade de Farmácia da Universidade de CoimbraOs gliomas são subdivididos em astrocitomas, oligodendrogliomas e ependimomas com base na semelhança imunofenotípica da célula que lhe deu origem. Várias alterações moleculares têm sido detetadas em gliomas, tais como a perda combinada dos braços dos cromossomas 1p e 19q, a presença de mutação nos genes que codificam a enzima isocitrato desidrogenase (IDH) e a hipermetilação do promotor do gene MGMT, com valor de diagnóstico, prognóstico e preditivo. (Kros et al., 2015) É conhecida a importância clínica de marcadores genéticos ou imunohistoquímicos derivados da resseção ou biópsia do tumor mas a recolha frequente de amostras de tecido tumoral não é fácil e os biomarcadores circulantes são necessárias para evitar biópsias repetidas. Têm sido feitos esforços na tentativa de validar biomarcadores que reflitam o perfil genético de um tumor. Na circulação, esses biomarcadores incluem células tumorais e ácidos nucleicos, que podem tanto circular livremente no plasma ou estar inseridos em vesículas extracelulares. (Westphal e Lamszus, 2015) A inclusão de biomarcadores circulantes na prática clínica vem permitir um prognóstico mais efetivo, uma terapia personalizada e a monitorização da terapia dos futuros doentes.Gliomas are subdivided into astrocytoma, oligodendroglioma and oligoastrocytoma based on immunophenotypical similarity to a cell of putative origin. Various molecular aberrations of gliomas such as, the combined loss of chromosome arms 1p and 19q, the presence of isocitrate dehydrogenase (IDH) mutation and MGMT promoter hypermethylation, harbor diagnostic, prognostic, or predictive information. (Kros et al., 2015) The clinical importance of genetic or immunohistochemical biomarkers derived from the resected tumour or biopsy is well established, but repeated sampling of tumour tissue is not always appropriate, and circulating biomarkers are necessary to avoid repeated biopsies. Great efforts have been made to validate biomarkers reflecting the genetic profile of a tumour. In the circulation, such biomarkers include circulating tumour cells, and cell-free nucleic acids that can either circulate freely in the plasma or be packaged into extracellular vesicles. (Westphal e Lamszus, 2015) Inclusion of circulating biomarkers in clinical daily practice is warranted in an effort for more effective prognosis, personalized therapy and therapy monitoring in the future of patients

Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr

Statins, Fibrates and Myopathy: pathophysiological mechanism, risk factors and laboratory markers / Estatinas, Fibratos e Miopatia: mecanismos fisiopatológicos, fatores de risco e marcadores laboratoriais

With the increasing life expectancy of the world population, the elderly experiences the occurrence of multiple chronic diseases, a phenomenon called multimorbidity. Such condition induces the need for the elderly to engage in combined pharmacological treatments, giving rise to polypharmacy, leading to the often unnecessary and inadequate consumption of some drugs. Among these, we can mention fibrates and statins, widely used in the control and treatment of dyslipidemia. Both classes of drugs present as the main adverse effect of concern the genesis of myalgias and myositis, with evolution to rhabdomyolysis. In view of the above, this study aimed to understand the mechanism responsible for inducing muscle damage in the administration of these drugs, also considering the factors that favor their appearance and the laboratory markers used for diagnostic purposes. This work was carried out from a bibliographic review using scientific articles published in English, Portuguese and Spanish, available in the PubMed, Scielo, LILACS and Google academic databases

Safety and immunomodulatory effects of three probiotic strains isolated from the feces of breast-fed infants in healthy adults: SETOPROB study

We previously described the isolation and characterization of three probiotic strains from the feces of exclusively breast-fed newborn infants: Lactobacillus paracasei CNCM I-4034, Bifidobacterium breve CNCM I-4035 and Lactobacillus rhamnosus CNCM I-4036. These strains were shown to adhere to intestinal mucus in vitro, to be sensitive to antibiotics and to resist biliary salts and low pH. In the present study, a multicenter, randomized, double-blind, placebo-controlled trial with 100 healthy volunteers in three Spanish cities was carried out to evaluate the tolerance, safety, gut colonization and immunomodulatory effects of these three probiotics. Volunteers underwent a 15-day washout period, after which they were randomly divided into 5 groups that received daily a placebo, a capsule containing one of the 3 strains or a capsule containing a mixture of two strains for 30 days. The intervention was followed by another 15-day washout period. Patients did not consume fermented milk for the entire duration of the study. Gastrointestinal symptoms, defecation frequency and stool consistency were not altered by probiotic intake. No relevant changes in blood and serum, as well as no adverse events occurred during or after treatment. Probiotic administration slightly modified bacterial populations in the volunteers’ feces. Intestinal persistence occurred in volunteers who received L. rhamnosus CNCM I-4036. Administration of B. breve CNCM I-4035 resulted in a significant increase in fecal secretory IgA content. IL-4 and IL-10 increased, whereas IL-12 decreased in the serum of volunteers treated with any of the three strains. These results demonstrate that the consumption of these three bacterial strains was safe and exerted varying degrees of immunomodulatory effects.Part of the research currently in progress in the authors' laboratory is funded by the company Hero Spain, S. A. through the grant #3582 managed by the Fundacion General Empresa-Universidad de Granada

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Relatório de estágio em farmácia comunitária

Relatório de estágio realizado no âmbito do Mestrado Integrado em Ciências Farmacêuticas, apresentado à Faculdade de Farmácia da Universidade de Coimbr