Systemic therapy of Cushing’s syndrome

Cushing’s disease (CD) in a stricter sense derives from pathologic adrenocorticotropic hormone (ACTH) secretion usually triggered by micro- or macroadenoma of the pituitary gland. It is, thus, a form of secondary hypercortisolism. In contrast, Cushing’s syndrome (CS) describes the complexity of clinical consequences triggered by excessive cortisol blood levels over extended periods of time irrespective of their origin. CS is a rare disease according to the European orphan regulation affecting not more than 5/10,000 persons in Europe. CD most commonly affects adults aged 20–50 years with a marked female preponderance (1:5 ratio of male vs. female). Patient presentation and clinical symptoms substantially vary depending on duration and plasma levels of cortisol. In 80% of cases CS is ACTH-dependent and in 20% of cases it is ACTH-independent, respectively. Endogenous CS usually is a result of a pituitary tumor. Clinical manifestation of CS, apart from corticotropin-releasing hormone (CRH-), ACTH-, and cortisol-producing (malign and benign) tumors may also be by exogenous glucocorticoid intake. Diagnosis of hypercortisolism (irrespective of its origin) comprises the following: Complete blood count including serum electrolytes, blood sugar etc., urinary free cortisol (UFC) from 24 h-urine sampling and circadian profile of plasma cortisol, plasma ACTH, dehydroepiandrosterone, testosterone itself, and urine steroid profile, Low-Dose-Dexamethasone-Test, High-Dose-Dexamethasone-Test, after endocrine diagnostic tests: magnetic resonance imaging (MRI), ultra-sound, computer tomography (CT) and other localization diagnostics. First-line therapy is trans-sphenoidal surgery (TSS) of the pituitary adenoma (in case of ACTH-producing tumors). In patients not amenable for surgery radiotherapy remains an option. Pharmacological therapy applies when these two options are not amenable or refused. In cases when pharmacological therapy becomes necessary, Pasireotide should be used in first-line in CD. CS patients are at an overall 4-fold higher mortality rate than age- and gender-matched subjects in the general population. The following article describes the most prominent substances used for clinical management of CS and gives a systematic overview of safety profiles, pharmacokinetic (PK)-parameters, and regulatory framework

Analysing the eosinophil cationic protein - a clue to the function of the eosinophil granulocyte

Eosinophil granulocytes reside in respiratory mucosa including lungs, in the gastro-intestinal tract, and in lymphocyte associated organs, the thymus, lymph nodes and the spleen. In parasitic infections, atopic diseases such as atopic dermatitis and asthma, the numbers of the circulating eosinophils are frequently elevated. In conditions such as Hypereosinophilic Syndrome (HES) circulating eosinophil levels are even further raised. Although, eosinophils were identified more than hundred years ago, their roles in homeostasis and in disease still remain unclear. The most prominent feature of the eosinophils are their large secondary granules, each containing four basic proteins, the best known being the eosinophil cationic protein (ECP). This protein has been developed as a marker for eosinophilic disease and quantified in biological fluids including serum, bronchoalveolar lavage and nasal secretions. Elevated ECP levels are found in T helper lymphocyte type 2 (atopic) diseases such as allergic asthma and allergic rhinitis but also occasionally in other diseases such as bacterial sinusitis. ECP is a ribonuclease which has been attributed with cytotoxic, neurotoxic, fibrosis promoting and immune-regulatory functions. ECP regulates mucosal and immune cells and may directly act against helminth, bacterial and viral infections. The levels of ECP measured in disease in combination with the catalogue of known functions of the protein and its polymorphisms presented here will build a foundation for further speculations of the role of ECP, and ultimately the role of the eosinophil

O potencial pedagógico da Hora do Conto para o desenvolvimento da Comunicação Oral

O presente relatório é produto de um projeto de investigação que pretendeu caracterizar a adequação e dinamização da hora do conto com a finalidade de promover o desenvolvimento da comunicação oral, implementada numa sala de 3/4 anos e a adequação didática de um processo de intervenção educativa de estratégias para a promoção do desenvolvimento da Oralidade (incidindo na dinamização da hora conto) implementado numa turma de 3.º ano do 1.º Ciclo do Ensino Básico. Tendo consciência da desvalorização que é atribuída à temática em análise, acreditamos que os profissionais de educação se tornam responsáveis pelo desenvolvimento e aperfeiçoamento das capacidades de comunicação das crianças/alunos. Neste sentido, consideramos que foi extremamente importante investir neste domínio e nas competências a ele associado, nas vertentes de compreensão e expressão orais. Para atingir os objetivos delineamos, planificamos, construímos, aplicamos e avaliamos em sala de aula, um conjunto de intervenções educativas adotando como estratégia principal a dinamização da hora do conto. Assim sendo, podemos verificar através dos resultados obtidos, que efetivamente, a hora do conto e a utilização de diferentes estratégias para a dinamização da mesma, contribuíram positivamente para o desenvolvimento das competências orais dos intervenientes, potenciando melhorias, a vários níveis, nomeadamente na vertente de compressão e de expressão oral dos dois grupos de aplicação.This report is the product of a research project that aimed to characterize the adequacy and dynamization of the story time with the purpose of promoting the development of oral communication, implemented in a 3/4 year classroom and the didactic adequacy of a process of educational intervention strategies to promote the development of Orality (focusing on the dynamization of the story time) implemented in a 3rd year class of the 1st Cycle of Basic Education. Being aware of the devaluation that is attributed to the theme under analysis, we believe that education professionals become responsible for the development and improvement of communication skills of children/students. In this sense, we believe that it was extremely important to invest in this field and in the skills associated with it, in the areas of understanding and oral expression. In order to achieve the objectives, we delineate, plan, build, apply and evaluate in the classroom, a set of educational interventions adopting as the main strategy the dynamization of the story time. Therefore, we can verify through the results obtained, that effectively, the story time and the use of different strategies for the dynamization of the tale, contributed positively to the development of the oral skills of the participants, enhancing improvements, at various levels, particularly in the compression and oral expression of the two groups of application. Keywords: Oral Communication; Compression and Oral Expression; Story Time; Pre-School; 1st Cycle of Basic Education