The Innate Immune System via Toll-Like Receptors (TLRs) in Type 1 Diabetes - Mechanistic Insights

Type 1 diabetes (T1D) is a form of diabetes mellitus resulting from the lack of insulin secretion by the pancreatic beta cells and which accounts for approximately 5% of the total number of patients with diabetes worldwide. T1D is one of the most common endocrine disorders of children, and its incidence is steadily increasing. T1D is largely considered an autoimmune disorder resulting from the specific destruction of the pancreatic beta-cells that produce insulin. However, T1D pathophysiology is still not completely understood, and although insulin and other therapies ameliorate the manifestations of the disease, no cure is currently available. Traditionally, T1D has been thought of as a condition of cellular adaptive immunity, but evidence exists that components of the innate immune system, such as Toll-like receptors (TLRs), play a critical role in T1D development. TLRs have a central role in sensing microbial infections as well as endogenous alarm signals and trigger the release of inflammatory cytokines. The involvement of these receptors in the pathophysiology of several chronic diseases has become a major research interest, and in the last two decades, many studies have suggested the involvement of the innate immune system in the mechanism triggering T1D. Furthermore, microvascular complications in diabetic patients result in considerable morbidity, particularly diabetic nephropathy, retinopathy, and atherosclerosis. A hallmark of diabetic vascular pathology is inflammation and endothelial dysfunction. Recent literature suggests that TLR signaling is involved in vascular inflammation and endothelial dysfunction and that TLR activation may play a crucial role in diabetic microangiopathy. However, the mechanisms by which TLRs and their ligands contribute to T1D are not yet clear, and further investigation is needed. The goal of the present chapter is to address the contribution of TLRs to the mechanisms leading to the development and progression of T1D and to review current possibilities of targeting TLRs to forestall diabetic complications

Classificação de hidrópsia endolinfática em pacientes com suspeita de doença de Menière utilizando ressonância magnética

Mestrado em Radiações Aplicadas às Tecnologias da Saúde - Ramo de especialização: Imagem por Ressonância Magnética.A doença de Ménière (DM) é uma patologia idiopática do ouvido interno, caracterizada por episódios de vertigem recorrentes, hipoacusia flutuante e acufenos. Esta tríade de sintomas foi descrita pela primeira vez em 1861 por Prosper Ménière, apontando a disfunção do ouvido interno como a origem do complexo de sintomas auditivo e vestibular. Quando a etiologia de Hidrópsia Endolinfática (HE) é conhecida, designa-se por Síndrome de Ménière (SM). A classificação morfológica da HE no vestíbulo e na cóclea é feita com recurso à utilização de imagem por Ressonância Magnética (RM) através da escala de Nagoya, 2008. Esta dissertação tem como objetivos compreender os benefícios da utilização da RM na Doença de Ménière, avaliar a sensibilidade da RM para a diferenciação entre ouvido sintomático e ouvido assintomático e comparar a sintomatologia associada a estes pacientes com o grau atribuído pelo observador através da análise das imagens de RM. Para a elaboração deste estudo foi utilizada uma amostra de 51 pacientes que foram submetidos a exame de RM dos ouvidos. Para a aquisição das imagens de RM foi utilizado um protocolo específico com administração de contraste endovenoso (Gadolíneo) e 4h após a sua injeção foram incluídas as sequências específicas, sendo estas T1 3D IR e 3D Fluid Atennuation Inversion Recovery (3D-FLAIR). As regiões de interesse para a análise deste estudo foram o vestíbulo e a cóclea. A RM evidenciou uma sensibilidade de 74,5% para a deteção da DM em pacientes com sintomas característicos da patologia, bem como que um maior numero de sintomas associados à mesma é fator preponderante para um diagnóstico de DM confirmado pelas imagens de RM. A RM permite a realização de um diagnóstico diferencial para a caracterização de um paciente com ouvido sintomático.ABSTRACT - Ménière's disease (MD) is an idiopathic pathology of the inner ear, characterized by episodes of recurrent vertigo, fluctuating hearing loss, and tinnitus. This triad of symptoms was first described in 1861 by Prosper Ménière, pointing to dysfunction of the inner ear as the origin of the complex of auditory and vestibular symptoms. When the etiology of Endolymphatic Hydropsy (HE) is known, it is called Ménière's Syndrome (SM). The morphological classification of HE in the vestibule and cochlea is made using the Magnetic Resonance Imaging (MR) image using the Nagoya scale, 2008. This dissertation aims to understand the benefits of using Ménière's Disease, to evaluate MRI sensitivity for the differentiation between the symptomatic ear and asymptomatic ear, and to compare the symptomatology associated with these patients with the degree assigned by the observer through the analysis of MRI. For the preparation of this study, a sample of 51 patients who underwent MRI of the ears was used. For the acquisition of MR imaging, a specific protocol with intravenous contrast administration (Gadolíneo) and 4h after its injection were included in the specific sequences, being these T1 3D IR and 3D Fluid Attenuation Inversion Recovery (3D-FLAIR). The regions of interest for the analysis of this study were the vestibule and the cochlea. MRI showed a sensitivity of 74.5% for the detection of DM in patients with symptoms characteristic of the pathology, as well as a greater number of symptoms associated with it, which is a preponderant factor for a diagnosis of DM confirmed by MR images. MRI allows the performance of a differential diagnosis for the characterization of a patient with the symptomatic ear.N/

Major Topics in Type 1 Diabetes

Type 1 diabetes (TD1) is one of the most common endocrine disorders in children and can occur at any age. Incidences of T1D have steadily increased worldwide, and it is largely considered an autoimmune disorder resulting from the specific destruction of pancreatic beta-cells producing insulin. However, T1D pathophysiology is still not completely understood, and although insulin and other therapies ameliorate the manifestations of the disease, no cure is currently available. This book has been written by widely acknowledged experts, with each chapter providing unique information on emerging aspects of T1D. Because a large body of information has been available regarding T1D, this book highlights lesser explored topics linked to the subject using important and recent knowledge that presages directions for further research. Current possibilities to forestall diabetic complications are also explored

New insights into hypertension-associated erectile dysfunction

Purpose of review Erectile dysfunction is recognized as a quality-of-life disorder that needs to be treated. Currently, it is estimated to affect as many as 30 million American men. Thirty percent of hypertensive patients complain of erectile dysfunction. The understanding of common mechanisms involved in the cause of erectile dysfunction associated with hypertension, and the investigation of antihypertensive drugs that impact erectile dysfunction, will provide important tools toward identifying new therapeutic targets that will improve the quality of life for patients in these conditions. Recent findings Hypertension and erectile dysfunction are closely intertwined diseases, which have endothelial dysfunction as a common base. During hypertension and/or erectile dysfunction, disturbance of endothelium-derived factors can lead to an increase in vascular smooth muscle (VSM) contraction. Hypertension can lead to erectile dysfunction as a consequence of high blood pressure (BP) or due to antihypertensive treatment. However, growing evidence suggests erectile dysfunction is an early sign for hypertension. Also, some phosphodiesterase-5 inhibitors used to treat erectile dysfunction can improve BP, but the link between these conditions has not been totally understood. Summary This review will discuss the interplay between hypertension and erectile dysfunction, exploring newest insights regarding hypertension-associated erectile dysfunction, as well as the effect of antihypertensive drugs in erectile dysfunction patients