Brazilian consensus for diagnosis, management and treatment of transthyretin familial amyloid polyneuropathy / Consenso Brasileiro para o diagnóstico, manejo e tratamento da Polineuropatia Amiloidótica Familiar associada à Transtirretina

ABSTRACT Transthyretin familial amyloid polyneuropathy is an autosomal dominant inherited sensorimotor and autonomic polyneuropathy, which if untreated, leads to death in approximately 10 years. In Brazil, liver transplant and tafamidis are the only disease-modifying treatments available. This review consists of a consensus for the diagnosis, management and treatment for transthyretin familial amyloid polyneuropathy from the Peripheral Neuropathy Scientific Department of the Brazilian Academy of Neurology. The first and last authors produced a draft summarizing the main views on the subject and emailed the text to 10 other specialists. Relevant literature on this subject was reviewed by each participant and used for the individual review of the whole text. Each participant was expected to review the text and send a feedback review by e-mail. Thereafter, the 12 panelists got together at the city of Fortaleza, discussed the controversial points, and reached a consensus for the final text.

RESUMO Polineuropatia amiloidótica familiar é uma polineuropatia sensitivo-motora e autonômica de herança autossômica dominante, que caso não seja tratada leva a morte em aproximadamente 10 anos. O transplante de fígado e o tafamidis são os únicos tratamentos disponíveis no Brasil. Essa revisão consiste em um consenso do Departamento Científico de Neuropatias Periféricas da Academia Brasileira de Neurologia. O primeiro e último autores produziram um texto resumindo os principais aspectos sobre o tema e enviaram para os outros 10 especialistas por email. A literatura relevante sobre o assunto foi revisada por cada participante e utilizada para revisão individual do texto. Foi esperado que cada participante revisasse o texto e enviasse suas sugestões por e-mail. Finalmente, os 12 panelistas se encontraram na cidade de Fortaleza para discutir os pontos controversos e chegar a um consenso sobre texto final.

Spinal muscular atrophy 5Q - Treatment with nusinersen

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Nuevos fármacos para el tratamiento de la hipercolesterolemia / New lipid lowering agents

Statins are the preferred treatment for hypercholesterolemia and several studies have demonstrated their long-term safety and efficacy in reducing cardiovascular morbidity and mortality. However, in some cases of severe hypercholesterolemia such as homozygous and heterozygous familial hypercholesterolemia or statin intolerant patients, statins can be less efficient. In recent years, new lipid-lowering agents with novel mechanisms of action have been developed to reduce LDL-cholesterol in patients with severe hypercholesterolemia, associated or not to conventional lipid-lowering therapy. These therapies include microsomal transfer protein inhibitor (Lomitapide), antisense oligonucleotide to Apo B100 (Mipomersen) and monoclonal antibodies against Proprotein convertase subtilisin/kexin type 9 (PCSK9). Different studies have shown the great effectiveness of these new therapies. Short-term studies confirmed their adequate security profile, especially in patients with homozygous familiar hypercholesterolemia or severe hypercholesterolemia. Some of these agents have been also tested in statin-intolerant patients. However, long-term studies are needed to evaluate their safety, effectiveness and impact on cardiovascular risk reduction.

Diseño de un sistema de PCR para la detección del virus del papiloma humano mediante el uso de oligonucleótidos degenerados de la región E6 / Desing of PCR system for detection of human papilloma virus by using degenerate oligonucleotides of the E6 region

Diseñar y estandarizar un sistema de PCR para detectar un amplio espectro de tipos de VPH en una sola reacción utilizando como blanco la región E6 del genoma viral. Utilizando secuencias del gen E6 de distintos tipos de VPH del NCBI y las herramientas informáticas Mult Alin versión 5.4.1. y Oligo Analyzer 1.1.2 se diseñaron oligonucleótidos degenerados que permitían la amplificación de un fragmento de aproximadamente 214 pb. Las muestras seleccionadas incluyen: 25 muestras de ADN, cada una positiva para un solo tipo de VPH tipificados por el sistema PCR-RFLP MY11/MY09 del gen L1. Se obtuvieron amplificados de aproximadamente 214 pb de 25 tipos distintos de VPH, se detectaron amplificados de E6 en muestras negativas para el sistema MY09/MY11. Se pudo determinar que el diseño de los oligonucleótidos degenerados fue altamente eficiente para la amplificación de por lo menos 25 tipos distintos de VPH lo que facilitaría la detección en muestras clínicas

Design and standardize a PCR system to detect a broad spectrum of HPV types in a single reaction using target the E6 region of the viral genome. Using E6 gene sequences of different HPV types and NCBI tools Mult Alin Oligo Analyzer version 1.1.2 5.4.1. Degenerate oligonucleotides were designed that allowed amplification of a fragment of approximately 214 bp. Selected samples include: 25 DNA samples, each positive for a single HPV type typified by PCR-RFLP system MY11/MY09 L1 gene. We obtained approximately 214 bp amplified from 25 different HPV types were detected in samples amplified from E6 negative MY09/MY11 system. It was determined that the design of degenerate oligonucleotides was highly efficient for amplification of at least 25 different HPV types which would facilitate detection in clinical samples

Emerging Molecular Targets for the Treatment of Asthma.

Current therapeutic approaches for the treatment of asthma have limitations in their ability to target all the features of the disease. Indeed, existing pharmacological asthma therapies are based on decades old strategies that were developed prior to the rapid growth in knowledge stemming from cell and molecular biology in the past decade. Thus, there is an unmet need for developing new drugs to target these features along with improved efficacy and safety. In the present review, the limitations of prevalent pharmacological asthma therapy are discussed briefly, and some explanations are suggested as to why new therapeutic targets are required to treat asthma, and finally directions for novel asthma therapies are proposed.