Development of L-Asparaginase Biobetters: Current Research Status and Review of the Desirable Quality Profiles

L-Asparaginase (ASNase) is a vital component of the first line treatment of acute lymphoblastic leukemia (ALL), an aggressive type of blood cancer expected to afflict over 53,000 people worldwide by 2020. More recently, ASNase has also been shown to have potential for preventing metastasis from solid tumors. The ASNase treatment is, however, characterized by a plethora of potential side effects, ranging from immune reactions to severe toxicity. Consequently, in accordance with Quality-by-Design (QbD) principles, ingenious new products tailored to minimize adverse reactions while increasing patient survival have been devised. In the following pages, the reader is invited for a brief discussion on the most recent developments in this field. Firstly, the review presents an outline of the recent improvements on the manufacturing and formulation processes, which can severely influence important aspects of the product quality profile, such as contamination, aggregation and enzymatic activity. Following, the most recent advances in protein engineering applied to the development of biobetter ASNases (i.e., with reduced glutaminase activity, proteolysis resistant and less immunogenic) using techniques such as site-directed mutagenesis, molecular dynamics, PEGylation, PASylation and bioconjugation are discussed. Afterwards, the attention is shifted toward nanomedicine including technologies such as encapsulation and immobilization, which aim at improving ASNase pharmacokinetics. Besides discussing the results of the most innovative and representative academic research, the review provides an overview of the products already available on the market or in the latest stages of development. With this, the review is intended to provide a solid background for the current product development and underpin the discussions on the target quality profile of future ASNase-based pharmaceuticals

LÁCTEOS COM BAIXO TEOR DE LACTOSE: UMA NECESSIDADE PARA PORTADORES DE MÁ DIGESTÃO DA LACTOSE E UM NICHO DE MERCADO

Lactose is the main carbohydrate in milk, containing in nutrients food to health maintenance. Lactose intolerance is the term commonly used to describe the symptoms reported by people with lactose maldigestion after eating dairy products, being a very important topic for food professionals, consumers and health professionals. It is estimated that 65% of the world adult population manifesting symptoms of lactose maldigestion. Haven misconceptions about its manifestation and development, inducing the belief that milk and its derivatives should be excluded from the diet of people who have symptoms of lactose intolerance. This article aims to review the main concepts related to lactose comprising: their properties nutritional and industrial importance, the distinction between poor digestion, allergies and lactose intolerance, labeling, methods of diagnosis and treatment, as well as the diversity of products with low levels of lactose as alternatives for individuals with lactose maldigestion. A lactose é o principal carboidrato presente no leite, um alimento composto por nutrientes fundamentais à manutenção da saúde. A intolerância à lactose é o termo habitualmente usado para descrever os sintomas relatados por pessoas que apresentam má digestão da lactose após ingerirem leite e derivados, sendo um tema de extrema relevância para profissionais da área de alimentos, consumidores e profissionais de saúde. Estima-se que 65% da população mundial adulta manifestem sinais e sintomas de má digestão da lactose. Ideias equivocadas sobre sua manifestação e desenvolvimento, induzem a crenças de que o leite e seus derivados devem ser excluídos da alimentação de pessoas que manifestam sintomas de intolerância à lactose. Este artigo visa revisar os principais conceitos relacionados à lactose compreendendo: suas propriedades, importância nutricional e industrial, a distinção entre a má digestão, alergia e a intolerância à lactose, rotulagem, métodos de diagnóstico e de tratamento, bem como a diversidade de produtos com baixos teores de lactose como alternativas para os portadores de má digestão da lactose

Boletín meteorológico diario: Número 24 - 2007 Enero 24

A obesidade é um grave problema de saúde pública, com prevalência crescente em níveis epidêmicos. Tratamento farmacológico é uma das abordagens terapêuticas, mas deve ser precedido de mudança de hábitos alimentares e prática regular de atividades físicas. Há preocupação com o uso não racional de medicamentos anorexígenos, independente da condição de doença. O estudo avaliou as dispensações destes psicotrópicos realizadas em 2009, Juiz de Fora, MG. Realizou-se a pesquisa em boletins de consumo, enviados mensalmente à VISA municipal, e em registros obtidos no SNGPC. De 7.759 notificações pesquisadas, 93,3% foram dispensadas por farmácias magistrais e 6,7% por drogarias. Daquele total, 55,4% foram de anfepramona, 33,1% de femproporex e 11,5% de mazindol. Com base em relatório da Anvisa, as três substâncias apresentaram consumo maior no município (DDD/mil hab/ano) do que no país como um todo, para o mesmo período. O profissional com maior número de receitas aviadas teve 3.535 dispensações. Todas foram dispensadas em farmácias, sendo 99,5% em um único estabelecimento. O cenário mostra a dispensação de anorexígenos como problema relevante de saúde coletiva e indica a necessidade de reavaliação dos critérios de monitoramento de sua prescrição, dispensação e consumo.Obesity is a serious public health issue of epidemic proportions. Although drug therapy is one of the therapeutic approaches, it should be preceded by a change in eating habits along with regular exercise. This study assessed prescription of such drugs in 2009, in Juiz de Fora, Minas Gerais, Brazil. Data were collected from consumption bulletins sent monthly to the municipal sanitary surveillance agency (VISA), and from the Brazilian National Management System of Controlled Products. Of the 7,759 notifications assessed, 93.3% were dispensed by prescription pharmacies and 6.7% by drugstores. Of that total, 55.4% were for amphepramone, 33.1% for femproporex, and 11.5% for mazindol. The three drugs had a larger consumption rate in the municipality (daily defined dose/1,000 inhabitants/day) than in the country as a whole, during the period under study. The professional with the highest prescription rate was responsible for 3,535 prescriptions. All of these were dispensed by prescription pharmacies, a single outlet being responsible for 99.5% of these prescriptions. This scenario shows that anorectic psychotropic drug prescription is a relevant public health issue and the criteria for monitoring the prescription and consumption of these drugs should be re-evaluated