Oxidative stress in sickle cell disease: An overview of erythrocyte redox metabolism and current antioxidant therapeutic strategies

Erythrocytes have an environment of continuous pro-oxidant generation due to the presence of hemoglobin (Hb), which represents an additional and quantitatively significant source of superoxide (O2 •-) generation in biological systems. To counteract oxidative stress, erythrocytes have a self-sustaining antioxidant defense system. Thus, red blood cells uniquely function to protect Hb via a selective barrier allowing gaseous and other ligand transport as well as providing antioxidant protection not only to themselves but also to other tissues and organs in the body. Sickle hemoglobin molecules suffer repeated polymerization/depolymerization generating greater amounts of reactive oxygen species, which can lead to a cyclic cascade characterized by blood cell adhesion, hemolysis, vaso-occlusion, and ischemia-reperfusion injury. In other words, sickle cell disease is intimately linked to a pathophysiologic condition of multiple sources of pro-oxidant processes with consequent chronic and systemic oxidative stress. For this reason, newer therapeutic agents that can target oxidative stress may constitute a valuable means for preventing or delaying the development of organ complications. © © 2013 Elsevier Inc. All rights reserved.

Draft project: creole discourse and social development

Presenta el proyecto preliminar sobre la promocion del desarrollo social y el lenguaje criollo en el Caribe. Incluye antecedentes, objetivos, programa de actividades, instituciones regionales participantes, y aspectos institucionales.

Creole discourse and social development

Contiene el informe del proyecto sobre la promoción del desarrollo social y el lenguaje criollo en el Caribe

Reflections on the need for a new discourse on development

This issue of the FAL bulletin reflects on the need to place a new discourse at the centre of the academic, social and political debate, in relation to developing infrastructure services in a sustainable way.

Discurso moderno e psiquiatria reformada: considerações sobre um Centro de Atenção Psicossocial (CAPS)

A presente dissertação tem o objetivo de discutir a relação entre um dos novos serviços de intervenção e cuidados sobre a loucura, o Centro de Atenção Psicossocial (CAPS), e o olhar psiquiátrico que se construiu ao longo do século XIX. O CAPS, amparado pelos preceitos da Reforma Psiquiátrica Brasileira, visa, tal como outros dispositivos, combater o modelo asilar de assistência à loucura que se deu ao longo dos séculos, sobretudo sustentado, a partir do período moderno, no discurso psiquiátrico que tomou a loucura como objeto de seu saber, transformando-a em doença mental. O método utilizado para investigação foi a observação participante que se deu através da presença direta da pesquisadora no campo de estudo, descrevendo os elementos que circunscreveram o objeto de pesquisa, tais como: oficinas terapêuticas, grupos de psicologia e de família, acolhimento, assembleias e demais atividades, coletivas ou individuais, que fazem parte da dinâmica própria do serviço investigado. Inicia com a descrição do objeto, CAPS II: Santa Izabel, desde sua implantação no município de Santa Izabel do Pará, em 2001, até suas configurações atuais. Em seguida fundamenta os preceitos da Reforma Psiquiátrica que regulamentam ideologicamente este serviço, situando as referências históricas que culminaram neste movimento reformista, a partir das contribuições teóricas foucaultianas sobre o poder psiquiátrico e transformação da loucura em doença, bem como referencia demais autores que se apropriaram desta temática no contexto europeu, brasileiro e paraense. A Psicanálise é tomada, nesta dissertação, como uma possibilidade de apostar no sujeito possível de advir e existir, destacando as contribuições de Freud e Lacan sobre a teoria psicanalítica da psicose. Finaliza com análise dos dados coletados, aproximados ao referencial bibliográfico, demonstrando que, apesar do CAPS propor a ruptura com o modelo asilar instituído pelo saber psiquiátrico, naquele século, várias ações que se sustentam nesse objetivo, atualizam práticas asilares que, ao invés de darem um novo lugar à loucura, reeditam o enclausuramento imposto aos sujeitos que vivenciavam tal experiência subjetiva. Conclui que o CAPS precisa problematizar e relativizar as exigências regulamentadas pela Reforma e por sua lei, para conseguir resistir ao saber medicalizante que se faz tanto presente quanto antes, e assim conseguir reinventar práticas, conceitos, e modos de existência à loucura.

Evaluation of the therapeutic response of hepatitis C in coinfected patients (HIV/HCV): a study of cases from a hospital for chronic liver diseases in the Eastern Brazilian Amazon

INTRODUCTION: The aim of this study was to evaluate the therapeutic response of hepatitis C in patients coinfected with human immunodeficiency virus (HIV-1). METHODS: A retrospective study of 20 patients coinfected with HIV-1/HCV who were treated in the outpatient liver clinic at the Sacred House of Mercy Foundation Hospital of Pará (Fundação Santa Casa de Misericórdia do Pará - FSCMPA) from April 2004 to June 2009. Patients were treated with 180µg PEG interferon-α2a in combination with ribavirin (1,000 to 1,250mg/day) for 48 weeks. The end point was the sustained virological response (SVR) rate (HCV RNA negative 24 weeks after completing treatment). RESULTS: The mean age of the patients was 40±9.5 years, of which 89% (n=17) were male, and the HCV genotypes were genotype 1 (55%, n=11/20), genotype 2 (10%, n=2/20) and genotype 3 (35%, n=7/20). The mean CD4+ lymphocyte count was 507.8, and the liver fibrosis stages were (METAVIR) F1 (25%), F2 (55%), F3 (10%) and F4 (10%). The early virological response (EVR) was 60%, the end-of-treatment virological response (EOTVR) was 45% and the SVR was 45%. CONCLUSIONS: The median HCV viral load was high, and in 85% of cases in which highly active antiretroviral therapy (HAART) was used, none of the patients with F3-F4 fibrosis responded to treatment. Of the twenty patients treated, 45% achieved SVR and 45% achieved EOTVR. Studies that include cases from a wider region are needed to better evaluate these findings.

Clinical, epidemiological, and therapeutic profile of dermatophytosis

BACKGROUND: The cutaneous mycoses, mainly caused by dermatophyte fungi, are among the most common fungal infections worldwide. It is estimated that 10% to 15% of the population will be infected by a dermatophyte at some point in their lives, thus making this a group of diseases with great public health importance. OBJECTIVE: To analyze the clinical, epidemiological, and therapeutic profile of dermatophytosis in patients enrolled at the Dermatology service of Universidade do Estado do Pará, Brazil, from July 2010 to September 2012. METHOD: A total of 145 medical records of patients diagnosed with dermatophytosis were surveyed. Data were collected and subsequently recorded according to a protocol developed by the researchers. This protocol consisted of information regarding epidemiological and clinical aspects of the disease and the therapy employed. RESULTS: The main clinical form of dermatophyte infection was onychomycosis, followed by tinea corporis, tinea pedis, and tinea capitis. Furthermore, the female population and the age group of 51 to 60 years were the most affected. Regarding therapy, there was a preference for treatments that combine topical and systemic drugs, and the most widely used drugs were fluconazole (systemic) and ciclopirox olamine (topical). CONCLUSION: This study showed the importance of recurrent analysis of the epidemiological profile of dermatophytosis to enable correct therapeutic and preventive management of these conditions, which have significant clinical consequences, with chronic, difficult-totreat lesions that can decrease patient quality of life and cause disfigurement.

Therapeutic concentration of morphine reduces oxidative stress in glioma cell line

Morphine is a potent analgesic opioid used extensively for pain treatment. During the last decade, global consumption grew more than 4-fold. However, molecular mechanisms elicited by morphine are not totally understood. Thus, a growing literature indicates that there are additional actions to the analgesic effect. Previous studies about morphine and oxidative stress are controversial and used concentrations outside the range of clinical practice. Therefore, in this study, we hypothesized that a therapeutic concentration of morphine (1 μM) would show a protective effect in a traditional model of oxidative stress. We exposed the C6 glioma cell line to hydrogen peroxide (H₂O₂) and/or morphine for 24 h and evaluated cell viability, lipid peroxidation, and levels of sulfhydryl groups (an indicator of the redox state of the cell). Morphine did not prevent the decrease in cell viability provoked by H₂O₂) but partially prevented lipid peroxidation caused by 0.0025% H₂O₂) (a concentration allowing more than 90% cell viability). Interestingly, this opioid did not alter the increased levels of sulfhydryl groups produced by exposure to 0.0025% H₂O₂), opening the possibility that alternative molecular mechanisms (a direct scavenging activity or the inhibition of NAPDH oxidase) may explain the protective effect registered in the lipid peroxidation assay. Our results demonstrate, for the first time, that morphine in usual analgesic doses may contribute to minimizing oxidative stress in cells of glial origin. This study supports the importance of employing concentrations similar to those used in clinical practice for a better approximation between experimental models and the clinical setting.

Justiça terapêutica: o tribunal das drogas na sociedade de controle

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Leprosy: a review of laboratory and therapeutic aspects - Part 2

Leprosy is a chronic infectious condition caused by Mycobacterium leprae(M. leprae). It is endemic in many regions of the world and a public health problem in Brazil. Additionally, it presents a wide spectrum of clinical manifestations, which are dependent on the interaction between M. leprae and host, and are related to the degree of immunity to the bacillus. The diagnosis of this disease is a clinical one. However, in some situations laboratory exams are necessary to confirm the diagnosis of leprosy or classify its clinical form. This article aims to update dermatologists on leprosy, through a review of complementary laboratory techniques that can be employed for the diagnosis of leprosy, including Mitsuda intradermal reaction, skin smear microscopy, histopathology, serology, immunohistochemistry, polymerase chain reaction, imaging tests, electromyography, and blood tests. It also aims to explain standard multidrug therapy regimens, the treatment of reactions and resistant cases, immunotherapy with bacillus Calmette-Guérin (BCG) vaccine and chemoprophylaxis.

Supplementation and therapeutic use of vitamin D in patients with multiple sclerosis: Consensus of the Scientific Department of Neuroimmunology of the Brazilian Academy of Neurology

A esclerose múltipla (EM) é uma doença inflamatória, autoimune, desmielinizante e degenerativa do sistema nervoso central. Estudos epidemiológicos têm identificado associações de hipovitaminose D com doenças autoimunes. O principal objetivo desta revisão é responder se há evidências que indiquem o uso terapêutico de vitamina D em monoterapia para pacientes com EM. Por meio dos sites PUBMED, EMBASE, LILACS e Scielo foram realizadas buscas usando os descritores “vitamin D”, e “multiple sclerosis” até 12/09/2013. Estudos clínicos randomizados, controlados e duplo-cegos foram selecionados para avaliar a resposta terapêutica da vitamina D na EM. Não foram encontradas evidências científicas que justifiquem o uso da vitamina D em monoterapia no tratamento da EM, na prática clínica.

TWIST1 Is a Molecular Marker for a Poor Prognosis in Oral Cancer and Represents a Potential Therapeutic Target

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Genetic and biochemical markers of hydroxyurea therapeutic response in sickle cell anemia

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Citral: A monoterpene with prophylactic and therapeutic anti-nociceptive effects in experimental models of acute and chronic pain

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)