2-Bromo-1,4-naphthoquinone: a potentially improved substitute of menadione in Apatone™ therapy

Apatone™, a combination of menadione (2-methyl-1,4-naphthoquinone, VK3) and ascorbic acid (vitamin C, VC) is a new strategy for cancer treatment. Part of its effect on tumor cells is related to the cellular pro-oxidative imbalance provoked by the generation of hydrogen peroxide (H2O2) through naphthoquinone redox cycling. In this study, we attempted to find new naphthoquinone derivatives that would increase the efficiency of H2O2 production, thereby potentially increasing its efficacy for cancer treatment. The presence of an electron-withdrawing group in the naphthoquinone moiety had a direct effect on the efficiency of H2O2 production. The compound 2-bromo-1,4-naphthoquinone (BrQ), in which the bromine atom substituted the methyl group in VK3, was approximately 10- and 19-fold more efficient than VK3 in terms of oxygen consumption and H2O2 production, respectively. The ratio [H2O2]produced / [naphthoquinone]consumed was 68 ± 11 and 5.8 ± 0.2 (µM/µM) for BrQ and VK3, respectively, indicating a higher efficacy of BrQ as a catalyst for the autoxidation of ascorbic acid. Both VK3 and BrQ reacted with glutathione (GSH), but BrQ was the more effective substrate. Part of GSH was incorporated into the naphthoquinone, producing a nucleophilic substitution product (Q-SG). The depletion of BrQ by GSH did not prevent its redox capacity since Q-SG was also able to catalyze the production of reactive oxygen species. VK3/VC has already been submitted to clinical trials for the treatment of prostate cancer and has demonstrated promising results. However, replacement of VK3 with BrQ will open new lines of investigation regarding this approach to cancer treatment.

Practices and ethical concerns regarding preimplantation diagnosis. Who regulates preimplantation genetic diagnosis in Brazil?

Preimplantation genetic diagnosis (PGD) was originally developed to diagnose embryo-related genetic abnormalities for couples who present a high risk of a specific inherited disorder. Because this technology involves embryo selection, the medical, bioethical, and legal implications of the technique have been debated, particularly when it is used to select features that are not related to serious diseases. Although several initiatives have attempted to achieve regulatory harmonization, the diversity of healthcare services available and the presence of cultural differences have hampered attempts to achieve this goal. Thus, in different countries, the provision of PGD and regulatory frameworks reflect the perceptions of scientific groups, legislators, and society regarding this technology. In Brazil, several texts have been analyzed by the National Congress to regulate the use of assisted reproduction technologies. Legislative debates, however, are not conclusive, and limited information has been published on how PGD is specifically regulated. The country requires the development of new regulatory standards to ensure adequate access to this technology and to guarantee its safe practice. This study examined official documents published on PGD regulation in Brazil and demonstrated how little direct oversight of PGD currently exists. It provides relevant information to encourage reflection on a particular regulation model in a Brazilian context, and should serve as part of the basis to enable further reform of the clinical practice of PGD in the country.

Plasticity of neutrophils reveals modulatory capacity

Neutrophils are widely known as proinflammatory cells associated with tissue damage and for their early arrival at sites of infection, where they exert their phagocytic activity, release their granule contents, and subsequently die. However, this view has been challenged by emerging evidence that neutrophils have other activities and are not so short-lived. Following activation, neutrophil effector functions include production and release of granule contents, reactive oxygen species (ROS), and neutrophil extracellular traps (NETs). Neutrophils have also been shown to produce a wide range of cytokines that have pro- or anti-inflammatory activity, adding a modulatory role for this cell, previously known as a suicide effector. The presence of cytokines almost always implies intercellular modulation, potentially unmasking interactions of neutrophils with other immune cells. In fact, neutrophils have been found to help B cells and to modulate dendritic cell (DC), macrophage, and T-cell activities. In this review, we describe some ways in which neutrophils influence the inflammatory environment in infection, cancer, and autoimmunity, regulating both innate and adaptive immune responses. These cells can switch phenotypes and exert functions beyond cytotoxicity against invading pathogens, extending the view of neutrophils beyond suicide effectors to include functions as regulatory and suppressor cells.

Randomized controlled trials of serotonin-norepinephrine reuptake inhibitor in treating major depressive disorder in children and adolescents: a meta-analysis of efficacy and acceptability

New generation antidepressant therapies, including serotonin-norepinephrine reuptake inhibitor (SNRIs), were introduced in the late 1980s; however, few comprehensive studies have compared the benefits and risks of various contemporary treatments for major depressive disorder (MDD) in young patients. A comprehensive literature search of PubMed, Cochrane, Embase, Web of Science, and PsycINFO databases was conducted from 1970 to January 2015. Only clinical trials that randomly assigned one SNRI or placebo to patients aged 7 to 18 years who met the diagnostic criteria for major depressive disorder were included. Treatment success, dropout rate, and suicidal ideation/attempt outcomes were measured. Primary efficacy was determined by pooling the risk ratios (RRs) of treatment response and remission. Acceptability was determined by pooling the RRs of dropouts for all reasons and for adverse effects as well as suicide-risk outcomes. Five trials with a total of 973 patients were included. SNRIs were not significantly more effective than placebo for treatment response but were for remission. The comparison of patients taking SNRIs that dropped out for all reasons and those taking placebo did not reach statistical significance. Significantly more patients taking SNRIs dropped out for adverse effects than those taking placebo. No significant difference was found in suicide-related risk outcomes. SNRI therapy does not display a superior efficacy and is not better tolerated compared to placebo in these young patients. However, duloxetine has a potential beneficial effect for depression in young populations, showing a need for further research.

BK polyomavirus in Kidney transplant recipients: screening, monitoring and clinical management

BK polyomavirus (BKPyV) is a causal agent of nephropathy, ureteral stenosis and hemorrhagic cystitis in kidney transplant recipients, and is considered an important emerging disease in transplantation. Regular screening for BKPyV reactivation mainly during the first 2 years posttransplant, with subsequent pre-emptive reduction of immunosuppression is considered the best option to avoid disease progression, since successful clearance or reduction of viremia is achieved in the vast majority of patients within 6 months. The use of drugs with antiviral properties for patients with persistent viremia has been attempted despite unclear benefits. Clinical manifestations of BKPyV nephropathy, current strategies for diagnosis and monitoring of BKPyV infection, management of immunosuppressive regimen after detection of BKPyV reactivation and the use of antiviral drugs are discussed in this review.

Desesperança, ideação suicida e depressão em pacientes renais crônicos em tratamento por hemodiálise ou transplante

Introdução: Sintomas de desesperança, ideação suicida e depressão influenciam na qualidade e expectativa de vida de doentes renais crônicos. Objetivo: Avaliar se existe diferença nos sintomas de desesperança, ideação suicida e depressão entre pacientes renais crônicos em hemodiálise ou transplantados. Analisamos também se variáveis sociodemográficas como atividade laboral, ter dependentes, sexo e estado civil interferem nesses sintomas. Métodos: Estudo comparativo, de corte transversal, em que 50 pacientes em hemodiálise crônica e 50 transplantados renais, clinicamente estáveis, sem psicopatologias, pareados por sexo e idade, foram selecionados aleatoriamente. Instrumentos -Beck Hopelessness Scale (BHS), Beck Scale for Suicide Ideation (BSI) e Beck Depression Inventory (BDI). Resultados: BHS: 2% de cada grupo tiveram escore > 8 (p = 1,00). BSI: 4% em hemodiálise e 6% dos transplantados tinham escore > 1 (p = 1,00). BDI: 20% em hemodiálise e 12% dos transplantados apresentaram escore > 14 (p = 0,275). Não houve relação entre as variáveis testadas e os sintomas de desesperança e ideação suicida. Não exercer atividade laboral implicou mais sintomas depressivos (escore médio BDI: 10,5 vs. 7,3, p = 0,027). Transplantados de doadores falecidos apresentaram mais sintomas depressivos comparados aos receptores de doadores vivos (escore médio BDI: 11,0 vs. 6,7, p = 0,042). Conclusão: Não houve diferença na intensidade dos sintomas de desesperança, ideação suicida e depressão entre pacientes estáveis em hemodiálise e transplantados. Não exercer atividade laboral e receber transplante de doador falecido levou a mais sintomas depressivos. A prevalência de ideação suicida e sintomas depressivos, nas duas modalidades, merece atenção e indica a necessidade de monitorização e cuidados nesses pacientes.

Still the century of government savings banks? The Caixa Econômica Federal

This article explores general concerns about government banking, social inclusion, and democracy through case study of the Brazilian federal government savings bank (Caixa Econômica Federal). Review of government savings banks in Brazilian history suggests that these institutions have been at the center of domestic political economy, expanding and contracting under a variety of political regimes and economic conditions. Since capitalization to meet central bank and Basel Accord guidelines in 2001, the Caixa has attempted to modernize, continue to serve as agent for government policies, and expand both popular credit and savings and investment banking activities.