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The antioxidant nuclear factor erythroid 2-related factor 2 (Nrf2) is a desirable therapeutic target for a broad range of pathologies, including chronic diseases of the lung and liver, and autoimmune, neurodegenerative, and cardiovascular disorders. However, current Nrf2 activators are limited by unwanted effects due to non-specificity, and systemic distribution and action. Here we report that a 1,2-dicarbonyl moiety masks the electrophilic reactivity of the Nrf2 activator monomethyl fumarate (MMF), otherwise responsible for its non-specific effects. The 1,2-dicarbonyl compound is highly susceptible to Baeyer-Villiger oxidation, with generation of MMF specifically on exposure to pathological levels of hydrogen peroxide or peroxynitrite. Oral treatment with the MMF generating 1,2-dicarbonyl compound reversed chronic neuropathic and osteoarthritis pain in mice, and selectively activated Nrf2 at sites of oxidative stress. This 1,2-dicarbonyl platform may be used to treat additional disorders of oxidative stress, and to selectively target other therapeutics to sites of redox imbalance.

Growing evidence implicates the renin–angiotensin system (RAS) in multiple facets of neuropathic pain (NP). This narrative review focuses primarily on the major bioactive RAS peptide, Angiotensin II (Ang II), and its receptors, namely type 1 (AT1R) and type 2 (AT2R). Both receptors are involved in the development of NP and represent potential therapeutic targets. We first discuss the potential role of Ang II receptors in modulation of NP in the central nervous system. Ang II receptor expression is widespread in circuits associated with the perception and modulation of pain, but more studies are required to fully characterize receptor distribution, downstream signaling, and therapeutic potential of targeting the central nervous system RAS in NP. We then describe the peripheral neuronal and nonneuronal distribution of the RAS, and its contribution to NP. Other RAS modulators (such as Ang (1-7)) are briefly reviewed as well. AT1R antagonists are analgesic across different pain models, including NP. Several studies show neuronal protection and outgrowth downstream of AT2R activation, which may lead to the use of AT2R agonists in NP. However, blockade of AT2R results in analgesia. Furthermore, expression of the RAS in the immune system and a growing appreciation of neuroimmune crosstalk in NP add another layer of complexity and therapeutic potential of targeting this pathway. A growing number of human studies also hint at the analgesic potential of targeting Ang II signaling. Altogether, Ang II receptor signaling represents a promising, far-reaching, and novel strategy to treat NP.

BACKGROUND 80% of childhood cancer are located in low- and middle-income countries (LMIC). The most common form of presentation is disseminated or metastatic disease. The rate of survival has not been equitable across the world, since in these countries only 1 of 5 children are cured. OBJECTIVE To evaluate the clinical and histopathological features of patients with metastatic pediatric solid tumors, in a single referral cancer center in Honduras. METHODS We conducted a retrospective review of patients diagnosed with pediatric solid tumors from January 2010 to April 2020. Among the 260 patients through a collection form, we obtained: sociodemographic characteristics, clinical presentation at diagnosis, common histological subtypes, sites of metastasis, treatment and outcome at the time of follow-up. RESULTS During the last 10 years, 260 cases of childhood cancer were referred to our center for treatment. 127 patients (48.8%), have a solid tumor, patients ranged in age from 1 to 18 years and distribution for sex were 38% for males and 62% females. At the time of initial diagnosis 40/127 (31%) have advanced disease (stages III and IV). We found brain metastases in 22/40 cases (55%), the primary cancer was localized at CNS in 13/22 (59%) and the most common extracranial tumors causing brain metastases were neuroblastoma (4/22), rhabdomyosarcoma (3/22), retinoblastoma (2/22). Currently in the follow-up there were 18/22 (82%) died and 4/22 (18%) are in treatment with palliative intent. CONCLUSION There is a lack of information about the epidemiology of brain metastases among children with solid tumors in the low/middle income countries (LMIC) where the prognosis of metastatic disease is very poor, despite efforts, multimodal therapy and multidisciplinary management, in absence of other options like bone marrow transplantation, and reliable access to high-quality medicines. For our countries, timely diagnosis is still the main determining factor for cure.

INTRODUCTION: The risk of seizures varies between 60% and 100% among low-grade gliomas. The frequency of seizures differs widely according to tumor type. OBJECTIVE: To evaluate the clinical and histopathological features of patients with low grade gliomas. METHODS: We conducted a retrospective review of patients who underwent initial surgery for low grade glioma in a pediatric institution, between 2010 and 2017. Some variables are analyzed such as: age, sex, tumor location, histopathological findings, clinical characteristics of the seizures, surgical treatment, antiepileptic drugs. RESULTS: The main diagnoses were: desembrioplastic tumor, ganglioma, astrocytoma, all as WHO grade I, most of them with seizures as a main symptom, tumors involving the frontal, temporal, and parietal lobs with partial resection or biopsies. And epilepsy that merits treatment with up to two anticonvulsants during follow-up. DISCUSSION: Tumor location and histology influence the risk of epilepsy. Glioneuronal tumors, are typically associated with chronic drug-resistant epilepsy in up to 90% -100% of patients. Total macroscopic resection is the strongest predictor of the absence of attacks in addition to clinical factors, such as duration of preoperative attacks, type and control with antiepileptic drugs. CONCLUSION: The management of seizures represents an important aspect of the low grade gliomas, since tumor-related epilepsy affects patients’ quality of life, causes cognitive deterioration, and may result in significant morbidity.

RESUMO: A liberdade de expressão é um direito fundamental presente na Constituição de 1988 e funciona como um princípio fundamental para a democracia. Corolária do direito fundamental à liberdade, possui uma grande extensão quanto ao seu significado, sendo elemento base para outros diversos direitos e garantias, como o direito à informação, a liberdade de imprensa. No entanto, a liberdade de expressão pode sofrer algumas limitações, torna-se importante discriminar de modo mais sistemático tal limitação. Não se busca no presente trabalho o esgotamento do tema, mas sim a demonstração de sua grandeza e amplitude por meio de uma seleta bibliografia sobre o tema, como pesquisas, obras acadêmicas de variados tipos desde livros à outros artigos científicos, notícias e reportagens e paralelos do direito brasileiro por meio do direito comparado com precedentes americanos, alemães e espanhóis. Assim percebe-se que a liberdade de expressão está amalgada a qualquer democracia e sem seus fundamentos, não é possível ter um Estado Democrático de Direito no mundo contemporâneo. Palavras chave: Liberdade de expressão, conceito, espécies, limites.