Molecular Aspects Involved in the Mechanisms of Bothrops jararaca Venom-Induced Hyperalgesia: Participation of NK1 Receptor and Glial Cells.

Accidents caused by Bothrops jararaca (Bj) snakes result in several local and systemic manifestations, with pain being a fundamental characteristic. The inflammatory process responsible for hyperalgesia induced by Bj venom (Bjv) has been studied; however, the specific roles played by the peripheral and central nervous systems in this phenomenon remain unclear. To clarify this, we induced hyperalgesia in rats using Bjv and collected tissues from dorsal root ganglia (DRGs) and spinal cord (SC) at 2 and 4 h post-induction. Samples were labeled for Iba-1 (macrophage and microglia), GFAP (satellite cells and astrocytes), EGR1 (neurons), and NK1 receptors. Additionally, we investigated the impact of minocycline, an inhibitor of microglia, and GR82334 antagonist on Bjv-induced hyperalgesia. Our findings reveal an increase in Iba1 in DRG at 2 h and EGR1 at 4 h. In the SC, markers for microglia, astrocytes, neurons, and NK1 receptors exhibited increased expression after 2 h, with EGR1 continuing to rise at 4 h. Minocycline and GR82334 inhibited venom-induced hyperalgesia, highlighting the crucial roles of microglia and NK1 receptors in this phenomenon. Our results suggest that the hyperalgesic effects of Bjv involve the participation of microglial and astrocytic cells, in addition to the activation of NK1 receptors.

Chikungunya Arthritis Treatment with Methotrexate and Dexamethasone: A Randomized, Double-blind, Placebo-controlled Trial.

BACKGROUND: Chikungunya fever is a reemerging epidemic disease caused by a single-stranded RNA alphavirus transmitted throughout by Aedes mosquitoes. Chikungunya virus infection is a biphasic disease in which 72% to 95% of affected individuals manifest acute chikungunya fever. Following the acute phase, more than 40% of affected individuals develop arthritis, often lasting more than 3 months, referred to as chronic chikungunya arthritis, which frequently mimics rheumatoid arthritis. OBJECTIVE: This study aimed to evaluate the efficacy and safety of treatment of chronic chikungunya arthritis with methotrexate and dexamethasone in a randomized, double-blind, placebo-controlled clinical trial. METHODS: The patients were reassessed for treatment response by the DAS28-ESR, tender joint count and swollen joint count, Patient Global Assessment, and for secondary measures, including the Health Assessment Questionnaire Disability Index and Pain Visual Analog Scale. RESULTS: Thirty-one subjects were randomized (placebo, n = 16; methotrexate, n = 15); 27 completed treatment and 4 discontinued during the 8-week blinded period. Among the participants, 96.8% were female, with mean ± SD age was 52.9 ± 13. The mean ± SD disease duration prior to treatment was 220.9 ± 51.2 days. At 8 weeks, methotrexate-treated subjects showed a greater numerical trend towards improvement, but there were no significant differences between methotrexate- dexamethasone group and dexamethasone (placebo) group. CONCLUSION: In this relatively small cohort, all of whom received background dexamethasone, there was a greater numerical improvement trend in prespecified outcome measures, but methotrexate in combination with dexamethasone was not superior to dexamethasone in chronic chikungunya arthritis.

Uso terapêutico do canabidiol: a demanda judicial no estado de Pernambuco, Brasil / Therapeutic use of cannabidiol: the lawsuit in the state of Pernambuco, Brazil

Resumo A Cannabis sativa L. vem sendo utilizada, antes mesmo da Era Cristã, para tratar inúmeras enfermidades, mas, no início do século 20, seu uso passou a ser proibido em vários países, inclusive com escopo medicinal, por ser considerada droga ilícita. Entretanto, a necessidade de obter alternativas aos tratamentos convencionais aumentou o interesse pelo uso terapêutico dessa droga vegetal, razão por que diversos estudos passaram a ser realizados, constatando que o Canabidiol (CBD), um dos principais compostos da planta, possui grande potencial terapêutico. No Brasil, a comercialização do CBD permanece proibida, mas, a partir de 2015, o uso compassivo e importação da substância foram autorizados pelo Conselho Federal de Medicina (CFM) e pela Agência Nacional de Vigilância Sanitária (Anvisa), porém, a demanda por CBD continua sendo judicializada. Justamente neste aspecto residiu o objetivo da pesquisa interdisciplinar, que foi analisar o exterior constitutivo do problema do acesso ao referido fármaco para tratamento de doenças. Para tanto, foi realizada pesquisa documental e exploratória, utilizando a abordagem qualitativa, além da revisão bibliográfica. O estudo de caso foi realizado com os processos judiciais do Tribunal de Justiça de Pernambuco (TJ/PE) sobre o assunto, localizados a partir da inserção agrupada das palavras-chave "fornecimento" e "Canabidiol" no campo "jurisprudência" do sítio virtual desse Tribunal. Como resultado, constatou-se que os sujeitos que ingressam com ação judicial atendem aos requisitos exigidos pelos órgãos reguladores, o que permite concluir que a negativa administrativa de fornecimento do medicamento pelo estado de Pernambuco caracteriza violação ao direito à saúde deles.

Abstract Cannabis sativa L. has been used since before the Christian Era to treat numerous diseases, but in the early 20th century, its use has been banned in several countries, including for medicinal purposes, for being considered illicit drug. However, the need to obtain alternatives to conventional treatments increased the interest for the therapeutic use of this plant, reason why several studies have been carried out, which verified that Cannabidiol (CBD), one of the main compounds of the plant, has great therapeutic potential. In Brazil, its internal commercialization is prohibited, but since 2015 the compassionate use and importation of the substance has been authorized by the Federal Council of Medicine (CFM) and by the National Health Surveillance Agency (Anvisa); however, the demand for CBD continues to be judicialized. The objective of this interdisciplinary research was precisely in this aspect, which was to analyze the constitutive exterior of the problem of access to the referred drug. For that, a documentary and exploratory research was performed, using the qualitative approach, in addition to the bibliographic review. The case study was carried out with the Judicial Processes of the Court of Justice of Pernambuco (TJ/PE) on the subject, located from the grouped insertion of the keywords "supply" and "Cannabidiol" in the field "jurisprudence" of the virtual site of this Court. As a result, it was found that individuals who file a lawsuit meet the requirements of regulatory agencies, which allows to conclude that the administrative refusal to provide the drug by the state of Pernambuco characterizes violation of their right to health.