Abstract Adenosine is an important regulator within the cardiovascular system and modulates various processes through four distinct G protein-coupled receptors (A1, A2A, A2B, and A3), causing hypotension and reduced renal blood flow, which contributes to ischemia tissue and organ dysfunction. Caffeine causes most of its biological effects by blocking adenosine receptors. Although caffeine is vastly used as a pharmacological tool in basic research, there is a lack of studies characterizing the caffeine doses necessary for blocking the cardiovascular effects of adenosine. Therefore, we evaluated the effect of different doses of caffeine (10, 30 and 100 mg/kg, s.c) on the cardiovascular changes induced by adenosine. In addition, the adenosine response was evaluated at different times (4 and 8 hours) after caffeine administration. The bolus injection of increasing doses of adenosine dose-dependently reduced blood pressure, renal blood flow and heart rate. The dose of 30 mg/kg was the most effective in blocking adenosine-induced cardiovascular events. However, the higher dose of caffeine (100 mg/kg) fails to block the adenosine effect on heart rate. The effect of caffeine lasts for 4 hours. Therefore, caffeine in the dose of 30 mg/kg can block the effects of adenosine for up to 4 hours. These data provide valuable information on the dose and frequency of caffeine administration for future studies in rats.

Abstract Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects many people worldwide and is the most common inflammatory joint disease of autoimmune origin. In Brazil, the treatment for RA is guided by clinical protocols and therapeutic guidelines. This work aims to investigate the profile of patients with RA through the analysis of sociodemographic, clinical, and pharmacotherapy data. A cross-sectional and descriptive study was carried out in the Specialized Component of Pharmaceutical Services (CEAF) in Ponta Grossa, Paraná, Brazil. Patients with RA that received regular pharmacological therapy were included. Most were female, adults between 40 and 59 years old, and exhibited a disease activity score classified as remission. The majority of patients in remission of disease utilized at least a conventional synthetic disease-modifying antirheumatic drug (csDMARD) or biological synthetic disease-modifying antirheumatic drug (bDMARD) in monotherapy or associated with other drugs. The treatment costs were high, mainly by utilizing bDMARDs followed by csDMARDs. Most patients exhibited adequate control of disease progression, and fortunately, only a few cases of drug-related problems were identified. This profile is associated with the therapeutic guidelines for RA treatment in Brazil. The SUS has an important role in guaranteeing high-cost drugs access by health judicialization and access to multidisciplinary health professionals for patients with RA.

Abstract The gut is the main organ that mediates the contact between antigens with our organism, controlling the immune response against environmental factors, such as microbiota and food. Innate lymphoid cells participate in the gut-associated lymphoid tissue (GALT) maturation during the prenatal and early postnatal periods. After birth, breast milk provides the essential elements for the continuity of development of this tissue, leading to structural changes and healthy microbiota installation. The microbiota participates in the organogenesis of the GALT, as in the formation of intestinal villi, stimulating the proliferation of stem cells and maintaining the integrity of epithelial barrier. Foods are also involved in maturation of the GALT, where the protein source depletion reduced the number of resident lymphocytes. This unique microenvironment present in the intestinal lamina propria (LP) and mesenteric lymph nodes (mLN) induce tolerance to innocuous antigens from the diet, known as Oral Tolerance. Antigens sampled by intestinal epithelium cells are transferred to specialized dendritic cells, residing in the LP, which migrate to the mesenteric lymph nodes where they participate in the induction of regulatory T cells (Treg). Understanding these phenomena may establish the intestinal mucosa as a tool in therapy of inflammatory bowel diseases and immunological disorders.

Abstract Objective: Periodontitis is associated with endothelial dysfunction, which is clinically characterized by a reduction in endothelium-dependent relaxation. However, we have previously shown that impairment in endothelium-dependent relaxation is transient. Therefore, we evaluated which mediators are involved in endothelium-dependent relaxation recovery. Material and methods: Rats were subjected to ligature-induced experimental periodontitis. Twenty-one days after the procedure, the animals were prepared for blood pressure recording, and the responses to acetylcholine or sodium nitroprusside were obtained before and 30 minutes after injection of a nitric oxide synthase inhibitor (L-NAME), cyclooxygenase inhibitor (Indomethacin, SC-550 and NS- 398), or calcium-dependent potassium channel blockers (apamin plus TRAM- 34). The maxilla and mandible were removed for bone loss analysis. Blood and gingivae were obtained for C-reactive protein (CRP) and myeloperoxidase (MPO) measurement, respectively. Results: Experimental periodontitis induces bone loss and an increase in the gingival MPO and plasmatic CRP. Periodontitis also reduced endothelium-dependent vasodilation, a hallmark of endothelial dysfunction, 14 days after the procedure. However, the response was restored at day 21. We found that endothelium-dependent vasodilation at day 21 in ligature animals was mediated, at least in part, by the activation of endothelial calcium-activated potassium channels. Conclusions: Periodontitis induces impairment in endothelial-dependent relaxation; this impairment recovers, even in the presence of periodontitis. The recovery is mediated by the activation of endothelial calcium-activated potassium channels in ligature animals. Although important for maintenance of vascular homeostasis, this effect could mask the lack of NO, which has other beneficial properties.