Search

Background: despite limited long-term survival, kidney transplantation is the best form of renal replacement therapy for terminal disease patients. Components of extracellular purinergic signaling plays a fundamental role on inflammation and immune response related to organ transplantation. They could be alternative targets to avoid graft rejection. Materials and Methods: The hydrolysis of ATP, ADP and AMP nucleotides was analyzed in both lymphocytes and platelets, as well as the quantification of ATP and ADA activity. A sample of 30 patients who underwent kidney transplants was obtained, of which 15 had a transplant time of less than one year (acute response) and 15 had a transplant time between one and three years (chronic response). Results: In the group with transplantation time between one and three years, it was possible to identify a significant decrease in the amount of ATP, increase in ATP hydrolysis in platelets, decrease in AMP hydrolysis and increase in ADA activity, also in platelets. In the lymphocyte sample, there was a significant reduction in ADA activity as well as a decrease in the amount of ATP. Conclusions: From the data obtained in the study, it can be inferred that adenosine can reduce pro-inflammatory cytokines, providing greater graft survival and reducing the intensity of graft-versus-host disease. ATP signaling exerts inflammatory effects and modulates the purinergic signaling cascade, offering new avenues for drug therapies to combat chronic graft rejection.

In the last years, it has become evident that both acute and chronic physical exercise trigger responses/adaptations in the purinergic signaling and these adaptations can be considered one important mechanism related to the exercise benefits for health improvement. Purinergic system is composed of enzymes (ectonucleotidases), receptors (P1 and P2 families), and molecules (ATP, ADP, adenosine) that are able to activate these receptors. These components are widely distributed in almost all cell types, and they respond/act in a specific manner depending on the exercise types and/or intensities as well as the cell type (organ/tissue analyzed). For example, while acute intense exercise can be associated with tissue damage, inflammation, and platelet aggregation, chronic exercise exerts anti-inflammatory and anti-aggregant effects, promoting health and/or treating diseases. All of these effects are dependent on the purinergic signaling. Thus, this review was designed to cover the aspects related to the relationship between physical exercise and purinergic signaling, with emphasis on the modulation of ectonucleotidases and receptors. Here, we discuss the impact of different exercise protocols as well as the differences between acute and chronic effects of exercise on the extracellular signaling exerted by purinergic system components. We also reinforce the concept that purinergic signaling must be understood/considered as a mechanism by which exercise exerts its effects.

Breast cancer (BC) is the most frequent cause of death among women, representing a global public health problem. Here, we aimed to discuss the correlation between the purinergic system and BC, recognizing therapeutic targets. For this, we analyzed the interaction of extracellular nucleotides and nucleosides with the purinergic receptors P1 and P2, as well as the influence of ectonucleotidase enzymes (CD39 and CD73) on tumor progression. A comprehensive bibliographic search was carried out. The relevant articles for this review were found in the PubMed, Scielo, Lilacs, and ScienceDirect databases. It was observed that among the P1 receptors, the A1, A2A, and A2B receptors are involved in the proliferation and invasion of BC, while the A3 receptor is related to the inhibition of tumor growth. Among the P2 receptors, the P2X7 has a dual function. When activated for a short time, it promotes metastasis, but when activated for long periods, it is related to BC cell death. P2Y2 and P2Y6 receptors are related to BC proliferation and invasiveness. Also, the high expression of CD39 and CD73 in BC is strongly related to a worse prognosis. The receptors and ectonucleotidases involved with BC become possible therapeutic targets. Several purinergic pathways have been found to be involved in BC cell survival and progression. In this review, in addition to analyzing the pathways involved, we reviewed the therapeutic interventions already studied for BC related to the purinergic system, as well as to other possible therapeutic targets.

BACKGROUND AND METHODS Essential arterial hypertension triggers a chronic inflammatory process that seems to be linked to purinergic signaling. Physical exercise exhibit anti-inflammatory properties and is able to modulates purinergic system. The aim of this study was to evaluate the effect of 6 months of resistance training on inflammatory markers, purinergic system components, hemodynamic and anthropometric parameters in hypertensive woman. METHODS A total of 31 hypertensive group and 28 normotensive (control group) middle-aged sedentary women were submitted to 6 months of resistance training. All measurements and blood collection were carried out before (pretest), after 3 months and after 6 months (posttest) of training. Purinergic enzymes [nucleoside triphosphate diphosphohydrolase (NTPDase) and adenosine deaminase] were assessed in lymphocytes; IL-6, IL-10, ATP and C-reactive protein levels were measured in serum. RESULTS Six months of resistance training was able to significantly reduce blood pressure (BP), IL-6, C-reactive protein, ATP levels as well as NTPDase and adenosine deaminase activities in hypertensive group. Physical training was also able to increase IL-10 levels in hypertensive group. A positive correlation was found between BP, enzyme activities and levels of ATP and IL-6. A negative correlation was found between BP and IL-10. Positive correlation was found between NTPDase and IL-6 levels (P

Introducao: A utilizacao de contraceptivos orais combinados (COC) e bastante difundida, porem alem dos beneficios podem ocorrer efeitos adversos importantes, que precisam ser esclarecidos para as usuarias. Objetivos: identificar o conhecimento de estudantes de uma universidade publica sobre o uso e efeitos beneficos e adversos dos COC. Metodos: Trata-se de um estudo descritivo e quantitativo, em que um questionario com questoes objetivas foi aplicado a 471 estudantes dos cursos de graduacao, e analisados posteriormente atraves de qui-quadrado e Anova. Resultados: O motivo predominante para o uso de COC foi a contracepcao (37,52%). A insatisfacao com o conhecimento sobre o uso de COC foi apontada por 51,75% das estudantes. Foi verificada correlacao positiva (r=0,9970; p < 0,0001) entre as estudantes que receberam orientacao medica satisfatoria e se sentem satisfeitas com o conhecimento sobre o uso de COC. Conclusao : A pesquisa evidenciou que as estudantes manifestaram insatisfacao pessoal sobre os conhecimentos acerca do uso de COC, sinalizando a importância de maior aconselhamento profissional e de elaboracao de estrategias de Educacao em Saude relacionadas a contracepcao.

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, responsible for the synthesis of the CFTR protein, a chloride channel. The gene has approximately 2000 known mutations and all of them affect in some degree the protein function, which makes the pathophysiological manifestations to be multisystemic, mainly affecting the respiratory, gastrointestinal, endocrine, and reproductive tracts. Currently, the treatment of the disease is restricted to controlling symptoms and, more recently, a group of drugs that act directly on the defective protein, known as CFTR modulators, was developed. However, their high cost and difficult access mean that their use is still very restricted. It is important to search for safe and low-cost alternative therapies for CF and, in this context, natural compounds and, mainly, caffeic acid phenethyl ester (CAPE) appear as promising strategies to assist in the treatment of the disease. CAPE is a compound derived from propolis extracts that has antioxidant and anti-inflammatory activities, covering important aspects of the pathophysiology of CF, which points to the possible benefit of its use in the disease treatment. To date, no studies have effectively tested CAPE for CF and, therefore, we intend with this review to elucidate the role of inflammation and oxidative stress for tissue damage seen in CF, associating them with CAPE actions and its pharmacologically active derivatives. In this way, we offer a theoretical basis for conducting preclinical and clinical studies relating the use of this molecule to CF.

The exacerbate inflammatory response contributes to the progressive loss of lung function in cystic fibrosis (CF), a genetic disease that affects the osmotic balance of mucus and mucociliary clearance, resulting in a microenvironment that favors infection and inflammation. The purinergic system, an extracellular signaling pathway characterized by nucleotides, enzymes and receptors, may have a protective role in the disease, through its action in airway surface liquid (ASL) and anti-inflammatory response. To make up this review, studies covering topics of CF, inflammation, ASL and purinergic system were selected from the main medical databases, such as Pubmed and ScienceDirect. We propose several ways to modulate the purinergic system as a potential therapy for CF, like inhibition of P2X7, activation of P2Y2, A2A and A2B receptors and blocking of adenosine deaminase. Among them, we postulate that the most suitable strategy is to block the action of adenosine deaminase, which culminates in the increase of Ado levels that presents anti-inflammatory actions and improves mucociliary clearance. Furthermore, it is possible to maintain the physiological levels of ATP to control the hydration of ASL. These therapies could correct the main mechanisms that contribute to the progression of CF.