Treatment with a novel chemokine-binding protein or eosinophil lineage-ablation protects mice from experimental colitis.

Eosinophils are multifunctional leukocytes implicated in numerous inflammatory diseases. The present study was conducted to clarify the precise role of eosinophils in the development of colitis by using eosinophil-depleted mice and a novel chemokine-binding protein that neutralizes CCL11 action. Colitis was induced by administration of dextran sodium sulfate (DSS) to wild-type and eosinophil-deficient DeltadblGATA-1 mice. Accumulation of eosinophils in the gut of mice given DSS paralleled worsening of clinical score and weight loss. In response to DSS, DeltadblGATA-1 mice showed virtual absence of eosinophil recruitment, amelioration of clinical score, weight loss, and tissue destruction, and no lethality. There was a decrease in CXCL1 and CCL3 production and decreased neutrophil influx in the intestine of DeltadblGATA-1 mice. Transfer of bone marrow cells from wild-type mice reconstituted disease manifestation in DSS-treated DeltadblGATA-1 mice, and levels of CCL11 were increased after DSS treatment and localized to inflammatory cells. Treatment with the chemokine-binding protein evasin-4 at a dose that prevented the function of CCL11 greatly ameliorated clinical score, weight loss, overall tissue destruction, and death rates. In conclusion, the influx of eosinophils is critical for the induction of colitis by DSS. Treatment with a novel chemokine-binding protein decreased eosinophil influx and greatly ameliorated colitis, suggesting that strategies that interfere with the recruitment of eosinophils may be useful as therapy for colitis.

Educação em saúde para idosos de um grupo de terceira idade em Governador Valadares: enfoque no uso racional de medicamentos / Health education for a group of elderly in Governador Valadares: focus on the rational use of medicines

Os idosos frequentemente apresentam doenças que requerem a administração de vários medicamentos. A ampla utilização da farmacoterapia contribui para o aparecimento de problemas relacionados ao uso de medicamentos na população idosa. O objetivo deste trabalho é relatar as atividades de educação em saúde, com enfoque no uso racional de medicamentos, desenvolvidas com o grupo de idosos do Serviço Social do Comércio (SESC) de Governador Valadares. As intervenções foram conduzidas por docentes e discentes do Núcleo de Estudos da Pessoa Idosa (NEPI) da Universidade Federal de Juiz de Fora campus Governador Valadares. Foram realizados jogos de tabuleiro, feiras, oficinas e rodas de conversa. Acredita-se que a experiência promoveu impacto positivo no conhecimento dos idosos contribuindo para melhorar a qualidade de vida desta crescente parcela da população, influenciando ainda na formação dos estudantes, tornando-os mais conscientes sobre as questões relacionadas ao envelhecimento.

Elderly people often have diseases that require the administration of various medicines. The widespread use of pharmacotherapy contributes to the emergence of drug-related problems in the elderly population. The aim of this study is to report on health education activities, focused on the rational use of medicines, developed with the group of elderly people from Social Service of Commerce (SESC) of Governador Valadares. The interventions were conducted by lecturers and students from the Center for the Study of the Elderly Person (NEPI) of the Federal University of Juiz de Fora, Governador Valadares campus. Board games, fairs, workshops and conversation circles were held. It is believed that the experience had a positive impact on the knowledge of the elderly, contributing to improve the quality of life of this growing part of the population, also influencing the training of students, making them more aware of issues related to aging.

The role of CCL22 (MDC) for the recruitment of eosinophils during allergic pleurisy in mice.

Eosinophils are important inflammatory cells in allergic diseases. In the present study, we have investigated the effects of CCL22 on the recruitment of eosinophils in vivo and in vitro. CCL22 induced a dose- and time-dependent recruitment of eosinophils into the pleural cavity of mice, and this was dependent on the release of platelet-activating factor (PAF) and subsequent generation of CCL11. However, in an allergic pleurisy model, an anti-CCL22 polyclonal antibody given during sensitization or before challenge had no significant effect on eosinophil recruitment. CCL22 did not induce eosinophil chemotaxis in vitro but was able to induce eosinophil degranulation in vitro and in vivo. In conclusion, we show that although exogenously added CCL22 may induce eosinophil migration in vivo via release of PAF and CCL11 (eotaxin), endogenous production of CCL22 does not drive eosinophil migration during allergic inflammation. However, CCL22 may be an important activator of eosinophils once these cells have migrated into tissue.

Mechanisms underlying the inhibitory effects of tachykinin receptor antagonists on eosinophil recruitment in an allergic pleurisy model in mice.

The activation of tachykinin NK receptors by neuropeptides may induce the recruitment of eosinophils in vivo. The aim of the present study was to investigate the effects and underlying mechanism(s) of the action of tachykinin receptor antagonists on eosinophil recruitment in a model of allergic pleurisy in mice. Pretreatment of immunized mice with capsaicin partially prevented the recruitment of eosinophils after antigen challenge, suggesting the potential contribution of sensory nerves for the recruitment of eosinophils Local (10-50 nmol per pleural cavity) or systemic (100-300 nmol per animal) pretreatment with the tachykinin NK1 receptor antagonist SR140333 prevented the recruitment of eosinophils induced by antigen challenge of immunized mice. Neither tachykinin NK2 nor NK3 receptor antagonists suppressed eosinophil recruitment. Pretreatment with SR140333 failed to prevent the antigen-induced increase of interleukin-5 concentrations in the pleural cavity. Similarly, SR140333 failed to affect the bone marrow eosinophilia observed at 48 h after antigen challenge of immunized mice. SR140333 induced a significant increase in the concentrations of antigen-induced eotaxin at 6 h after challenge. Antigen challenge of immunized mice induced a significant increase of Leucotriene B4 (LTB4) concentrations at 6 h after challenge. Pretreatment with SR140333 prevented the antigen-induced increase of LTB4 concentrations. Our data suggest an important role for NK1 receptor activation with consequent LTB4 release and eosinophil recruitment in a model of allergic pleurisy in the mouse. Tachykinins appear to be released mainly from peripheral endings of capsaicin-sensitive sensory neurons and may act on mast cells to facilitate antigen-driven release of LTB4.

Pharmacological strategies to resolve acute inflammation.

The inflammatory response is a physiological process that has the major role of restoring tissue homeostasis. However, uncontrolled or unresolved inflammation may cause tissue damage and contribute to the pathogenesis of chronic inflammatory and autoimmune diseases. Current pharmacological therapies to treat inflammatory maladies focus on inhibition of the productive phase of the inflammatory response including inhibition of leukocyte influx. Resolution of inflammation is an active process, which relies on the production of pro-resolving molecules and activation of intracellular pathways. Here, we will discuss mechanisms and therapeutic potential of pharmacological strategies, which accelerate resolution in animal models of acute inflammation by mimicking or inducing natural pathways of resolution phase of inflammation.