Murine myeloid progenitor responses to GM-CSF and eosinophil precursor responses to IL-5 represent distinct targets for downmodulation by prostaglandin E(2)

1. Because Prostaglandin E(2) (PGE(2)) and dibutiryl cyclic AMP (dbcAMP) modulate the production and effects of haemopoietic cytokines in allergy, we examined their ability to modulate responses of myeloid progenitors to GM-CSF, and of eosinophil precursors to IL-5. 2. The ability of PGE(2), dbcAMP, rolipram, forskolin, dbcGMP and PGD(2), to modulate the responses to GM-CSF and IL-5 in colony formation (progenitor) and eosinophil differentiation (precursor) assays using bone-marrow from nonsensitized or from intranasally-challenged, ovalbumin-sensitized mice of five strains was studied. 3. PGE(2) (10(−7) M) inhibited GM-CSF-stimulated colony formation in bone-marrow from BP-2 mice. This effect was duplicated by dbcAMP (0.3–1×10(−6) M), Rolipram (10(−5) M) and forskolin (3×10(−5) M), but not Prostaglandin D(2) (10(−6) M). Inhibition affected similarly all myeloid colony types. Progenitors from sensitized and challenged BP-2 mice were also inhibited by PGE(2) and cyclic AMP. PGE(2) inhibited progenitors from C57BL/10, CBA/J and A/J, but not BALB/c mice. However, BALB/c progenitors were sensitive to dbcAMP and Forskolin (10(−4) M). In contrast, in precursor assays, PGE(2) (10(−7)–10(−9) M) blocked responses to IL-5 in bone-marrow from BP-2 and BALB/c mice, either naïve or sensitized and challenged, to a similar extent. PGD(2) (10(−6) M) was ineffective, as was PGE(2) (10(−7) M), if added after 48 h of culture. 4. In conclusion, PGE(2) inhibits the responses of bone-marrow myeloid progenitors to GM-CSF and of eosinophil precursors to IL-5, in naïve or ovalbumin sensitized and challenged mice. These effects are duplicated by cyclic AMP-elevating agents. In the BALB/c strain, the resistance of progenitors, but not precursors, to PGE(2) inhibition, indicates these developmental stages are separate targets for PGE(2) modulation

Uma história de conceitos na saúde pública: integralidade, coordenação, descentralização, regionalização e universalidade A history of public health concepts: integrity, coordination, decentralization, regionalization, and universality

O Sistema Único de Saúde conferiu visibilidade a uma série de conceitos próprios da organização de sistemas de saúde. Entre eles a integralidade, que delimita fronteiras comuns com quase todos os demais princípios do Sistema, tem sido objeto de ampla literatura no Brasil. Com base em extensa revisão de fontes primárias e secundárias, este artigo apresenta uma recuperação histórica dos conceitos de integralidade, descentralização, regionalização e universalidade - ideias e conceitos que em grande parte se conformam e se interligam no ideário da organização dos serviços sanitários pelo modelo dos Centros de Saúde distritais.<br>Brazil's Unified Health System (Sistema Único de Saúde) has highlighted a series of concepts specific to the organization of healthcare systems. Among these, integrity - which shares boundaries with almost all other System principles - has been the object of much academic production in Brazil. Based on an extensive review of primary and secondary sources, the article offers a historical recovery of the concepts of integrity, decentralization, regionalization, and universality - ideas and concepts that in good measure are shaped by and interlinked with the set of ideals of the organization of sanitary services according to the district health centers model