76 research outputs found

    Spironolactone-induced inhibition of aldosterone biosynthesis in primary aldosteronism: Morphological and functional studies

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    Twenty-five patients harboring aldosterone-producing adenomas were treated with spironolactone for 2-170 days immediately preoperatively. In the early period of administration of the drug (up to 27 days), plasma and urinary aldosterone decreased sharply while plasma renin activity (PRA) and serum potassium were rising. During this period of time, spironolactone bodies (SB), which form exclusively in cells actively producing aldosterone, were forming rapidly in the tumor cells but not in the inactive glomerulosa cells proper. The SB appear to be a morphological expression of a block in aldosterone biosynthesis. Since SB do not occur in normal fasciculata cells, which, like glomerulosa cells, also synthesize corticosterone, it is concluded that spironolactone inhibition of aldosterone biosynthesis occurs between corticosterone and aldosterone. Recent studies in vitro by others have suggested that the inhibition occurs at the corticosterone-methyl oxidase step, I (Ulick's nomenclature). The great diuresis of sodium and retention of potassium resulting from continued administration of the drug sharply activates aldosterone stimulatory factors. Aldosterone production may return to baseline levels in several weeks but it is inappropriately low in relation to the levels of PRA and serum potassium. With the further passage of time (average 4-6 wk), aldosterone production may increase 50%-100% above baseline levels, suggesting that the block has disappeared or is receding. At this time SB are diminishing in number and by 170 days of the drug they have virtually disappeared. We have hypothesized, among other possibilities, that recovery of the ability to convert corticosterone to aldosterone occurs by virtue of a mechanism activated by sodium deficiency, independent of angiotensin, which stimulates step 1 of the corticosterone-methyl oxidase system. As the block in the final step(s) of the biosynthetic pathway recedes, the existing elevated levels of angiotensin become much more effective in stimulating the production of aldosterone.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/22806/1/0000363.pd

    Toward an internally consistent astronomical distance scale

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    Accurate astronomical distance determination is crucial for all fields in astrophysics, from Galactic to cosmological scales. Despite, or perhaps because of, significant efforts to determine accurate distances, using a wide range of methods, tracers, and techniques, an internally consistent astronomical distance framework has not yet been established. We review current efforts to homogenize the Local Group's distance framework, with particular emphasis on the potential of RR Lyrae stars as distance indicators, and attempt to extend this in an internally consistent manner to cosmological distances. Calibration based on Type Ia supernovae and distance determinations based on gravitational lensing represent particularly promising approaches. We provide a positive outlook to improvements to the status quo expected from future surveys, missions, and facilities. Astronomical distance determination has clearly reached maturity and near-consistency.Comment: Review article, 59 pages (4 figures); Space Science Reviews, in press (chapter 8 of a special collection resulting from the May 2016 ISSI-BJ workshop on Astronomical Distance Determination in the Space Age

    Do problema, do desenho e dos métodos. Variabilidade biológica humana em Moçambique: a visão, as pessoas e a estrutura de um projecto nacional de impacto internacional

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    O estudo de Calanga a que refere o presente livro está enquadrado num projecto multididciplinar de pesquisa intitulado Variabilidade biológica humana em Moçambique: implicações para a educação física, desporto, medicina preventiva e saúde pública (VBH). Este projecto pretende ser uma continuidade de uma linha de pesquisa na área da saúde, crescimento e desenvolvimento em populações Moçambicanas, a qual teve início em 1990 e que deu origem a múltiplas publicações científicas sob a forma de livros, artigos, comunicações e teses. O estudo constitui-se numa abordagem multivariada que cruza informação proveniente da biologia humana, da auxologia, da genética, da antropologia física, da epidemiologia e das ciências da actividade física numa proposta de visão que reclama um olhar integrado e integrador, e que possibilite um esclarecimento sólido acerca do estado de saúde individual e populacional, do estilo de vida e bem-estar
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