The chief medical residency in the 1980s.
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Biomedical subjects
Publications and source records attributed to G J Martin.
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The transport of various organic anions via the pathway that mediates the exchange of urate or p-aminohippurate (PAH) for OH- or Cl- in dog renal microvillus membrane vesicles was investigated. The pH gradient-stimulated uptakes of tracer urate and PAH were significantly inhibited by 5 mM PAH, n-valerate, lactate, beta-hydroxybutyrate, pyruvate, acetoacetate, maleate, succinate, alpha-ketoglutarate, oxaloacetate, and cis-aconitate but not by 5 mM acetate, malate, oxalate, or citrate. the pH dependence of inhibition suggested that it was in their monovalent forms that these acid anions interacted with the urate exchange pathway. Outwardly directed gradients of succinate, lactate, and PAH stimulated uphill urate accumulation. Imposition of an inside-alkaline pH gradient stimulated the uphill accumulation of lactate and succinate. Na+ cotransport pathways for lactate and succinate were also present. In the presence of an inwardly directed Na+ gradient, lactate stimulated the uphill accumulation of urate, indicating that the pathways mediating Na+-lactate cotransport and lactate-urate exchange coexisted in at least some membrane vesicles. We conclude that the anion exchange pathway for urate in dog renal microvillus membrane vesicles has affinity for additional organic anions and can function in multiple exchange modes. Exchange of luminal urate or Cl- for intracellular organic anions or OH- is a possible mechanism for effecting uphill anion reabsorption in the proximal tubule.
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In a preliminary paper [Thérapie 34, 397 (1979), we showed that cysteine enhances bismuth digestive absorption in rats. In this paper, we have studied in rats the effects of various thiol compounds (mercaptopropionic acid, penicillamine, cysteine, homocysteine, 2-mercaptoethylamine, mercaptoethane) and nonthiol compounds (methionine, serine, alanine) orally administered on the absorption and elimination of bismuth also given orally. Bismuth was measured in blood and urine by electrothermal atomic absorption spectrophotometry. All of the thiol substances, and particularly cysteine, homocysteine, and mercaptopropionic acid, have considerably enhanced bismuth absorption and elimination; whereas, nonthiol substances have had no effect. Moreover, the acute toxicity of bismuth was enhanced when bismuth was given as a complex with cysteine (LD50 = 156 +/- 20 mg/kg). Studies by nmr spectroscopy of interactions between bismuth and these organic compounds have shown that bismuth induces an important chemical shift of the protons of the alpha carbon of the sulfhydrile group. Mainly, studies of C and N have confirmed this fact. The selectivity of such a complexation, in our pH conditions, may be tentatively explained on the ground of hard and soft acid and base (HSAB) theory. We have suggested that an increase in the concentration of thiol compounds in the gastrointestinal tract arising from food, or more probably from microorganism synthesis, could be an explanation for human encephalopathies.
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