Emergency ‘constitutional plumbing’ has reached its limits coping with devolution. it’s time for a new institutional architecture

The British way of bodged, incremental constitutional reform is patently inadequate for the demands of devolution to Scotland and elsewhere, James Mitchell argues. Whatever the outcome of a future referendum in Scotland, much better planned reforms and a new institutional architecture are needed in the UK or rUK – such as replacing the House of Lords with a House of Nations and Regions

Oral magnesium supplements reduce erythrocyte dehydration in patients with sickle cell disease.

Intracellular polymerization and sickling depend markedly on the cellular concentration of sickle hemoglobin (Hb S). A possible therapeutic strategy for sickle cell disease is based on reducing the cellular concentration of Hb S through prevention of erythrocyte dehydration. The K-Cl cotransporter is a major determinant of sickle cell dehydration and is inhibited by increasing erythrocyte Mg content. We studied 10 patients with sickle cell disease before treatment and after 2 and 4 wk of treatment with oral Mg supplements (0.6 meq/kg/d Mg pidolate). Hematological parameters, erythrocyte Na, K, and Mg content, erythrocyte density, membrane transport of Na and K, and osmotic gradient ektacytometry were measured. We found significant increases in sickle erythrocyte Mg and K content and reduction in the number of dense sickle erythrocytes. Erythrocyte K-Cl cotransport was reduced significantly. We also observed a significant reduction in the absolute reticulocyte count and in the number of immature reticulocytes. Ektacytometric analysis showed changes indicative of improved hydration of the erythrocytes. There were no laboratory or clinical signs of hypermagnesemia. Mild, transient diarrhea was the only reported side effect. We conclude that oral Mg supplementation reduces the number of dense erythrocytes and improves the erythrocyte membrane transport abnormalities of patients with sickle cell disease

alpha-ketoglutarate (AKG) absorption from pig intestine and plasma pharmacokinetics

To study the absorption, metabolism and kinetics, the AKG ( in different concentrations) was administered intravenously, intra-portally, orally and directly into the ileum or duodenum of pigs, chronically fitted with portal and jugular catheters and T-shaped cannula at the duodenum and ileum. Additionally, this study was conducted to determine the influence of low pH, Fe2+ or/ and SO42- on AKG gut absorption and conversely FeSO4 and FeSO4/AKG on Fe2+ gut absorption. It is concluded that AKG was significantly better absorbed from the upper small intestine than from the distal sections. Furthermore, low pH, Fe2+ and/or SO42- ions enhanced AKG absorption. The AKG administered to the portal vein was rapidly eliminated from the blood (half-life less than 5 min). The short lifetime for AKG is probably dependent on quick metabolism in the enteorcyetes and liver. However, the prolonged half-life can be related to its low AKG blood concentration. The Fe2+ concentrations in blood increased after FeSO4 and FeSO4/AKG duodenal infusion. The implication of above observations is important for practical application of the AKG in animal and human nutrition as well in medicine