Intestinal Structure and Function after Small Bowel by-Pass in the Rat

1. To study further the influence of luminal nutrition on small bowel structure and function, segments of rat jejunum and ileum were completely excluded from intestinal continuity by Thiry-Vella by-pass operations. The effect of partial deprivation of luminal nutrition was also studied in jejunal segments that had been surgically transposed to a distal position in the intestinal tract. 2. Macroscopically, by-passed jejunum and ileum both became narrowed and atrophic, whereas the intestine in continuity showed hypertrophic changes similar to those seen after intestinal resection. 3. In by-passed intestine the pattern of villi changed from mucosal ridges to ‘fingers’ and ‘leaves’. Although villous height and total mucosal thickness were both reduced, light microscopy showed that even 6 months after exclusion from intestinal continuity villous morphology was still retained. 4. Epithelial-cell migration rate and turnover time were diminished in both jejunum and ileum after by-pass. In intestine in continuity the migration rate was increased, but the turnover time remained the same as in controls. 5. In by-passed jejunum, in vivo glucose absorption diminished progressively with time, but did not change in excluded ileal segments. 6. After ileo-jejunal transposition, the jejunum showed no major morphological changes, but glucose absorption became significantly depressed. 7. These results further support the concept that intraluminal nutrition exerts a major influence on cell turnover, villous morphology and absorptive function in the small intestine.

Somatomedin (Sulphation Factor)-Like Activity of Homocystine

1. Homocystine (10 mg/100 ml) has a significant effect on the incorporation of inorganic sulphate by rat costal cartilage in vitro. 2. The characteristic skeletal changes associated with homocystinuria due to defective cystathionine synthetase could therefore be caused by the elevated plasma concentration (1–10 mg/100 ml) of homocystine present in this disease.

Composition of Pteroylpolyglutamates (Conjugated Folates) in Guinea-Pig Liver and Their Formation from Folic Acid

1. The composition of guinea-pig liver folates and the biochemical route of formation of liver folates from injected tritium-labelled pteroylglutamic acid (folic acid) have been studied. 2. Endogenous folate was measured by microbiological assay with Lactobacillus casei and Streptococcus faecalis, with and without deconjugation of whole liver pteroylpolyglutamates (conjugated folates). Individual folate compounds were identified by microbiological assay after fractionation of liver folates by DEAE cellulose ion-exchange column chromatography. 3. Liver folate in the guinea-pig consists of about 84–87% reduced pteroylpolyglutamates with more than three glutamate moieties/molecule, about 12–15% reduced pteroyltriglutamates, about 1% reduced pteroyldiglutamates and only traces of reduced pteroylmonoglutamates. 4. About 53% of the liver folate consists of methylated derivatives. 5. Injected pteroylglutamic acid was first rapidly reduced and formylated or methylated. Glutamate moieties were then added, probably singly, to form di-, tri- and poly-glutamates. This was a relatively slow process with a hold-up at the triglutamate stage. 6. The proportion of the labelled pteroylglutamic acid in the polyglutamate form approximated to the proportion of endogenous folates in this form after 3–4 days. 7. The amount of radioactive folate in the liver increased progressively from 1 to 84 h after injection of a standard amount of radioactive pteroylglutamic acid.

Subcellular Localization of Folate and Effect of Methotrexate on the Incorporation of Radioactive Folic Acid into Guinea-Pig Liver Folate

1. The subcellular distribution of endogenous folate and of injected [3H]folic acid has been studied in guinea-pig liver. 2. Endogenous folate was found to be concentrated in the mitochondrial and cell-sap fractions. 3. At 1 h after injection, labelled folic acid (pteroylglutamic acid) was concentrated in the microsomes (where it is possibly reduced to tetrahydrofolic acid). 4. At all subsequent times after injection of labelled pteroylglutamic acid (4, 24 and 84 h) radioactivity was concentrated in mitochondria and cell sap and it is, therefore, likely that conjugation of glutamates to form pteroylpolyglutamates occurs in one or both of these subcellular fractions in mammalian cells. 5. Methotrexate-treated animals converted at least some labelled pteroylglutamic acid into non-reduced pteroyl di-, tri- and poly-glutamic acids by 4 h after the injection. 6. Reduction of pteroylglutamic acid is, therefore, not essential for pteroylpolyglutamate formation in liver cells. 7. Methotrexate blocks the reduction of pteroyl di-, tri- and poly-glutamic acids, as well as of pteroylglutamic acid.

Evidence for Active Transport of the Dipeptide Glycylsarcosine by Hamster Jejunum in Vitro

1. Glycylsarcosine, a peptide which is slowly hydrolysed by the intestine, is transported into the jejunal mucosal cells of the hamster by an active Na+-dependent process. 2. Uptake of glycylsarcosine is inhibited by l-methionyl-l-methionine but not by l-methionine, suggesting that l-methionyl-l-methionine and glycylsarcosine share an uptake mechanism which is independent of that for free methionine, and that l-methionyl-l-methionine may also enter the cells.

Normal Urine Concentrating Ability in Magnesium Depletion

1. We studied urine concentrating ability in ten magnesium-depleted puppies and compared the results with those of match-fed, littermate controls. 2. The experimental puppies became hypomagnesaemic and hypocalcaemic without evidence of potassium depletion. After 24 h of food and water deprivation, urine osmolality increased to 1350 ± 340 mosm/kg of water. This value did not differ from that of control animals. 3. We also studied urine concentrating ability in a child with primary hypomagnesaemia and secondary hypocalcaemia. He could achieve a urine concentration of 1080 mosm/kg of water after 20 h of water deprivation when he was hypomagnesaemic and hypocalcaemic. 4. We conclude that urine concentrating ability is normal in magnesium depletion uncomplicated by hypercalcaemia or severe potassium depletion.

Sodium Conservation in Chronic Renal Failure: Studies Using Oral Diazoxide

1. The defect in sodium conservation shown by patients with advanced chronic renal failure has been studied during the administration of diazoxide. 2. All nine patients showed a reduction in urinary sodium concentration to levels substantially lower than those which can normally be produced in such patients even with prolonged sodium depletion. Seven patients produced a nearly sodium-free urine. In all patients this effect could be reversed by the administration of high doses of frusemide. The fall in urinary sodium concentration was associated with a sustained fall in creatinine clearance in only two cases. 3. One patient with salt-losing renal disease showed a more modest fall in sodium concentration on treatment with diazoxide. 4. It is concluded that since the defect in sodium conservation shown by patients with chronic renal failure can be corrected without diminishing the osmotic load, it cannot be solely due to the effect of the osmotic diuresis upon residual functioning nephrons. It is suggested that the distal tubular transport mechanism for sodium is saturated by the increased delivery of sodium from the proximal tubule.