1. Mass balance studies were carried out in fasted ileostomy subjects ( n = 5) given an oral physiological dose (10 mg) of β-carotene [all- trans : 9- cis , 84:16 (w/w)] dispersed in vegetable oil. Blood and ileal effluent samples were collected and analysed for β-carotene. 2. Results showed that 90% (range 97.0–74.3%) of the total β-carotene was absorbed without measurable perturbation of plasma total β-carotene concentration, or change in the all- trans : 9- cis β-carotene ratio. Peak loss of β-carotene in ileal effluent occurred at 4.9 h (range 2.9–8.4 h) postingestion, and no further loss was detected after 5.4–12.4 h, depending upon the individual. Comparison of the ratio of all trans -β-carotene to 9 cis -β-carotene in the test meal and effluent indicated that isomerization did not occur during passage through the gastrointestinal tract and that both isomers were similarly absorbed. However, the all- trans : 9- cis β-carotene ratio of the plasma did not change. Reasoned assumptions allowed the construction of a mathematical model of plasma β-carotene disposal. 3. It is concluded that physiological doses of isolated all- trans and 9- cis β-carotene are well absorbed without necessarily causing detectable excursions in plasma β-carotene concentrations, or altering the ratio of all- trans to 9- cis β-carotene. Isomerization of β-carotene does not occur during passage through the gastrointestinal tract. Absorbed β-carotene is rapidly cleared from the plasma to an unobservable pool at a rate similar to that of chylomicron triacylglycerol.

1. Recent initiatives which advocate an increase in dietary polyunsaturated fat intake have led to the study of the effects of this upon gastrointestinal function. 2. Weanling rats were for 21 weeks fed diets containing 10% fat that were either high or low in polyunsaturated fats. Jejunal function was studied in vitro in an Ussing chamber. 3. Basal intestinal short-circuit was similar in both groups. 4. A decreased EC 50 for the non-neural electrogenic secretory responses to acetylcholine, bethanecol and isobutylmethylxanthine was apparent in the jejuna of rats fed a diet high in polyunsaturated fatty acids. 5. Submaximal electrogenic galactose absorption was increased in the rats fed a diet high in polyunsaturated fatty acids. 6. Changing the composition of dietary lipid resulted in a change in the fatty composition of the apical enterocyte membrane. 7. Diets high in polyunsaturated fatty acids may be both prosecretory and proabsorptive in the small intestine.

1. Stable isotope methods are being used to investigate the absorption of dietary iron. In order to be certain that this new methodology is accurate, we have compared results obtained using stable isotopes and inductively coupled plasma mass spectrometry with those determined using a radioisotope and whole body counting. 2. The stable isotope 54 Fe (2.8 mg) was given to 10 healthy non-pregnant women. Six women received the isotope in aqueous form, and four took it with a meat meal. The 54 Fe served as a carrier for 10 ng of the radioisotope 59 Fe. An ampoule (200 μg) of the isotope 57 Fe or 58 Fe was then given intravenously, and in serum samples taken over the next 10 h the ratios of the stable iron isotopes were measured by inductively coupled plasma mass spectrometry and the oral iron absorption was calculated. This was then compared with the results obtained by using a whole body counter to measure (on day 0 and day 14) the γ-activity emitted by the radioisotope. 3. The mean iron absorption measured by both methods ranged from 8% to 45%. Measurement of the post-absorptive serum enrichment of the stable isotopes provided estimates of absorption from both aqueous and food iron which were similar to that yielded by whole body counting, the mean difference being −1.5% (95% confidence interval −5.2 to 2.1%). Absorption estimated by stable isotopes exhibited the same inverse relationship with the serum ferritin level (body iron stores) to that known to exist with whole body counting. Similar estimates of food iron absorption were obtained irrespective of the type of isotope used as an extrinsic label, implying that stable isotopes are as valid as radioisotopes in reflecting intrinsic food iron absorption. 4. This study validates the use of stable isotopes and post-absorption curves as a new and accurate technique in the measurement of iron absorption.

1. The potential contribution of enteric pathways to the extra-renal excretion of uric acid in chronic renal failure was evaluated by measuring [ 14 C]-urate and 36 Cl − transport in isolated, short-circuited segments of jejunum, ileum and distal colon from normal rats and rats with chronic renal failure (five-sixths nephrectomized) 6 weeks after surgery. Plasma and urine creatinine and urate concentrations were also determined to establish urate status in chronic renal failure. 2. A 40% reduction in creatinine clearance was observed in the group with chronic renal failure, resulting in a two-fold increase in plasma creatinine concentration (0.064 ± 0.001 mmol/l, n = 9, to 0.120 ± 0.008 mmol/l, n = 14). In contrast, there was no change in plasma urate concentration, despite a 75% reduction in urate clearance. 3. The transport studies demonstrated alterations in intestinal urate transport in rats with chronic renal failure compared with normal rats. Net absorption of urate was observed in the distal colon of control rats, whereas a significant secretory flux was observed in rats with chronic renal failure (from 0.88 ± 0.16 to −1.62 ± 0.81 nmol h −1 cm −2 , n = 12). Urate secretion was induced in the jejunum of the group with chronic renal failure (−0.15 ± 0.25 in control and −1.67 ± 0.35 nmol h −1 cm −2 in chronic renal failure, n = 11). Urate transport across the ileum was not altered in chronic renal failure and there was no net flux of urate in either the normal group or the group with chronic renal failure. Net Cl − absorption, which was observed in all segments of the control animals, was reversed to net secretion in chronic renal failure. 4. These studies indicate that urate homoeostasis is maintained in chronic renal failure and both the jejunum and colon may be actively involved in the extra-renal excretion of urate. These studies do not exclude the possibility that urate metabolic pathways are involved in urate homoeostasis in chronic renal failure.

1. The purpose of the present study was to examine the effects of various diuretics on intestinal oxalate transport. Transmural oxalate fluxes were measured across isolated, short-circuited tissue segments removed from rabbits and placed in Ussing chambers. 2. The net absorptive flux of oxalate across the distal colon was significantly reduced in the presence of trichlormethiazide at 10 −4 mol/l. In contrast, this diuretic had no effect on oxalate transport in the other intestinal segments examined. Several of the thiazide diuretics tested had some inhibitory effect on colonic oxalate absorption, but at higher concentrations of 10 −3 mol/l or 10 −2 mol/l. 3. We conclude that the previously reported hypooxaluric effects of hydrochlorothiazide and chlorthalidone are most likely not the result of an exclusive or primary effect on intestinal oxalate transport. It is suggested that the reduction in colonic oxalate absorption that was observed with the thiazides probably involves the transport system responsible for oxalate efflux across the basolateral membrane of the colonocyte.

1. Human calcitonin was administered into the distal colon and by intravenous infusion in eight healthy subjects in an open, fixed sequence, cross-over bioavailability study. 2. Intravenously infused human calcitonin elicited a standard pharmacokinetic profile in eight healthy subjects with a biphasic elimination with half-lives of 10.2 ± 0.7 min and 37.8 ± 2.5 min. 3. Colonoscopically administered human calcitonin was absorbed across the distal colonic mucosa in low amounts with a bioavailability of 0.00–0.22%. 4. Absorption from the distal colon was impeded by the presence of faecal material in three of the eight subjects. 5. We conclude that human calcitonin crosses the gastrointestinal epithelium of man. This may demonstrate the feasibility of an oral form for clinical use.

1. We studied the absorption of human calcitonin across the colon of juvenile female rats in vivo. Both pharmacokinetic and pharmacodynamic parameters were monitored to measure absorption. 2. Intracolonically administered human calcitonin at doses of 0.1–5.0 mg/kg resulted in a dose-dependent reduction in plasma calcium levels. 3. The bioavailability of intracolonically administered human calcitonin at doses of 5.0, 1.0 and 0.1 mg/kg was 0.5%, 0.9% and 0.2%, respectively. 4. Immunohistochemistry showed that human calcitonin transport across the rat colon was rapid and that a significant amount was via a transcellular pathway. 5. We conclude that human calcitonin crosses the gastrointestinal tract of rats in significant amounts and that this demonstrates the feasibility of an oral form for clinical use.

1. The measurement of the intestinal metabolism of the nitrogen moiety of glutamic acid has been investigated by oral ingestion of l -[ 15 N]glutamic acid and sampling of arterialized blood. 2. Measurements have been made in six normal adults weighing an average of 72.8 kg ingesting 100 mg of l -[ 15 N]glutamic acid after an overnight fast. 3. Measurement of the enrichment of arterial glutamic acid, glutamine and alanine was by gas chromatography–mass spectrometry. Isotopic enrichment of the amino acids was followed for 150 min after the ingestion of the amino acid. 4. Arterialized venous blood amino acid concentrations, measured by h.p.l.c., demonstrated no significant changes during the course of the experiment. 5. From the observed appearance of label in arterialized glutamic acid, alanine and glutamine, little luminal glutamic acid reaches the extracellular pool. The majority of the administered nitrogen label appears in the arterial alanine and glutamine components.

1. Intestinal epithelial cell production and intestinal absorption were measured in fed, starved and refed rats. 2. Four days' starvation significantly decreased the crypt cell production rate (CCPR), absorption, small intestinal length and crypt cell population. 3. There was an immediate increase in absorption 1 day after refeeding, which preceded a slower increase in CCPR. The absorption rate then decreased progressively after refeeding, and was significantly lower than control levels 1 week after refeeding. The CCPR, however, increased more gradually, reaching control levels after 2 days and then ‘overshooting’ control values. 4. There was no significant change in the crypt cell population immediately after refeeding; thus we propose that the initial increase in absorption on refeeding is either due to an accelerated maturation rate of the enterocytes or to the migration of enterocytes from the base of the villus to the functional zone. 5. The rapid recruitment of absorptive function appeared to be a ‘one-off’ event, the villus compartment then having to wait for increased cell production in the crypts to repopulate the villi.

1. Absorption of carbohydrate probe molecules from ligated loops of rat small intestine was studied. Absorption was determined by measuring recovery of molecules in the urine, corrected for incomplete recovery after intravenous injection, and was examined for correlation with several parameters of molecular dimension. 2. Absorption depended on molecular volume rather than relative molecular mass, molecular radius or molecular area. 3. Molecules with a molecular volume below 225 × 10 −3 nm 3 were absorbed to a greater extent than larger molecules, and absorption was affected critically by molecular volume, small changes in volume producing considerable variation in absorption. 4. Absorption of larger molecules was not affected by changes in volume within the range 362 × 10 −3 –1128 × 10 −3 nm 3 . 5. These findings support the concept that there are at least two aqueous diffusion pathways across the intestinal mucosa, small molecules diffusing through a small channel of finite dimension, compatible with a transcellular aqueous pore, whilst large molecules diffuse through a less frequent pathway of considerably larger dimensions.

1. The structural integrities of various preparations of rat small intestine for the study of absorption in vitro have been compared after incubation or perfusion. 2. Perfused intestines removed from anaesthetized rats, and thus never deprived of a supply of oxygen, maintain their structural integrity even after perfusion for 1 h provided that a Krebs–Henseleit bicarbonate perfusate is used. However, intestines removed from freshly killed rats show severe villus disruption and oedema after perfusion for only 20 min. 3. Extensive damage to both crypts and villi is observed in everted sacs of small intestine incubated for 20 min, regardless of the buffer system used. Intestinal rings show damage at the tips of the villi after incubation for 2 min, but otherwise remain morphologically intact; this damage is progressive with time. 4. It is concluded that the exact mode of preparation of intestinal tissue is critical for preservation of structural and functional integrity and that this is especially important in quantitative studies on transport processes. Further, it is recommended that routine monitoring of the integrity of intestinal preparations in vitro is desirable and that histological assessment is an appropriate technique.

1. The transport of 5-fluorouracil, uracil and thymine has been studied with isolated jejunal loops of rat small intestine. High performance liquid chromatography was used to identify the pyrimidines and measure their concentrations. 2. When the lumen of the intestine was perfused with 5-fluorouracil or uracil at 0.1 mmol/l or 0.2 mmol/l, the concentration in the serosal secretions was significantly higher than that in the lumen. For thymine the serosal concentration exceeded that in the lumen only at 0.1 mmol/l. 3. Analysis of the mucosal tissue water at the end of the perfusion demonstrated that when the intestinal lumen was perfused with any one of the three pyrimidines at 0.1 mmol/l or 0.2 mmol/l the concentration within the tissue was significantly above that in the lumen. 4. After an initial lag period linear rates of transport from the lumen to the serosal secretions were obtained for all three pyrimidines over a 10-fold concentration range from 0.1 mmol/l to 1 mmol/l. 5. Uracil and thymine inhibited the transmural transport of 5-fluorouracil. 6. The transport of 5-fluorouracil was also studied with a vascularly perfused preparation of rat small intestine. At 0.1 mmol/l the rate of transmural transport of the drug in this preparation was substantially higher than in the jejunal loops. This difference was eliminated by adding 5-fluorouracil to the vascular perfusate, suggesting that the higher transport rate in the vascularly perfused preparation was due to the lower serosal drug concentrations in the mesenteric circulation of the perfused intestine. 7. At a concentration of 5 mmol/l 5-fluorouracil inhibited water transport in the isolated loops and transmural D-galactose transport in the vascular perfusions.

1. The jejunal absorption of glucose from (1–4)-linked glucose oligomers including maltotriose has been compared with that from free glucose and sucrose in normal subjects. 2. A steady-state perfusion technique in vivo was used to study proximal jejunal assimilation of isotonic sugar-saline solutions isocaloric with 140 mmol/l glucose. Endogenous α-amylase was excluded from the test segment by proximal balloon occlusion. The glucose oligomer mixture consisted mainly of maltotriose, maltotetraose, maltopentaose and maltoheptaose. 3. Glucose absorption was significantly faster from maltotriose alone and from the glucose oligomer mixture than from 140 mmol/l glucose controls, whereas glucose absorption from 70 mmol/l sucrose was similar to that from 70 mmol/l glucose plus 70 mmol/l fructose. 4. Hydrolysis in vivo of maltotriose, the oligomer mixture and sucrose were similar, indicating that capture of glucose released by brush border sucrose hydrolysis was less efficient than that associated with (1–4)-linked oligomer hydrolysis. This suggests that the stoichiometric relationship of the active hydrolysis sites for sucrose to the glucose transport system is less advantageous than that of active sites for maltose hydrolysis. 5. Hydrolysis of oligomers larger than maltohexaose may be rate limiting for glucose absorption in the absence of luminal amylase activity.

1. In studies on intestinal adaptation it is often important to obtain contemporaneous data on the rate of cell production and the functional status of the intestine. 2. The measure of the rate of accumulation of vincristine arrested metaphases in microdissected intestinal crypts to determine the crypt cell production rate (CCPR), is one of the most effective methods of estimating intestinal epithelial cell proliferation which is robust enough to withstand scrutiny. However, studies in the field of intestinal adaptation could be much more informative if a valid measure of intestinal function could also be included. One such method is the water absorption capacity in vitro . 3. The intraperitoneal injection of vincristine sulphate (1 mg/kg) had no significant effect on the water absorption capacity of the small intestine, as measured by the segmented flow single pass perfusion method; thus the CCPR of the jejunum and intestinal water absorption were both measured in 19 groups of hypo- and hyper-proliferative rats which should have been in a relatively ‘steady state’ of cell production and turnover. 4. The minimum values were obtained after hypophysectomy and the maximum values were observed in lactation. CCPR and absorption were significantly correlated ( P < 0.001) with each other. There was a significant ( P < 0.001) correlation between both CCPR and absorption and dry weight of the intestinal segment studies with food intake. Body weight was a poor predictor of either CCPR or absorption. 5. The combined study of CCPR and water absorption is a practical and convenient approach to the study of intestinal cell proliferation and intestinal adaptation, and shows that in ‘steady state’ models of hypoplasia and hyperplasia, cell production is closely linked to functional capacity and both of these are also related to the food intake.

1. To compare the effects of intravenous and intraluminal hydrocortisone on jejunal transport, the proximal jejunum was perfused with glucose (28 mmol/l) in saline in two groups of normal subjects. 2. In the first group of seven subjects, compared with the control period results there were no changes in sodium, water and glucose absorption during the intravenous administration of hydrocortisone. In contrast, intraluminal hydrocortisone (100 mg/l) increased sodium, water and glucose absorption by 169%, 223% and 81% respectively ( P < 0.001 in each case) above the control values, when peripheral plasma cortisol levels were similar to those achieved with intravenous hydrocortisone. 3. In the second group of three subjects, intraluminal hydrocortisone (10 mg/l and 30 mg/l), followed by an intravenous infusion of hydrocortisone, had no effects on sodium, water and glucose absorption. 4. In a third group of six normal subjects perfused with fructose (28 mmol/l) in saline and bicarbonate (28 mmol/l) in saline intraluminal hydrocortisone (100 mg/l) had no effect on solute and water absorption. 5. These results suggest that intraluminal hydrocortisone stimulates glucose-coupled sodium transport by exerting a topical effect on the apical membrane of the jejunal mucosa.

1. Re-examination of data for the chemical analysis of peptide-bound amino acids in the mesenteric venous blood of anaesthetized guinea-pigs suggests that there are small, but significant, amounts of small peptides in the blood of fasted animals. 2. Furthermore, there is a significant increase in the peptide content of the mesenteric venous blood during intraduodenal infusion of a partial digest of casein. 3. The data are consistent with the view that some 10% of the amino nitrogen entering the mesenteric blood during absorption of a casein digest in vivo may be in the form of small peptides, although it is not possible to define confidence limits for this estimate.

1. The intestinal absorption of a mixture of [ 3 H]cellobiotol and [ 14 C]mannitol was determined by measuring the 3 H/ 14 C ratio in urine after oral administration of the labelled sugars to rats. This index of intestinal permeability was used to identify cellular dysfunction in experimental enteropathy in rats. 2. Rats with mucosal damage induced with ethanol showed an increased uptake of [ 3 H]cellobiotol and a decreased uptake of [ 14 C]mannitol compared with normal controls. The increased 3 H/ 14 C ratio in urine reflected the abnormal cell function known to be caused by ethanol. 3. Methotrexate treatment reduced the absorption of the two sugars whereas cetrimide treatment enhanced their absorption. However, in both methotrexate-induced and cetrimide-induced enteropathy the 3 H/ 14 C ratio in urine was unaffected by the mucosal damage. Here the permeability change was not related to absorptive dysfunction of the mucosal cells. 4. It is concluded that this labelled sugar absorption test enables the rapid and accurate identification of malfunction of intestinal mucosal cells in the rat. Moreover, the test distinguishes between changes in permeability caused by abnormal cell function and changes caused by gross disturbance of the structure of the mucosal surface.

1. To compare the bioavailability and the elimination of propranolol in seven untreated coeliac patients and six normal subjects, plasma concentrations were measured after oral and intravenous propranolol. The bioavailability and clearance of propranolol were similar in both groups. 2. With the use of a perfusion technique, propranolol absorption in the proximal jejunum was found to be decreased by 71% in five untreated coeliac patients, compared with the absorption in four normal subjects. 3. These results indicate that propranolol absorption is decreased in the proximal jejunum in untreated coeliac disease but overall absorption in the small bowel is not impaired.

1. Four different methods of calculating calcium absorption by radioactive calcium procedures have been compared with each other and with net calcium absorption in calcium-balance studies in 100 consecutive studies on 71 patients. 2. All four isotope procedures yielded highly significant correlations with net calcium absorption derived from the balance studies, but there was little to choose between the validity of the double-isotope and single-isotope procedure judged by these criteria. 3. The rate of calcium absorption calculated from one or other isotope procedure correlated better with net calcium absorption than did the fraction of the radioactive calcium absorbed. 4. The measurement of plasma radioactivity 1 h after single-isotope administration, corrected for body weight, proved almost as useful as the more complex procedures but would be expected to underestimate calcium absorption in states of very high bone turnover.

1. Experiments were performed to study the absorption of two simultaneously administered polar probes of different molecular size from closed intestinal loops in rats subjected to various mucosal structural lesions. 2. Absorption of mannitol (molecular radius approximately 0.40 nm) was significantly decreased in rats with villous atrophy and crypt hypoplasia induced by the cytostatic agent methotrexate. The absorption of lactulose (radius approximately 0.54 nm) was also decreased, in contrast to the increased absorption which was found in an earlier study when villous atrophy with crypt hyperplasia was induced by infection by a nematode. The effect of local damage to villous tips, produced by the intraluminal presence of a detergent, was to increase significantly the absorption of lactulose. 3. In conjunction with the findings of earlier studies, these results support the hypothesis that there are at least two routes for the permeation of polar molecules. Small molecules such as mannitol probably pass through numerous cellular pores with a maximum radius lying between 0.40 and 0.54 nm and absorption is closely related to mucosal surface area. Larger molecules such as lactulose are probably restricted to less numerous extracellular pathways and absorption may be related to cell shedding or other areas of mucosal damage.

1. Intestinal phosphate absorption in human subjects was studied by the technique of triple lumen intestinal perfusion in vivo. 2. Ileal phosphate absorption increased as the intraluminal phosphate concentration was increased. 3. Ileal rates of phosphate absorption were lower at any given intraluminal phosphate concentration than previously described jejunal rates. Acidification of the ileal lumen did not increase phosphate absorption. 4. Phosphate absorption was shown in the jejunum to be dependent on the intraluminal sodium concentration. 5. Phosphate absorption in the human small intestine consists of at least two components, one directly proportional to water movement and the second apparently independent of water movement.

1. Water absorption and cytoplasmic dipeptidase activities were determined in isolated rat small intestine after animals had fed on various ‘elemental’ diets or a standard rat diet and after a single injection of 5-fluorouracil. 2. Vivonex diets were associated with a decrease in dry weight of the small intestine and an increase in glucose and water absorption in vitro. 3. The nature of the dietary nitrogen profoundly affects the activities of intestinal peptidases. 4. Water absorption was severely depressed 3 days after 5-fluorouracil administration: the extent of depression was independent of the diet. Thus, any ameliorative effects of ‘elemental’ diets on 5-fluorouracil toxicity are unlikely to be mediated by direct protection of intestinal absorption.

1. Glucose absorption, water absorption and dipeptide hydrolase activities have been determined in isolated rat small intestine at 1, 3, 5 and 21 days after a single intraperitoneal injection of 5-fluorouracil. 2. Absorption rates and enzyme activities were elevated 1 day after treatment, but were reduced to 40% of control values at 3 and 5 days. Changes were seen regardless of whether absorption was expressed per unit length or per unit dry weight of intestine. 3. There were highly significant positive correlations between glucose or water absorption rates and peptidase activities, especially in proximal jejunum. The most significant correlation was observed between water absorption rate and jejunal l-Leu-Gly hydrolase activity. 4. Malabsorption may account for some of the gastrointestinal side effects associated with treatment with 5-fluorouracil. Enzyme measurements may be useful as an index of intestinal function.

1. The validity of evidence for intact peptide absorption, derived from analysis of the relation of water and total solute absorption, has been tested. 2. Solute and water absorption from saline solutions of the disaccharide maltose have been studied in the normal human jejunum, using a double-lumen perfusion technique with a proximal occlusive balloon. It was expected that maltose would yield very different results from peptides, because maltose is virtually completely hydrolysed before absorption, whereas a proportion at least of some peptides is transported into the intestinal mucosal cells before hydrolysis. This expectation was not confirmed by experiment. 3. The assumption that the absorbate is always isotonic with plasma has been tested by altering the osmolality of glucose/saline solutions perfused in the jejunal lumen. This assumption was not substantiated by experiment, as when the luminal fluid was hypertonic to plasma, so was the absorbate. 4. It is suggested that our findings with peptides and saccharides could be explained by the production of a hypertonic absorbate by hydrolysis of these solutes to their monomer units. We therefore conclude that analyses of the relation of net solute and water absorption cannot be used to predict the form in which peptides enter the mucosal cells.

1. A jejunal perfusion technique has been used in normal volunteer subjects to study jejunal absorption of amino acid residues from a partial enzymic hydrolysate of casein in which about 50% of the amino acids existed as small peptides, and also from an equivalent mixture of free amino acids. 2. The effect of a high concentration of the dipeptide glycylglycine on the absorption of amino acid residues from these preparations was studied to quantify the importance of mucosal uptake of intact peptides during absorption of the partial hydrolysate of casein. 3. The results were unexpected. Glycylglycine significantly inhibited absorption of several amino acid residues (aspartic acid + asparagine, serine, glutamic acid + glutamine, proline, alanine, phenylalanine, threonine and isoleucine) from the free amino acid mixture, whereas it significantly inhibited the absorption of only two (serine, glutamic acid + glutamine) from the peptide-containing partial casein hydrolysate. 4. The effect of glycylglycine on absorption of amino acids from the mixture of free amino acids was apparently due to inhibition of amino acid uptake by free glycine liberated from the dipeptide during perfusion. The reason for the failure of glycylglycine to cause extensive inhibition of absorption from the partial hydrolysate is not clear. It may be due to glycylglycine being only a weak inhibitor of peptide uptake, but the possibility that some peptides are taken up by a system unavailable to glycylglycine has to be considered.

1. Absorption of [ 3 H]glycine and [ 14 C]-glycyl-l-proline at concentrations between 0·5 and 4 mmol/l was studied by perfusion in vivo of rat jejunal and ileal segments. Absorption was defined as net removal of radioisotope from the perfusate. Radioactivity assays and amino acid analyses were performed on perfusates and on mucosal tissue samples obtained from the perfused segments. 2. At the concentrations studied, absorption rates of glycine and glycylproline were proportional to concentration. Ileal rates were approximately 60% of jejunal rates. Glycylproline absorption was slightly faster than glycine absorption and was associated with the appearance in the perfusate of free glycine and proline in the ratio approximately 3:1. Intraluminal hydrolysis was insufficient to account for the amounts of free amino acids found and glycylproline hydrolase activity at the brush border is known to be minimal. 3. Glycylproline absorption apparently occurred by transport of the intact peptide followed by its intracellular hydrolysis. However, more than one-third of absorbed glycine and one-eighth of absorbed proline returned to the lumen as free amino acid. This reflux of glycine and proline was not proportional to their concentrations in the mucosa.

1. To study the relative contributions of luminal nutrition, bile and pancreatic secretions and hormonal factors in intestinal adaptation, lactation hyperphagia was chosen as a model for increased luminal nutrition, either alone (intestinal transection control group) or in combination with (i) exclusion of bile and pancreatic secretions from the jejunum (by transposition of the jejunum above the Ampulla of Vater) or (ii) exclusion of bile, pancreatic secretions and exogenous luminal nutrition from the jejunum (proximal Thiry—Vella by-pass group). 2. The results confirm that in lactation there is mucosal hyperplasia with increases in villus height and crypt depth, and in small-bowel wet and defatted dry-tissue weights per unit length of intestine. 3. There are corresponding changes in absorptive function with increased glucose and water absorption per unit length of intestine. 4. These structural and functional adaptive changes are proportionately greater in ileum than in jejunum. 5. The exclusion of exogenous luminal nutrition, bile and pancreatic secretions from the jejunum did not diminish the degree of intestinal mucosal hyperplasia and functional adaptation seen in lactation. 6. Diversion to the ileum of greater than normal amounts of bile, pancreatic secretions and luminal nutrition did not further increase the degree of mucosal hyperplasia and enhanced absorption seen in the lactating intestinal transection control group. 7. Unlike other models of intestinal adaptation, the changes in small-bowel mucosal structure and function seen in lactation are problaby due to hormonal factors.

1. Pteroylmonoglutamic acid (PteGlu) absorption has been measured by using the technique of small-intestinal perfusion with tritiated PteGlu in normal subjects and in patients with coeliac disease. 2. At similar intrajejunal pH, patients with untreated coeliac disease have significantly less PteGlu than normal subjects and patients with treated coeliac disease. 3. The ‘resting’ pH in the jejunum did not differ markedly between normal subjects and patients with coeliac disease. 4. Increasing pH decreased PteGlu absorption in patients with coeliac disease and in normal subjects. 5. These findings suggest that PteGlu malabsorption in coeliac disease is not due to abnormally high pH in the jejunum.

1. Certain sugars were transported across the buccal mucosa by a carrier-mediated mechanism. 2. The metabolic loss of sugars from the mouth in a 5 min test period was negligible. 3. The buccal mucosal transport process was stereospecific for d-glucose and l-arabinose. 4. The absorption of d-glucose, galactose and 3- O -methyl-d-glucose was at least partly dependent on the presence of sodium ions in the luminal fluid. 5. The transport of d-glucose was inhibited by galactose and 3- O -methyl-d-glucose, suggesting at least one common carrier system.

1. The absorption in vivo of d-galactose by the rat small intestine has been examined in proximal jejunum and distal ileum by use of a recirculation—perfusion technique. 2. Multiple sequential perfusions over 4 h produced no subsequent functional or morphological damage in the perfused segments. 3. Absorption of galactose from 8 and 64 mmol/l solutions was found to be independent of flow rate over the range 1·0–6·5 ml/min. 4. Galactose absorption in both the jejunum and the ileum exhibited saturation kinetics of the Michaelis—Menten type, and phlorrhizin sensitivity. Sorbose was only absorbed minimally. These observations demonstrate that galactose is absorbed by carrier-mediated transport and that there is no significant passive diffusive component in vivo. 5. Under the stated experimental conditions, the maximum absorptive capacity was 4·5 times greater in the jejunum than in the ileum. The Michaelis constant for galactose was higher in the jejunum than in the ileum. 6. Enterocytes were isolated from perfused segments and quantified by DNA assay with a correction for yield. In this manner, the absorptive capacity per enterocyte was calculated. 7. The maximum absorptive capacity per enterocyte was 3·5 times greater in the jejunum than in the ileum.

1. The effects in rats of an oral pharmacological dose of prednisolone on mucosal function, enzymology, lysosomal membrane fragility, morphology and cell kinetics have been examined in proximal jejunum and distal ileum. 2. The maximum absorptive capacity for galactose was significantly greater in both the jejunum and the ileum of the steroid-treated animals. This was due to an increase in carrier-mediated transport in the individual enterocytes and not to a change in the cell population. The Michaelis constant for galactose was not significantly altered by prednisolone. 3. Activities of brush-border and mitochondrial enzymes and of RNA were increased in isolated enterocyte preparations from the jejunum and ileum of the steroid-treated group. 4. Lysosomal membrane fragility was unaltered in the prednisolone-treated group. 5. Morphometrical observations confirmed that the size of the enterocyte population was unaltered by prednisolone. Studies on cell kinetics indicate that the effects of prednisolone are due to a direct action on the enterocyte and not secondary to changes in migration rate.

1. Human gastrointestinal secretions formed soluble copper complexes when labelled in vitro with 64 Cu. 2. Copper-binding substances of low molecular weight were demonstrated in the saliva, gastric juice and secretin-stimulated duodenal aspirate of normal subjects by dialysis and gel-chromatography studies. 3. The nature of the copper complexes formed by secretions obtained from patients with Wilson's disease was similar to that of complexes formed by secretions of normal subjects. 4. Bile contained a copper-binding fraction of high molecular weight which was more concentrated in gall-bladder than hepatic bile. Between pH 5 and pH 8, this component had a greater binding affinity for copper than the other alimentary secretions or EDTA at a concentration of 10 mmol/l. 5. Absorption of 64 Cu from 64 Cu-labelled saliva, gastric juice or l-histidine solution (100 mmol/l) administered intraduodenally into groups of rats was similar to that observed in a control series given [ 64 Cu]cupric acetate in sodium chloride solution. In contrast, the absorption of 64 Cu from labelled hepatic and gall-bladder bile was significantly reduced. 6. The results suggest that dietary copper forms soluble complexes with the alimentary secretions and that these complexes influence absorption of the metal according to their molecular size. The net uptake of ingested copper from the gut lumen may represent a balance between the influence of dietary chelates, low-molecular-weight ligands in the alimentary secretions and a macromolecular copper-binding complex of bile.

1. Ammonia and urea transport across the colonic mucosa was studied by a perfusion technique in four subjects with colonic exclusion for chronic hepatic encephalopathy. 2. Reduction of luminal pH inhibited net and unidirectional transport of ammonia from lumen to plasma, but net absorption from high luminal concentrations persisted at low pH. 3. Neither addition of urea to the perfusate nor intravenous infusion of urea produced a consistent increase in the colonic excretion of ammonia when ammonia-free solutions were perfused. 4. In one subject intravenous infusion of [ 15 N]-ammonium chloride produced rapid labelling of colonic effluent ammonia and within 60 min the specific enrichments of ammonia in effluent and in arterial plasma were approximately equal. 5. During perfusion of nitrogen-free solutions, only small amounts of urea appeared in the effluent, suggesting limited permeability of the colonic mucosa to urea. 6. These results are discussed in relation to the equilibration of ammonia across the colonic mucosa by both ionic and non-ionic diffusion. The lack of evidence of ‘juxtamucosal’ (as opposed to luminal) ureolysis is in contrast to other observations on the intact colon. The possible reasons for and implications of this discrepancy are discussed.

1. The two diastereoisomers of 5-methyltetrahydropteroylglutamate, the form of folate that predominates in food and bile, were prepared chemically. 2. Their intestinal absorption was compared by means of the urinary-excretion method of 3 H-labelled compounds and it was found that the naturally occurring biologically active isomer was excreted to a greater extent. Studies of the clearance of the two forms after intravenous injection showed that this difference was due to preferential intestinal absorption of the naturally occurring isomer. 3. In four patients with coeliac disease, the absorption of the naturally occurring isomer was depressed to the same range as the inactive isomer. 4. Since the two diastereoisomers are chemically inseparable, these results indicate that a carrier-mediated process is involved in the human intestinal absorption of this form of reduced folate.

1. Gall-bladder bile was obtained at cholecystectomy from seven patients who had been given [ 64 Cu]cupric acetate intravenously. 2. Studies using dialysis and Sephadex gel filtration indicated that most of the 64 Cu in the bile was in a heat-stable complex of molecular weight exceeding 50 000. The remaining biliary 64 Cu was in a low-molecular-weight component. 3. Above pH 4, 64 Cu could not readily be removed from the macromolecular complex either by excess carrier copper ions, by d-penicillamine or by EDTA. 4. Absorption of 64 Cu from 64 Cu-labelled bile injected intraduodenally into rats was significantly less than from [ 64 Cu]cupric acetate similarly injected. 5. These observations suggest that limitation of an entero-hepatic circulation of copper by a biliary macromolecule which differs from caeruloplasmin, may be a significant factor in copper homeostasis in man.

1. Using a double-lumen tube perfusion system the rates of glycine, glycylglycine, and glycylglycine and glucose absorption from a 30-cm jejunal segment have been studied in vivo in a group of relatively normal Zambian African subjects. 2. To determine the kinetic curve for glycine absorption, four subjects were given consecutive perfusions of 50, 100 and 150 mm-glycine. 3. Six other subjects had consecutive perfusions of (1) a 100 mm-glycine and (2) a 50 mm-glycylglycine solution. Five of the six had a higher absorption rate of glycine from the glycylglycine solution. When data from a further six similar subjects in another study are included, the mean rate of glycine absorption is significantly greater from the glycylglycine compared with the glycine solution ( P < 0·001). 4. A further six subjects were given consecutive perfusions of (1) 50 mm-glycylglycine, (2) 50 mm-glycylglycine and 200 mm-glucose, and (3) 200 mm-glucose. The absorption rate of glycine from glycylglycine was lower in all subjects when glucose was present in the perfusing fluid ( P < 0·01). Although the mean glucose absorption rate was lower when glycylglycine was present in the perfusing fluid, the difference was not significant.

1. Ammonia, bicarbonate and pH were measured in samples of faecal dialysate from thirteen healthy subjects taking free diets. To observe the effect of marked changes in faecal pH, three subjects were also studied while taking 25 mmol/day of MgCO 3 or Na 2 SO 4 by mouth. Both salts increased stool weight without causing diarrhoea, but stool pH was significantly increased by MgCO 3 and decreased by Na 2 SO 4 . 2. The total ammonia concentration and pH of faecal dialysate were very variable, but showed a highly significant negative correlation similar to that already established in man between urinary excretion of ammonia and urine pH. This relationship was more marked when individual subjects were studied while faecal pH was deliberately varied by administration of MgCO 3 and Na 2 SO 4 . 3. Faecal bicarbonate concentrations were positively correlated with pH. Faecal P co 2 was usually in the range 40–120 mmHg, the higher P co 2 values being found in the more acid samples. Faecal total ammonia concentrations were negatively correlated with faecal bicarbonate. 4. These findings suggest that passive non-ionic diffusion is the main mechanism by which ammonia is absorbed by the colon, but do not exclude a minor contribution from diffusion of ionized ammonium. Colonic secretion of bicarbonate facilitates non-ionic diffusion of ammonia by providing an anion which is also absorbed by non-ionic diffusion, so maintaining an alkaline intraluminal reaction that continues to generate unionized ammonia.

1. To investigate the effect of different intraluminal concentrations on the mutual inhibitive effect of glycine and glucose on their jejunal absorption rates, eighteen convalescent Zambian African patients who had no clinical evidence of intestinal disease or of malnutrition were given constant intrajejunal infusions with those solutes either together or alone. A double-lumen tube perfusion system was used, and three solutions containing (A) glycine, (B) glycine and glucose, and (C) glucose, all of which were rendered iso-osmotic with sodium chloride, were perfused in random order at 12·0 ml/min. The concentration of glycine in the perfusing fluid was either 10 or 20 mm, and that of glucose either 100, 200 or 280 mm. By reference to polyethylene glycol 4000, the absorption rates of the solutes and water were calculated for a 30 cm jejunal segment. 2. At a glucose concentration of 200 or 280 mm, but not 100 mm, the mean rate of glycine absorption was decreased by approx. 30%. Glucose absorption rates were not significantly altered by glycine. 3. These observations, taken in conjunction with those from a previous investigation, are consistent with the view that there are two mechanisms for the jejunal absorption of glycine in man, one of which is inhibited by glucose at high intraluminal concentration.