Prolonged small-intestinal transit time in cystic fibrosis.

A lactulose hydrogen breath test was performed on 10 patients with cystic fibrosis and 15 control subjects matched for age and sex. All normal subjects had a fasting breath hydrogen concentration of less than 20 ppm. In contrast, seven of the patients with cystic fibrosis had high concentrations (25-170 ppm), which fell to 20 ppm or below on prolonged fasting (14-23 hours). Two patients showed no rise in breath hydrogen concentrations after lactulose, and in one patient the breath hydrogen concentration rose at 15 minutes, suggesting bacterial colonisation of the small bowel. Seven of the patients had prolonged small-bowel transit times (160-390 minutes) compared with those in the control group (50-150 minutes).     

Gut hormones in tropical malabsorption.

Concentrations of various gut hormones were measured after a test breakfast in eight patients with severe tropical malabsorption and 12 controls. The patients with tropical malabsorption had greatly raised basal plasma motilin and enteroglucagon concentrations, but their postprandial release of both gastric inhibitory polypeptide and insulin was significantly reduced. The pattern of gut hormone release differed from that found in coeliac disease. The measurement of gut hormones, each of which has a specific site and function, thus throws new light on the pathophysiology of tropical malabsorption and may suggest approaches of treatment.     

Immunoelectrophoretic studies on human small-intestinal brush-border proteins.

The amounts of lactase (beta-D-galactosidase, EC 3.2.1.23), sucrase (sucrose alpha-D-glucohydrolase, EC 3.2.1.48), maltase (alpha-D-glucosidase, EC 3.2.1.20) microvillus aminopeptidase (EC 3.4.11.2) and dipeptidyl peptidase IV (EC 3.4.14.-) in tangentially sectioned biopsies from jejunum were studied by quantitative immunoelectrophoresis and enzymic assays. All enzymes had their maximum activities near the mid-region of the villi and their lowest activities at the bases of the crypts. The ratio between enzyme activity and immunoreactive protein was constant along the villus-crypt axis. This result is consistent with a continuous brush-border-enzyme synthesis as the enterocytes migrate up the villi.     

Sodium ion/L-lactate co-transport in rabbit small-intestinal brush-border-membrane vesicles.

Uptake of L-lactate into rabbit jejunal brush-border-membrane vesicles prepared by a Ca2+-precipitation procedure was studied by a rapid filtration technique with L-[14C]-lactate as tracer. Transport of L-lactate into an intravesicular (osmotically reactive) space could be established. An inwardly directed NaCl gradient (outside 21 mM/inside 0mM) stimulated the uptake of L-lactate at 15 s 2-4-fold compared with that observed with an equal KCl gradient. A transient accumulation of L-lactate inside the vesicles (overshoot) was observed in the presence of an NaCl gradient. Gradients of LiCl, RbCl, CsCl or choline chloride were not able to replace NaCl in the stimulation of L-lactate uptake. L-Lactate uptake was saturable only in the presence of Na+. D-Lactate, DL-thiolactate (2-DL-mercaptopropionate), pyruvate and propionate inhibited the Na+-stimulated L-lactate uptake; D-lactate, thiolactate and pyruvate provoked trans-stimulation of L-lactate uptake. Artificially imposed diffusion potentials (inside negative) did not exert any effect on the Na+-dependent L-lactate uptake. The results are consistent with the existence of an electroneutral Na+/L-lactate co-transport system in the brush border of rabbit small intestine.     

A hydrophobic form of the small-intestinal sucrase-isomaltase complex.

A large scale preparation of brush border membranes is described. Solubilized by either papain or Triton X-100, the sucrase-isomaltase complex is purified in a three-step procedure, including differential centrifugation, Sephadex G-200 and DEAE-cellulose chromatography. Detergent solubilized and protease solubilized sucrase-isomaltase differ in tendency to aggregate but not in enzymatic characteristics. The chemical composition and the molecular weight of the two enzyme complexes are almost identical. Limited digestion of the Triton-solubilized sucrase-isomaltase complex by papain produces a protein electrophoretically indistinguishable from papain-solubilized sucrase-isomaltase together with low molecular proteolytic fragments.     

Subunit structured of pig small-intestinal brush-border aminopeptidase N.

Aminopeptidase N (EC 3.4.11.2), when isolated from pig intestine in either the proteinase- or detergent-released form, frequently appears to contain three polypeptide chains, here termed alpha, beta and gamma. We have established by an immunological technique that the beta- and gamma-polypeptides are derived from the alpha-chain and that the intact enzyme is a dimer, alpha 2. Each alpha-chain of the detergent form was shown to contain a hydrophobic anchor peptide about 35 amino acid residues in length, which included the N-terminal sequences. A peptide bond in the alpha-chain was very sensitive to proteolysis. Its cleavage generated the commonly observed forms: alpha beta gamma and beta 2 gamma 2. The gamma-fragment, which lacked the anchor peptide, was derived from the C-terminal part of the alpha-chain.     

Small intestinal transit in diabetics.

Small intestinal transit was assessed in diabetic patients and healthy controls by measuring the breath hydrogen appearance time after the ingestion of lactulose. Transit in diabetics with autonomic neuropathy was significantly slower than in diabetics without neuropathy and controls. Delayed transit is probably due to vagal denervation. These slower transit times would allow bacteria to proliferate, which might explain why some diabetics have diarrhoea. The test cannot be used in patients with bacteria in the small bowel because these may metabolise lactulose and release hydrogen prematurely.     

Protein-losing enteropathy and malabsorption in acute measles enteritis.

Gastrointestinal protein loss and xylose and lactose absorption were both abnormal in underweight children with acute measles and diarrhoea. The protein loss was equivalent to a mean absolute albumin loss of 1.68 plus or minus 0.21 g/day, while the mean one-hour blood xylose level was 0.93 plus or minus 0.38 mmol/l (14.0 plus or minus 5.7 mg/100 ml) in the acute stage and 1.71 plus or minus 0.43 mmol/l (25.6 plus or minus 6.5 mg/100 ml) after recovery (P less than 0.01). Lactose intolerance was found in four children out of 17 tested. Thus faecal protein loss and malabsorption may contribute significantly to the development of malnutrition after measles.     

Methotrexate-induced malabsorption in children with acute lymphoblastic leukaemia.

A one-hour D-xylose absorption test was performed on 18 children with acute lymphoblastic leukaemia. Xylose absorption was normal in children who had not received methotrexate, but there was a significant degree of malabsorption in those who had taken methotrexate within the previous seven days. There was a progressive and significant increase in malabsorption related to the cumulative dose of methotrexate. These findings provide further evidence that regular methotrexate treatment every seven days is more toxic than if it is more widely spaced. The spacing of treatment is currently under investigation.