AB S T R A C T The ability of products of digestion to stimulate pancreozymin secretion in man wa... more AB S T R A C T The ability of products of digestion to stimulate pancreozymin secretion in man was investigated using a bioassay procedure, based on duodenal perfusion, which quantified the total outputs of pancreatic enzymes evoked by intraduodenal stimuli under steady-state conditions. Patterns of response resulting from physiologic intraduodenal concentrations of test material were basal output (with isotonic saline), washout of enzymes (with dextrose, micellar fatty acid, and amino acids), and sustained output of enzymes (with amino acids and micellar fatty acid). The sustained secretion of pancreatic enzymes found during the 2nd hr of perfusion and subsequently was characteristic of pancreozymin-induced secretion. The enzyme output in response to a mixture of essential and nonessential amino acids was significantly higher than that evoked by micellar fatty acid and was comparable with that resulting from the maximally tolerated dose of pancreozymin given by vein.
The effect of three liquid meals on the serum level of conjugates of cholic acid was determined b... more The effect of three liquid meals on the serum level of conjugates of cholic acid was determined by radioimmunoassay. In eight healthy subjects, these bile acids peaked 90 to 120 minutes after each meal, and returned to base line by four hours. This pattern was meal related ...
A B S T R A C T Perfusion studies were performed in healthy volunteers to test whether the secret... more A B S T R A C T Perfusion studies were performed in healthy volunteers to test whether the secretory effect of conjugated bile acids, previously shown for the colon, was also present in the jejunum. A perfusion system with a proximal occlusive balloon (and continuous aspiration of duodenal secretions) was used; isotonic test solutions contained glycine-conjugated bile acids with or without lecithin. Fluid movement was measured by changes in the concentration of polyethylene glycol (PEG, mol wt 4,000). Conjugated dihydroxy bile acids inhibited electrolyte and fluid absorption and, at higher concentrations, evoked secretion of an isotonic fluid. Glucose absorption continued, despite fluid secretion, but its rate decreased. The secretory effects of bile acids were abolished by the addition of lecithin to the bile acid solutions. A trihydroxy bile acid (cholylglycine) had no effect on jejunal absorption. Small amounts (6-9%) of conjugated bile acids were absorbed in the jejunum; lecithin was well absorbed (72-90%). The results indicate that dihydroxy bile acids influence salt and water transport in the human jejunum but that this effect may be abolished when a polar lipid such as lecithin is present. We speculate that this effect of bile acids may modify fluid movement in the small intestine postprandially after fat absorption has occurred. methods previously described (3). Bile acids were obtained from the following sources: deoxycholic acid (Schuchardt, Munich, Germany), cholic acid (Matheson, Coleman and Bell, East Rutherford, N. J.), and chenodeoxycholic acid (Weddell Pharmaceuticals, London, England). Bile acids were purified by crystallization and were then conjugated with glycine methyl ester. The reaction product was extracted into ethyl acetate-benzene, 1: 1 (vol/vol), which was washed three times with an equal volume of 1 M sodium carbonate and three times with equal volumes of 1 M sodium chloride to remove unreacted free acid and glycine methyl ester. The washing procedure was repeated; the ethyl acetate phase was then reduced to dryness on a rotary evaporator and saponified in ethanol-i N NaOH, 1: 1 (vol/vol), for 2 h at room temperature. The saponification mixture was extracted three times with equal volumes of petroleum hydrocarbon to remove tri-n-butylamine. The
An informal review of the author's five decades of research on the chemistry and biology of bile ... more An informal review of the author's five decades of research on the chemistry and biology of bile acids in health and disease is presented. The review begins with a discussion of bile acid structure and its remarkable diversity in vertebrates. Methods for tagging bile acids with tritium for metabolic or transport studies are summarized. Bile acids solubilize polar lipids in mixed micelles; progress in elucidating the structure of the mixed micelle is discussed. Extensive studies on bile acid metabolism in humans have permitted the development of physiological pharmacokinetic models that can be used to simulate bile acid metabolism. Consequences of defective bile acid biosynthesis and transport have been clarified, and therapy has been developed. Methods for measuring bile acids have been improved. The rise and fall of medical and contact dissolution of cholesterol gallstones is chronicled. Finally, principles of therapy with bile acid agonists and antagonists are given. Advances in understanding bile acid biology and chemistry have helped to improve the lives of patients with hepatobiliary or digestive disease.
AB S T R A C T The ability of products of digestion to stimulate pancreozymin secretion in man wa... more AB S T R A C T The ability of products of digestion to stimulate pancreozymin secretion in man was investigated using a bioassay procedure, based on duodenal perfusion, which quantified the total outputs of pancreatic enzymes evoked by intraduodenal stimuli under steady-state conditions. Patterns of response resulting from physiologic intraduodenal concentrations of test material were basal output (with isotonic saline), washout of enzymes (with dextrose, micellar fatty acid, and amino acids), and sustained output of enzymes (with amino acids and micellar fatty acid). The sustained secretion of pancreatic enzymes found during the 2nd hr of perfusion and subsequently was characteristic of pancreozymin-induced secretion. The enzyme output in response to a mixture of essential and nonessential amino acids was significantly higher than that evoked by micellar fatty acid and was comparable with that resulting from the maximally tolerated dose of pancreozymin given by vein.
The effect of three liquid meals on the serum level of conjugates of cholic acid was determined b... more The effect of three liquid meals on the serum level of conjugates of cholic acid was determined by radioimmunoassay. In eight healthy subjects, these bile acids peaked 90 to 120 minutes after each meal, and returned to base line by four hours. This pattern was meal related ...
A B S T R A C T Perfusion studies were performed in healthy volunteers to test whether the secret... more A B S T R A C T Perfusion studies were performed in healthy volunteers to test whether the secretory effect of conjugated bile acids, previously shown for the colon, was also present in the jejunum. A perfusion system with a proximal occlusive balloon (and continuous aspiration of duodenal secretions) was used; isotonic test solutions contained glycine-conjugated bile acids with or without lecithin. Fluid movement was measured by changes in the concentration of polyethylene glycol (PEG, mol wt 4,000). Conjugated dihydroxy bile acids inhibited electrolyte and fluid absorption and, at higher concentrations, evoked secretion of an isotonic fluid. Glucose absorption continued, despite fluid secretion, but its rate decreased. The secretory effects of bile acids were abolished by the addition of lecithin to the bile acid solutions. A trihydroxy bile acid (cholylglycine) had no effect on jejunal absorption. Small amounts (6-9%) of conjugated bile acids were absorbed in the jejunum; lecithin was well absorbed (72-90%). The results indicate that dihydroxy bile acids influence salt and water transport in the human jejunum but that this effect may be abolished when a polar lipid such as lecithin is present. We speculate that this effect of bile acids may modify fluid movement in the small intestine postprandially after fat absorption has occurred. methods previously described (3). Bile acids were obtained from the following sources: deoxycholic acid (Schuchardt, Munich, Germany), cholic acid (Matheson, Coleman and Bell, East Rutherford, N. J.), and chenodeoxycholic acid (Weddell Pharmaceuticals, London, England). Bile acids were purified by crystallization and were then conjugated with glycine methyl ester. The reaction product was extracted into ethyl acetate-benzene, 1: 1 (vol/vol), which was washed three times with an equal volume of 1 M sodium carbonate and three times with equal volumes of 1 M sodium chloride to remove unreacted free acid and glycine methyl ester. The washing procedure was repeated; the ethyl acetate phase was then reduced to dryness on a rotary evaporator and saponified in ethanol-i N NaOH, 1: 1 (vol/vol), for 2 h at room temperature. The saponification mixture was extracted three times with equal volumes of petroleum hydrocarbon to remove tri-n-butylamine. The
An informal review of the author's five decades of research on the chemistry and biology of bile ... more An informal review of the author's five decades of research on the chemistry and biology of bile acids in health and disease is presented. The review begins with a discussion of bile acid structure and its remarkable diversity in vertebrates. Methods for tagging bile acids with tritium for metabolic or transport studies are summarized. Bile acids solubilize polar lipids in mixed micelles; progress in elucidating the structure of the mixed micelle is discussed. Extensive studies on bile acid metabolism in humans have permitted the development of physiological pharmacokinetic models that can be used to simulate bile acid metabolism. Consequences of defective bile acid biosynthesis and transport have been clarified, and therapy has been developed. Methods for measuring bile acids have been improved. The rise and fall of medical and contact dissolution of cholesterol gallstones is chronicled. Finally, principles of therapy with bile acid agonists and antagonists are given. Advances in understanding bile acid biology and chemistry have helped to improve the lives of patients with hepatobiliary or digestive disease.
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Papers by Alan Hofmann