Fred Kern

CLINICAL RELATIONSHIPS OF GALLSTONES

Abstract Many factors and diseases have been claimed to be associated with increased frequency of cholesterol gallstone formation. Not all these claims stand up to critical examination. Age, sex, and race are associated with gallstone frequency and stones are unusually common in patients with gallbladder cancer or pancreatitis. For parity, body-weight, cirrhosis, ileal disease (or resection), and diabetes mellitus an association is probable but not definite. For the many other associations which have been proposed the evidence is contradictory, inadequate, or both.

Protein starvation and the small intestine: I. The Growth and Morphology of the Small Intestine in Weanling Rats☆

Abstract Weanling rats completely deprived of dietary protein fail to increase in weight, fail to add length to the small intestine, and fail to exhibit villous growth in the ileum. By contrast, jejunal villi of protein-starved rats grow at a rate approximating that of control rats. It is suggested that amino acids present in the chyme are preferentially utilized for maintenance of jejunal structure.

Binding of bile acids by dietary fiber.

Binding of bile salts to food residue was studied in vitro and in vivo. In the in vitro experiments, residues of a number of foods were incubated with each of several bile salts at different concentrations and pHs. All food residues tested adsorbed more dihydroxy than trihydroxy bile salts. Bile salt binding increased as bile salt concentration increased and was greater at a low pH. The extent of bile salt adsorption to some food residues could be clinically important. In patients with short ileal resections, we compared the rates of fecal excretion of labelled cholic and chenodeoxycholic acids and of a nonabsorable marker during ingestion of an ordianry diet (approximately 5 g of fiber) and a residue-free liquid diet. Coefficients of bile salt adsorption were calculated. Both bile acids were absorbed more efficiently during the liquid diet. Chenodeoxycholic acid was preferentially bound to the particulate matter of stools of patients eating the fiber-containing diet. It seems possible that dietary fiber could affect the enterohepatic circulation of bile salts in certain patients with ileal resection.

The absorption of bile salt and fatty acid by hamster small intestine.

Abstract 1. 1. Hamster intestinal rings were incubated at 37° in a micellar solution containing 2.4 μmoles of sodium taurodeoxycholate, 0.6 pnole of oleic acid, 0.3 μmole of monoolein, and trace amounts of sodium [carboxy-14C]taurodeoxycholate and [9,10-3H2]oleic acid in Krebs-Ringer phosphate buffer (pH 6.3). Adsorbed radioactivity was removed by thorough rinsing. The tissue was weighed, homogenized and the radioactivity assayed. Lipids were extracted, separated by thin-layer chromatography and the radioactivity in each class was measured. 2. 2. There was no evidence of destruction of the tissue during incubation. Radioactive bile salt was recovered from the tissue and was shown to be localized in the mucosa. 3. 3. In 30-min incubations the jejunal uptake of sodium taurodeoxycholate was 1.71 ± 0.36 μmoles/g tissue; the uptake of oleic acid was exactly the same. At each time during the incubation the ratio of jejunal sodium taurodeoxycholate to oleic acid was 1.0; furthermore, 75% of the absorbed fatty acid was always esterified into higher glycerides. Thus, the ratio of tissue sodium taurodeoxycholate to unesterified fatty acid was 4:1, as in the incubation medium. 4. 4. In the ileum there was greater uptake of sodium taurodeoxycholate and less uptake of oleic acid than in the jejunum. When lipids were omitted from incubation medium, both the jejunum and ileum, especially the latter, absorbed more sodium taurodeoxycholate. 5. 5. The uptake of sodium taurodeoxycholate by the tissue and its stoichiometric relationship to absorbed oleic acid suggests that bile salts function in the transport of lipid across the jejunal microvillus membrane.

EXPERIMENTAL CHRONIC PORTAL VEIN BACTEREMIA.

Summary Chronic portal bacteremia has been experimentally produced in calves. Some of the changes in hepatic structure and function have been studied. Preliminary results suggest that: 1) the experimental preparation is satisfactory for studying the chronic infusion of bacteria, toxins, etc. into the portal vein; and 2) chronic portal bacteremia can cause a lesion resembling pericholangitis. More comprehensive experiments have been undertaken to study the effect of bacterial perfusion on the liver and biliary tract. We gratefully acknowledge the assistance of Drs. Erick Ratzer, and Robert Malowney, Dept. of Surgery, and the technical aid of Mrs. Dcnna Schultz.

Absorption of lactic acid from an isolated intestinal segment in the intact rat.

Summary Lactic acid absorption was studied in anesthetized rats by perfusing isolated segments of small intestine or colon with sodium lactate-1-14C for 2 hours. The concentration and pH of the perfusate were varied. Absorption was maximum at pH 2.8, near the pK of lactate, and minimum at physiologic pH. Absorption was directly related to concentration of the lactate perfused and it was not affected by a metabolic inhibitor. The jejunum was the site of maximum absorption. Absorbed lactate was metabolized to 14CO2. Poor lactate absorption at physiologic pH and in the distal intestine might lead to an osmotic diarrhea in certain patients with malabsorption.

Characteristics of conjugated bile salt absorption by hamster jejunum.

Abstract The physical state of conjugated bile salt during its passive absorption by the jejunum is not known and may be important in understanding the mechanism of jejunal lipid absorption. We studied the absorption of sodium taurocholate from media with and without oleic acid and monoolein and of sodium glycocholate and sodium glyco-deoxycholate from media without lipid. Everted hamster jejunal sacs were incubated in solutions which contained concentrations of bile salt ranging from zero to well above their critical micellar concentrations; the net amount of bile salt taken up by the tissue at each concentration was determined. The net absorption of sodium taurocholate and sodium glycocholate increased 2-fold at concentrations above their critical micellar concentrations; the net sodium glycodeoxycholate absorption was constant below and above its critical micellar concentration. Below their critical micellar concentrations, the net sodium glycocholate absorption was 1.5 times that of sodium taurocholate and 0.33 times that of sodium glycodeoxycholate. Above their critical micellar concentrations the net absorption of sodium taurocholate and sodium glyco-cholate were equal but sodium glycodeoxycholate was absorbed almost twice as rapidly as the cholate conjugates. Although fatty acids and monoglyceride were not present in all incubations, their presence did not affect the net bile salt absorption. The movement of sodium taurocholate from the tissue into the solution bathing the mucosal surface of everted jejunal sacs was found to be significant. The findings are consistent with, but do not prove, passive diffusion of intact primary micelles into the jejunal mucosa and support the concept that conjugated bile salts may facilitate the transport of lipid across the microvillous membrane.

Measurement of bile acid synthesis by 14CO2: The metabolism of propionyl CoA

The relationship between 14CO2 evolution from the catabolism of [26 or 2714C] cholesterol to bile acids was studied in rats with biliary fistulae. When equal quantities of [26 or 2714C] cholesterol and [414C] cholesterol were administered, there was a significant linear relationship between 14CO2 expiration in the breath and [414C] bile acid excreted in the bile. Bile acid synthesis calculated as the ratio of 14CO2: molar specific activity of biliary cholesterol correlated highly with biliary bile acid excretion in the bile acid depleted rat. Phenobarbital, a known inducer of gamma-amino levulenic acid formation from succinyl CoA did not alter the relationship between the 14CO2 estimation of bile acid synthesis and biliary bile acid excretion, indicating that the relationship between [26 or 2714C] cholesterol side chain cleavage and 14CO2 formation was not altered. Phenobarbital, however, did cause a reduction in bile acid synthesis measured by 14CO2 evolution and by biliary bile acid excretion. The 14CO2 method underestimated bile acid excretion. 8.7% in untreated and phenobarbital treated rats respectively. Since 11% of the radioactivity which was expired as 14CO2 was isolated as bile acids, radioactivity cleaved as [1 or 314C] propionyl CoA may enter cholesterol-bile acid biosynthesis resulting in the underestimation of bile acid synthesis. To test whether radioactivity from propionyl CoA enters steroid biosynthesis [114C] propionate and [214C] propionate were given to untreated biliary fistula rats and the biliary lipids excreted in 60 hours were analyzed. Incorporation of radioactivity into cholesterol and bile acids was greater after the administration of [214C] propionate than after [114C] propionate than after [114C] propionate, suggesting that radioactivity from propionyl CoA may enter steroid biosynthesis by metabolic events in which the methylene and carboxyl carbon atoms are differentiated. Although the use of 14CO2 expiration from [26 or 2714C] cholesterol catabolism underestimates the rate of bile acid synthesis, it should have many applications because of the constant relationship between 14CO2 formation and cholesterol side chain cleavage.

The lack of gastric tissue fibrinolysis in hemorrhagic gastritis in the rat.

Summary Gastric mucosal fibrinolytic activator activity was measured in rats with aspirin or cold/restraint stress-induced hemorrhagic gastritis, compared to paired controls. No significant difference in FAA was found in the gastric mucosa of the experimental and control rats. It is unlikely that local gastric fibrinolysis plays a major role in the causing or maintaining hemorrhagic gastritis.