Search PubMed⌕ Search

Biomedical subjects

E W Moore

Publications and source records attributed to E W Moore.

At least 55 records · Page 3Linked to original sources
PubMed1990

Human gallbladder mucosal function. Effect of concentration and acidification of bile on cholesterol and calcium solubility.

The most recognized function of the human gallbladder is to store bile. However, this organ is not a static reservoir. It actively modifies bile by two processes: concentration and acidification. This study was designed to simultaneously evaluate the relationship between these two physiological processes in the normal human gallbladder and to define their effects on biliary cholesterol and calcium solubility. Bile was sampled directly from the gallbladder of 78 morbidly obese patients undergoing elective gastric bypass procedures. All had negative results of intra-operative ultrasound examinations for sludge and gallstones, normal liver function tests, and no history of hepatobiliary disease. Bile salt concentrations, an indirect index of concentration by the gallbladder, ranged from 15.1-272.8 mmol/L. As [bile salt] increased, [Na+], [K+], free [Ca2+], [cholesterol], [phospholipid], and [total lipid] increased linearly; [Cl-1] decreased linearly. Molar percent cholesterol decreased from 17.2% in dilute bile to 10.1% in fully concentrated bile, suggesting that cholesterol was absorbed by the gallbladder. As bile was concentrated, cholesterol saturation index decreased curvilinearly from a maximum of 3.7 in dilute bile to 1.0-1.5 in concentrated bile. Concentration of gallbladder bile was accompanied by progressive acidification. Bile pH decreased linearly with increasing [bile salt]; [CO3(2-)] decreased curvilinearly. Despite increasing [Ca2+], CaCO3 saturation index decreased curvilinearly with increasing [bile salt] from a maximum of 3.62 in dilute bile to a minimum of 0.12 in concentrated and acidified bile. CaCO3 saturation index also decreased exponentially with decreasing pH. This study concludes that concentration of bile enhances cholesterol solubility while acidification enhances calcium salt solubility. By increasing the solubilities of these two species, gallbladder mucosal function may play a key role in preventing gallstone formation.

Analysis of Variance↗
PubMed1990

Biliary calcium secretion in the dog occurs primarily by passive convection and diffusion and is linked to bile flow.

Despite the importance of biliary calcium in the pathogenesis of gallstones, little is known about the sites or modes of entry of calcium into bile. We here examine the mechanisms of calcium entry into canine bile by comparing the entry of calcium, over a wide range of bile flows (2.4 to 38.0 microliters/kg per minute), with that of potassium, a small ion that is passively distributed throughout the biliary tract and that is also subject to alteration by Gibbs-Donnan forces. It is shown that (1) the concentrations of free ionized calcium, [Ca++], increases in an apparently linear fashion with increasing total bile salt concentration at low bile flow, whereas the rise in [Ca++] is strongly blunted at high rates of flow; (2) the entry of both calcium and potassium into bile is tightly linked to bile flow; and (3) calcium outputs are linearly related to potassium outputs with an intercept at the origin. These results indicate that the canaliculus is permeable to Ca++ ions, and that Ca++ enters bile primarily by passive convection and diffusion. Calcium entry is thus tightly linked to the water flux generated by bile salt secretion. Such passive entry and distribution indicate that calcium will always be present in bile and that possible therapeutic reduction of biliary [Ca++] for treatment, and possibly prevention of calcium-containing gallstones, will require sustained chelation of calcium within the lumen of the biliary tract.

Animals↗
PubMed1990

Biliary calcium and gallstone formation.

The purpose of this paper is to present a brief overview of the current status of the field of biliary calcium and the role of calcium in the formation and maturation of gallstones. The study of free Ca+(+) ions in bile by electrochemical potentiometric measurements using Ca+(+)-selective ion-exchange electrodes is a relatively new field, but much progress has been made in the past few years. Using this powerful analytical tool, new concepts and findings have arisen in almost every aspect of biliary calcium. Although the current symposium is targeted primarily toward cholesterol gallstones, there are several areas in which understanding of biliary calcium may significantly contribute to a better understanding of the pathogenesis of cholesterol, as well as "pigment" (calcium salt), gallstones. Five broad areas are considered in relation to biliary calcium: (a) physiology (calcium entry into bile), (b) biophysics (the regulation of biliary free [Ca+(+)] as related to Gibbs-Donnan equilibria, (c) physical chemistry (the physicochemical state of calcium in bile, (d) thermodynamics (calcium solubility in bile), and (e) kinetics (pronucleating and antinucleating factors and metastable states). With more specific reference to cholesterol stones, consideration is also made of (a) the calcium salt "seed" hypothesis in cholesterol stone pathogenesis; (b) the interactions of Ca+(+) with phospholipid-cholesterol vesicles, with consideration of possible structural requirements and (c) thermodynamic and kinetic factors as related to peripheral or "eggshell" calcification of existing cholesterol stones.

Animals↗
PubMed1990

Premicellar taurocholate avidly binds ferrous (Fe++) iron: a potential physiologic role for bile salts in iron absorption.

Two of the major divalent cations in human physiology, Ca++ and Fe++, are poorly soluble at the pH of intestinal contents, and active "uphill" transport mechanisms exist for both ions in proximal small intestine. We have recently demonstrated significant binding of Ca++ to both premicellar and micellar bile salts and have postulated that high-affinity premicellar binding involves interposition of Ca++ between terminal carboxyl (COO-) and 7-OH or 12-OH groups of the steroid ring. The present studies were made to determine whether such binding extends to other divalent cations, and specifically to Fe++, which, like Ca++, has a hydrated diameter of 6 A. Equilibrium dialysis studies of sodium taurocholate were made at 25 degrees C with solutions containing 0.5 to 150 mmol/L taurocholate and 0.018 to 1.8 mmol/L iron 59-labeled FeSO4 at pH 3.0 to 6.3 and a total ionic strength of 0.15 mol/L. In control (saline dialysand) cells, [Fe++] was virtually equal in dialysands and dialysates within 5 hours. In sharp contrast, taurocholate-containing dialysands showed significantly higher counts than dialysates, indicating Fe++ binding to taurocholate, independent of pH and Fe concentration. After correction for taurocholate-induced Gibbs-Donnan effects across the membrane, the apparent taurocholate affinity constant (K'f) for Fe++ in micellar solutions (5 to 150 mmol/L) was essentially constant at about 3.1 (mol/L)-1, then increased dramatically below the critical micellar concentration to greater than 100 (mol/L)-1 at [taurocholate] = 0.5 mmol/L. The hyperbolic rise in K'f below the critical micellar concentration is similar to that which we have previously reported for Ca++, indicating significant high-affinity binding of Fe++ to premicellar taurocholate anions and low-affinity binding to micellar anions. It is postulated that Fe++ binding, particularly by premicellar bile salts, may play an important physiologic role in increasing iron solubility within the intestinal lumen, thus increasing iron absorption. The possible role of bile salts in increasing divalent cation solubility and absorption from the intestine is a new field of bile acid research.

Bile Acids and Salts↗
PubMed1989

Binding of calcium by organic anions, determined by perturbation of the equilibrium solubility of [14C]calcium oxalate.

Confirmation is needed of the reported binding of calcium ions (Ca2+) by bile salts, which is believed to decrease the activity of free calcium ions [Ca2+] available for precipitation of insoluble calcium salts of organic anions in pigment gallstones. We report a new method to determine the association constants (K'f) of calcium for organic anions, from the perturbation by the added anion of the equilibrium solubilization of calcium [14C]oxalate monohydrate crystals (CaOx*). CaOx* crystals were prepared by stepwise conversion of [14C]oxalic acid to its K+ and Ca2+ salts. Structure and purity were confirmed by X-ray diffraction of the crystals. CaOx* was incubated (37 degrees C, under N2) in 0.15 M NaCl in CO2-free deionized H2O at pH 6.3. Dissolution of CaOx*, estimated by radioassay of the 0.22-micron Millipore filtrate, attained equilibrium at 3 days, with K'sp = [Ca2+] * [Ox=] = 2.34 X 10(-8) M2, calculated using known affinity constants for the soluble complexes of NaOx- (K'NaOx = 3.215 M-1) and CaOx (K'CaOx = 195.0 M-1). Keeping total [Na+] = 0.15 M, we added anions that formed soluble complexes with Ca2+. This decreased free [Ca2+], causing more CaOx* to dissolve in amounts related to the concentration of added anion and its K'f for Ca2+. With this method, K'f values for citrate, malonate and malate were similar to the values we determined with the Ca2+ ion electrode, and to published values obtained with the Ca2+ ion electrode and other methods. The sensitivity of the CaOx method permits determination of K'f values with small quantities and low concentrations of the anions and calcium.

Calcium↗
PubMed1989

Canine common duct and gallbladder bile contain antinucleating factors that inhibit CaCO3 precipitation.

We performed studies involving large incremental additions of calcium to bile to examine the degree of CaCO3 supersaturation that can be achieved in bile, as compared with that in simple NaCl-NaHCO3 solutions. The addition of CaCl2 to bile increased total and free ionized calcium by from four to 12 times their original values and by from two to three times the highest concentrations encountered in bile in vivo. The increase in [Ca++] resulted in fourfold to 12-fold increases in the saturation indexes of bile, with the saturation index reaching as high as 73.4 in a common duct sample. Despite the markedly elevated CaCO3 saturation indexes, evidence of CaCO3 precipitation was not observed in either common duct or gallbladder bile over a 24-hour period. For comparison, calcium added to NaCl-NaHCO3 solutions resulted in the precipitation of CaCO3 within 4 hours if saturation indexes were greater than 12. These results indicate that native bile contains potent antinucleating factors that markedly inhibit CaCO3 precipitation, and they confirm our previous in vivo observations in canine common duct bile.

Animals↗
PubMed1987

Evidence for H+ secretion by the in vivo canine gallbladder.

In humans and most other species, a decline in pH of gallbladder contents occurs during the concentration of bile. Recent in vitro studies in rabbit, guinea pig, and Necturus gallbladders have strongly suggested mucosal H+ secretion during sodium reabsorption, presumably representing a Na+/H+ exchange. The present in vivo studies are the first attempt to determine whether H+ secretion by the gallbladder can be demonstrated in the living animal. Gallbladder bile was obtained from 27 anesthetized dogs after 12-24-h fasts; 12 samples of common duct bile were also obtained in 3 dogs during variable taurocholate infusion. In common duct bile, observed ranges were as follows: pH, 7.37-7.85; CO2 partial pressure (PCO2), 21-32 mmHg; total CO2 concentration ([TCO2]), 16.4-41.4 mM; total bile salt concentration ([TBS]), 16-93 mM; and [Na], 153-192 mM. In gallbladder bile, respective ranges were as follows: pH, 5.72-7.29; PCO2, 36-101 mmHg; [TCO2], 1.21-15.5 mM; [TBS], 150-305 mM; and [Na], 199-266 mM. In all samples [Na] was linearly related to [TBS]. Carbon dioxide partial pressure increased from a mean of 27.3 mmHg in common duct bile to greater than 100 mmHg in gallbladder bile at [TBS] = 180 mM, then declined to approximately 36 mmHg as [TBS] increased to greater than 300 mM. Peak PCO2 occurred at pH approximately 6.4-6.6, then declined as pH decreased to approximately 5.7. Bile to plasma PCO2 ratios increased from a mean of 1.08 in common duct samples to greater than 2.0 in gallbladder samples at pH approximately 6.3, then declined to approximately 1.0 in fully concentrated bile. If the high PCO2 values in bile were solely due to tissue CO2 production, a sustained increase in PCO2 throughout Na+ reabsorption might be expected. The results strongly suggest H+ secretion (HCO3- neutralization), as peak PCO2 occurred when [TBS] was only about 180 mM, long before sodium absorption was complete. It is hypothesized that H+ secretion may have important favorable effects on calcium lithogenicity, reducing the likelihood of the formation of CaCO3- containing gallstones.

Animals↗
PubMed1987

Pancreatic calcification and stone formation: a thermodynamic model of calcium in pancreatic juice.

CaCO3 is a major constituent of pancreatic stones, salivary stones, and many pigment gallstones. Elucidation of the physicochemical state of calcium is necessary for definition of calcium solubility in these systems. Pancreatic stones are observed in both humans and cattle, and are approximately 95% CaCO3 (calcite) in both species. Despite its importance, little is known about the physicochemical state of calcium in pancreatic juice. This paper presents an a priori model, based on established physicochemical principles, for the state of calcium in the juice at all levels of secretion. Two postulates of the model are the following: the limiting free [Ca2+] in the juice is governed by the solubility product (K' sp) for CaCO3; if K' sp is exceeded, the juice is supersaturated and precipitation of CaCO3 is thermodynamically possible; total calcium, [Ca], in the juice is the sum of four distinct species: free ionized calcium, Ca2+; calcium-bicarbonate complex, CaHCO3+; calcium carbonate ion-pair, CaCO3(0); and protein-bound calcium, CaProt. Overall equations of the model and graphical corollaries are presented. The model predicts an inverse hyperbolic relationship between [Ca2+] or [Ca] and [HCO3-]. Calcium solubility is maximal at low [HCO3-]; as [HCO3-] increases, both [Ca2+] and [Ca] decline to respective limiting values of approximately 0.015 and 0.15 mM. At low [HCO3-], most of [Ca] is present as Ca2+ and CaProt, whereas at high [HCO3-], most [Ca] is CaHCO3+ and CaCO3(0). Protein, HCO3-, and CO3(2-) ions are thus important buffers for Ca2+ in the juice. The model provides a quantitative framework for further elucidation of calcium lithogenicity in the pancreas, salivary gland, and biliary tract.

Calcinosis↗
PubMed1987

Absorption of biliary calcium from the canine gallbladder: protection against the formation of calcium-containing gallstones.

Calcium salts are the major components of pigment gallstones. The calcium species in bile that is critical for Ca++ precipitation is free ionized calcium, [Ca++]. Factors that regulate biliary [Ca++] in bile are therefore of great importance in the pathogenesis of pigment gallstones. The fate of biliary Ca++ on entry into the gallbladder has not previously been studied. We here report that a minimum of 51.3% +/- 8.8% (SEM) of Ca++ is absorbed from the canine gallbladder on concentration of bile during a 24-hour fast. In addition, there was absorption of least 70.9% +/- 6.2% of Na+, 56.5% +/- 8.6% of K+, and nearly all (greater than 98%) of Cl-. Absorption, neutralization, or both, of HCO3- was also nearly complete (greater than 98%). During concentration of bile by the gallbladder, the concentrations of all biliary cations increased as total bile salt concentration increased, whereas anion concentrations declined. These results are consistent with a Gibbs-Donnan effect induced by impermeable, negatively charged bile salt molecules. Comparison of bile/plasma [Ca++] ratios with those for [K+], a passively distributed ion, was also consistent with, although not proof of, the passive absorption and distribution of Ca++ across the gallbladder epithelium. The absorption of Ca++ by the gallbladder may be a factor in the prevention of pigment gallstones, because it limits free Ca++ ion in bile, and thus decreases the likelihood of precipitation of calcium.

Animals↗
PubMed1986

Pathogenesis of calcium-containing gallstones. Canine ductular bile, but not gallbladder bile, is supersaturated with calcium carbonate.

Calcium precipitation in bile is a requisite event in the initiation and growth of all pigment gallstones. Calcium solubility in bile is thus of great importance. This is the first attempt to define the ion-product of CaCO3 in bile in any species. If the ion-product: [Ca++] X [CO = 3] exceeds solubility product (K'sp), the sample is supersaturated and CaCO3 precipitation is thermodynamically possible. We have recently determined K'sp of calcite to be 3.76 X 10(-8) mol/liter at 37 degrees C and total ionic strength = 0.16 M. Gallbladder (GB) bile was obtained from 15 anesthetized dogs after 12-24-h fasts. Duct bile was obtained from three dogs (n = 12) during variable taurocholate infusion. Samples were assayed for pH, partial pressure of carbon dioxide (PCO2), total bile salt concentration ([TBS]), total calcium concentration ([Ca]), and free calcium ion concentration ([Ca++]). With increasing [TBS] in both GB and duct bile, there was a linear decline in pH, a curvilinear decline in [HCO-3] and [CO = 3], and linear increase in [Ca++] and [Ca]. All ductular samples were supersaturated with CaCO3, with saturation indices (SI) as high as 17.5 and a mean of 8.36 +/- 1.43 (SE). In sharp contrast, none of the GB samples were supersaturated, due to the marked decline in [CO = 3] upon concentration and acidification of bile. In GB bile, the SI ranged from 0.006 to 0.126, with a mean of 0.039 +/- 0.011. The gallbladder thus produced a change in the SI from a value as high as 17.5 to a value as low as 0.006 in concentrated GB bile, which is a nearly 3,000-fold change. The average change in the SI was approximately 215-fold. Since all duct samples were supersaturated, and since the dog does not normally form gallstones, the data support our previous hypotheses that: (a) in canine bile, as in canine pancreatic juice, a nucleating factor is necessary for CaCO3 precipitation; (b) bile salts are important buffers for Ca++ in bile; and (c) normal GB mucosal function (concentration and acidification of bile) plays an important role in reducing CaCO3 lithogenicity in GB bile.

Animals↗
PubMed1985

Pathogenesis of pancreatic and biliary CaCO3 lithiasis: the solubility product (K'sp) of calcite determined with the Ca++ electrode.

There are three digestive secretory fluids with high bicarbonate and high pH values: bile, pancreatic juice, and saliva. Each is subject to development of CaCO3-containing stones. In bile, calcium precipitation is a requisite event in the initiation and growth of all pigment gallstones and is postulated to initiate cholesterol gallstone formation by forming a nidus for cholesterol precipitation. In the pancreas, stones in both humans and cattle are composed largely of calcite. Knowledge of appropriate solubility product constant (K'sp) values is essential in defining lithogenicity in each of these secretions. Only two studies of calcite solubility at physiologic total ionic strength (u) have been found, both of which used total calcium measurements to estimate free Ca++ ion in calculating K'sp. The Ca++ electrode has allowed a fresh appraisal of this problem. Studies of calcite were made at 24 degrees C and 37 degrees C and u = 0.16 mol/L over an 11-day period. At each temperature, pH declined slightly with time, reflecting atmospheric CO2 uptake. As predicted by theory, this decline was associated with increase in free Ca++ ion and total calcium concentration, but K'sp remained constant because of corresponding decline in [CO=3]. Mean K'sp at 24 degrees C was 1.33 +/- 0.04 X 10(-8) mol/L, and at 37 degrees C it was 3.76 +/- 0.09 X 10(-8) mol/L. A lithogenicity diagram, applicable to bile, pancreatic juice, saliva, plasma, and other body fluids at u = 0.16 mol/L, is presented for [Ca++]sat, the free Ca++ ion concentration at the limit of a stable thermodynamic state.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1981

Pancreatic calcification: formation constants of CaHCO3+ and CaC03(0) complexes determined with Ca2+ electrode.

Pancreatic calcification is a frequent complication of chronic pancreatitis, and pancreatic stones (95% CaCO3 as calcite) are observed in both humans and cattle, but little is known about the complex equilibriums governing calcium solubility. Using the Ca2+ electrode and equilibrium dialysis of NaHCO3-CaCl2-NaCl solutions (24 +/- 2 degrees C; total ionic strength = 0.153-0.161), studies were made at variable pH and total calcium and carbonate concentrations to determine the formation constants of the three possible calcium complexes: CaHCO3+, CaC03(0), and Ca(HCO3)20. If the first two complexes were present, a plot of ([Ca]/[Ca2+]-1)/[HCO3-] against the ionic ratio [C03(2)-]/[HCO3-] should be linear with intercept of the CaHCO3+ formation constant (K'aB) and slope of the CaC03(0) formation constant (K'aC). This was found to be the case in both dialysands and dialysates, using two different methods ("pH" and "K'sp") for estimation of [CO32-] values. Two other methods of data analysis were also used: simultaneous equations and multiple linear regression by matrix analysis. For all three methods, mean K'aB = 12.48 and mean K'aC = 1,870. There was no evidence for a Ca(HCO3)2(0) complex. We conclude that CaHCO3+ and CaC03(0) complexes may account for a substantial fraction of total soluble calcium is pancreatic juice. These studies provide a necessary step toward the construction of a quantitative physicochemical model of pancreatic calcium solubility.

Bicarbonates↗
PubMed1979

Pancreatic bicarbonate response to a meal.

In dogs with gastric and pancreatic fistulas, the rate of delivery of acid from the stomach to the duodenum and the rate of pancreatic bicarbonate secretion were measured in response to a meal of liver extract. The time course of changes in quantity of bicarbonate secreted per minute closely paralleled that of changes in quantity of hydrogen ions delivered to the duodenum per minute. For each mole of hydrogen ion entering the duodenum, about 5 moles of bicarbonate were secreted.

Animals↗
PubMed1977

Effects of intravenous calcitonin on water, electrolyte, and calcium movement across in vivo rabbit jejunum and ileum.

The influence of intravenously administered synthetic salmon calcitonin on water, electrolyte and calcium fluxes in in vivo rabbit jejunum and ileum was examined. Rabbits were divided into four groups: those receiving (1) saline intravenously while a glucose-free isotonic saline solution perfused the jejunum and ileum; (2) calcitonin intravenously while the same intestinal perfusate was used as in group 1; (3) intravenous saline while 10 mM glucose-isotonic saline solution perfused jejunum and ileum; and (4) intravenous calcitonin while the intestinal perfusate was of the same composition as in group 3. Calcitonin provoked a significant increase in jejunal and ileal water, sodium, and bicarbonate secretion in both the glucose-free and glucose-containing perfusate groups. No influence on calcium movement was noted. These results, similar to findings of Gray et al. (J Clin Invest 52:3084-3088, 1975) in human jejunum, suggest that calcitonin may play a role in the pathogenesis of the watery diarrhea noted in about one-third of patients with medullary carcinoma of the thyroid. In addition, these studies demonstrate the usefulness of the rabbit as an animal model with which to investigate further the effects of calcitonin upon intestinal fluid and electrolyte transport.

Animals↗