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D G Oelberg

Publications and source records attributed to D G Oelberg.

17 recordsLinked to original sources
PubMed1991

Taurine-conjugated bile acids act as Ca2+ ionophores.

The ionophoretic properties of several taurine-conjugated bile acids have been investigated in two experimental systems: in a two-phase bulk partitioning system and in proteoliposomes. In the former, a bile acid/Ca2+ complex was extracted into the bulk organic phase and had an experimental stoichiometry of 1.75. Extraction was specific for Ca2+ over Mg2+; Na+ and K+ did not compete with the extraction of Ca2+. In the second system, bile acids at concentrations as low as 5-100 molecules/vesicle lowered the steady-state Ca2+ gradient maintained by a reconstituted sarcoplasmic reticulum Ca(2+)-ATPase. The effect was not due to nonspecific membrane perturbation. In addition to releasing intravesicular Ca2+ in a transmembraneous process, bile acids caused partition of Ca2+/bile acid complexes into the hydrophobic core of the bilayer. In both experimental systems, the Ca2+ ionophoretic activity correlated well with the concentration and the hydrophobicity of the bile acid. Taurolithocholate was most active, with a significant effect measurable at 10 microM in either system. Since bile acid concentrations equal to those used in our experiments can occur in the blood in certain liver diseases, the results support the notion that bile acids can increase the intracellular Ca2+ concentration bypassing the regulatory systems that maintain cellular Ca2+ homeostasis.

Animals↗
PubMed1990

Bile salt-induced intracellular Ca++ accumulation in type II pneumocytes.

The pathogenesis of pneumonitis associated with meconium aspiration is poorly understood. To explore the possibility of pulmonary cytotoxicity in association with bile salt exposure and calcium accumulation, we compared cell viability, radiolabeled calcium accumulation, and intracellular [calcium] in the presence and absence of bile salts, chenodeoxycholate, and 3 beta-OH-5-cholenoate. We assessed viability of type II pneumocytes in culture by cell permeability to trypan blue dye, incorporation of leucine into cellular proteins, and cellular morphology. Intracellular calcium concentrations were monitored with fluorescent dye methodology. At micromolar concentrations, the above bile salts increased cell permeability by as much as 9-fold and decreased leucine incorporation by as much as 5-fold. Radiolabeled calcium accumulation increased by as much as 2.5-fold and intracellular [calcium] transiently increased by as much as 6-fold. Studies using bile salts extracted from meconium yielded similar results. Correlation of calcium accumulation to viability studies yielded a direct relationship with cell permeability and an inverse relationship with leucine incorporation. We speculate that bile salt-induced accumulation of intracellular calcium in lung cells may contribute to the pathogenesis of meconium aspiration pneumonitis.

Animals↗
PubMed1990

Neurocristopathy syndrome: review of four cases.

Aberrant embryologic development of the neural crest may clinically result in one of several patterns of malformation. Four examples of the neurocristopathy syndrome are described that collectively feature a very broad range of expression in these infants. Because of the many expressions, the syndrome may not be recognized. We believe that greater familiarity with the disorder will aid in the discovery of unsuspected anomalies and provide clues about predisposing etiologies.

Abnormalities, Multiple↗
PubMed1989

Effect of bile acids on calcium efflux from isolated rat hepatocytes and perfused rat livers.

The changes in intracellular Ca2+ concentration [( Ca2+]i) of hepatocytes induced by certain bile acids are biphasic: an initial increase is followed by a more gradual decrease. This latter decline in [Ca2+]i may be due to an efflux of Ca2+ across the plasma membrane. This hypothesis was tested by studying the effect of different bile acids on the efflux of 45Ca from preloaded rat hepatocytes and isolated perfused rat livers. The following bile acids were studied: cholic (C), ursodeoxycholic (UDC), chenodeoxycholic (CDC), and deoxycholic (DC) acids; their taurine (T) conjugates (TC, TUDC, TCDC, and TDC); and the taurine, sulfate (S), and glucuronide (Glu) derivatives of lithocholic acid (TLC, LS, TLS, and LGlu, respectively). At 0.3 mM, all bile acids except C, TC, TCDC, UDC, and TUDC significantly increased 45Ca efflux from preloaded hepatocytes without affecting cell viability. Dose-response studies revealed that the minimum effective concentration needed to induce 45Ca efflux was 0.06 mM for LS, 0.8 mM for TCDC, and 10 mM for TC. Efflux of 86Rb from preloaded hepatocytes was not significantly altered by 0.1 mM LS, indicating relative specificity for calcium. TDC and DC, but not TC, increased 45Ca efflux from preloaded perfused rat livers. These results showed that bile acids known to increase [Ca2+]i (CDC, DC, TDC, and TLC) also increased 45Ca efflux from hepatocytes and perfused livers and that efflux was also stimulated by LS, TLS, and LGlu. The extent of this efflux was related to the hydrophobicity of the steroid nucleus of the bile acid. It is speculated that bile acid-induced increases in [Ca2+]i activate the plasma membrane Ca2+ pump resulting in increased Ca2+ efflux.

Animals↗
PubMed1989

Maternal-neonatal serum vitamin A concentrations.

Prevention of neonatal vitamin A deficiency is related to the adequacy of maternal vitamin A stores. In this study we investigated maternal and cord serum vitamin A and retinol-binding protein (RBP) values in an Indian population including, for the first time, clinically vitamin A-deficient mothers. Twenty-eight maternal-neonatal pairs were selected from maternal cohorts of high socioeconomic status without clinical evidence of vitamin A deficiency (group I) and low socioeconomic status with conjunctival xerosis and Bitot's spots (group II). Maternal education, caloric and vitamin A intakes, weight, height, hemoglobin, and birth weight were significantly lower in group II. Serum vitamin A levels were significantly higher in group I mothers and newborns as were RBP levels in group I mothers. However, a significant difference between groups I and II in cord blood RBP was not observed. Upon correlation of maternal vitamin A levels with cord blood vitamin A levels, a logarithmic relationship was revealed, suggesting saturable transplacental transport of vitamin A.

Adult↗
PubMed1988

Bile salt-induced calcium fluxes in artificial phospholipid vesicles.

The ionic permeability of selected biological membranes is increased by bile salts. To examine changes in calcium permeability during the exposure of artificial membranes to bile salts, we investigated calcium uptake by unilamellar and multilamellar phospholipid vesicles. In the presence of 750 microM taurodeoxycholate, uptake of radiolabelled calcium by unilamellar vesicles increased 2.5-fold over control values. Calcium uptake by multilamellar vesicles as measured with a free calcium indicator, arsenazo III, increased 2.2- or 21-fold in the presence of 60 microM lithocholate or 3 beta-hydroxy-5-cholenoate, respectively. Results were directly influenced by experimental variables such as bile salt hydrophobicity, external calcium concentration, and the bile salt/lipid molar ratio. Observed membrane solubilization was minimal despite increased calcium permeability. Comparison of radiolabelled calcium uptake with radiolabelled sodium or radiolabelled rubidium uptake indicated that bile salt-dependent calcium uptake was 60-140-times greater than bile salt-dependent uptake of either monovalent cation. In an effort to delineate forces affecting calcium translocation, vesicles were exposed either to valinomycin, which induced an electrochemical gradient across the membrane, or to nigericin, which induced a proton gradient. Exposure to valinomycin minimally influenced bile salt-induced calcium uptake while exposure to nigericin significantly promoted uptake by 40-70%. The results suggest that bile salts promote calcium uptake by a mechanism which may be similar to those of other carboxylic ionophores.

Arsenazo III↗
PubMed1988

Intestinal absorption of bile acid glucuronides in rats.

While the intestinal absorption of taurine, glycine, and sulfate conjugates of bile acids has been studied extensively, nothing is known about the absorption of bile acid glucuronides. In the present study, the intestinal phase of the enterohepatic circulation of two bile acid glucuronides was examined. [3 beta-3H]cholic acid 3-O-beta-D-glucuronide or [3 beta-3H]lithocholic acid 3-O-beta-D-glucuronide was perfused through isolated segments of ileum or jejunum with intact blood supply in rats prepared with a biliary fistula. [14C]Taurocholic acid was perfused simultaneously with each glucuronide to compare glucuronide absorption with that of an actively transported bile acid. Intestinal absorption was determined by measuring the rate of secretion of labeled bile acid in bile. The absorption of [3H]cholic acid glucuronide by the ileum and jejunum was one fortieth and one eighth, respectively, that of [14C]taurocholic acid. Comparison of the two glucuronides show that [3H]lithocholic acid glucuronide absorption was 18 and 10 times greater than [3H]cholic acid glucuronide absorption from the jejunum and ileum, respectively. Collectively, the above observations suggest that glucuronidation of bile acids markedly reduces absorption from the small intestine.

Animals↗
PubMed1988

Vitamin concentrations in very low birth weight infants given vitamins intravenously in a lipid emulsion: measurement of vitamins A, D, and E and riboflavin.

Because total parenteral nutrition with vitamins added to the glucose-amino acid mixture is often associated with a reduction in blood levels of vitamin A (retinol) during the routine treatment of many very low birth weight (VLBW) infants (less than 1500 gm), and because retinol losses in the plastic delivery system can be prevented by adding the vitamins to an intravenous lipid emulsion, seven VLBW infants with a mean birth weight of 900 gm (range 450 to 1360 gm) were given 40% of a unit dose vial, per kilogram of body weight, of a multivitamin preparation (M.V.I. Pediatric) (280 micrograms retinol; 160 IU vitamin D; 2.8 mg tocopherol; 0.68 mg riboflavin) in a lipid emulsion, Intralipid. After treatment with the intralipid-vitamin mixture for 19 to 28 days, plasma vitamin A (retinol) concentrations increased significantly from 11.0 +/- 0.76 (mean +/- SEM) before intralipid to 19.2 +/- 0.97 micrograms/dl after the intralipid-vitamin mixture (p less than 0.01); 25-hydroxyvitamin D concentrations increased from an initial value of 12.6 +/- 2.6 to 20.2 +/- 1.9 mg/dl (p less than 0.01); alpha-tocopherol concentrations increased from an initial value of 0.31 +/- 0.06 to 2.44 +/- 0.13 mg/dl (p less than 0.01); and riboflavin levels increased from 64.1 +/- 7.8 ng/ml to concentrations between 20 and 100 times the initial level. Erythrocyte riboflavin levels increased from 71.8 +/- 14 initially to 166 +/- 41 ng/gm hemoglobin, and erythrocyte flavin-adenine dinucleotide levels increased similarly from 972 +/- 112 initially to 2005 +/- 294 ng/gm hemoglobin. These results show that the addition of M.V.I. Pediatric to Intralipid decreases the extensive in vivo loss of retinol and is associated with an increase in plasma retinol concentrations in VLBW infants. The daily doses of vitamins D (160 IU/kg) and E (2.8 mg/kg) appear sufficient, but the dose of vitamin A (280 micrograms/kg) is insufficient to raise blood levels of all infants into the normal range. The current dose of riboflavin is excessive and may be harmful.

Erythrocytes↗
PubMed1988

Intracranial hemorrhage in term or near-term newborns with persistent pulmonary hypertension.

To substantiate the clinical impression of an increased incidence of intracranial hemorrhage (ICH) in term and near-term infants with persistent pulmonary hypertension (PPH), a retrospective chart review of 35 affected patients was performed. ICH was diagnosed in 40 percent of the patients. Multiple regions of the brain were affected; in many patients, at more than one location. In addition, 43 percent of ICH victims had hemorrhages of the type associated with periventricular bleeding in preterm newborns. Of multiple obstetric and neonatal factors analyzed, many of which are identified risk factors for periventricular hemorrhage, only thrombocytopenia (p = 0.02) was significantly associated with ICH. We conclude that the risk of ICH in newborns with PPH is significant and warrants consideration by clinicians caring for this population. Risk factors (except thrombocytopenia) previously implicated in other types of neonatal ICH, particularly periventricular hemorrhage, do not significantly correlate with ICH in infants with PPH.

Cerebral Hemorrhage↗
PubMed1986

Cellular mechanisms of cholestasis.

Concepts regarding the pathogenesis of cholestasis continue to evolve as investigational techniques improve and molecular mechanisms of bile formation are clarified. With the accumulation of information it is becoming increasingly evident that cholestasis results from not one but multiple disturbances in the sequence of events responsible for bile production. In addition to the inhibition of bile flow attributable to initiating events, cholestasis itself may inhibit bile flow by altering the intra- and extracellular environments of liver cells. Many questions about cholestasis remain unanswered, but future directions for research are suggested by the information currently available.

Actin Cytoskeleton↗
PubMed1984

Calcium binding by lithocholic acid derivatives.

Lithocholic acid (LCA) and its sulfate (LCS) and glucuronide (LCG) derivatives are potent cholestatic agents. During the course of LCG-induced cholestasis in rats, calcium (Ca) salts of LCG precipitate in bile. To characterize the affinity of bile salts for Ca, solutions of selected bile salts were titrated with Ca. Apparent equilibrium constants (KcaBS) were determined from the unbound Ca ion concentrations that were measured spectrophotometrically with metallochromic indicators antipyrylazo III or murexide or with a Ca-selective electrode. KCaBS values were 1.12 +/- 0.04 X 10(-4) M for LCS, 2.88 +/- 0.26 X 10(-4) M for LCG, 3.09 +/- 0.21 X 10(-4) M for LCA, 1.93 +/- 0.07 X 10(-3) M for taurocholic acid (TC), 2.69 +/- 0.08 X 10(-3) M for glycocholic acid (GC), and 6.07 +/- 0.27 X 10(-3) M for taurolithocholic acid sulfate (TLCS). The KCaBS for LCG measured by a Ca-selective electrode under identical conditions was 5.53 +/- 2.75 X 10(-4) M. Comparing relative cholestatic potential with affinity for Ca, cholestatic bile salts LCS, LCG, and LCA bind Ca 10-60 times more avidly than TC, GC, and TLCS. At the unbound Ca ion concentrations of serum or bile (approx 1 mM), only LCS, LCG, and LCA would be expected to bind significant amounts of Ca.

Animals↗
PubMed1984

Lithocholate glucuronide is a cholestatic agent.

Lithocholic acid and its taurine, glycine, and sulfate derivatives are potent cholestatic agents. Lithocholate glucuronide is present in the plasma and urine of patients with cholestatic syndromes, but little is known of its metabolism, excretion, and cholestatic potential. [3 beta-3H]lithocholate 3-O-beta-D-glucuronide was synthesized, and chemical and radiochemical purity were established. The aqueous solubility of lithocholate glucuronide was determined and found to be greater than that of lithocholic acid or several of its derivatives. In the range of concentrations examined, calcium ions precipitated lithocholate glucuronide stoichiometrically. The material was administered to rats prepared with an external biliary fistula. When 17-25 micrograms quantities were administered, 89.1 +/- 4.5% (mean +/- SEM) of the radiolabel was secreted in bile within the first 20 h after administration, the major fraction being secreted in less than 20 min. Four-fifths of the radiolabeled material in bile was the administered unaltered parent compound, while a minor fraction consisted of a more polar derivative(s). We showed that increasing biliary concentrations of more polar derivatives were observed with milligram doses of [3H]lithocholate glucuronide, and with time after the administration of these loading doses. Milligram doses of [3H]lithocholate glucuronide resulted in partial or complete cholestasis. When induced cholestasis was partial, secretion in bile remained the primary excretory route (82.5-105.6% recovery in bile), while, when complete cholestasis was induced, wide tissue distribution of radiolabel was observed. Cholestasis developed rapidly during infusion of [3H]lithocholate glucuronide. Bile flow was diminished within 10-20 min of the start of an infusion of 0.05 mumol, 100 g-1 body weight, minute-1, administered concomitantly with an equimolar infusion of taurocholate. The results establish that lithocholate glucuronide exerts cholestatic effects comparable to those exerted by unconjugated lithocholic acid.

Animals↗
PubMed1983

Endocarditis in high-risk neonates.

The clinical spectrum of neonatal endocarditis, including bacterial and nonbacterial types, is examined in five case reports that were drawn from nursery experiences over a recent 2-year period. In contrast to previous reports of 100% mortality from neonatal endocarditis, one patient survived. Changing heart murmur and hematuria were most frequently associated with bacterial and nonbacterial endocarditis in four of the five cases. Pulmonary hypertension, thrombocytopenia, and coagulopathy were also associated with nonbacterial endocarditis. Echocardiograms were performed on four of the patients; only one was suggestive of endocarditis. Staphylococcus aureus was isolated from both cases of bacterial endocarditis, including the single survivor. Thus, it is suggested that the initial antibiotic coverage of any neonate with the clinical syndrome of sepsis, hematuria, and a heart murmur include antistaphylococcal coverage for the possibility of bacterial endocarditis.

Echocardiography↗
PubMed1981

Hospitalization of adolescents: collecting the data base. Variations and implications.

A survey of 2208 adolescents (aged 12 through 18 years) hospitalized during 1977 identified variations in data-base development and unrecognized health problems. Forty-eight percent were admitted to obstetrics and gynecology, 29% to surgery, 13% to pediatrics/internal medicine combined, and 10% to psychiatry. Historical, physical, and laboratory data bases and diagnoses were examined from 325 records. All records included a history of present illness and blood pressure, and most included a past medical and family history. Excluding pediatric records, a minority of records included social, immunization, school, or perinatal histories. Pediatric records were lacking in histories of alcohol or tobacco use. Most records lacked dietary or drug-abuse histories. A majority of records contained growth parameters, hemoglobin, urinalysis, and chest x-ray. Despite a high prevalence of anemia, the diagnosis was infrequently recorded. This survey suggests that clinical departments collect data on sick adolescents in differing ways--none of which seems optimal. Clinical departments should examine their training programs regarding the collection and interpretation of the data base in order to provide optimal care for hospitalized adolescents.

Adolescent↗
PubMedDate not supplied

Bile salts induce calcium uptake in vitro by human erythrocytes.

At high concentrations, bile salts induce hemolysis by comicellization of lipid components of the cell membrane. However, bile salts are also associated with hemolysis at lower concentrations by mechanisms which have not been characterized. To investigate the possibility that bile salts promote calcium uptake by red blood cells and that bile salt-associated hemolysis is, in part, calcium-mediated, calcium uptake by red blood cells was measured in the presence of individual bile salts, and hemolysis dependence upon calcium availability was examined. Washed human red blood cells with or without ATP depletion were incubated with 1 mM CaCl2 and tracer amounts of 45CaCl2 in the presence of selected bile salts at concentrations (0.01 to 0.3 mM) reported to be below critical micellar concentrations. Calcium uptake (defined for the purposes of this study as 45Ca retained in red blood cells) was monitored over 5 hr, after which hemolysis and membrane phospholipid content were determined. The presence of bile salts stimulated calcium uptake 4- to 25-fold--the magnitude of which was partly related to the lipid solubility of the bile salts. ATP depletion or exposure to trifluoperazine, procedures which inhibit calcium pump activity in red blood cells, enhanced bile salt-induced calcium uptake relative to controls. The percentage of associated hemolysis (2 to 14%) at the end of 5 hr correlated directly with the observed calcium uptake. Removal of calcium from the extracellular space reduced hemolysis in the presence of bile salts to control levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile Acids and Salts↗