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Biomedical subjects

H Wolters

Publications and source records attributed to H Wolters.

At least 37 records · Page 2Linked to original sources
PubMed1994

Characterization of transport in isolated human hepatocytes. A study with the bile acid taurocholic acid, the uncharged ouabain and the organic cations vecuronium and rocuronium.

The uptake and efflux of three categories of substrates were measured in isolated human hepatocytes and compared to those in rat hepatocytes. In addition, the extent to which the in vitro experiments quantitatively reflect liver function in vivo in both species was investigated. The anionic bile acid taurocholic acid was taken up by isolated human hepatocytes at a considerably lower rate than observed in isolated rat hepatocytes. Taurocholic acid uptake both in human hepatocytes and in liver plasma membrane vesicles showed sodium dependency. The uptake rate of taurocholic acid in isolated hepatocytes of both species was quantitatively compatible with the reported liver clearance of the bile acid in vivo. Ouabain uptake rate in isolated human hepatocytes was lower than in rat hepatocytes. This species difference was in accordance with pharmacokinetic studies in vivo on hepatic clearance of ouabain in man and rat. Uptake of vecuronium into human hepatocytes was about a factor of 10 lower than that in rat hepatocytes. Uptake into and efflux from human hepatocytes was comparable for the two short acting muscle relaxants vecuronium and rocuronium. Since distribution to the liver is considered to be a major factor in termination of action of vecuronium and rocuronium these observations were in line with the human pharmacokinetic profiles. In conclusion, the uptake rate of the studied model compounds in human hepatocytes appeared to be lower than that in rat hepatocytes. These observed transport rates reflected the relative hepatic transport rates observed in these species in the intact organism, but the absolute values in both species for some substrates may have been somewhat lower than calculated from in vivo data. It is concluded that transport studies in isolated hepatocytes are suitable for comparative drug transport studies, but are less precise in the prediction of quantitative membrane transport.

Androstanols↗
PubMed1994

Ionic currents during action potentials in mammalian skeletal muscle fibers analyzed with loose patch clamp.

The loose patch-clamp technique was applied to analyze transmembrane currents during propagating action potentials in superficial fibers of musculi extensor digitorum longus of the mouse in vitro. Experimentally three components were identified in the transmembrane current: 1) a capacitive, 2) an inward sodium, and 3) an outward potassium current. Other components were negligible. The capacitive current was similar in shape to the first derivative of the intracellularly measured action potential. Tetrodotoxin, tetraethylammonium, and 4-aminopyridine, applied in the pipette, were used to identify the contribution in the current by sodium and potassium ions. With extracellularly applied depolarization steps only a sodium current was observed, not a potassium current. Occasionally found outward currents were artifactual. The behaviour of delayed rectifier potassium channels in muscle fiber membranes is discussed in the light of these unexpected findings. We conclude that potassium channel activity contributing to and measured during action potential generation is in some way inaccessible to loose patch extracellular voltage-clamp stimulation and that loose patch action current recording is a useful noninvasive method to analyze membrane conductances involved in action potential generation.

4-Aminopyridine↗
PubMed1994

Effects of dietary corn and olive oil versus coconut fat on biliary cholesterol secretion in rats.

We have studied the effects of dietary corn and olive oil versus coconut fat on bile formation and fluidity of hepatic plasma membranes in rats. After 4 weeks of feeding the purified diets containing 9% (w/w) of the test fats, there was no difference in plasma cholesterol concentration between the dietary groups. The amount of free and esterified cholesterol in the liver was significantly higher in rats fed either corn oil or olive oil as compared with coconut fat. In the rats fed olive oil, but not in those fed corn oil this was associated with lower rates of biliary phospholipid excretion. Bile flow was not differently influenced by the three dietary fats. Hepatic plasma membranes of the rats fed corn or olive oil contained more cholesterol and less phospholipids than those on coconut fat, which was, however, not accompanied by changes in fluidity of the membranes. These results indicate that in rats the type of dietary fat can induce considerable changes in hepatic cholesterol metabolism without affecting plasma cholesterol concentrations, and without consistent effects on biliary cholesterol secretion.

Animals↗
PubMed1993

The bioelectrical source in computing single muscle fiber action potentials.

Generally, single muscle fiber action potentials (SFAPs) are modeled as a convolution of the bioelectrical source (being the transmembrane current) with a weighting or transfer function, representing the electrical volume conduction. In practice, the intracellular action potential (IAP) rather than the transmembrane current is often used as the source, because the IAP is relatively easy to obtain under experimental conditions. Using a core conductor assumption, the transmembrane current equals the second derivative of the IAP. In previous articles, discrepancies were found between experimental and simulated SFAPs. Adaptations in the volume conductor slightly altered the simulation results. Another origin of discrepancy might be an erroneous description of the source. Therefore, in the present article, different sources were studied. First, an analytical description of the IAP was used. Furthermore, an experimental IAP, a special experimental SFAP, and a measured transmembrane current scaled to our experimental situation were applied. The results for the experimental IAP were comparable to those with the analytical IAP. The best agreement between experimental and simulated data was found for a measured transmembrane current as source, but differences are still apparent.

Action Potentials↗
PubMed1993

[Liver diseases in infants. Metabolism and transport of bilirubin and bile acids].

Bilirubin, a degradation product of heme, is taken up from the blood by the liver parenchymal cells (hepatocytes), metabolized and secreted into bile. Bile acids are synthesized from cholesterol in hepatocytes and secreted into bile. After secretion into the intestine, metabolites of bilirubin and bile acids are partially taken up in the portal circulation and transferred to the liver, where these substances are extracted from the blood and secreted again into bile (enterohepatic circulation). In this article, we discuss several aspects of hepatic uptake, metabolism and secretion of bilirubin and bile acids.

Animals↗
PubMed1993

Mechanism of biliary lipid secretion in the rat: a role for bile acid-independent bile flow?

Bile acid-induced lipid secretion was compared in unanesthetized normal control and Groningen Yellow Wistar rats during variations in endogenous bile acid output. Groningen Yellow rats express a genetic defect in the biliary secretion of various organic anions. During a 5-hr period after interruption of the enterohepatic circulation, bile acid secretion decreased from 36.4 +/- 1.8 to 1.9 +/- 0.3 mumol per 30 min in normal control rats and from 37.1 +/- 2.8 to 1.8 +/- 0.2 mumol per 30 min in Groningen Yellow rats, respectively (mean +/- S.E.M., n = 5). The relationship between bile acid secretion and bile flow showed similar slopes (normal control, 8.74 +/- 0.44 microliter/mumol and Groningen Yellow rats, 7.71 +/- 0.42 microliter/mumol) but different y-intercepts (normal control, 243 +/- 8 and Groningen Yellow, 127 +/- 4 microliters per 30 min; p < 0.001), corresponding to a 47% reduction of the bile acid-independent fraction of bile flow in Groningen Yellow rats. During the course of the experiment, the ratio of lipids (phospholipids plus cholesterol) to bile acids increased in both strains more than threefold but was permanently higher in Groningen Yellow than in normal control rats (p = 0.035), implying that Groningen Yellow rats continuously secreted more lipid per bile acid. No differences in bile acid pool composition or in bile canalicular membrane composition and fluidity between the two strains were detected. The results indicate that apart from previously demonstrated factors (bile acid concentration, bile acid composition and hydrophilic organic anion concentration in bile), another parameter affects the efficacy of bile acids to induce biliary lipid secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Identification of an anion-transport ATPase that catalyzes glutathione conjugate-dependent ATP hydrolysis in canalicular plasma membranes from normal rats and rats with conjugated hyperbilirubinemia (GY mutant).

Rat liver canalicular plasma membranes were found to contain a 37-kDa protein that is immunologically cross-reactive with the dinitrophenyl glutathione-stimulated ATPase previously identified in human tissues. The protein, which was partially purified by affinity chromatography, exhibited ATPase activity dependent on dinitrophenyl glutathione, bilirubin ditaurate, and other dianionic compounds. The localization of this protein in the canalicular membrane and its measured enzymatic activity indicate that it is involved in the transport of glutathione derivatives and other dianionic organic compounds. A rat mutant in which the above transport activities are impaired contained the protein in amounts similar to those in a normal control.

Adenosine Triphosphatases↗
PubMed1992

Closing sounds and related complaints after heart valve replacement with St Jude Medical, Duromedics Edwards, Björk-Shiley Monostrut, and Carbomedics prostheses.

OBJECTIVE: To measure the noise produced and related subjective complaints after implantation of four different mechanical heart valve prostheses and to identify further factors related to the patient and prosthesis that influence noise generation and complaints. DESIGN: Sound pressure was measured 5 and 10 cm and 1 m from the point of maximal impulse on the body surface by a calibrated meter in quiet rooms with either a decibel(A) filter or octave filters. The patients were asked about their complaints and examined physically. SETTING: The measurements were conducted in silent rooms of ear, nose, and throat departments. The patients had been operated on either in a university hospital or a community hospital. MAIN OUTCOME MEASURES: Sound pressures of frequency bands and sound pressures measured in dB(A) at various distances. Complaints registerd were: sleep disturbance, disturbance during daytime, "wants a less noisy prosthesis," and "can hear the closing click". PATIENTS: 143 patients after heart valve replacement with St Jude Medical (n = 35), Duromedics Edwards (n = 38), Carbomedics (n = 34) and Björk-Shiley Monostrut (n = 36) prostheses operated on between 1984 and 1988 were matched for valve position, ring size, and body surface area. RESULTS: Duromedics Edwards (33.5 (6) dB(A)) and Björk-Shiley Monostrut valves (31 (4) dB(A)) were significantly louder than St Jude Medical (24 (4) dB(A)) and Carbomedics (25 (6) dB(A)) prostheses (p = 0.0001) (mean (SD)). The louder valves were significantly more often heard by the patients (p = 0.0012) and caused more complaints both during sleep (p = 0.024) and during the daytime (p = 0.07). Patients with these valves were more likely to want a less noisy valve (p = 0.0047). Patients with symptoms were younger, had better hearing, and were more likely to be in sinus rhythm. As well as the type of prostheses, the valve diameter and body height also had an effect on sound emission. CONCLUSIONS: The intensity of the closing click of mechanical valve prostheses was significantly different for various designs. Patient complaints were related to the objectively measured sound pressure. Noise production should be considered when a mechanical valve is selected.

Adult↗
PubMed1992

Adenosine triphosphate-dependent taurocholate transport in human liver plasma membranes.

Transport systems involved in uptake and biliary secretion of bile salts have been extensively studied in rat liver; however, little is known about these systems in the human liver. In this study, we investigated taurocholate (TC) transport in canalicular and basolateral plasma membrane vesicles isolated from 15 human livers (donor age 6-64 yr). ATP stimulated the uptake of TC into both canalicular and basolateral human liver plasma membrane vesicles (cLPM and blLPM, respectively). Considerable interindividual variations in the transport velocity were observed in the different membrane preparations used: 9.0 +/- 1.3 (mean +/- SEM, n = 17; range 1.6-18.0) and 9.3 +/- 2.0 (range 1.1-29.8) pmol TC.mg protein-1.min-1 at 1.0 microM TC for cLPM and blLPM, respectively. TC transport was temperature sensitive and showed saturation kinetics with a high affinity for TC (Km 4.2 +/- 0.7 microM and 3.7 +/- 0.5 microM for cLPM and blLPM, respectively). Transport was dependent on the ATP concentration and saturable (Km 0.25 +/- 0.03 mM, n = 3). Neither nitrate, which reduces membrane potential, nor the protonophore FCCP strongly inhibited ATP-dependent TC transport, indicating that membrane potential and proton gradient are not involved in this process. TC transport was significantly inhibited by the classical anion transport inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonate (250 microM) and the glutathione conjugate S-(2,4-dinitrophenyl)glutathione (100 microM). In conclusion, high affinity ATP-dependent TC transport is present in human liver at both the canalicular and the basolateral sides of the hepatocyte.

Adenosine Triphosphate↗
PubMed1991

Isolation and characterization of canalicular and basolateral plasma membrane fractions from human liver.

A method is described for the isolation of subfractions from human liver plasma membranes, enriched in canalicular domains (cLPM) and basolateral domains (blLPM), respectively, and the results are compared to those obtained with rat liver. The studies were performed in 18 human livers. The cLPM (isolated at densities 1.103-1.127 for human and 1.036-1.127 for rat cLPM) from human as well as rat liver showed a lower density than the blLPM (1.141-1.161 for human and 1.151-1.172 for rat blLPM). Human and rat blLPM were characterized by increased levels of (Na+/K+)-ATPase (relative enrichment 33 and 21, respectively). Both human and rat cLPM showed high specific activities of leucine aminopeptidase; relative enrichment factors were 42 and 31, respectively. Mg(2+)-ATPase and alkaline phosphatase, specific canalicular enzymes in rat liver, were only slightly enriched in the cLPM of human liver, which indicates that these enzymes are not suitable as marker enzymes for human liver cLPM. Both cLPM and blLPM of human and rat origin were only slightly contaminated with mitochondria, lysosomes, Golgi membranes and endoplasmic reticulum. Total recoveries of cLPM and blLPM were 0.02 mg protein/g liver each for the human membrane preparations, compared to 0.07 and 0.16 mg protein/g liver for the membranes prepared from rat liver. Analysis of membrane fluidity revealed that the human liver cLPM were more rigid than blLPM (mean difference in fluorescence polarization PDPH 0.024). They contained more cholesterol (0.43 vs. 0.30 mumol/mg protein) and phospholipids (0.54 vs. 0.39 mumol/mg protein, respectively), which was compatible to rat liver plasma membrane fractions. This study shows that besides similarities, there are several differences between human and rat liver plasma membrane fractions.

Adolescent↗
PubMed1991

Dietary fish oil-induced changes in intrahepatic cholesterol transport and bile acid synthesis in rats.

Hepatic cholesterol metabolism was studied in rats fed purified diets supplemented (9% wt/wt) with either fish oil (FO) (n-3 fatty acids) or corn oil (CO) (n-6 fatty acids) for 4 wk. Rats were equipped with permanent catheters in heart, bile duct, and duodenum to allow studies under normal feeding conditions. [3H]-cholesteryl oleate-labeled small unilamellar liposomes, which are rapidly endocytosed by hepatocytes, were intravenously injected to label intrahepatic cholesterol pools, and plasma and bile were collected. FO as compared to CO induced a lowering of plasma cholesterol levels by 38% and of triglyceride levels by 69%. This reduction in plasma lipids in FO rats was accompanied by: (a) an increased bile acid pool size (28%); (b) a fourfold increase in the ratio cholic acid/chenodeoxycholic acid in bile; (c) increased biliary excretion of cholesterol (51%); (d) accelerated excretion of endocytosed free cholesterol into bile; (e) accelerated incorporation of endocytosed cholesterol in bile acids; (f) a significant increase in the bile acid-independent fraction of bile flow; and (g) a threefold increase in hepatic alkaline phosphatase activity. The results show that FO induces changes in transport and metabolic pathways of cholesterol in the rat liver, which result in a more rapid disposition of plasma-derived cholesterol into the bile.

Alkaline Phosphatase↗
PubMed1991

Closing click of St Jude Medical and Duromedics Edwards bileaflet valves: complaints created by valve noise and their relation to sound pressure and hearing level.

The metallic clicking sound created by mechanical heart valve prostheses frequently bothers patients. To test whether sounds generated by different bileaflet valves correlate to complaints related to the prosthetic clicking 73 patients were investigated after valve replacement with Duromedics Edwards (DE) (n = 38) and St Jude Medical (SJM) (n = 35) valves. The patients were asked about their complaints, sound pressure levels were recorded and audiometry was performed. Sixty-five percent of patients could hear their valve, 18% had sleeping disturbances, 5% felt bothered during daytime and 12% would prefer a less noisy valve. In symptomatic patients, sound pressure levels were higher than in asymptomatic patients (valve audible 45 +/- 8 db(A) vs not audible 39.9 +/- 10 db(A) at 10 cm; P = 0.016). These differences were most apparent in the high frequency bands, corresponding to the metallic click. Symptomatic patients had better hearing and were younger than patients without complaints. Fifty-one percent could hear their valve by conduction through the body, after eliminating air conduction by the use of headsets. The DE prostheses were louder than the SJM valves in general (47.4 +/- 7 vs 39.8 +/- 5 db (A) at 10 cm; P = 0.001) and in each valve position. Patients with DE prostheses had significantly more complaints. The intensity of the closing click of mechanical valves correlates to the complaints caused by prosthetic clicking and thus sound emission should be considered when a mechanical heart valve prosthesis is selected.

Adult↗
PubMed1990

Noise level and perception of the closing click after heart valve replacement with St. Jude Medical and Björk Shiley Monostrut prostheses.

The metallic click generated by the closure of mechanical heart valve prostheses may severely bother patients, but generated sound energy and the extent of complaints after implantation are not known. In 62 patients, after valve replacement with St. Jude Medical (SJM) (n = 35) and Björk Shiley Monostrut (BSM) (n = 27) prostheses, sound energy was recorded with a calibrated noise level analyzer at 5, 10, and 100 cm distance from patients and correlated with their complaints. At a distance of 100 cm, the BSM valves produced a significantly higher sound pressure level, 30.5 +/- 5 db(A), compared to the SJM valves, 24.1 +/- 4 db(A) (p = 0.0001). There was no significant difference at shorter distances. After splitting into frequency bands the highest sound pressure levels were observed in the high frequency ranges (8 to 16 kHz) representing the metallic click. BSM valves produced higher sound levels in all frequency ranges at 1 m distance. Seventy-three percent of all patients were aware of the noise generated by the valve; 20% had disturbed sleep; and 26% preferred a less noisy valve type. Twelve of 27 patients with BSM valves wanted less noisy valves, whereas only 4 of 35 patients with SJM valves wished to have a less noisy valve type (Chi-square p = 0.003). In patients who could hear their valve measured, sound level was higher than in patients who could not. In 9 of 27 patients with BSM (33%), versus 3 of 35 with SJM prostheses (9%), the clicking caused sleep disturbances.(ABSTRACT TRUNCATED AT 250 WORDS)

Acoustics↗
PubMed1989

[Subjective noise perception and objective measurement of loudness following heart valve replacement with the St. Jude Medical and Duromedics Edwards bileaflet prostheses].

The performance of heart valve prostheses is generally judged by the rate of valve-related complications and the hemodynamic performance. Patients may be severely bothered by the metallic click generated by the closure of the valve. In 74 patients after valve replacement with Duromedics Edwards (DE) (n = 38) and St. Jude Medical (SJM) (n = 36) prostheses the sound energy was recorded and correlated to the complaints of the patients. At a distance of 10 cm the DE valves produced a significantly higher sound pressure with 47 +/- 7 db(A) compared to the SJM valves with 39.8 +/- 5 db(A) (p = 0.001). The noise level was also different for the valves in aortic or mitral position. After splitting into frequency bands the highest sound pressure was observed in the high frequency ranges (8 to 16 kHz) which represents the metallic click. 65% of patients were aware of the noise generated by the valve, 16% had sleep disturbances and 22% would prefer a more silent valve type. 12 of 38 patients with DE valves and 4 of 36 patients with SJM valves wished to have a less noisy valve type (Chi square p = 0.003). In annoyed patients the valves produced a higher sound amplitude of 49 +/- 8 db(A) as compared to undisturbed patients with 42 +/- 6 db(A) (p = 0.002). The noise level of mechanical heart valves should be considered before selection of a prosthesis, because the metallic click bothers patients and the complaints correlate with measured sound energy.

Adult↗
PubMed1987

Radiation-induced lipid peroxidation: influence of oxygen concentration and membrane lipid composition.

Radiation-induced lipid peroxidation in phospholipid liposomes was investigated in terms of its dependence on lipid composition and oxygen concentration. Non-peroxidizable lipid incorporated in the liposomes reduced the rate of peroxidation of the peroxidizable phospholipid acyl chains, possibly by restricting the length of chain reactions. The latter effect is believed to be caused by interference of the non-peroxidizable lipids in the bilayer. At low oxygen concentration lipid peroxidation was reduced. The cause of this limited peroxidation may be a reduced number of radical initiation reactions possibly involving oxygen-derived superoxide radicals. Killing of proliferating mammalian cells, irradiated at oxygen concentrations ranging from 0 to 100 per cent, appeared to be independent of the concentration of peroxidizable phospholipids in the cell membranes. This indicates that lipid peroxidation is not the determining process in radiation-induced reproductive cell death.

Animals↗
PubMed1987

Effect of hyperthermia on the repair of sublethal radiation damage in normal and membrane fatty acid substituted fibroblasts.

The interaction of heat and X irradiation was studied in normal and polyunsaturated fatty acid (PUFA) substituted mouse fibroblast LM cells. As a result of the substitution the membranes of the PUFA cells were more fluid than the membranes of the normal cells. Three different heat doses were applied (60 min 42 degrees C, 20 min 43 degrees C, and 10 min 44 degrees C) in combination with single or split doses of X rays. Heat radiosensitization was the largest for the 60 min 42 degrees C treatment. Heat radiosensitization and the heat-induced inhibition of the rate of sublethal damage repair were the same for the normal and the PUFA cells. It is concluded from the experiments reported that the processes of hyperthermic inhibition of SLD repair and hyperthermic radiosensitization are independent of membrane fluidity and membrane fatty acid composition.

Animals↗
PubMed1985

Membrane radiosensitivity of fatty acid supplemented fibroblasts as assayed by the loss of intracellular potassium.

Leakage of potassium from mouse fibroblast LM cells, X-irradiated at 0 degrees C with doses up to 400 Gy is shown to be related to plasma membrane lipid composition. Fatty acid supplemented cells, containing about 40 per cent polyunsaturated fatty acids (PUFA) in their membranes were much more sensitive to radiation, as measured by increased permeability, than normal cells, which contained 7 per cent PUFA. The damage observed after irradiation at 0 degrees C was partially repaired during a post-irradiation incubation at 22 degrees C. The o.e.r. for potassium leakage was about 4 for normal fibroblasts and 8 for the PUFA-supplemented cells. No oxygen-dependent radiation damage could be observed in cells treated with high amounts of vitamin E. Depletion of glutathione in PUFA cells sensitized oxic cells to radiation damage, resulting in an increase of the o.e.r. from 8 to 17. No lipid peroxidation (malondialdehyde production and disappearance of fatty acyl chains) could be demonstrated. While PUFA, normal and vitamin E grown cells showed a differential sensitivity in radiation-induced potassium leakage and trypan blue uptake (high doses, interphase death), no difference in radiation-induced clonogenic ability (reproductive death) could be observed after the different cell treatments. The experiments reported are supportive of a role of membranes in the mechanism of radiation-induced interphase death and show that increased damage may be expected when high amounts of polyunsaturated membrane lipids are present under conditions of low amounts of appropriate antioxidants.

Animals↗