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M J Hardonk

Publications and source records attributed to M J Hardonk.

At least 73 records · Page 4Linked to original sources
PubMed1985

Zonal heterogeneity of rat hepatocytes in the in vivo uptake of 17 nm colloidal gold granules.

The in vivo uptake in hepatocytes of intravenously injected colloidal gold granules with a diameter of 17 nm or 79 nm and coated with bovine serum albumin or with polyvinyl-pyrrolidone was studied. Irrespective of coating only the 17 nm granules were taken up in hepatocytes. Perivenous hepatocytes did take up much more gold granules than periportal hepatocytes. The gold granules were found in lysosomes around bile canaliculi. Two hours after injection hepatocytes contained the maximal amount of granules. At least a portion of the granules was discharged into the bile. The observed zonal gradient in the uptake of 17 nm gold granules might be caused by the greater supply of granules to the perivenous hepatocytes as a combined result of the higher porosity of the endothelial lining and the smaller number of Kupffer cells with a low endocytic activity in this zone.

Animals↗
PubMed1985

A histochemical study about the involvement of rat liver cells in the uptake of heterologous immune complexes from the circulation.

Intravenously injected immune complexes (ICx) composed of bovine serum albumin (BSA) and rabbit anti-BSA were taken up by the liver. Insoluble complexes, made in antibody excess, were rapidly taken up by Kupffer cells and were metabolized within 24 h. Soluble complexes, made in antigen excess, were only partly taken up by Kupffer cells. In addition these complexes were bound, taken up and metabolized by endothelial cells. Until 2 h after injection soluble complexes could also be observed along the microvilli of hepatocytes. No signs of endocytosis in hepatocytes could be observed. It is concluded, that ICx can be taken up by Kupffer cells as well as by endothelial cells. The physical state of the complexes, soluble or insoluble, determines the cell type in which uptake occurs.

Animals↗
PubMed1985

The glomerular polyanion (GPA) of the rat kidney. III. Further characterization of a vaso-active serum factor which reduces GPA.

Fractions of normal rat serum were purified using gel chromatography and their molecular weights were analysed using gradient polyacrylamide gel electrophoresis (PAGE). The fractions were tested for their capacity to affect in vitro glomerular polyanion (GPA) in rat kidney tissue whereas their vascular enhancing capacity in vivo after intradermal injection into the rat skin was analysed. GPA impairment in vitro was estimated after incubation of the fractions with tissue sections for 2 h at 37 degrees C and subsequent staining for sialoproteins with colloidal iron. Enhanced vascular responses were assayed using a standard vascular permeability test in the rat skin. The results show that a factor with an estimated molecular weight of 120 000 was responsible for a dose-related activity in both test systems studied. The activity of this fraction could be inhibited by various plasma kallikrein-inhibiting protease inhibitors, whereas in addition the skin response could be inhibited by pyridinolcarbamate and not by histamine- or serotonin-inhibiting drugs. From the inhibition patterns in vivo and in vitro as well as from the estimated molecular weight of the fraction, it is suggested that a plasma kallikrein-like factor might be responsible for the activities observed. We feel that further study of this fraction in rat or human serum is worthwhile in particular with respect to nephrotic conditions associated with GPA loss.

Animals↗
PubMed1984

Genesis of unusual vesicles in rat periportal hepatocytes after administration of N-hydroxy-2-acetylaminofluorene.

Administration of N-hydroxy-2-acetylaminofluorene (90 mumol/kg, iv) to rats results in damage to periportal hepatocytes. The most prominent ultrastructural changes are the appearance of numerous unusual vesicles of about 200 nm diameter and the proliferation of the endoplasmic reticulum to form fingerprint-like structures. In order to characterize these vesicles and to investigate their possible origin, their enzymatic activity was studied by ultrastructural enzyme histochemistry. The vesicles as well as the fingerprint-like structures exhibited glucose-6-phosphatase activity. Continuities between the vesicles and the membranes of both the RER and the SER were frequently seen. The vesicles lacked ATPase, 5'nucleotidase and catalase activity. From these results we conclude that the vesicles may be an unusual proliferation of the endoplasmic reticulum.

2-Acetylaminofluorene↗
PubMed1983

Acinar heterogeneity in hepatic transport of dibromosulfophthalein and ouabain studied by autoradiography, normal and retrograde perfusions and computer simulation.

This study is aimed to investigate the relative involvement of periportal (zone 1) and perivenous (zone 3) hepatocytes in the uptake and biliary excretion of the organic anion dibromosulfophthalein (DBSP) and the uncharged cardiac-glycoside ouabain. The localization in the acinus of [35S]BSP (sulfobromophthalein, the tetra-bromo-analogue of DBSP) and [3H]ouabain administered to livers perfused with normal and retrograde flow, was detected by autoradiography. The plasma disappearance and biliary excretion rates of DBSP and [3H]ouabain were determined in normal and retrograde perfusions. In addition, computer simulations were performed to predict the effect of reversal of the perfusate flow on the plasma disappearance and biliary excretion rate curves and on the concentration of label in zones 1 and 3. Autoradiography showed that 2 and 10 min after injection of [35S]BSP to normally and retrogradely perfused livers, the label was uniformly distributed in the liver acinus. The same results were found 30 sec and 10 min after injection of [3H]ouabain to normally and retrogradely perfused livers. The plasma disappearance and biliary excretion rate of DBSP were slightly faster in retrograde perfusions compared to normal perfusions both with and without a basal bile salt infusion of 15 mumole/hr. This could not be explained by an acinar heterogeneity with respect to any of the DBSP transport steps (plasma to liver, liver to plasma, liver to bile) as was shown by computer simulations. The plasma disappearance and biliary excretion rate of ouabain were similar in normal and retrograde perfusions. It is concluded that periportal and perivenous hepatocytes are equally involved in the uptake of (D)BSP and ouabain from the medium. However, due to the particular distribution patterns no conclusions can be drawn from normal and retrograde perfusions about the relative involvement of these cells in biliary excretion, as was shown by computer simulation. The unaffected kinetic behaviour of the retrogradely perfused livers indicated that no liver damage occurs during retrograde perfusion with respect to transport function.

Animals↗
PubMed1983

Heterogeneity of rat hepatocytes in transport and hepatic binding of asialoalkaline phosphatase studied after induction of selective acinar damage by N-hydroxy-2-acetylaminofluorene and carbon tetrachloride.

In order to investigate rat hepatocyte heterogeneity in asialoglycoprotein transport, rats were pretreated with N-hydroxy-2-acetylaminofluorene (N-OH-AAF, 90 mumol/kg, i.v.) to damage zone 1 hepatocytes, or with carbon tetrachloride (CCl4, 2.1 mmole/kg, p.o.) to damage zone 3 hepatocytes. Twenty-four hours after pretreatment, the asialoglycoprotein dog intestinal alkaline phosphatase (As-ALPase) was injected and plasma disappearance and biliary excretion were measured. In addition, the acinar distribution of the hepatic binding of As-ALPase 10 min after injection in vivo, or after incubation of fixed liver sections with As-ALPase in vitro, was determined by enzyme histochemistry. In control rats, a rapid biexponential plasma disappearance was observed and 6.4 +/- 1.5% of the dose was excreted into bile after 60 min. Hepatocyte binding occurred predominantly in zone 3, both after administration in vivo and after incubation with liver sections in vitro. In rats with zone 1 liver damage, both the half-lives of the first and of the second phase were strongly increased, but biliary excretion did not change significantly. Both in vivo and in vitro the relatively weak binding of As-ALPase in zone 1 of the liver was abolished, whereas binding to zone 3 cells was normal or only slightly decreased. After CCl4-pretreatment histochemically detectable binding to zone 3 cells was completely abolished, leaving only the relatively weak binding in zone 1. Unexpectedly, a normal plasma disappearance and biliary excretion rate were found in these rats. The discrepancy between the pharmacokinetic results, which point to a predominant involvement of zone 1 cells in As-ALPase transport, and the enzyme histochemical studies, which show preferential binding of As-ALPase in zone 3, is discussed.

2-Acetylaminofluorene↗
PubMed1983

Cytochemical demonstration of phosphatases in the rat liver by a cerium-based method in combination with osmium tetroxide and potassium ferrocyanide postfixation.

Acid phosphatase, alkaline phosphatase, glucose-6-phosphatase, Mg-activated adenosine triphosphatase and 5'nucleotidase were demonstrated in the rat liver using a cerium-based method. This method can be applied routinely and yields better results than the lead-based method. The tissue was postfixed in osmium tetroxide and potassium ferrocyanide which considerably enhances the membrane contrast in comparison with solely osmium tetroxide postfixation. This facilitates the precise localization of the reaction product.

Acid Phosphatase↗
PubMed1983

Trophoblast alterations in the placental bed in relation to physiological changes in spiral arteries.

Ninety-three placental bed biopsies containing a segment of a spiral artery at the level of the decidual-myometrial junction (53 with and 40 without physiological changes) were histologically investigated for depth of trophoblastic penetration of the uterine wall, formation of trophoblastic multinucleated giant cells and the enzyme histochemical characteristics of the interstitial (stromal) and vascular (intramural) trophoblast. The depth of trophoblastic penetration was not related to the presence or absence of the physiological changes. Conversely, in the absence of physiological changes, a significant accumulation of multinucleated giant cells at the decidual-myometrial junction was found before 36 weeks of gestation. The enzyme histochemical characteristics of the placental bed trophoblast suggest a stromal migration of trophoblast to the proximal (decidual-myometrial) part of the spiral artery whereas the distal part might be invaded by intraluminal (upstream) invasion. The hypothesis is put forward that in the absence of physiological changes a disturbed stromal migration is caused by intrinsic (trophoblastic) or extrinsic (interstitial of vascular) factors expressed by the augmentation of the multinucleated cells at the decidual-myometrial junction.

Female↗
PubMed1983

Influence of taurocholate on hepatic clearance and biliary excretion of asialo intestinal alkaline phosphatase in the rat in vivo and in isolated perfused rat liver.

We have used canine intestinal alkaline phosphatase, an asialoglycoprotein, as a tool to study the effect of taurocholate on hepatic asialoglycoprotein transport. After bolus injections of 20 U of alkaline phosphatase into anesthetized rats in vivo and isolated perfused rat livers, a biexponential disappearance pattern was observed; 6.2% of the dose and 0.8% of the dose was excreted in bile, respectively. Taurocholate infusion in vivo and in isolated perfused livers resulted in a virtually complete abolition of the plasma disappearance of alkaline phosphatase in the second slow phase of the curve, whereas the primary disappearance rate was not affected. Wash out experiments showed release of exogenous alkaline phosphatase from the liver, which was strongly increased by taurocholate. Liver perfusion experiments with two subsequent doses of alkaline phosphatase indicated that the taurocholate effect was completely reversible. It is concluded that taurocholate enhances exocytosis of interiorized alkaline phosphatase from liver into plasma. The taurocholate effect on hepatic exocytosis of the asialoglycoprotein may also occur when bile salt concentrations in the systemic or portal circulation, or both, are elevated due to certain liver diseases and postprandial bile salt absorption.

Alkaline Phosphatase↗
PubMed1982

The role of the liver in clearance of glycoproteins from the general circulation, with special reference to intestinal alkaline phosphatase.

Glycoproteins represent a wide variety of macromolecules with important physiological functions. Characteristic variations in carbohydrate composition and plasma concentration of these proteins may occur during pathological conditions. Steady-state plasma concentrations are determined by release from normal or diseased tissues and simultaneous clearance from the general circulation. The liver occupies a central position in the production but also clearance and catabolism of such glycoproteins. A number of specialized receptor-mediated transport processes for different types of glycoproteins in this organ is reviewed. Membrane recognition is generally followed by absorptive endocytosis and vesicle transport to lysosomes, Golgi system and/or bile canaliculis. The charge of the protein, the nature of the terminal sugar residue or complex formation with other glycoproteins may determine the extent of uptake in the various cell types of the liver. By means of these transport processes the liver is able to remove potentially dangerous macromolecules such as denatured proteins, aggressive enzymes and immunocomplexes from the general circulation. Drugs can bind to some of these proteins or may interact with the hepatic transport or catabolism processes. Special attention is paid to the hepatic clearance of asialoglycoproteins with terminal galactose groups. Intestinal alkaline phosphatase is used as a model compound to characterize the pharmacokinetic profiles of hepatic uptake and biliary excretion in the rat in vivo and isolated perfused rat livers. Histochemical and electron-microscopic studies demonstrated a galactose-specific, receptor-mediated endocytotic process, mainly but not exclusively localized in centrolobular hepatocytes. Drug interactions with these processes will be the subject of further investigations.

Alkaline Phosphatase↗
PubMed1982

A kinetic study of hepatic uptake of canine intestinal alkaline phosphatase in the rat.

This study describes the "plasma" disappearance and biliary excretion of injected purified canine intestinal alkaline phosphatase in the isolated perfused rat liver and in the intact rat. The plasma disappearance curve of the enzyme showed, apart from an initial rapid phase, a secondary phase, which may result from "exocytosis" of interiorized canine intestinal alkaline phosphatase into the circulation or from exhaustion of receptors involved in uptake of the enzyme during the process of endocytosis. A small fraction of the injected enzyme was found to be excreted into the bile and it was shown that there is a "kinetic" relationship between the biliary excretion pattern and the "plasma" disappearance of the enzyme. In addition, the effect of various sugars, sugar polymers and glycoproteins on plasma disappearance and biliary excretion of the enzyme was studied. Intravenous administration of galactose, lactose, galactan and especially asialofetuin prior to injection of canine intestinal alkaline phosphatase, resulted in inhibition of plasma disappearance of the enzyme, while the biliary excretion pattern of the enzyme was also changed. It is concluded that the rapid removal of injected canine intestinal alkaline phosphatase is predominantly, or even exclusively, achieved by the liver and that the hepatic uptake of the enzyme is most likely mediated by the "galactose-specific lectin" present on the plasma membrane of the hepatocytes.

Alkaline Phosphatase↗
PubMed1982

A histochemical study on the distribution of injected canine intestinal alkaline phosphatase in rat liver.

After intravenous administration to rats, the distribution of injected canine intestinal alkaline phosphatase in the liver was studied morphologically by means of histochemical and cytochemical methods on liver sections and pellets of homogenized livers. The interference of various sugars, sugar polymers and glycoproteins with the receptor-bound injected enzyme was investigated in rat liver sections. Injected canine intestinal alkaline phosphatase, being an asialoglycoprotein, is captured by the galactose-specific lectin present on the plasma membrane of the hepatocytes and can be displaced by incubation with galactose-containing sugars and proteins. The enzyme is subsequently taken up by a process of "adsorptive endocytosis" and was found first in a plasma membrane fraction and later in a pellet enriched in lysosomes. This hepatic handling of the enzyme predominantly occurs in the area around the central vein (zone 3 of Rappaport). This is the first evidence for zonal heterogeneity in hepatic disposition of an asialoglycoprotein.

Alkaline Phosphatase↗
PubMed1982

Autoradiographic and kinetic demonstration of acinar heterogeneity of taurocholate transport.

A combination of autoradiography of water-soluble compounds and normal and retrograde perfusions was used to study whether there was a heterogeneity in bile salt transport between zone 1 and zone 3 hepatocytes of the rat and, if so, whether such a heterogeneity was due to the localization of these cells in the liver blood-stream, to intrinsic cellular differences, or to both. When a low dose of [3H]taurocholate was administered under pentobarbital sodium anesthesia in vivo or to normally perfused livers, the label was localized primarily in zone 1; in livers perfused in a retrograde direction, it appeared predominantly in zone 3. High doses of [3H]taurocholate administered in vivo and in normal and retrograde perfusions resulted in a more homogeneous labeling of the acini. The plasma disappearance of [3H]taurocholate was similar in normal and retrograde perfusions, but in the latter biliary excretion occurred at a considerably slower rate. From these results it is concluded that at low doses bile salts are primarily transported by zone 1 cells. Zone 3 cells appear to be able to take up taurocholate with ease, but their biliary excretion is slower compared with zone 1 cells.

Animals↗
PubMed1981

Mechanisms underlying the prolonged duration of action of muscle relaxants caused by extrahepatic cholestasis.

The neuromuscular blocking effects of Org 6368 and Org NC 45 were studied in rats with experimental cholestasis and in controls. The effect of Org NC 45 during infusion of taurocholate was investigated. In cholestatic rats we observed a three-fold increase of the duration of action of Org 6368 and Org NC 45. The same was observed for Org NC 45 with taurocholate. In the rat phrenic nerve-hemidiaphragm preparation taurocholate potentiated the neuromuscular blockade of Org 6368, pancuronium and gallamine, but not Org NC 45. Increased bile salt concentrations caused strong inhibition of hepatic uptake and biliary excretion of Org 6368 and tubocurarine in isolated perfused livers. Taurocholate and glycocholate were more potent than cholate and chenodeoxycholate. Cholestatic livers exhibited a clearance of Org 6368 which was 50% of control. We conclude that the prolonged duration of action of certain muscle relaxants because of cholestasis results from both inhibition of hepatic uptake by the accumulated bile salts and a general deterioration of liver transport function.

Animals↗