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F Roels

Publications and source records attributed to F Roels.

At least 91 records · Page 5Linked to original sources
PubMed1987

Peroxisomal proliferation in heart and liver of mice receiving chlorpromazine, ethyl 2(5(4-chlorophenyl)pentyl) oxiran-2-carboxylic acid or high fat diet: a biochemical and morphometrical comparative study.

Chlorpromazine and related drugs including trifluoperazine, clopenthixol, and fluphenazine are in vitro inhibitors of mitochondrial carnitine palmitoyltransferase and cytochrome c oxidase and of peroxisomal carnitine octanoyltransferase from mouse heart and liver. By contrast with 0.1% ethyl 2(5(4-chlorophenyl)pentyl) oxiran-2-carboxylic acid or 0.1% clofibrate-containing diets, the treatment of mice with 0.1% chlorpromazine-containing diet fails to induce peroxisomal proliferation in liver and heart. An 0.5% chlorpromazine-containing diet did induce peroxisomal proliferation. Inhibition of peroxisomal beta-oxidation presumably via the reduction of carnitine octanoyltransferase by chlorpromazine elicits the appearance in liver of lamellar structures resembling those seen in human peroxisomal disorders and induces accumulation of very long-chain fatty acids in plasma. The peroxisomal proliferation induced by administration of high dose chlorpromazine is ascribed to its ability to depress mitochondrial fatty acid oxidation by impairing cytochrome c oxidase and carnitine palmitoyltransferase activities.

Animals↗
PubMed1986

Cytochrome P-450-dependent H2O2 production demonstrated in vivo. Influence of phenobarbital and allylisopropylacetamide.

By administration of allylisopropylacetamide, an inhibitor of cytochrome P-450, we demonstrated that cytochrome P-450 is involved in the production of H2O2 during aminopyrine metabolism and phenobarbital induction in both the unanaesthetized guinea pig and rat. In the guinea pig we also found evidence for the existence of a basal cytochrome P-450-dependent H2O2 production, i.e. in the absence of exogenous substrate. Catalase participates in the decomposition of H2O2 produced in the endoplasmic reticulum where cytochrome P-450 is localized.

Acetamides↗
PubMed1986

Hepatic peroxisomes are deficient in infantile refsum disease: a cytochemical study of 4 cases.

We examined liver biopsies from 4 patients with the infantile form of Refsum disease. No peroxisomes were visualized by light microscopy after cytochemical staining for catalase, a marker enzyme for this organelle. Absence of peroxisomes was confirmed by electron microscopy in 3 patients; in the 4th patient we observed organelles of peculiar size and structure and with minimal catalase activity. Light microscopy also showed birefringent macrophages containing P.A.S.-positive material; they were abundant in the 3 older children, and rare in the youngest (8 months). Peroxisomes and birefringent macrophages were absent in 2 patients with the cerebrohepatorenal syndrome of Zellweger. The simultaneous presence of these unique light microscopical characteristics may be of diagnostic value.

Birefringence↗
PubMed1986

Pseudo-Zellweger syndrome: deficiencies in several peroxisomal oxidative activities.

We describe an infant girl with a clinical, chemical, and pathologic syndrome remarkably similar to Zellweger cerebrohepatorenal syndrome but whose liver parenchymal cells contained abundant peroxisomes. Peroxisomal L-alpha hydroxy acid oxidase, catalase, and the plasmalogen synthesizing enzyme dihydroxy acetone phosphate-acyl transferase activities were normal; other peroxisomal enzymatic activities, including fatty acyl-CoA oxidase and D-amino acid oxidase, were reduced by 80% to 85%. Oxidation of bile acids and pipecolic acid was also deficient. Autopsy revealed the presence of neuronal heterotopia, renal cortical cysts, adrenal atrophy, and accumulation of very long chain fatty acids. The clinical and pathologic features of this case of "pseudo-Zellweger syndrome" reflect a deficiency in multiple peroxisomal activities rather than a defect in peroxisomal biogenesis. The deficient enzymatic activities require flavin adenine dinucleotide, and the underlying defect may be in the utilization of this cofactor.

Acyl-CoA Oxidase↗
PubMed1986

Phytol and peroxisome proliferation.

Infantile Refsum's disease is characterized by high levels of phytanic acid and the absence of normal hepatic peroxisomes. We investigated the in vivo influence of phytol, a precursor of phytanic acid, on peroxisomes by both biochemical and morphological methods. Enhanced supply of phytol in the diet of adult mice causes proliferation of hepatic peroxisomes. The peroxisomal beta-oxidizing capacity as well as exchanges of acyl moieties between peroxisomes and mitochondria are raised around 5- and 2-fold, respectively. In parallel a 1.5-fold increase of total catalase and mitochondrial butyryl-CoA dehydrogenase activities occurs, whereas peroxisomal urate oxidase and glycolate oxidase remain normally active. Serum triglyceride levels are decreased after 3 wk of phytol feeding; serum cholesterol levels remain unaffected. Phytol feeding also induces peroxisome proliferation in duodenal epithelium, in myocardium and in skin sebaceous glands, but not in kidney.

Animals↗
PubMed1986

Cyclosporine nephrotoxicity: comparative cytochemical study of rat kidney and human allograft biopsies.

The aim of this study was to detect early renal changes in the rat. Female Wistar rats received oral doses of cyclosporine (12.5, 25 or 50 mg/kg daily). The duration of the experiment was 1, 2, and 3 weeks. Controls received the vehicle only (olive oil). The following alterations were seen by light microscopy: Hypertrophy of the juxtaglomerular apparatus (PAS stain). Cytoplasmic droplets of neutral fat (Oil Red 0) in clusters of cortical tubules, probably belonging to the same nephron. Both the above phenomena increased with dosage and duration of treatment and were absent in controls. In the fat containing tubulus (FCT) brush border staining (alkaline phosphatase) was decreased or absent. Since after PAS the brush border was visualized in many FCT, it is concluded that many FCT were proximal tubulus (PT) of which the brush border has been damaged. In FCT mitochondrial staining (Cytochrome oxidase activity) was strongly decreased or absent. Mean lysosomal volume (acid phosphatase and dipeptidase II) is increased in the PT; in some cyclosporine animals, lysosomes were enlarged, while in others they were comparable to controls. Electron microscopy showed in some PT cells an increased number of empty vacuoles and focal alteration of mitochondria. Normal mitochondria were present next to grossly altered mitochondria. Autophagocytosis of mitochondria was clearly present. The lysosomes appeared swollen and contained electron dense material, not organised in the typical 50 A pattern of myeloid figures. These morphological changes suggest a defect of mitochondrial metabolism, leading to lipid deposition in PT. The mitochondrial metabolism can be disturbed by a direct toxic effect of cyclosporine or indirectly via ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Thioridazine: a selective inhibitor of peroxisomal beta-oxidation in vivo.

In vivo administration of the phenothiazine drug, thioridazine, inhibits hepatic peroxisomal beta-oxidation in mice. In starving animals, 3-hydroxybutyrate concentration is not decreased by thioridazine treatment. These results provide the first demonstration of thioridazine as a selective inhibitor of peroxisomal beta-oxidation in intact animals. Thioridazine might supply a tool for simulation of pathological conditions in which peroxisomal beta-oxidation is impaired.

3-Hydroxybutyric Acid↗
PubMed1985

Peroxisomal beta-oxidation and sodium valproate.

The influence of sodium valproate on peroxisomal beta-oxidation was investigated in rats, by evaluating in vivo changes in hepatic H2O2 production, using a combination of the catalase inhibitor 3-amino-1,2,4-triazole, and methanol. In rats starvation causes an increased flux of fatty acids through the peroxisomal beta-oxidation pathway. Valproate inhibits the formation of 3-hydroxybutyrate but not increased H2O2 production during starvation. There is no inhibitory effect of valproate on the peroxisomal oxidase. At low valproate concentrations it is possible that peroxisomes partially take over impaired mitochondrial function.

Animals↗
PubMed1985

Demonstration of H2O2 production in vivo during aminopyrine metabolism and phenobarbital induction.

It has been shown previously that, by using methanol and a catalase inhibitor, 3-amino-1, 2, 4,-triazole, changes in hepatic H2O2 production in vivo can be detected. Using this method in guinea pigs and rats we could demonstrate increased H2O2 production during metabolism in vivo of aminopyrine, especially in phenobarbital-pretreated animals. In contrast, administration of antipyrine does not lead to H2O2 production. In the guinea pigs, phenobarbital induction also stimulates the H2O2 production in vivo without administration of exogenous substrates. The rate and extent of this additional H2O2 production depend on the induction state, drug metabolism and species; the major findings are in agreement with and extend previous research in vitro on microsomes, isolated hepatocytes and perfused liver.

Aminopyrine↗
PubMed1985

Specific cytochemical stains in the image analysis of subcellular organelles.

This paper describes our work concerning densitometry and morphometry of subcellular structures in thin sections. The techniques of automatic image analysis were applied to light and electron microscopic observations of enzymatically stained lysosomes, renal brush borders and mitochondria (in human and rat kidney) and peroxisomes (in human liver). To obtain significant measurements of the enzymatic activity, specific staining techniques were developed and applied, including an improved staining of acid phosphatase for lysosomes. Optical densities were obtained by videodensitometry and electron densities of peroxisomes were obtained by digitizing and processing scanning transmission electron microscopic images. In subsequent steps, delineations and parameter estimation are performed by software. Included was an examination of delineation techniques, which showed improved results from the use of a newly developed local boundary search algorithm. The combination of these techniques was used to study changes in peroxisome and lysosome compartment in liver and kidney, some results of which are also reported.

Acid Phosphatase↗
PubMed1984

Peroxisomal beta-oxidation from endogenous substrates. Demonstration through H2O2 production in the unanaesthetized mouse.

A system was developed in which it is possible to detect in vivo changes in hepatic H2O2 production, using a combination of the catalase inhibitor, 3-amino-1,2,4-triazole and methanol. In mice, starvation significantly increases hepatic H2O2 production and plasma non-esterified fatty acid concentrations. Short-term refeeding after a 24 h starvation period brings H2O2 production and plasma non-esterified fatty acid concentration back to normal in 3h. Administration of insulin 24 h after the onset of starvation normalizes H2O2 production in less than 2h and decreases non-esterified fatty acid concentration below normal values. The suppression by insulin of H2O2 production, as well as its coherence with plasma non-esterified fatty acid concentration, indicate that increased H2O2 production in starved mice reflects peroxisomal beta-oxidation.

Amitrole↗
PubMed1984

On the topology of the catalase biosynthesis and -degradation in the guinea pig liver. A cytochemical study.

The biosynthesis, transport and degradation of catalase have been studied in the guinea pig liver parenchymal cell using 2-allyl-2-isopropylacetamide (AIA) as an inhibitor of de novo formation of catalase. Total catalase activity was assayed biochemically; cytoplasmic catalase was measured microspectrophotometrically after quantitative diaminobenzidine staining of the liver. By morphometry, number and size of peroxisomes in catalase stained sections were determined. From our data we conclude that (1) the final step in the catalase formation takes place inside peroxisomes, (2) catalase is transported from the peroxisomes into the cytoplasm, (3) in the cytoplasm catalase is degraded. These conclusions in part confirm the topological model on the intracellular catalase biosynthesis pathway of Lazarow and de Duve (1973) except for the presence of cytoplasmic catalase which is released from the peroxisomes as proposed earlier by Jones and Masters (1975).

Allylisopropylacetamide↗
PubMed1984

Lysosomal modifications in human proximal tubule induced by aminoglycoside treatment: visualisation by light microscopical cytochemistry.

In cryostat sections of kidney biopsies, lysosomes were visualized for light microscopy by staining for acid phosphatase. Twenty patients treated with the antibiotics gentamycin, tobramycin, amikacin or netelmicin during four days were compared to ten untreated control biopsies. Because of the marked heterogeneity of enzyme reaction product through the nephron, the most strongly stained tubular sections were used for comparison. With the exception of one biopsy, all treated kidneys display heavier staining than all controls; the difference is significant. Biochemical assays of acid phosphatase activity in homogenates have not revealed this difference. The cytochemical method may be used to detect early alterations caused by nephrotoxic drugs.

Acid Phosphatase↗
PubMed1984

Early effects of gentamicin, tobramycin, and amikacin on the human kidney.

The early alterations at the level of the proximal tubule of the human kidney caused by the three most currently used aminoglycosides, gentamicin, tobramycin, and amikacin, were studied. A prospective, randomized, and comparative approach using multidisciplinary methods was used. The patients received either no treatment or one of the three aminoglycosides at a therapeutic dose for 4 days preceding nephrectomy for neoplasia partly involving one kidney. The three aminoglycosides studied induce an early lysosomal phospholipidosis. Gentamicin and tobramycin cannot be distinguished on the basis of drug tissue accumulation, lysosomal overloading, or effect on lysosomal phospholipase A1. Amikacin induces significantly lower lysosomal overloading and no loss of phospholipase A1 activity.

Adult↗
PubMed1984

The accessory costotransverse foramen: a radioanatomical study.

One hundred fifty-six anatomical specimens of cervical vertebrae and 55 C1 and 53 C2 vertebrae were examined for the presence of an accessory costotransverse foramen. We also reviewed 60 cervical spine computed tomographic (CT) scans. The variations of the costotransverse and accessory foramen are discussed. The frequency of the latter is 19% in the anatomical specimens and 45% in CT scans. The local anatomy and the excellent visualization on axial transverse CT are stressed.

Cervical Vertebrae↗
PubMed1984

Automated measurement of acid phosphatase reaction product in human kidneys treated with aminoglycoside antibiotics.

The acid phosphatase reaction product was measured by automated image analysis densitometry in histologic sections from 23 human kidney biopsies. Optical density was proportional to incubation time, section thickness and enzyme activity. After a four days' treatment with aminoglycoside antibiotics, optical density was increased and paralleled the lysosomal changes previously observed by electron microscopy.

Acid Phosphatase↗