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Biomedical subjects

G Spiteller

Publications and source records attributed to G Spiteller.

118 records · Page 7Linked to original sources

Human neutrophil chemotaxis in response to diepoxides of linolenic acid.

Diepoxides of linolenic acid were found to be chemoattractants. The concentration that produces 50% of maximal chemotaxis was 4.5 10(-7) mol/l for human neutrophils when investigated in a chemotaxis test based on the method of spectrophotometric determination of myeloperoxidase activity with buffers containing bovine serum albumin. Leukotriene B4 was used as positive control. The concentration of leukotriene B4 that produces 50% of maximal chemotaxis was 1.8 nmol/l. No chemotactic activity was observed when monoepoxides of linoleic or linolenic acid, diepoxides of linoleic acid or triepoxides of linolenic acid were used. Mono-, di- and triepoxides of polyunsaturated fatty acids were synthesized with meta-chloroperbenzoic acid, separated by TLC and HPLC and identified by GC/MS.

Chemotaxis, Leukocyte↗

Increased levels of lipid oxidation products in rheumatically destructed bones of patients suffering from rheumatoid arthritis.

The new indicator for lipid peroxidation (LPO) processes--9-hydroxy-10,12-octadecadienoic acid (9-HODE)--was used to investigate, whether LPO processes are increased in destructed bone material of patients suffering from rheumatoid arthritis (RA) in comparison to surrounded non destructed bone material. The HODE content in destructed bones exceeded that of non destructed ones of the same patient for a factor of about 3. In addition similar increases in leukotoxines and epoxy oleic acid in the destructed bone material were observed, indicating an increase of LPO processes in affected bone parts of patients.

Arthritis, Rheumatoid↗

Strong increase of 9-hydroxy-10,12-octadecadienoic acid in low density lipoprotein after a hemorrhagic shock.

9-hydroxy-10,12-octadecadienoic acid (9-HODE) is generated by lipid peroxidation (LPO) processes in comparison to other marker compounds in at least 10 fold amount. A 10-25 fold increase of this new marker compound in relation to age matched healthy individuals was observed in the low density lipoprotein (LDL) fraction of ten patients suffering from a hemorrhagic shock. The 9-HODE values dropped to normal levels after recovery. Similarly the 9-HODE content in LDL of patients which had to undergo orthopedic surgery--replacement of their arthritic hip joints by endoprosthesis--were investigated. The rather high HODE values dropped also after recovery reflecting obviously the disappearance of inflammatory processes associated with arthritis.

Adolescent↗

Oxidation of plasmalogens produces highly effective modulators of macrophage function.

Model derivatives of plasmalogens and chemically synthesized oxidative degradation products as found e.g. during oxidation of low density lipoproteins show strong effects on phagocytosis induced secretion of reactive oxygen species of macrophages which was measured by luminol-enhanced chemiluminescence. Whereas a plasmalogen epoxide showed enhancing effects in submicromolar range, inhibition was found with higher concentrations as well as with alpha-hydroxyaldehydes. The substances showed only little effects on the non-cellular ROS-dependent chemiluminescence of the reaction between hydrogen peroxide and opsonized zymosan and no cytotoxic effects under the assay conditions used. These results show that oxidative modification and degradation of plasmalogens occuring also under pathophysiological situations in vivo produces effective modulators of macrophage function which could be important; e.g. during inflammation or atherogenesis.

Animals↗

10-Hydroxystearic acid--identified after homogenization of tissue--is derived from bacteria.

10-Hydroxystearic acid seems to be widely distributed in nature: Bacteria generate it by hydroxylation of oleic acid, but it was found also as constituent of plants, in cancer cell cultures and in mammalian tissue homogenates. Investigation of 10-hydroxystearic acid, obtained from mammalian tissue homogenates, revealed its identity with that of bacteria. Thus not 10-hydroxystearic acid is widely distributed in nature but its producers: bacteria. When biological material is processed in aqueous media, lipases are activated, these cleave membrane phospholipids. Thus liberated oleic acid is the substrate for widespread bacteria which are introduced into the media when the work up procedure is done in not sterile surrounding. The bacteria transform then oleic acid to 10R-hydroxystearic acid.

Animals↗

Transformations of 12,13-epoxy-11-hydroxy-9-octadecenoic acid and 4,5-epoxy-N-acetylsphingosine by incubation with liver homogenate and liver microsomes.

Transformation of 12,13-epoxy-11-hydroxy-9-octadecenoic acid and 4,5-epoxy-N-acetylsphingosine by addition of porcine liver homogenate and human liver microsomes, respectively was investigated. Both epoxides were converted to corresponding dioles by porcine liver homogenate, but not by human liver microsomes, suggesting location of the hydrolyzing enzymes not in the microsomes, but within the cell wall.

Animals↗

Plant constituents interfering with human sex hormone-binding globulin. Evaluation of a test method and its application to Urtica dioica root extracts.

A test system is described, which allows the search for compounds interfering with human sex hormone-binding globulin (SHBG) even in complex plant extracts. The method has been evaluated and applied to Urtica dioica root extracts. The lignan secoisolariciresinol (5) as well as a mixture of isomeric (11 E)-9,10,13-trihydroxy-11-octadecenoic and (10 E)-9,12,13-trihydroxy-10-octadecenoic acids (3 and 4, resp.) were demonstrated to reduce binding activity of human SHBG. Methylation of the mixture of 3 and 4 increased its activity about 10-fold.

Dihydrotestosterone↗

Thiodiacetic acid--a metabolite of Ethylene oxide.

Urine samples of premature babies contain high amounts of thiodiacetic acid (TDA). Since these pre-term infants are exposed to an increased oxygen atmosphere in the incubator, we supposed that these high levels of thiodiacetic acid might be produced from ethylene, generated in the course of lipid peroxidation processes. Considering that conversion of ethylene to ethylene oxide (EO) is well known in biology we investigated whether ethylene oxide is metabolised to thiodiacetic acid or not. Therefore Sprague-Dawley rats and NMRI mice were exposed to ethylene oxide for six hours. Urine specimens were collected after exposure and the amount of thiodiacetic acid was determined by gas chromatography/mass spectrometry. The quantity of excreted TDA increased enormously compared to control samples. So thiodiacetic acid seems to be a metabolite of ethylene oxide in vivo.

Animals↗

Interaction of lignans with human sex hormone binding globulin (SHBG).

Lignans bind to sex hormone-binding globulin (SHBG). The lignan with the highest binding affinity is (+/-)-3,4-divanillyltetrahydrofuran. In a double Stobbe condensation--without use of protecting groups--a wide variety of lignans with different substitution pattern in the aromatic and aliphatic part of the molecule was synthesized. These lignans were tested in a SHBG-binding assay which allowed to deduce the following relationship between structure and activity: 1) (+/-)-diastereoisomers are more active than meso compounds 2.) the 4-hydroxy-3-methoxy (guajacyl) substitution pattern in the aromatic part is most effective 3.) the activity increases with the decline in polarity of the aliphatic part of the molecule.

Binding, Competitive↗

The course of enzymatically induced lipid peroxidation in homogenized porcine kidney tissue.

Homogenization of mammalian tissue--exemplified by porcine kidney-- causes enzymatically induced lipid peroxidation (LPO) processes proven by measuring the amounts of the typical lipid peroxidation products 9- and 13-hydroxy-octadecadienoic acid (HODE) either after homogenization in aqueous (activation of enzymes) or an organic (inactivated enzymes) solvent. A kinetic study revealed that the level of the 9- and 13-isomer reached maximum values 6 hours after tissue injury. Within one day the amount of these primary oxidation products was reduced fast, indicating that they undergo degradation in their biological environment. In contrast, the level of 10-hydroxy-octadecanoic acid--obviously derived from LPO of oleic acid--increased continuously even after one day. These observations reflect that the generation and degradation of hydroperoxides occurs at different rates which might be of interest in pathological processes connected with tissue injury, e.g. myocardial infarction.

Animals↗