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Biomedical subjects

J Bremer

Publications and source records attributed to J Bremer.

At least 37 records · Page 2Linked to original sources
PubMed1999

Short-term regulation of carnitine palmitoyltransferase I in cultured rat hepatocytes: spontaneous inactivation and reactivation by fatty acids.

Liver carnitine palmitoyltransferase I (CPT I), the rate-limiting enzyme of mitochondrial beta-oxidation, rapidly loses its activity when hepatocytes are put in culture. 3-Thia fatty acids reactivate the enzyme and can increase its activity 3-4-fold in 5-10 min. Normal fatty acids are also able to stimulate CPT I, but to a limited extent, compared to 3-thia fatty acid. This activation does not affect malonyl-CoA sensitivity. CPT I in hepatocytes from both fasted and fasted-carbohydrate refed rats is inactivated and reactivated to a similar extent. Free dodecylthioacetic acid (DTA) is at least as efficient as DTA-CoA as activator. CPT I activity in isolated mitochondria is not influenced by incubation with DTA, suggesting that the regulation of CPT I depends on an extramitochondrial component(s) in the cell. It is concluded that fatty acids activate pre-existing, inactive CPT I without involvement of gene transcription and independently of malonyl-CoA.

Animals↗
PubMed1999

Bile salts: natural detergents for the prevention of sexually transmitted diseases.

The development of new, safe, topical microbicides for intravaginal use for the prevention of sexually transmitted diseases is imperative. Previous studies have suggested that bile salts may inhibit human immunodeficiency virus infection; however, their activities against other sexually transmitted pathogens have not been reported. To further explore the potential role of bile salts in preventing sexually transmitted diseases, we examined the in vitro activities and cytotoxicities of select bile salts against Chlamydia trachomatis, herpes simplex virus (types 1 and 2), Neisseria gonorrhoeae, and human immunodeficiency virus in comparison to those of nonoxynol-9 and benzalkonium chloride using both primary cells and cell lines derived from the human female genital tract. We found that taurolithocholic acid 3-sulfate and a combination of glycocholic acid and taurolithocholic acid 3-sulfate showed excellent activity against all of the pathogens assayed. Moreover, taurolithocholic acid 3-sulfate alone or in combination was less cytotoxic than nonoxynol-9 and benzalkonium chloride. Thus, taurolithocholic acid 3-sulfate alone or in combination warrants further evaluation as a candidate topical microbicidal agent.

Bile Acids and Salts↗
PubMed1998

Alpha- and beta- alkyl-substituted eicosapentaenoic acids: incorporation into phospholipids and effects on prostaglandin H synthase and 5-lipoxygenase.

Alpha-ethyl-, alpha-methyl- and beta-methyl eicosapentaenoic acid (EPA) were prepared and their incorporation into cell lipids and effects on eicosanoid synthesis compared with EPA and docosahexaenoic acid (DHA). alpha- and beta-methyl EPA were incorporated into hepatocyte triacylglycerols as efficiently as EPA, whereas lesser amounts were found in phospholipids. alpha-ethyl EPA was not incorporated into phospholipids but small amounts were detected in triacylglycerol. All derivatives inhibited the synthesis of arachidonic acid, although less efficiently than EPA and DHA. The derivatives were poor substrates of prostaglandin H (PGH) synthase and 5-lipoxygenase, and they all inactivated PGH synthase. In isolated platelets, alpha-methyl EPA was a stronger inhibitor of TxB2 production than EPA, alpha-ethyl- and beta-methyl EPA. All derivatives were stronger inducers of peroxisomal beta-oxidation than EPA and DHA. This increased induction probably is a consequence of the blocked mitochondrial beta-oxidation of the derivatives.

Animals↗
PubMed1998

Absolute copy number and relative change in determinations of human immunodeficiency virus type 1 RNA in plasma: effect of an external standard on kit comparisons.

Use of a common set of human immunodeficiency virus type 1 (HIV-1) RNA standards eliminated differences among absolute HIV-1 RNA copy number estimates made with three commercially available assays. The relative changes in the viral RNA levels determined by the commercial assays were similar and were unaffected by the use of a common set of standards.

Female↗
PubMed1997

[A 100 year old thesis. Amanuensis Hans Christian Geelmuyden].

Hans Christian Geelmuyden (1861-1945) was amanuensis (assistant professor) at the Institute of Physiology, University of Oslo from 1889 to 1931. In 1897 he was awarded the degree "Doctor of Medicine" for his thesis "Om aceton som stofvexelprodukt" (On acetone as a metabolic product). The Nobel laureate Feodor Lynen referred to this thesis, which was also published in German, stating that Geelmuyden was the first to establish that ketone bodies are formed from fatty acids. Geelmuyden also established that acetone is metabolized in rabbits and dogs. Geelmuyden was a prolific writer on fat metabolism and diabetes and wrote a series of extensive reviews on these topics in Ergebnisse der Physiologie. Geelmuyden was active in the treatment of diabetic patients.

Academic Dissertations as Topic↗
PubMed1997

Thia fatty acids as substrates and inhibitors of stearoyl-CoA desaturase.

Thia fatty acids are fatty acid analogues, where sulfur atoms substitute methylene groups in the carbon chain. In 7800 C1 Morris hepatoma cells and in hepatocytes 9-thia and 10-thia stearic acid are strong inhibitors of stearoyl-Co desaturase, while 3,9-dithia stearic acid and 3,10-dithia stearic acid are much weaker inhibitors. No effect on the stearoyl-CoA desaturase can be observed with 3-thia stearic acid. In microsomes, an equimolar concentration of 9-thia stearoyl-CoA inhibits the delta9 desaturation of [1-14C]stearoyl-CoA approximately 75%, while 3,9-dithia stearoyl-CoA and 3,10-dithia stearoyl-CoA again are weak inhibitors. 3-Thia stearoyl-CoA has no effect on the desaturation of [1-14C]stearoyl-CoA. [2-14C]3-Thia stearoyl-CoA is delta9 desaturated to [2-14C]thia oleic acid. This desaturation is inhibited by unlabelled stearoyl-CoA, which therefore is the preferred substrate. These results show that a sulfur atom in the 3 position reduces the affinity of the CoA ester for the enzyme, but permits desaturation. A sulfur in the 9 or 10 position does not affect binding to the enzyme. The 9-thia and 10-thia stearoyl-CoA, which cannot be desaturated, therefore are strong inhibitors.

Acyl Coenzyme A↗
PubMed1997

Polyunsaturated thia- and oxa-fatty acids: incorporation into cell-lipids and their effects on arachidonic acid- and eicosanoid synthesis.

EPA, DHA, C15SCH2COOH (n-3), C15SCH2COOH (n-6) and C18SCH2COOH (n-3) are extensively incorporated into phospholipids and triacylglycerol in rat hepatocytes after 24 h incubation with 80 microM fatty acid/derivative. Only traces of polyunsaturated 3-oxa fatty acids (C15OCH2COOH, C18OCH2COOH) were incorporated. C15-S-butyric acid (n-3) is a stronger inhibitor of delta6-desaturase in rat liver-microsomes than C15SCH2COOH (n-3), C15-S-propionic acid (n-3), EPA and DHA. It inhibits delta5-desaturase in a similar manner to EPA and DHA. Arachidonic acid and C15SCH2COOH, (n-6) are better substrates for PGH-synthase than EPA and C15SCH2COOH, (n-3), showing the inhibitory effect of the n-3 bond. The n-3 polyunsaturated fatty acids, including the sulfur-substituted fatty acid derivatives, are poor substrates for PGH-synthase. However, they inactivate the PGH-synthase activity at least as efficiently as arachidonic acid. C15SCH2COOH (n-3), C15S(CH2)2COOH (n-3) and C18SCH2COOH (n-3) induce peroxisomal beta-oxidation more than EPA and DHA.

Acyl-CoA Oxidase↗
PubMed1997

Thia fatty acids, metabolism and metabolic effects.

(1) The chemical properties of thia fatty acids are similar to normal fatty acids, but their metabolism (see below: points 2-6) and metabolic effects (see below: points 7-15) differ greatly from these and are dependent upon the position of the sulfur atom. (2) Long-chain thia fatty acids and alkylthioacrylic acids are activated to their CoA esters in endoplasmatic reticulum. (3) 3-Thia fatty acids cannot be beta-oxidized. They are metabolized by extramitochondrial omega-oxidation and sulfur oxidation in the endoplasmatic reticulum followed by peroxisomal beta-oxidation to short sulfoxy dicarboxylic acids. (4) 4-Thia fatty acids are beta-oxidized mainly in mitochondria to alkylthioacryloyl-CoA esters which accumulate and are slowly converted to 2-hydroxy-4-thia acyl-CoA which splits spontaneously to an alkylthiol and malonic acid semialdehyde-CoA ester. The latter presumably is hydrolyzed and metabolized to acetyl-CoA and CO2. (5) Both 3- and 4-thiastearic acid are desaturated to the corresponding thia oleic acids. (6) Long-chain 3- and 4-thia fatty acids are incorporated into phospholipids in vivo, particularly in heart, and in hepatocytes and other cells in culture. (7) Long-chain 3-thia fatty acids change the fatty acid composition of the phospholipids: in heart, the content of n-3 fatty acids increases and n-6 fatty acids decreases. (8) 3-Thia fatty acids increase fatty acid oxidation in liver through inhibition of malonyl-CoA synthesis, activation of CPT I, and induction of CPT-II and enzymes of peroxisomal beta-oxidation. Activation of fatty acid oxidation is the key to the hypolipidemic effect of 3-thia fatty acids. Also other lipid metabolizing enzymes are induced. (9) Fatty acid- and cholesterol synthesis is inhibited in hepatocytes. (10) The nuclear receptors PPAR alpha and RXR alpha are induced by 3-thia fatty acids. (11) The induction of enzymes and of PPAR alpha and RXR alpha are increased by dexamethasone and counteracted by insulin. (12) 4-Thia fatty acids inhibit fatty acid oxidation and induce fatty liver in vivo. The inhibition presumably is explained by accumulation of alkylthioacryloyl-CoA in the mitochondria. This metabolite is a strong inhibitor of CPT-II. (13) Alkylthioacrylic acids inhibits both fatty acid oxidation and esterification. Inhibition of esterification presumably follows accumulation of extramitochondrial alkylthioacryloyl-CoA, an inhibitor of microsomal glycerophosphate acyltransferase. (14) 9-Thia stearate is a strong inhibitor of the delta 9-desaturase in liver and 10-thia stearate of dihydrosterculic acid synthesis in trypanosomes. (15) Some attempts to develop thia fatty acids as drugs are also reviewed.

Acyl-CoA Dehydrogenase, Long-Chain↗
PubMed1997

Heneicosapentaenoate (21:5n-3): its incorporation into lipids and its effects on arachidonic acid and eicosanoid synthesis.

6,9,12,15,18-Heneicosapentaenoic acid (21:5n-3) (HPA), present in small amounts in fish oils, has been prepared by chemical elongation of eicosapentaenoic acid (EPA) and its biological properties compared with EPA and docosahexaenoic acid (DHA). All the double bonds of HPA are displaced one carbon away from the carboxyl group when compared to EPA. HPA is incorporated into phospholipids and into triacylglycerol in cell culture to a similar extent as EPA and DHA. HPA is a stronger inhibitor of the conversion of alpha-linoleic acid and dihomo-gamma-linolenic acid to arachidonic acid (AA) in hepatoma cells than are EPA, DHA, and AA. HPA is a poor substrate for prostaglandin H synthase and for 5-lipoxygenase, but it inactivates prostaglandin H synthase as rapidly as do AA, EPA, and DHA. HPA inhibits thromboxane synthesis in isolated platelets as efficiently as EPA. EPA, HPA, and DHA are all weak inducers of acyl-CoA oxidase in hepatoma cells. Therefore, since fish oils contain only small amounts of HPA, it is unlikely that this fatty acid is of particular significance for the biological effects of these oils, possibly with the exception that it is a strong inhibitor of AA synthesis.

Animals↗
PubMed1997

Sulfated carbohydrate compounds prevent microbial adherence by sexually transmitted disease pathogens.

Heparan sulfate (HS) serves as a receptor for adherence of herpes simplex viruses, Chlamydia trachomatis, Neisseria gonorrhoeae, and, indirectly, human immunodeficiency virus. Using primary human culture systems, we identified sulfated carbohydrate compounds that resemble HS and competitively inhibit infection by these pathogens. These compounds are candidates for intravaginal formulations for the prevention of sexually transmitted diseases.

Bacterial Adhesion↗
PubMed1997

Stabilities of free and complexed human immunodeficiency virus p24 antigens during short- and long-term storage.

By the standard p24 assay there was a 25 to 27% decrease in free p24 antigen in serum after storage at 4 degrees C over 14 days but no loss at -70 degrees C. There was no loss at either temperature by the immune complex dissociation (ICD) procedure. Furthermore, there was no significant loss of detectable p24 in serum by either the ICD or the standard p24 assay after 700 days of storage at -70 degrees C.

Antigen-Antibody Complex↗
PubMed1996

Effects of chain length and sulphur position of thia fatty acids on their incorporation into phospholipids in 7800 C1 hepatoma cells and isolated rat hepatocytes, and their effects on fatty acid composition of phospholipids.

Incorporation of thia fatty acids and their effects on the fatty acid composition in phospholipids has been investigated in 7800 C1 hepatoma cells and cultured hepatocytes. 3-Thia fatty acids of chain lengths from dodecyl-to hexadecyl-thioacetic acid were incorporated into phospholipids during a 3-day incubation. Longer and shorter 3-thia fatty acids were barely detectable. Tetradecylthioacetic acid, 3-thia stearate, and their delta9- desaturated derivatives were maximally incorporated into whole-cell phospholipids. The amount of tetradecylthioacetic acid incorporated into phospholipids of hepatoma cells remained almost identical in cells cultured for 3 days or adapted over a period of 1 year. Delta9-desaturated metabolites of long chain thia fatty acids (C13-to C16-S-acetic acid) were identified by GC-MS in phospholipids. 3-Thia stearate appeared to be the best substrated for delta9 desaturase. Incubation of hepatoma cells with thia fatty acids led to alterations in the amount of normal fatty acids in total phospholipids. The amounts of 16:0 and 18:1 decreased and 18:2 (n-6) and 20:5 (n-3) increased. Changes in the normal fatty acid composition of phospholipids were seen both with thia acids incorporated into phospholipids and those not incorporated. These effects, therefore, may be only partially dependent on displacement of normal fatty acids by thia fatty acids. Morris 7800 C1 hepatoma cell acyl-CoA synthetase (ACS) and peroxisomal acyl-CpA oxidase (ACO) were induced by thia fatty acids of all chain lengths, and with the sulphur atom(s) in different positions. Control experiments with hepatocytes revealed a similar incorporation of thia fatty acids in these physiologically more normal cells.

Acyl-CoA Oxidase↗
PubMed1996

Peroxidative oxidation of leuco-dichlorofluorescein by prostaglandin H synthase in prostaglandin biosynthesis from polyunsaturated fatty acids.

Prostaglandin H synthase can oxidize arachidonic acid with leuco-dichlorofluorescein as reducing cosubstrate. Addition of 0.5 mM phenol increases the oxidation of leuco-dichlorofluorescein to dichlorofluorescein 5-fold, probably by acting as a cyclic intermediate in the oxidation. Tetramethyl-p-phenylenediamine is also oxidized as cosubstrate. Its oxidation is not influenced by phenol. A stoichiometry of close to one mole of tetramethyl-p-phenylenediamine or leuco-dichlorofluorescein consumed per mole of arachidonic acid was found in the initial phase of the reaction. In the presence of phenol + leuco-dichlorofluorescein, the oxidation rate of arachidonic acid is about 40% lower than with phenol alone as cosubstrate. Since dichlorofluorescein has a molar extinction coefficient of 91 . 10(3) at 502 nm, the oxidation of less than 1 microM leuco-dichlorofluorescein can be detected spectrophotometrically. The rate of extinction change with leuco-dichlorofluorescein (at 502 nm) is about 4-fold more rapid than with tetramethyl-p-phenylenediamine (at 611 nm). With this spectrophotometric assay we have confirmed that arachidonic acid, linolenic acid, adrenic acid, gamma-linolenic acid, eicosapentaenoic acid, are substrates for prostaglandin H synthase with decreasing reaction rates in the mentioned order. The same order of reaction rates were found when oxygen consumption was measured. The assay also shows that docosahexaenoic acid is substrate for the enzyme. The reaction rate of the enzyme evidently is decreased both by a n-3 double bond and by deviation from a 20 carbon chain length of the fatty acid substrate.

Animals↗