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Biomedical subjects

P Ludwig

Publications and source records attributed to P Ludwig.

At least 55 records · Page 3Linked to original sources
PubMed1985

The share of lipoxygenase in the antimycin-resistant oxygen uptake of intact rabbit reticulocytes.

The endogenous oxygen uptake of rabbit reticulocyte-rich red cell suspensions obtained by bleeding anaemia of rabbits amounted to 7.85 +/- 0.87 mumoles/h . ml of packed cells and was inhibited by antimycin A to 77.2 +/- 1.1%. The antimycin A-resistant oxygen uptake was further inhibited by the lipoxygenase inhibitors salicylhydroxamic acid, 5,8,11,14-eicosatetraynoic acid, nordihydroguaiaretic acid, 4-nitrocatechol or propylgallate by about 20-30% corresponding to 5-7% of the total oxygen uptake. The effects of the lipoxygenase inhibitors were most pronounced during the first period of bleeding anaemia (5th-9th day). 3-amino-1,2,4-triazole inhibited another part of the non-respiratory oxygen uptake and acted additively to 5,8,11,14-eicosatetraynoic acid; the two inhibitors together caused inhibition by one-half. Influx of calcium ions mediated by the ionophore A 23187 led to a two-fold increase in the non-respiratory oxygen uptake which was mainly due to stimulation of the lipoxygenase reaction. The rate of the lipoxygenase-mediated oxygen uptake was sufficient for a complete dioxygenation of the polyenoic fatty acids present in mitochondrial phospholipids during the maturational degradation of mitochondria in reticulocytes.

Animals↗
PubMed1985

Possible involvement of endogenous free fatty acids in the selective inactivation of the mitochondrial electron transfer system during hyperthermic incubation of rabbit reticulocytes.

Preincubation of rabbit reticulocyte-rich red cell suspensions at 45 degrees C for 1 h led to a lowering of the total endogenous oxygen uptake by 40%, a decrease of the CCCP-stimulated antimycin-A-sensitive part of the oxygen uptake by 72%, an inhibition of the antimycin A-resistant oxygen uptake by only one-third, the loss of the response of cell respiration to the uncoupler CCCP and a slight enhancement of the degree of uncoupling which is however of minor importance for the changes in the cell respiration during hyperthermic incubation. The degree of inactivation of the respiratory chain increased continuously with the temperature of preincubation beginning at 39 degrees C. Addition of defatted human serum albumin to the cells caused protection from thermal inactivation. The protective action of serum albumin was lowered by loading it with myristic acid. It is concluded that the thermal inactivation of the respiratory chain in reticulocytes may be mediated by endogenous free fatty acids.

Animals↗
PubMed1983

Haemoglobin potentiates the respiration-inhibitory action of lipoxygenases via its pseudolipohydroperoxidase activity.

The inhibition of the NADH oxidase and of the succinate-cytochrome c oxidoreductase activities of beef heart submitochondrial particles (ETP) induced by reticulocyte lipoxygenase is strongly potentiated by haemoglobin added simultaneously or subsequently to lipoxygenase. Half-maximal potentiation was observed with 0.9 microM haemoglobin. Haemoglobin augments also the lipoxygenase-induced loss of acid-labile sulphur in ETP not related to respiratory inhibition. Soybean lipoxygenase produces only weak respiratory inhibition even at high concentrations in the absence of haemoglobin; strong inhibition is obtained, however, in the presence of haemoglobin. Among other haem compounds tested only free haemin but not cytochrome c and catalase exhibit identical effects. The action of haem compounds on the system ETP plus lipoxygenase is accompanied by their destruction. The experimental evidence indicates that the effects of haemoglobin described here are due to its ability to decompose catalytically hydroperoxy lipids generated by lipoxygenase. This catalytic property (pseudolipohydroperoxidase activity) was demonstrated with 13L-hydroperoxylinoleic acid as substrate. The relations between the various catalytic actions of haemoglobin related to lipid peroxidation are discussed.

Animals↗
PubMed1982

Therapy for acute cystitis in adult women. Randomized comparison of single-dose sulfisoxazole vs trimethoprim-sulfamethoxazole.

One hundred seventeen unselected women with symptoms of acute cystitis were randomized to groups for immediate therapy with one of the following four single-dose regimens: (1) 1 g of sulfisoxazole; (2) 2 g of sulfisoxazole; (3) a combination of trimethoprim, 160 mg, and sulfamethoxazole, 800 mg; and (4) a combination of trimethoprim, 320 mg, and sulfamethoxazole, 1,600 mg. Forty-one women were excluded, 13 did not return for follow-up, and 28 did not have significant bacteriuria in the pretherapy culture. Escherichia coli was isolated in 81% of infections. Antibacterial activity was significantly greater in urine collected during the 24 hours after therapy in those who received trimethoprim-sulfamethoxazole. However, overall cure varied from 85% to 95%, without any great differences between the regimens. The rate of cure of 69% in the 13 patients with presumptive evidence of renal infection (antibody-coated bacteria present) was significantly lower than the rate of cure of 95% in women without evidence of renal infection. Single-dose therapy with these regimens was safe and effective in adult women with symptoms of acute cystitis, regardless of the localization of the site of infection.

Acute Disease↗
PubMed1982

Self-inactivation by 13-hydroperoxylinoleic acid and lipohydroperoxidase activity of the reticulocyte lipoxygenase.

1. The self-inactivation of lipoxygenase from rabbit reticulocytes with linoleic acid at 37 degrees C is caused by the product 13-hydroperoxylinoleic acid. This inactivation is promoted by either oxygen or linoleic acid. 2. Lipohydroperoxidase activity was demonstrated with 13-hydroperoxylinoleic acid plus linoleic acid as hydrogen donor under anaerobic conditions at 2 degrees C. The products were 13-hydroxylinoleic acid, oxodienes and compounds of non-diene structure similar to those produced by soybean lipoxygenase-1. 3. 13-Hydroperoxylinoleic acid also changed the absorbance and fluorescence properties of reticulocyte lipoxygenase. The results indicate that one equivalent of 13-hydroperoxylinoleic acid converts the enzyme from the ferrous state into the ferric state as described for soybean lipoxygenase-1. The spectral changes were reversed by sodium borohydride at 2 degrees C, but not at 37 degrees C; it is assumed that the ferric form of reticulocyte lipoxygenase suffers inactivation.

Animals↗
PubMed1981

On the site of action of the inhibition of the mitochondrial respiratory chain by lipoxygenase.

Treatment of beef-heart submitochondrial particles with reticulocyte lipoxygenases gives rise to a strong irreversible inhibition of the NADH and succinate oxidase activities. This is not accompanied by any loss of the Fe-S clusters of the respiratory chain as determined by EPR spectroscopy. The inhibitory blockage is located between both the NADH and succinate dehydrogenases and Q-10. The inhibitory action of treatment with lipoxygenase also takes place in the absence of Q-10. The Fe-S clusters of the mitochondrial outer membrane are destroyed by lipoxygenase treatment, without any effect on the rotenone-insensitive NADH: cytochrome c oxidoreductase activity. It is concluded that these clusters are not involved in this enzyme.

Animals↗
PubMed1980

[Electron transport particles from bovine heart as a test system in toxicological studies].

14 standard respiratory inhibitors and substances of toxicological interest were tested on the NADH oxidase and the succinate-cytochrome c oxidoreductase systems of beef heart electron transfer particles (ETP) in the presence and absence of human serum albumin (HSA). HSA did not influence the half-inhibition concentrations by cyanide, amytal and antimycin A. It had little effect on the inhibition by rotenone or carboxin, whereas the inhibition by free fatty acids and monoglyceride was greatly decreased. Lindan and DDT exerted a marked inhibition of the NADH oxidase system in the absence of HSA; the inhibition was weaker but still considerable in the presence of HSA. In the presence of HSA 10(-4) M DDT but not Lindan inhibited also the succinate-cytochrome c reductase system. The results show that ETP may be a useful test object in toxicological studies.

Amobarbital↗
PubMed1979

The lipoxygenase of reticulocytes. Purification, characterization and biological dynamics of the lipoxygenase; its identity with the respiratory inhibitors of the reticulocyte.

A lipoxygenase has been purified from rabbit reticulocyte-rich anaemic blood cells. It possesses a molecular weight of 78 000 and an isoelectric point of 5.5 and contains 5% neutral sugars and two iron atoms per enzyme molecule. The lipoxygenase has proved to be identical with the inhibitors of respiratory proteins described formerly. The actions of the lipoxygenase on linoleic acid, phospholipids, mitochondrial and erythrocyte membranes and electron transfer particles were studied. A special feature of the reticulocyte lipoxygenase is the suicidal character of its action on lipids. With electron transfer particles the reticulocyte lipoxygenase causes a loss of acid-labile sulfur which accompanies respiratory inhibition; the strong respiratory inhibition is not exerted by soybean lipoxygenase. The reticulocyte lipoxygenase acts preferably on mitochondrial membranes as compared with cell membranes of the erythrocyte; erythrocyte cytosol moderates the action on mitochondrial membranes. Furthermore, the lipoxygenase reaction can concomitantly and irreversibly inactivate sulfhydryl enzymes as demonstrated with muscle glyceraldehyde-3-phosphate dehydrogenase. The occurrence of the lipoxygenase here described is restricted to reticulocytes; very low amounts were observed in bone marrow and no lipoxygenase was detectable in normal blood. During the course of an experimental anaemia the lipoxygenase is produced owing to superinduction in large amounts, which may persist for a long time since they escape inactivation. Preliminary evidence was obtained for the occurrence of other lipoxygenases in tissues of lung, spleen, kidney and also epithelial tumours.

Amino Acids↗
PubMed1979

[Kinetics and load distribution of supported free-end prostheses. IV. Effect of the saddle curvature on the saddle resp. abutment kinetics and the load distribution in prosthesis beds without abutments].

The influence of the saddle curvature on abutment tooth kinetics and abutment tooth stress was studied with unilateral rigid and movable free-end saddle dentures. The results showed that, independent of the length of the saddle and/or of the saddle curvature, considerable horizontal and vertical extrusive abutment tooth stress is present in addition to vertical intrusive abutment tooth stress. The saddle kinetics are basically influenced by the form of the saddle. The kinetics cannot be altered appreciably because of the mechanical characteristics of the connecting elements; it can only be surpressed at the cost of increased pier stress.

Biomechanical Phenomena↗
PubMed1979

[Free fatty acids as inhibitors of the respiratory chain in testicular homogenates].

The supernatants of the 440 000 . g . min centrifugation of homogenates of rat, bull and boar testicles and sperm inhibit the NADH-oxidase activity of non-phosphorylating submitochondrial particles (ETP). Whereas no inhibitory activity was observed with young rats (150 g), a marked inhibition was detected with heavier animals. The inhibitory activity of testicles was located in the microsomal fraction. The reaction of the testicular inhibitor with the ETP is initiated by an instant reversible binding followed by a slow irreversible inhibition of the electron transport. The reason of the time-dependence is neither an interaction between the enzymes of the ETP and those of the microsomal electron transport nor a slow degradation of the ETP by microsomal phospholipases. Some observations indicate an indirect involvement of phospholipase via the formation of free fatty acids (FFA). The inhibitory fraction could be solubilized from the microsomes both by sodium cholate treatment and by ethanol extraction. After separation of the lipid classes by chromatography on silica gel and gas-chromatographic analysis the inhibitory fraction was identified as a mixture of free fatty acids (FFA) of different chain lengths and degree of saturation. Thus a new effect of FFA on the mitochondrial electron transport has been detected which is different from other actions known up till now. The degradation of the phospholipids of the endoplasmic reticulum in the spermatozoa may be the source of the enhanced formation of FFA. An inhibition of the cell respiration presumably does not occur in vivo. The high FFA level in the testicular homogenates of sexually mature animals is a consequence of an intensive FFA metabolism, especially of high phospholipase activity.

Animals↗
PubMed1978

Interrelated lipid alterations and their influence on the proliferation and fusion of cultured myogenic cells.

We have cultured myogenic cells derived from primary explants and a cell line (L6) in a lipid-depleted medium (LDM) and produced large alterations of the fatty acyl and polar headgroup composition and of the cellular sterol levels. These alterations were produced by altering the composition of the media as follows: removing biotin and providing exogenous fatty acid; removing choline and providing exogenous ethanolamine or choline analogues; and by adding 25-OH cholesterol, an inhibitor of 3-hydroxy-3-methylglutarate (HMG)-CoA reductase. Relatively small, secondary alterations of other lipid classes accompany the large primary alteration. In general, they are not obviously compensatory for the primary alteration by retaining some physical property. We have explored the influence of these lipid alterations on myoblast proliferation and fusion into myotubes. In general, considerable variability appears tolerated, but there also appear to be limits. Long-term cultures grown in media containing a single fatty acid do not proliferate indefinitely, and the fatty acid does not become the sole fatty acyl component of the phospholipids. This phenomenon is also observed for cultures enriched in phosphatidylethanolamine (PE) or phosphatidyldimethylethanolamine (PDME). The influence of the lipid alterations on fusion is particularly interesting. The inclusion of 25-OH cholesterol inhibits fusion. Enrichment of the fatty acyl chains with elaidate or the polar headgroups with PE also inhibits fusion, but in contrast to that by 25-OH cholesterol, a significant fraction of the myoblasts are aligned and interacting with each other. Oleate enrichment enhances the rate of fusion.

Animals↗