PubMed HealthSearch

Biomedical subjects

E F Elstner

Publications and source records attributed to E F Elstner.

At least 19 recordsLinked to original sources

Modulation of the production of reactive oxygen species by pre-activated neutrophils by aminoadamantane derivatives.

Aminoadamantane derivatives (AAD) such as amantadine or memantine have been used for the treatment of Morbus Parkinson and Morbus Alzheimer. In this communication, we report on the immunomodulatory activities of AAD. Luminol-dependent chemiluminescence of zymosan-, N-formylmethionylleucylphenylalanine(FMLP)- or experimental Ca2+-ionophore(A 231879)-preactivated polymorphonuclear leukocytes (PMN) was strongly enhanced by submicromolar concentrations of AAD and inhibited at higher concentrations than 0.1 mM. Light emission by phorbol-12-myristate-acetate(PMA)-preactivated cells was not further stimulated but inhibited by the elevated concentrations, just as with the other, above-mentioned activators. Ethylene formation from alpha-keto-methylthiobutyrate (KMB) as an indicator for production of OH.-type reactive oxygen species by the NADPH-oxidase ("respiratory burst") was augmented by AAD and completely inhibited by superoxide dismutase. In contrast, ethylene release from 1-amino-cyclopropyl-l-carboxylic acid (ACC) as relatively specific indicator for the myeloperoxidase reaction after degranulation was not influenced by AAD. As documented by several model reactions, AAD per se did not act as scavengers or quenchers of activated oxygen species such as superoxide, OH.-radical, hydrogen peroxide or hypochlorite. Altogether, these results suggest that submicromolar concentrations of AAD upregulate the respiratory burst, but apparently not the degranulation of prestimulated polymorphonuclear leukocytes. At higher concentrations of AAD, both respiratory burst and degranulation are inhibited, however. These effects can also be shown in complete blood samples.

Amantadine

Biological durability and oxidative potential of a stonewool mineral fibre compared to crocidolite asbestos fibres.

Experiments are described concerning the differences in redox properties and biodurability of natural asbestos fibres and an experimental stonewool fibre incubated in Gamble solution and reconstructed surfactant fluid. Crocidolite exhibits a significantly higher oxidative potential compared to the tested stonewool fibres. The oxidative activity of both types of fibres is not constant during incubation over several weeks, but rather shows a sinoidal curve including reactivities much higher than those at the beginning of the incubation. A continuous loss of mass is concluded not to be definitively connected with a continuous loss of toxicity.

Asbestos, Crocidolite

Interactions of different extracts of propolis with leukocytes and leukocytic enzymes.

Extracts of the "bee glue" propolis exhibit well-known antioxidative and anti-inflammatory properties. However, the biochemical mechanisms of propolis effects in wound healing and inflammatory processes are not yet fully understood. Therefore the effects of different ethanolic and aqueous extracts on leukocytes and some of their most important enzymes namely myeloperoxidase, NADPH oxidase and lipoxygenase were investigated. Only high concentrations of propolis extracts inhibited these enzymatic activities but especially the water-soluble derivatives showed stimulatory effect on the activity of commercially available human myeloperoxidase. Leukocytic myeloperoxidase and NADPH oxidase activities were clearly inhibited by propolis extracts probably indirectly due to their excellent radical scavenging properties.

Animals

Effects of extracts from Populus tremula L., solidago virgaurea L. and Fraxinus excelsior L. on various myeloperoxidase systems.

Extracts from Populus tremula, Solidago virgaurea and Fraxinus excelsior are used as anti-inflammatory drugs. The effects of these extracts on myeloperoxidase (MPO), an enzyme liberated by activated granulocytes and known to produce the destructive agent hypochloric acid, were investigated. Populus and Fraxinus inhibited this enzyme, Solidago was without effect. These results were obtained concordantly with four different MPO-assays (H2O2/MPO; X/XOD/MPO; activated PMN; and elastase/alpha 1-PI-MPO). Fractionation of Populus and Fraxinus extracts showed that this inhibition is due to several different compounds. Well known or wide spread substances as e.g. rutin, salicylic acid, chlorogenic acid etc. had no or only little effect on the enzyme.

Amino Acids

Gas chromatographic differentiation between myeloperoxidase activity and Fenton-type oxidants.

Several pathological situations are characterized by the production of reactive oxygen species (ROS), whereby different sources such as activated leukocytes and xanthine oxidase seem to be mainly responsible. The contribution of immigrating activated neutrophils to symptom development during inflammatory processes or after reperfusion of ischemic tissues is a matter of continuing discussion. We present a simple method for the differentiation between oxygen activating reactions in which neutrophil-derived myeloperoxidase is involved. The method is based on the gas chromatographic detection of ethylene, which is formed by the reaction of alpha-keto-gamma-methylthiobutyric acid (KMB) or 1-amino-cyclopropane-1-carboxylic acid (ACC) with ROS. In the presence of OH-radical-type oxidants, only KMB yields ethylene whereas ACC is fragmented by myeloperoxidase-derived species (OCl-, chloramines). The amounts of ethylene may be used as an indicator for the relative contribution of Fenton-type or myeloperoxidase-catalyzed reactions.

Amino Acids

Biological and biochemical effects of air pollutants: synergistic effects of sulphite.

Air pollution has become a major public and political concern since the beginning of industrialization, particularly motor exhaust over the past three decades. Epidemiological studies, together with clinical trials and experiments in exposition chambers (including biochemical model reactions), have contributed to our knowledge of potential dangers and increased our understanding of the corresponding mechanisms and dose-response effects. Comparison of the threatening reports that appear almost daily in the press with the digest of over 800 scientific publications allows the statement that the impact of ozone and nitric oxide on the health and performance of plants and animals is widely overestimated and appears to be used as a political instrument. In contrast, the combination of SO2 with soot and asbestos particles may represent an underestimated toxic potential. In this communication, we shall concentrate on basic redox mechanisms involving SO2 and important target molecules, as well as looking at the cooperative effects of sulphite and soot particles.

Air Pollutants

Sedative action of extract combinations of Eschscholtzia californica and Corydalis cava.

The herbal drug Phytonoxon N (abbreviated as PN) is indicated in nervousness induced insomnia, agitation and/or anxiety. It is composed of alcoholic drug extracts of the plants Corydalis cava (20%) and Eschscholtzia californica (80%). Both plants are rich in isoquinoline alkaloids derived from tyrosine metabolism. Recent research shows that they may influence the neurotransmitter metabolism.

Alkaloids

Modulation of key reactions of the catecholamine metabolism by extracts from Eschscholtzia californica and Corydalis cava.

Aqueous-alcoholic extracts from Eschscholtzia californica inhibit the enzymatic degradation of catecholamines as well as the synthesis of adrenaline, whereas aqueous-ethanolic extracts from Corydalis cava enhance the chemical oxidation of adrenaline and the synthesis of melanine from dihydroxyphenylalanine (DOPA). Both extracts dramatically shorten the lag phase in the catalysis of phenolase probably due to their o-diphenol content, where the Corydalis extracts are 10 times more active than the Eschscholtzia preparations. Dopamine beta-hydroxylase and monoamine oxidase (MAO-B) are especially inhibited by Eschscholtzia extracts. Diamine oxidases are inhibited by both preparations to a similar extent. The results of this study may be interpreted as a cooperative function of the two preparations in establishing and preserving high catecholamine levels thus explaining their sedative, antidepressive and hypnotic activities.

Alkaloids

Effects of ethanolic extracts from Eschscholtzia californica and Corydalis cava on dimerization and oxidation of enkephalins.

The endogenous pentapeptides, met-enkephalin and leuenkephalin, similar to their parent structures, beta-endorphin or dynorphin, bind to opioid receptors of the nociceptive system thus provoking analgesic responses. Peroxidases and phenolases (tyrosinase, catecholase) were shown to dimerize these pentapeptides thus possibly modulating their activity and/or lifetime. Extracts from plants from the order of the Papaverales contain isoquinoline alkaloids. Since the benzoisoquinolines are known to possess sedative-hypnotic activities, the potential effects of extracts from two species from this plant group, Eschscholtzia californica (Papaveraceae) and tyrosinase-catalyzed dimerization and/or oxidation of met-enkephalin were investigated. The results of the study show that the peroxidase-catalyzed dimerization via the tyr-residues is especially inhibited by the C. cava extract. The tyrosinase-catalyzed reaction yields five different products A-E, according to their HPLC-retention times. Consisting of the 4:1 (v/v) combination of the extracts from E. californica and C. cava, Phytonoxon N (abbreviated as PN) stimulates the formation of minor products A, B and E, whereas the formation of the major products C and D is inhibited. Only products C and D exhibit properties similar to the peroxidase-derived dimer. Product A is likely to be identical to DOPA-enkephalin.

Alkaloids

A combination of Populus tremula, Solidago virgaurea and Fraxinus excelsior as an anti-inflammatory and antirheumatic drug. A short review.

Anti-inflammatory properties of Populus tremula are mainly deduced from its components, the well investigated salicylates. Solidago extracts have spasmolytic, antihypertensive and diuretic effects. Fraxinus excelsior itself has hardly been investigated, but its coumarin components proved to have a variety of pharmacological properties, i.e. inhibition of T-cell activation and of the arachidonic acid cascade. Phytodolor N (abbreviated as PD) is a combination of the above mentioned plants. Various in vitro and especially in vivo studies proved its anti-inflammatory and antirheumatic properties, often comparable to non-steroidal anti-inflammatories, but with little or no side effects.

Animals

Inhibition of dihydrofolate reductase activity by alcoholic extracts from Fraxinus excelsior, Populus tremula and Solidago virgaurea.

Aqueous-ethanolic extracts of Fraxinus excelsior, Populus, tremula and Solidago virgaurea in a combination of 1: 3: 1 (v/v/v) are the components of the plant drug Phytodolor N (abbreviated as PD), which exhibits antipyretic, analgesic and antirheumatic activity. Similar to a broad variety of synthetic non-steroidal anti-inflammatories the mentioned plant extracts inhibit dihydrofolate reductase. The following concentrations as percentage in the test volumes represent the individual I50-values: F. excelsior = 0.26% (v/v); P. tremula = 0.46% (v/v) and S. virgaurea = 0.6% (v/v). The combined extracts in PD exhibit an I50 at 0.3% (v/v). Testing the activity of the water-soluble compounds of corresponding dry extracts, the activity of F. excelsior with an apparent I50-value of 0.008% (w/v) by far dominates the inhibitory overall effect of the combination (I50 = 0.014%, w/v).

Animals

Antioxidative properties of alcoholic extracts from Fraxinus excelsior, Populus tremula and Solidago virgaurea.

Aqueous-ethanolic extracts from Fraxinus excelsior, Populus tremula and Solidago virgaurea inhibit biochemical model reactions representing inflammatory situations to various extents. These model reactions include xanthine oxidase, diaphorase in the presence of the autoxidizable quinone juglone, lipoxygenase and photodynamic reactions driven by riboflavin or rose bengal. The tested extracts are the components of the phytomedicine Phytodolor N (abbreviated as PD) which possesses antipyretic, analgesic, antiinflammatory and antirheumatic activity. Since several reactive oxygen species produced by the mentioned model systems are also involved in inflammatory processes, the beneficial activities of the complete drug may at least in part be due to the reported antioxidative functions of the individual components.

Animals

The influence of magnesium-pyridoxal-5'-phosphate-glutamate in comparison with probucol, alpha-tocopherol and trolox on copper-induced oxidation of human low density lipoprotein in vitro.

Low density lipoprotein (LDL) in the presence of magnesium-pyridoxal-5'-phosphate-glutamate (MPPG), pyridoxal-5'-phosphate (PP), alpha-tocopherol, probucol or trolox is more resistant against copper-induced oxidation as control-LDL in vitro. The efficiency of the drugs is: probucol > MPPG > trolox > alpha-tocopherol > PP. LDL oxidation is determined by its increasing negative surface charge, fragmentation of apolipoprotein B-100 and changes of the fatty acid content of LDL. The protection of the drugs depends on their concentration and incubation time. Different experiments point to the fact that copper-induced oxidation of LDL in vitro starts with the binding of copper at the apolipoprotein B-100, resulting in an increasing negative surface charge and fragmentation of the apolipoprotein B-100. Afterwards a decrease of LDL-bound linoleic acid (18:2) is measurable.

Arteriosclerosis

Tetrachlorodecaoxygen, a wound healing agent, produces vascular relaxation through hemoglobulin-dependent inactivation of serotonin and norepinephrine.

We investigated the vasoactive actions of the wound-healing agent tetrachlorodecaoxygen (TCDO). TCDO (20 microM) had no direct effect on tone in isolated calf pulmonary arteries precontracted with potassium with or without 1 microM reduced hemoglobin under O2 or N2 atmosphere. However, TCDO, in a reduced hemoglobin-dependent manner, attenuated contraction produced by serotonin, associated with spectral changes consistent with destruction of serotonin. The loss of tone induced by serotonin catalyzed by TCDO plus reduced hemoglobin was not altered in the presence of superoxide dismutase (SOD) plus catalase. TCDO plus reduced hemoglobin also produced rapid relaxation of isolated rabbit aorta precontracted with norepinephrine (NE), whereas with phenylephrine (PE)-induced bone, the observed relaxation was slow to develop. Neither did TCDO, with or without reduced hemoglobin, alter soluble guanylate cyclase activity in pulmonary artery. Thus, a highly reactive species produced by interaction of TCDO with reduced hemoglobin appears to attenuate the contractile actions of serotonin, NE, and PE, selectively potentially by destroying these vasoactive agents. The vasodilator actions of TCDO (plus reduced hemoglobin) may contribute to wound healing by increasing nutrient blood flow and O2 delivery needed for repair processes and bactericidal activity.

Animals

Peroxide-dependent amino acid oxidation and chemiluminescence catalysed by magnesium-pyridoxal phosphate-glutamate complex.

Magnesium-pyridoxal-5'-phosphate-glutamate (MPPG) has been shown to ameliorate atherosclerotic symptoms in rabbits. In vitro, MPPG in the presence of peroxides such as cholesterolhydroperoxide or cumene hydroperoxide and Mn2+ ions produces "excited states" measurable as chemiluminescence or ethylene release from 1-aminocyclopropane-1-carboxylic acid (ACC). The reactions are stimulated synergistically by unsaturated fatty acids. Pyridoxal phosphate exhibits similar properties, but can be differentiated from the activities of MPPG or the sum of the components present in MPPG.

Amino Acids

Oxidative destruction of biomolecules by gasoline engine exhaust products and detoxifying effects of the three-way catalytic converter.

Aqueous solutions of engine exhaust condensation products were derived from cars powered by diesel or four-stroke gasoline engines (with and without three-way catalytic converter). The cars were operated on a static test platform. Samples of the different exhaust solutions accumulated in a Grimmer-type distillation trap (VDI 3872) during standard test programs (Federal Test Procedure) were incubated with important biomolecules. As indicators of reactive oxygen species or oxidative destruction, ascorbic acid, cysteine, glutathione, serum albumin, the enzymes glycerinaldehyde phosphate dehydrogenase and xanthine oxidase, and the oxygen free-radical indicator keto-methylthiobutyrate were used. During and after the incubations, oxygen activation (consumption) and oxidative destruction were determined. Comparison of the oxidative activities of the different types of exhaust condensates clearly showed that the exhaust condensate derived from the four-stroke car equipped with a three-way catalytic converter exhibited by far the lowest oxidative and destructive power.

Antioxidants

Oxygen radicals--biochemical basis for their efficacy.

In the last decade it has become quite clear that oxygen free radicals are involved in a vast amount of diseases such as cataract, atherosclerosis, rheumatism, arthritis, Parkinson's disease, reperfusion injuries and many others. The induction of defence systems against certain stresses (heat shock, inflammation) is also mediated by activated oxygen species. Oxygen-activation and -desactivation has to be regulated and well attenuated in aerobic cells and tissues. The biochemical basis of the biological efficacy of oxidants is thus based on a sophisticated balance between catalysis of production and reactivity of oxygen radicals by certain cofactors and transition metals on the one hand and on a reliable detoxification by antioxidants or metabolic chains on the other hand. In this communication, different oxygen activating principles are compared and the biochemical basis for the induction of repair processes by a synthetic heme oxidant, (Tetrachlorodecaoxide, TCDO) is presented.

Animals