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Biomedical subjects

B Ebert

Publications and source records attributed to B Ebert.

At least 91 records · Page 5Linked to original sources

Heart protection and radical trapping by DMPO during reperfusion in isolated working rat hearts.

The purpose of this study was to use a direct method, that of electron spin resonance (ESR) spectroscopy, to demonstrate that reperfusion after a period of ischemia results in a sudden increase in the production of free radicals in the myocardium. Furthermore, the role of free radicals in the development of reperfusion arrhythmias and functional disturbances also was investigated using a 30-min period of global ischemia followed by 30 min of reperfusion in the isolated working rat heart. The spin trapping agent 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) when it perfused the heart, 100 mumoles/liter, during the first 10 min of reperfusion attenuated the development of reperfusion arrhythmias and improved the functional recovery of the heart during reperfusion. Without treatment, 55% of hearts showed irreversible ventricular fibrillation, and this was completely prevented by DMPO. In DMPO-treated hearts, the recovery of heart function was improved; thus, coronary flow, aortic flow, left ventricular developed pressure, and first derivative of left ventricular developed pressure were significantly increased from their maximal control values of 16.2 +/- 1.9 ml/min, 12.7 +/- 0.9 ml/min, 11.1 +/- 0.5 kPa, and 426 +/- 31 kPa/s to 21.8 +/- 1.3 ml/min (p less than 0.05), 28.4 +/- 3.0 ml/min (p less than 0.001), 14.5 +/- 1.0 kPa (p less than 0.01), and 584 +/- 41 kPa/s (p less than 0.01), respectively. Left ventricular end-diastolic pressure was also significantly reduced from its control value of 2.8 +/- 0.2 kPa to 2.1 +/- 0.2 kPa (p less than 0.05), while the recovery of heart rate was not improved by DMPO treatment. Parallel ESR studies using DMPO as spin trap demonstrated the formation of .OH radicals in the effluent of the reperfused hearts. ESR signals of the formed DMPO-OH, alpha N = alpha beta H = 1.48 mT, were observed within the first seconds of reperfusion with peak concentrations after about 3 min. In the first series of ESR studies, DMPO (200 mmol/liter) was mixed up effluent and ESR signals were recorded, while in the second series of studies, DMPO was directly infused into the heart. Both methods were appropriate to demonstrate the radical formation that peaked at 3 min of reperfusion after 30 min of global ischemia. Cardiotoxic effects of DMPO can be excluded by using of the "mix-up" method (DMPO is added to effluent) because relatively high DMPO concentration (20-200 mmol/liter) is important for demonstration of free radical production.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Hydroxyl radical scavenging and antipsoriatic activity of benzoic acid derivatives.

The hydroxyl radical scavenging and antipsoriatic activity of a number of lipophilic and hydrophilic benzoic acid derivatives was investigated. To quantify antioxidative effects, a newly introduced test system based on the diminution of the ESR signal of DMPO-OH (generated by Fenton's reagent) by the tested compounds was applied. It was found that the in vitro antioxidative (toward hydroxyl radical) activity of benzoic acid esters decreases with increasing chain length whereas the antipsoriatic activity increases. This effect is discussed in terms of a larger lipophilicity of long-chain esters. Propyl gallate was found to be the most active OH scavenger since it is some orders of magnitude more efficient than "model" antioxidants like alpha-tocopherol or mannitol. The highest antipsoriatic activity was exhibited by hydroxy benzoic acid decyl ester.

Adult↗

Inverse relationship between ESR spin trapping of oxyradicals and degree of functional recovery during myocardial reperfusion in isolated working rat heart.

STUDY OBJECTIVE: The aim of the study was to investigate the generation of free oxyradicals as factors in myocardial ischaemia-reperfusion pathology. DESIGN: Isolated perfused rat hearts were subjected to 30 min global ischaemia followed by reperfusion. The spin trap 5,5-dimethyl-1-pyrroline-1-oxide was added to the effluent of the heart to avoid pharmacological interaction with the heart. The effluent was then analysed by electron spin resonance spectroscopy. MATERIALS: Studies were performed on hearts of 51 male Sprague-Dawley rats, weight 300-350 g. MEASUREMENTS AND RESULTS: During reperfusion, the formation of hydroxyl radical adducts of the trap was observed, with a maximal value after 3 min. The initial amount of radicals trapped during the first 3 min of reperfusion showed an inverse correlation with the degree of heart function restored within 30 min of reperfusion. Spearman's rank correlation coefficients were calculated to be -0.734 for heart rate, -0.825 for left ventricular developed pressure, -0.787 for the maximum of its first derivative, -0.787 for coronary flow, and -0.796 for aortic flow (p less than 0.05, n = 10, in each instance). No statistically significant correlation was found between the cumulative amount of radicals trapped in the effluent during the initial phase of reperfusion and the duration of ventricular fibrillation, duration of ventricular tachycardia, or number of ventricular ectopic beats (registered during 30 min reperfusion). CONCLUSIONS: The application of spin trapping to the effluent of isolated perfused hearts allows the generation of oxyradicals to be characterised without interaction of the trap with the heart. It also allows the time course of radical production to be investigated, and can detect relative changes in their intensity. These are important factors in the study of the pathogenic role of free radicals generated during reperfusion of an ischaemic heart.

Animals↗

Structural modifications of lipid vesicles by 8-methoxypsoralen.

On prolonged UV-A illumination the ESR spectrum of 16-doxylstearic acid in dimyristoyl phosphatidylcholine vesicles loaded with 8-methoxypsoralen changed dramatically as a second broad component gradually appeared. The composite nature of the spectrum was proven by digital subtraction and the two components were simulated using the modified Bloch equations. From the spectral anisotropy of the motionally averaged three-line component, the molecular order was found to decrease during UV-A illumination, and isotropic rotation of the spin probe was observed well below the phase transition temperature. In parallel an exchange averaged component dominated the central part of the spectrum, indicating the segregation of spin probes into separate domains. The build-up of the composite lineshape was followed by fitting weighted sums of the above two components to spectra recorded after various time intervals. It is concluded that PUVA therapy, which is routinely used against psoriasis, might also induce overlooked damage to the saturated lipid species of biological membranes.

Electron Spin Resonance Spectroscopy↗

Generation of free radicals by photoexcitation of pheophorbide alpha, haematoporphyrin and protoporphyrin.

An investigation of the production of radical species by photoexcitation pheophorbide alpha, haematoporphyrin and protoporphyrin was performed. In an aqueous solution containing different amounts of ethanol, the superoxide radical was detected by the spin trapping technique. In addition, secondary radicals were observed. The generation of oxygen radicals was found to dominate in solutions with a low ethanol content.

Chlorophyll↗

Spin trapping evidence for radical generation by isolated hearts and cultured heart cells.

The spin trap 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) has been applied to monitor the generation of free oxy-radicals in samples derived from isolated hearts and heart cells. .OH was trapped in the effluent of isolated hearts in the early phase of reperfusion following an ischemia time of only 10 min. Radical detection was possible even when the cardioactive DMPO was added to the effluent after draining off the heart, demonstrating that the short-lived .OH was generated by components released from the affected heart. These results support the hypothesis that radicals are of relevance for reperfusion injury. By omitting antioxidants commonly used for incubation media of cultured cells, it was possible for the first time to demonstrate the formation of .OH in the incubation solution of cardiac cells.

Animals↗

Effect of troxerutin and methionine on spin trapping of free oxy-radicals.

The cardioprotective agents troxerutin and methionine are radical scavengers and compete with the DMPO adduct formation of .OH generated by the Fenton reaction. The concentration of trapped .O2- generated by the xanthine oxidase/hypoxanthine reaction is lowered in the presence of troxerutin. The decay of DMPO-OH is decreased by troxerutin compared to the control. In the presence of methionine a carbon-centered radical is produced. The investigations support the opinion that the scavenging of oxygen derived free radicals is of importance for the cardioprotective action of these agents.

Anticoagulants↗

Sequential mechanism of refolding of carbonic anhydrase B.

The kinetics of refolding of bovine carbonic anhydrase B was studied by a variety of methods over a wide range of times (from milliseconds to hours). It has been shown that protein refolding proceeds through three stages. At the first stage (t1/2 approximately equal to 0.03 s) hydrophobic clusters and a compact state of the chain are formed. At the second stage (t1/2 approximately equal to 140 s) hydrophobic clusters are desolvated and the rigid native-like hydrophobic core is formed. At the third stage (t1/2 approximately equal to 600 s) the native active protein is formed.

Animals↗

ESR imaging of myelin basic protein induced vesicle aggregation.

Using a modulated magnetic field gradient technique, the conventional ESR spectrum of well-defined spatial sections and the one-dimensional-ESR image of the nitroxide centre line of spin-labeled stearic acid in phospholipid vesicles were recorded with a spatial resolution of 4.10(-5) m after pelleting the vesicles inside 1 mm (i.d.) sample capillaries in a slow centrifuge (2500 X g). The sedimentation characteristics of dimyristoylphosphatidylcholine and dimyristoylphosphatidylglycerol vesicles were quantitatively compared with particular reference to vesicle aggregation induced by myelin basic protein. Protein-induced changes in the effective molecular mass were determined from ESR images of sedimentation profiles. The present data lend further support to the notion that the primary target of myelin basic protein-lipid interaction is the acidic lipid pool of myelin.

Dimyristoylphosphatidylcholine↗

Parkinsonism--drug treatment: Part I.

The purpose of this two-part review is to explain current drug treatment in part I and discuss investigational drug therapy and miscellaneous drugs in the management of parkinsonism in part II. The medical approach to this disease is still based on the imbalance between a deficiency of dopamine and a functional increase in acetylcholine. Anticholinergic agents are used to treat the tremors in the early stages of the disease.

Antiparkinson Agents↗

Radical trapping and lipid peroxidation during myocardial reperfusion injury--radical scavenging by troxerutin in comparison to mannitol.

During ischemic perfusion and reperfusion of isolated rat hearts, OH and carbon-centered radicals were trapped in the perfusate. Both radicals were found to occur during LPO which was enhanced in the myocardium. The increase of LPO as well as of enzyme leakage were reduced by mannitol and the flavonoid troxerutin showing antioxidative action of greater than 500 and greater than 5 microM, respectively. The assumption is supported that radical-induced LPO is of pathogenetic relevance during myocardial reperfusion injury for which antioxidants could be of therapeutic advantage.

Animals↗

Parkinsonism--drug treatment: Part II.

This article, second in a two-part review, discusses investigational drug therapy and miscellaneous drug management of parkinsonism. Drug therapy should be individualized according to signs and changed as the disease progresses or if the patient develops intolerable side effects. Investigational drugs being examined include sustained-release and injectable dopaminergic formulations. Drug-induced parkinsonism is also examined.

Antiparkinson Agents↗

Microviscosity of water-containing heterogeneous systems. An ESR spin probe study.

The microstructure of maltodextrin gels was studied by ESR spin probe technique. From investigations of the time dependence of the gelling process and from the Arrhenius plot of the rotational correlation time, important information about the phase behaviour of the system is obtained. The microviscosity decreases with swelling time, whereas the macroviscosity increases. The conclusion is drawn that the maltodextrin gel is a two-phase system and can be characterized in the nomenclature of Papkov as a gel of the second type.

Electron Spin Resonance Spectroscopy↗

Articular chondrocalcinosis in a hospital population: an Australian experience.

A group of hospital patients aged 55 years or over (53 men, 74 women) were screened for articular chondrocalcinosis (ACC) with high-resolution radiographs of knees, wrists, hand and pelvis. Two men (4%) aged 79 and 86 years had ACC involving knees, wrists and symphysis pubis. Both had clinical joint disease and radiological osteoarthritis (OA). Eighteen women (24%) had ACC with sites affected including the knees (89%), wrists (39%) and symphysis pubis (44%). Metabolic screening did not reveal any predisposing factors in patients with ACC. Symptoms and signs of joint disease were not significantly more common in women with ACC compared to those without ACC, and 44% of those with knee calcification were clinically asymptomatic and had no evidence of OA radiologically. However, the presence of knee ACC significantly increased the risk for OA in the same knee by a factor of three-to-four while knee calcification was associated with the more severe grades of radiographic OA.

Aged↗

Study of H2O2-supported N-demethylations catalyzed by cytochrome P-450 and horseradish peroxidase.

H2O2-supported oxidative demethylation reactions catalyzed by cytochrome P-450 and horseradish peroxidase have been compared. In contrast to peroxidase catalyzed reactions no free substrate radicals could be detected by EPR stopped flow measurements in demethylation reactions catalyzed by highly purified cytochrome P-450 although the rate of product formation for both enzyme systems was identical. These findings cause doubts in a general peroxide dependent demethylation mechanism valid for all hemoproteins and in the hypothesis that free substrate radicals are principally formed during cytochrome P-450 catalysis.

Aminopyrine↗

Mechanism studies of enzymatically formed tolidine blue and determination of peroxidatic activities.

In aqueous solution peroxidase catalyzes the conversion of o-tolidine to tolidine blue by hydrogen peroxide. This reaction of practical significance for analytical tests was studied by optical and ESR spectroscopy. For the blue dye formed in aqueous solution a meriquinoidic structure was proposed which is in equilibrium with an instable radical compound. This equilibrium is shifted to higher radical concentrations by ethylene glycol. Naphthene derivatives stabilize the meriquinoidic structure by means of non-covalent interactions resulting in a decrease of the radical concentration. In crosslinked gelatin the dye formation runs analogously, so that this system is suitable for providing evidence for H2O2-forming reactions. Naphthene derivatives substituted by sufficiently long aliphatic groups are diffusion stable in crosslinked gelatin. By interacting with the dye they prevent its rapid chemical decomposition and diffusion into the sample solution. It was shown, furthermore, that by means of such systems with a suitable structure of the layers both substrates and enzymes participating in the reaction may be determined analytically. This does provide a basis for developing new analytical test variants.

Benzidines↗

Analysis of paramagnetic intermediates at the reaction of hemoglobin with nitrite using EPR.

The autocatalytic oxidation of hemoglobin by nitrite was analysed. It was shown that the obtained paramagnetic species have a strong temperature dependence. The time of annihilation of these species decreases about 4 times in the temperature region between 10 degrees C and 30 degrees C, whereas the time of formation decreases only 1.7 times. These data explain the strange temperature dependence of the formation of methemoglobin by nitrite and support the assumption that the short-lived radical is localized on the hemoglobin molecule.

Adult↗