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Biomedical subjects

W Osswald

Publications and source records attributed to W Osswald.

At least 19 recordsLinked to original sources
PubMed2005

Physiological changes of Fagus sylvatica seedlings infected with Phytophthora citricola and the contribution of its elicitin "citricolin" to pathogenesis.

Beech seedlings were infected with the root rot pathogen Phytophthora citricola to study its impact on leaf physiology and water status. Net photosynthesis rate decreased two days after inoculation in infected seedlings. In contrast, electron quantum yield of photosystem II, leaf water potential, and total water consumption were only slightly impaired until 6 dpi. At the same time, wilt symptoms occurred on leaves. These results indicate the involvement of a mobile signal triggering the early changes in leaf physiology by root infection. As the elicitin gene of P. citricola was induced during root infection, we purified and characterised the elicitin protein and tested its ability to change leaf physiological parameters of beech and tobacco plants. P. citricola produced a single acidic elicitin (citricolin), which caused necrosis and decreased gas exchange of tobacco leaves. Furthermore, it induced an oxidative burst in tobacco cell suspension culture. However, none of these effects were observed in beech.

Algal Proteins↗
PubMed2005

The plant's capacity in regulating resource demand.

Regulation of resource allocation in plants is the key to integrate understanding of metabolism and resource flux across the whole plant. The challenge is to understand trade-offs as plants balance allocation between different and conflicting demands, e.g., for staying competitive with neighbours and ensuring defence against parasites. Related hypothesis evaluation can, however, produce equivocal results. Overcoming deficits in understanding underlying mechanisms is achieved through integrated experimentation and modelling the various spatio-temporal scaling levels, from genetic control and cell metabolism towards resource flux at the stand level. An integrated, interdisciplinary research concept on herbaceous and woody plants and its outcome to date are used, while drawing attention to currently available knowledge. This assessment is based on resource allocation as driven through plant-pathogen and plant-mycorrhizosphere interaction, as well as competition with neighbouring plants in stands, conceiving such biotic interactions as a "unity" in the control of allocation. Biotic interaction may diminish or foster effects of abiotic stress on allocation, as changes in allocation do not necessarily result from metabolic re-adjustment but may obey allometric rules during ontogeny. Focus is required on host-pathogen interaction under variable resource supply and disturbance, including effects of competition and mycorrhization. Cost/benefit relationships in balancing resource investments versus gains turned out to be fundamental in quantifying competitiveness when related to the space, which is subject to competitive resource exploitation. A space-related view of defence as a form of prevention of decline in competitiveness may promote conversion of resource turnover across the different kinds of biotic interaction, given their capacity in jointly controlling whole plant resource allocation.

Energy Metabolism↗
PubMed2002

Ethical guidance on human embryonic and fetal tissue transplantation: a European overview.

This article presents an overview of regulations, guidelines and societal debates in eight member states of the EC about a) embryonic and fetal tissue transplantation (EFTT), and b) the use of human embryonic stem cells (hES cells) for research into cell therapy, including 'therapeutic' cloning. There appears to be a broad acceptance of EFTT in these countries. In most countries guidance has been developed. There is a 'strong' consensus about some of the central conditions for 'good clinical practice' regarding EFTT. International differences concern, amongst others, some of the informed consent issues involved, and the questions whether an intermediary organisation is necessary, whether the methods of abortion may be influenced by the possible use of EFT, and whether EFTT should only be used for the experimental treatment of rare disorders. The potential use of hES cells for research into cell therapy has given a new impetus to the debate about (human) embryo research. The therapeutic prospects with regard to the retrieval and research use of hES cells appear to function as a catalyst for the introduction of less restrictive regulations concerning research with spare embryos, at least in some European countries. It remains to be seen whether the prospect of treating patients suffering from serious disorders with transplants produced by therapeutic cloning will decrease the societal and moral resistance to allowing the generation of embryos for 'instrumental' use.

Bioethics↗
PubMed1994

Uptake of 3H-catecholamines by rat liver cells occurs mainly through a system which is distinct from uptake1 or uptake2.

Isolated rat hepatocytes were incubated with 200 nmol/l 3H-(-)-noradrenaline or 50 nmol/l 3H-(-)-adrenaline for 15 min, in Krebs-Henseleit solution at 37 degrees C, gassed with 95% O2 5% CO2. Monoamine oxidase and catechol-O-methyl transferase were inhibited with pargyline (500 mumol/l) and Ro 01-2812 (3,5-dinitropyrocatechol; 2 mumol/l), respectively. Total radioactivity present in the cells, which corresponded mostly to intact 3H-amine, was measured. The content of 3H-noradrenaline increased with time of incubation, a plateau having been reached after 15 min of incubation. After 15 min of incubation, the cell: medium ratio for 3H-noradrenaline and 3H-adrenaline was 0.6-0.7. Desipramine (an inhibitor of the neuronal uptake of catecholamines-uptake1; 1 mumol/l) did not affect the uptake of either 3H-noradrenaline or 3H-adrenaline into hepatocytes. Corticosterone (an inhibitor of the extraneuronal uptake of catecholamines-uptake2; 40 mumol/l) slightly inhibited (by 28%) the uptake of 3H-adrenaline, and did not significantly reduce 3H-noradrenaline uptake. Probenecid (an inhibitor of the renal transport of organic anions; 100 mumol/l) did not influence the amount of either 3H-noradrenaline or 3H-adrenaline in hepatocytes. Cyanine 863 (an inhibitor of the renal transport of organic cations; 10 mumol/l) decreased by 62% the uptake of 3H-adrenaline into cells but did not significantly affect 3H-noradrenaline uptake. Bilirubin (a substrate of a hepatic transport for organic anions; 200 mumol/l) produced a significant increase (50%) in the amount of 3H-noradrenaline and 3H-adrenaline present in the cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Effect of sympathetic denervation on the relaxing responses of rabbit arterial smooth muscle.

1. The present study reports on the influence of chemical denervation by 6-hydroxydopamine (6-OHDA) on the relaxing responses to carbachol, sodium nitroprusside, zaprinast, adenosine, forskolin and 3-isobutyl-1-methylxanthine (IBMX) of ring preparations of rabbit renal and femoral arteries. 2. Carbachol was found to induce a complete abolition of the tone induced by 5-hydroxytryptamine (0.1-1.0 microM), both in the renal and the femoral arteries. The profile of the carbachol-induced relaxation in both the renal and femoral arteries obtained from 6-OHDA-treated rabbits was similar to that observed in control animals; relaxing responses obtained with some of the concentrations of carbachol were, however, found to be greater (P < 0.01) in denervated arteries. Sodium nitroprusside was also found to be an effective relaxant agent in both renal and femoral arteries, though more potent in the former but was unaffected by denervation. Zaprinast relaxed both renal and femoral artery ring preparations, and again, no significant difference was observed between control and denervated animals. 3. The cyclic AMP-mediated relaxing responses to adenosine, forskolin and IBMX were found to be similar in renal and femoral arteries of control arteries, producing almost complete abolition of pre-existing tone. The adenosine- and IBMX-induced relaxing responses in renal and femoral arteries were found to be similar in control and denervated animals. However, the concentration-response curve to forskolin was shifted to the left by 2.5 and 1.5 log units in preparations of renal and femoral arteries of denervated rabbits, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-3-isobutylxanthine↗
PubMed1993

Extraneuronal uptake and O-methylation of 3H-adrenaline in the rabbit aorta.

The influence of uptake2 inhibitors on the O-methylation and accumulation of 3H-adrenaline by the isolated rabbit aorta was studied. Strips were incubated with 0.05 mumol/l 3H-(-)-adrenaline during 15 min. Monoamine oxidase and uptake1 were inhibited and the 3H-adrenaline present in the tissue was measured as well as the metabolites found in the tissue and in the incubation fluid. In another series of experiments, monoamine oxidase, uptake1 and catechol-O-methyl transferase (COMT) were inhibited, and tritium accumulation was measured in the tissue. When COMT was inhibited, inhibitors of uptake2 produced a maximal reduction of 3H-adrenaline accumulation that did not exceed 50%. When COMT was intact, inhibitors of uptake2 diminished total 3H-removal and, more markedly, O-methylation and concomitantly increased the tissue content of 3H-adrenaline. Mineralocorticoids (corticosterone and deoxycorticosterone acetate) inhibited 3H-adrenaline uptake (when COMT was inhibited) and 3H-metanephrine formation (when COMT was functional) as effectively as did sexual steroids (17-beta-oestradiol, progesterone and testosterone); hydrocortisone (hemisuccinate or phosphate) had no effect (for concentrations up to 120 mumol/l). At the end of the incubation some strips were washed out with amine-free solution. Compartmental analysis of the efflux showed that the amine had distributed into three extraneuronal compartments (compartment I, II and III, with half times of 0.4, 4 and 15 min, respectively). Corticosterone (120 mumol/l) decreased the amount of 3H-adrenaline in compartment III and simultaneously increased the amount of the amine in compartment I (extracellular space).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Uptake and metabolism of 3H-adrenaline and 3H-noradrenaline by isolated hepatocytes and liver slices of the rat.

Isolated rat hepatocytes were incubated with 0.05 mumol/l or 0.2 mumol/l 3H-(-)-noradrenaline or 0.05 mumol/l 3H-(-)-adrenaline for 15 min and the content of amines as well as the formation of metabolites was measured. The removal of both amines from the incubation medium was quantitatively similar, and mainly due to metabolism (which represented 96% of the removal of 3H-adrenaline and 98% of the removal of 3H-noradenaline). O-methylation predominated for 3H-adrenaline: O-methylated and deaminated metabolites (3H-OMDA) and 3H-metanephrine (3H-MN) were the most abundant metabolites, accounting for 63% and 34% of total metabolite formation, respectively. Deamination predominated for 3H-noradrenaline: 3H-OMDA and 3H-dihydroxymandelic acid (3H-DOMA) were the most abundant metabolites, representing respectively 56% and 36% of total metabolite formation. The following activities of monoamine oxidase and catechol-O-methyl transferase were determined for 3H-noradrenaline: kCOMT 0.70 +/- 0.15 min-1 and kMAO 2.27 +/- 0.14 min-1. In experiments with 3H-noradrenaline, inhibition of monoamine oxidase reduced the formation of 3H-OMDA and deaminated metabolites [3H-dihydroxphenylglycol (3H-DOPEG) and 3H-DOMA] and increased the formation of 3H-normetanephrine (3H-NMN). Inhibition of catechol-O-methyl transferase, on the other hand, decreased 3H-NMN and increased 3H-DOPEG formation. When both enzymes were inhibited, the formation of all metabolites was strongly reduced but surprisingly there was no accumulation of 3H-amines in the cells, as the cell: medium ratio for 3H-noradrenaline or 3H-adrenaline was about unity.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Predominance of oxidative deamination in the metabolism of exogenous noradrenaline by the normal and chemically denervated human uterine artery.

Longitudinal strips were prepared from human uterine arteries obtained at hysterectomy. The artery had a low content of noradrenaline and dopamine, contrasting with a high content of the deaminated catechols, dihydroxyphenylglycol (DOPEG) and dihydroxymandelic acid (DOMA), which together represented 98% of endogenous catechols. When incubated with 3H-noradrenaline (0.1 mumol/l), the uterine artery removed, accumulated and metabolized noradrenaline. Deaminated metabolites predominated, DOMA being the most abundant metabolite. Cocaine markedly reduced the accumulation of 3H-noradrenaline and abolished 3H-DOPEG formation, but did not change 3H-DOMA. Selective monoamine oxidase (MAO) inhibitors (clorgyline, selegiline and 2-amino ethyl carboxamide derivatives) caused a marked decrease in the amounts of 3H-DOPEG, 3H-DOMA and 3H-O-methylated and deaminated metabolites (OMDA) formed by the tissue and an increase in 3H-normetanephrine (NMN) formation. Inhibition of catechol-O-methyltransferase suppressed NMN formation and reduced that of OMDA; hydrocortisone slightly depressed the formation of DOMA and OMDA. Homogenates of the uterine artery deaminated 3H-5-HT, 14C-phenylethylamine and 3H-tyramine; inhibition curves of the deamination of 3H-tyramine by clorgyline and selegiline were compatible with the presence of both MOA A and MOA B. Exposure of the strips to 6-hydroxydopamine (1.5 mmol/l for 20 min; 3 exposure periods followed by washout periods of 15,15 and 30 min) resulted in complete and selective chemical denervation of the arterial tissue. This chemical denervation had effects which were similar to those of cocaine. The 2-amino ethyl carboxyamide derivatives markedly reduced the formation of deaminated metabolites by the denervated strips.(ABSTRACT TRUNCATED AT 250 WORDS)

Arteries↗
PubMed1992

The role of monoamine oxidase in the metabolism of exogenous noradrenaline by the human saphenous vein.

Human saphenous vein segments were obtained from patients subjected to coronary bypass surgery. As determined by HPLC-ED, the veins had a relatively low content of noradrenaline and high content of the deaminated metabolites, dihydroxyphenylglycol (DOPEG) and dihydroxymandelic acid (DOMA). In vein segments which had been incubated with 3H-noradrenaline (0.1 mumol/l), the oxidative deamination pathway predominated over the O-methylating one. Deamination occurred both at the neuronal and extraneuronal level; DOPEG appearing to be a good index of intraneuronal deamination, whereas DOMA and O-methylated and deaminated metabolites were mainly formed extraneuronally. Both MAO type A and MAO type B selective inhibitors reduced the deamination of noradrenaline; deamination was also found to be partially sensitive to semicarbazide. Inhibition of neuronal uptake or of deamination increased O-methylation. The human saphenous vein thus metabolizes exogenous noradrenaline following a pattern which substantially differs from that shown to occur in various blood vessels from other animal species.

Deamination↗
PubMed1992

Effects of nebivolol stereoisomers on the action of adrenaline on blood pressure, heart rate and blood levels of noradrenaline and DOPEG.

1. Nebivolol (a new beta 1-adrenoceptor blocking drug) has particular effects on the cardiovascular system, i.e. it induces hypotension without affecting cardiac function or increasing peripheral vascular resistances. In this study, we aimed to evaluate the effects of nebivolol and its stereoisomers on the actions of adrenaline (AD) at the cardiovascular level as well as at the prejunctional level (as ascertained by modification of noradrenaline (NA) and dihydroxyphenylglycol (DOPEG) plasma levels in the anaesthetized dog. 2. AD infusion (0.1 micrograms kg-1 min-1) did not induce statistically significant changes in mean blood pressure and heart rate; it caused a pronounced and sustained rise of AD levels, no significant alterations in NA levels and a marked, progressive and sustained increase in DOPEG levels. 3. Mean blood pressure was not affected by any of the nebivolol isomers. d- and dl-nebivolol in the two doses used (0.3 and 0.03 mg kg-1 in 15 min) caused a significant and dose-dependent decrease in heart rate. Plasma levels of AD and NA were not changed by any of the nebivolol isomers tested. However, all of them significantly reduced the increase in plasma levels of DOPEG induced by adrenaline infusion. 4. We conclude (1) that AD infusion in the dog facilitates NA release and that DOPEG is a good index of this effect; and (2) nebivolol appears to act at the prejunctional level, reducing the increase in NA release induced by adrenaline, as shown by the effect on DOPEG plasma levels.

Adrenergic beta-Antagonists↗
PubMed1992

[Ethics of animal research and application to humans].

Animal experimentation has proven to be of invaluable help in the understanding of biological functions, for the advancement of medical research and for the improvement of health conditions of both humans and animals. This phase of scientific progress is far from completed and there are no hints for substitution of all animal experiments by so called alternative methods. Therefore, there is a real need to analyse, without prejudice or undue dogmatic statements, the present situation in order to contribute to a responsible attitude, which should be transparent, understandable for lay people and useful as a background for the passing of adequate legislation. This process of analysis calls for the cooperation of scientists, a class which can neither be ignored nor treated as minor and should be above any suspicion of any part concerned. Finding a reasonable and just solution for the problem under debate can only result from the convergence of utilitarian and responsible ethical viewpoints. From utilitarian reasoning an overwhelming mass of evidence has resulted in favour of animal experimentation: medical progress would be severely maimed by prohibition or severe curtailing of animal experiments and catastrophic consequences would ensue. On the other hand, ethical considerations result in clear condemnation of useless or redundant experiments, of those causing disproportionate pain or suffering or of doubtful scientific standing: and to the recommendation that every effort should be undertaken in order to find and to establish on a sound scientific basis, alternative or complementary methods, i.e. those not involving animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Testing Alternatives↗
PubMed1991

Mediation by adenosine of the trophic effects exerted by the sympathetic innervation of blood vessels.

Chemical or surgical sympathetic denervation of blood vessels causes marked changes of the effector cells. Since postganglionic sympathetic cotransmission by noradrenaline and adenosine 5'-triphosphate is well established, the role of these transmitters as putative trophic factors was investigated. Whereas noradrenaline was ineffective in preventing morphological changes due to denervation, both adenosine and N-ethylcarboxamido-adenosine totally prevented them. In conscious rats, the adenosine receptor antagonist dipropylsulphophenylxantine (DPSPX) caused alterations of the blood vessel wall similar to those described for denervation. These results strongly suggest that adenosine is the trophic factor of sympathetic innervation.

Adenosine↗
PubMed1991

Superoxide dismutase partially prevents sympathetic denervation by 6-hydroxydopamine.

The effects of superoxide dismutase (S.O.D.) in two models of chemical denervation induced by 6-hydroxydopamine (6-OHDA) were studied. To evaluate the effects of S.O.D. on in vitro 6-OHDA-induced denervation, fragments of the lateral saphenous veins of mongrel dogs were pre-incubated in oxygenated Krebs-Henseleit solution with or without S.O.D. and then incubated under control conditions, with 6-OHDA or with 6-OHDA + S.O.D. Following the incubation period the fragments were repeatedly washed with Krebs solution and then used for determination of noradrenaline and for morphological study. 6-OHDA produced a profound depletion of noradrenaline. This depletion was significantly reduced although not prevented by S.O.D. The protective effect of S.O.D. was concentration-dependent. The ultrastructural study confirmed the 6-OHDA-induced sympathetic nerve degeneration as well as the protective effect afforded by S.O.D. In order to evaluate the effects of S.O.D. on in vivo 6-OHDA-induced denervation, male Wistar rats were anaesthetized and the tail vein cannulated. Saline or S.O.D. were intravenously delivered. 6-OHDA was injected five minutes after the beginning of infusions. Fragments of the left ventricle and vasa deferentia were used for determination of noradrenaline and for morphological study. 6-OHDA produced a significant depletion of noradrenaline in the left ventricle and vas deferens (to 8% and 18% of control values respectively). This depletion was reduced, though not prevented by S.O.D. Morphological data confirmed the neurotoxic effect of 6-OHDA and a protective role for S.O.D.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗