Search PubMed⌕ Search

Biomedical subjects

P Riederer

Publications and source records attributed to P Riederer.

536 records · Page 30Linked to original sources

Levodopa in the treatment of (pre) senile dementia.

A progressive decrease of dopamine and related enzyme activities and a decline in the dopaminergic receptor functions in the striatum and limbic system controlling behavior have been observed in senescent brain. These changes provide a neurochemical basis for some behavioral and mental disturbances of the aged and suggest the possibility of a substitution therapy of neurotransmitter deficiency of senile and presenile dementia. Previous reports on the effects of levodopa treatment of dementia in parkinsonism and aging have given conflicting results. A controlled double-blind study of 6 months' administration of levodopa plus decarboxylase inhibitor given at oral doses of 250 mg daily versus placebo in twelve patients aged 54--60 years showing initial signs of organic dementia was performed. Clinical rating of twelve parameters of organic brain syndrome and psychometric studies using three subtests of the HAWIE (digit span, coding B test and block design) indicate improvement in the overall scores of organic brain syndrome and in particular in the visuospatial functions, visual memory, and visual-motor coordination. In general, improvement increased with the duration of levodopa treatment. These preliminary data suggest some beneficial effect of levodopa treatment in early stages of presenile dementia and thus open new therapeutic aspects in neurogerontology.

Benserazide↗

Erythrocyte membrane proteins in psychiatric disorders and controls.

There are indications of abnormalities in membrane transport processes of erythrocytes in affective disorders. Therefore, it seemed worth while to investigate possible charge heterogeneities of erythrocyte membrane proteins in psychiatric disorders applying isoelectric focusing (IEF) in one- and two-dimensional procedures. At this level of analytical sensitivity the protein patterns did not discriminate between major affective disorder, schizophrenia and controls.

Adult↗

Lymphocyte glucocorticoid receptor binding during depression and after clinical recovery.

Lymphocyte glucocorticoid receptor binding parameters were studied in 15 severely depressed patients during depression and after clinical recovery, and in 15 healthy controls. There was no difference in glucocorticoid receptor number or affinity between depressed patients and recovered or control subjects. Afternoon ACTH and cortisol concentrations did not differ significantly between the three groups. No relationship could be established between glucocorticoid receptor binding and antidepressant medication. These data support the view of an impaired ligand-induced plasticity of glucocorticoid receptor regulation rather than the hypothesis of decreased glucocorticoid receptor numbers during depression.

Adolescent↗

Influence of neuromelanin on oxidative pathways within the human substantia nigra.

Neuromelanin (NM) is a dark-coloured pigment produced in the dopaminergic neurons of the human substantia nigra (SN). The function of NM within the pigmented neurons is unknown but other melanins are believed to play a protective role via attenuation of free radical damage. Experimental evidence suggests that NM may also exhibit this characteristic, possibly by directly inactivating free radical species or via its ability to chelate transition metals, such as iron. Increased tissue iron, however, may saturate iron-chelating sites on NM and a looser association between iron and NM may result in an increased, rather than decreased, production of free radical species. The death of NM-pigmented neurons in Parkinson's disease (PD) is associated with both a measurable increase in tissue iron concentrations and indices of free radical mediated damage, suggesting that NM is involved in the aetiology of this disorder. As yet, it is unknown whether NM in the parkinsonian brain differs to that found in healthy tissue and thus may fulfil a different role within this tissue.

Binding Sites↗

Expression, but not activity, of neuronal nitric oxide synthase is regionally increased in the alcoholic brain.

The regional distribution of nitric oxide synthase (NOS) was investigated in alcoholic post-mortem brains compared with brains of non-alcoholic control individuals. Total enzyme activity in 28 brain regions was determined using the [(3)H]l-citrulline formation assay, whereas Western blot analyses were used for semi-quantitative measurement of the neuronal isoform of NOS (nNOS). In the alcoholic brain, nNOS protein expression was increased in the following regions: frontal cortex (85%), the cingulate gyrus (294%), the nucleus accumbens (54%), the entorhinal cortex (85%) and the thalamus (51%). These increases were, however, not associated with higher total NOS activity. Interestingly, nNOS protein content was increased in the frontal cortex and the nucleus accumbens, brain regions which are suggested to be involved in the dopaminergic mesolimbic reward system. It is concluded that upregulation of signal transduction pathways, such as the adenosine 3',5'-monophosphate and the protein kinase C-dependent pathway, due to stimulation of G-protein-coupled neurotransmitter receptor regulation, as a form of functional tolerance, could be responsible for increased nNOS protein expression, and downregulation of NOS enzyme activity in these brain regions.

Adult↗

Immunoreactivity of cAMP response element binding protein is not altered in the post-mortem cerebral cortex or cerebellum of alcoholics.

We examined amounts of cAMP response element binding protein (CREB) and its phosphorylated form in post-mortem frontal and temporal cortices and cerebella from alcoholics and controls by immunoblotting. No significant differences were observed in the levels of these proteins in each brain region, suggesting that the assumed neuroadaptations to chronic ethanol intake may not be reflected by quantitative alterations of CREB in alcoholic brain.

Adult↗

Increased concentrations of manganese superoxide dismutase in serum of alcohol-dependent patients.

Oxidative stress-associated parameters [concentrations of lactoferrin, Cu,Zn-superoxide dismutase (SOD) and Mn-SOD] were determined in sera of 20 patients suffering from alcohol dependence immediately after detoxification and in 15 non-dependent healthy subjects as controls. In the patient group, the mean Mn-SOD concentration reached almost double the values of those from the control group (142.9 vs 76.0 ng/ml, P < 0.01). The other parameters tended to be increased in patients, but did not differ significantly between index and control groups. The findings are consistent with increased oxidative stress due to chronic alcohol intake, which might be responsible for secondary diseases such as brain atrophy, peripheral polyneuropathy and liver fibrinogenesis.

Adult↗

Platelet monoamine oxidase B activity in dementia. A 4-year follow-up.

Platelet monoamine oxidase B (MAO-B) activity has been found to increase significantly in demented patients. For the first time, a 4-year follow-up of platelet MAO-B activity and Mini-Mental State (MMS) was performed in patients with probable dementia of the Alzheimer type (DAT) and age-matched controls. MAO-B activity of DAT patients increased significantly 2 years after the beginning of the study as compared with controls and remained significantly higher for the entire period of the examinations (p < 0.0001). The decrease of the MMS scores did not correlate with the time course of the increase of platelet MAO-B activity (Spearman rank correlation test). The decline of the MMS scores of DAT patients preceded the elevation of MAO-B activity. Since degenerative processes in brain areas which are responsible for cognitive function and are reflected by the MMS scores rather affect cerebral cholinergic than monoaminergic neurotransmitter systems, degeneration of the latter at late stages of DAT might be reflected by increased platelet MAO-B activity.

Aged↗

Abnormal localization of two neuronal calcium sensor proteins, visinin-like proteins (vilips)-1 and -3, in neocortical brain areas of Alzheimer disease patients.

The anatomical distribution of the neuronal calcium sensor proteins visinin-like protein-1 and -3 (VILIP-1 and -3) was investigated in various neocortical areas of Alzheimer's disease (AD) patients and controls. In AD and normal brains their cellular localization was confined to pyramidal and non-pyramidal neurons. In AD brains the intracellular immunostaining for VILIP-1 and to a lesser extent for VILIP-3 was found to be reduced in comparison to controls. Also, significantly less VILIP-1-immunoreactive neurons were found in the temporal cortex of AD patients as compared to normal brains. Accordingly, Western blot analysis revealed that immunoreactivity for VILIP-1 is less concentrated in tissue extracts of the temporal cortex of AD patients compared to controls. Extracellularly, VILIP-1 and VILIP-3 immunoreactive material was detected in close association with typical pathologic hallmarks of AD such as dystrophic nerve cell processes, amorphous and neuritic plaques, and extracellular tangles. In control brains an extraneuronal localization of VILIP-1 or VILIP-3 was never observed. Our morphological and neurochemical findings point to an involvement of these two neuronal calcium sensor proteins in pathology and possibly pathophysiology of changed calcium homeostasis in AD.

Adult↗

In vivo and in vitro effects of glucocorticoids on lymphocyte proliferation in man: relationship to glucocorticoid receptors.

Interrelations between the hypothalamic-pituitary-adrenal system (HPA) and the immune system represent a well-documented biological phenomenon. While in vitro administration of glucocorticoids may inhibit concanavalin A (Con A)- and phytohemagglutinin (PHA)-induced T-cell proliferation, pokeweed mitogen (PWM)-driven B-cell mitogenesis is relatively resistant to glucocorticoids. To further explore the link between the HPA and the immune system in relation to glucocorticoid receptor function, dose-response curves were obtained for Con A- and PHA-induced T-cell mitogenesis, PWM-generated B-cell mitogenesis and spontaneous lymphocyte proliferation in 13 healthy controls. Glucocorticoid effects were assessed in vivo by depletion of endogenous glucocorticoids after oral administration of 1.5 g metyrapone (MET) and subsequent glucocorticoid replacement, and in vitro by incubation of the cells with different doses of dexamethasone (DEX). There was a significant decrease in PWM-induced B-cell mitogenesis and a more pronounced effect of DEX administered in vitro on spontaneous lymphocyte proliferation after MET treatment when compared with the DEX plus MET pretreated condition in vivo. These data suggest that the inhibition of spontaneous lymphocyte proliferation by glucocorticoids in vitro is related to glucocorticoid receptor function. The decrease in PWM-generated B-cell proliferation following cortisol depletion by MET may be seen in connection with impaired glucocorticoid-mediated induction of interleukin-1 receptor synthesis.

Adrenocorticotropic Hormone↗

Pro- and antioxidative properties of cortical tissue preparations from human brain exhibiting NMDA-receptor characteristics.

The effects of cortical tissue preparations (CTP) from human brain on the production of reactive oxygen species (ROS) has been investigated with several biochemical model reactions. As indicators for ROS, fragmentation of the methionine derivatives, alpha-keto-gamma-methylthiobutyric acid (KMB) or 1-amino-cyclopropane-1-carboxylic acid (ACC), yielding ethene have been used. With these systems we have shown that production of OH-radical-type oxidants by the xanthine oxidase (XOD)-system is strongly stimulated by CTP. This activity is due to intrinsic iron ions since ethene formation from KMB is stimulated by EDTA, inhibited by desferrioxamine (Desferal) and also visible with heat-denatured CTP. CTP by themselves have no XOD activity. 3-Hydroxykynurenine (3HK) is another possible substrate for XOD but produces H2O2 without XOD-catalysis, whereas allopurinol is not inhibiting. CTP contain measurable NAD(P)H oxidoreductase activity, producing OH- radical- type oxidants at the expense of NADPH and (to a lesser extent) NADH as electron donors, shown as redox-cycling of 2-methyl-5-hydroxy-1,4-naphthoquinone, plumbagin. Ethene formation from KMB is also driven by both morpholinosydnonimine (SIN) or ONOOH. The reaction driven by SIN is stimulated by CTP and inhibited by catalase, SOD and hemoglobin. Since ethene release from KMB driven by ONOOH is inhibited by CTP the mechanisms driving KMB fragmentation are different for SIN and ONOOH. Furthermore CTP contain approx. 4 U catalase activity per mg protein and very weak peroxidase (POD) activity shown as ACC fragmentation yielding ethene in the presence of both H2O2 and KBr or NaCl. Since ACC binds to CTP and both compounds, ACC and KMB are natural products, present in food (ACC) or synthesized from methionine in vivo (KMB), these compounds may represent protecting agents in systems where reactive oxygen species are formed. One might even speculate that the production of ethene at these membrane receptor sites may have biological functions, since ethene is known to possess anaesthetic activities.

Antioxidants↗