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H Beitinger

Publications and source records attributed to H Beitinger.

12 recordsLinked to original sources
PubMed1997

Guidelines for the implementation of drug utilization observation (DUO) studies in psychopharmacological therapy. The "Phase IV Research" Task-Force of the Association for Neuropsychopharmacology and Pharmacopsychiatry (AGNP).

The task-force on Phase-IV-Research of the Association for Neuropharmacology and Pharmacopsychiatry (AGNP) has developed guidelines for the implementation of scientifically sound drug utilisation observation studies (DUO studies). These guidelines have been adopted by the executive committee as the position of the association. DUO studies are prospective pharmacoepidemiological studies, by which prescription, illness, and patient data of individual patients are collected without interference with the routine course of treatment. They can answer questions on the interaction of treatment modalities with positive and negative treatment outcome. Scientific standards require that there is a study protocol which describes the epidemiological, statistical, procedural, and quality assurance methodology and states who is responsible for what. As such studies can violate data protection regulations or can be used for sales instead of scientific purposes, consultation of an ethics committee is recommended.

Clinical Trials, Phase IV as Topic↗
PubMed1994

Lack of pharmacokinetic interaction between vinpocetine and oxazepam.

The influence of multiple doses of vinpocetine (10 mg three times daily) on the steady state plasma concentrations of oxazepam (10 mg three times daily) was studied in 16 healthy subjects. The mean (+/- s.d.) AUC (ng ml-1h-1) of oxazepam over 24 h during combined treatment was 4716 +/- 2296 and for oxazepam treatment alone it was 4737 +/- 2448 (95% confidence intervals for ratio of means = 95.4-103.7%). The degree of plasma protein binding of oxazepam was 98.11 +/- 0.32% and was not affected by vinpocetine. Independent of vinpocentine treatment a significant diurnal change in the plasma binding of oxazepam was observed; the free drug fraction was 20% higher during the night than during the day. Cmax and AUC values based on total oxazepam in plasma were 10% lower during the night. The results indicate a lack of influence of vinpocetine on oxazepam kinetics. Diurnal changes in the plasma binding of oxazepam probably have no clinical consequences.

Adult↗
PubMed1992

Calcium-ganglioside interactions and synaptic plasticity: effect of calcium on specific ganglioside/peptide (valinomycin, gramicidin A)-complexes in mixed mono- and bilayers.

A controlled exchange of calcium between the extracellular space (mM Ca2+) and the neuroplasm (microM Ca2+) is considered to be an essential prerequisite for almost every stage of neuronal activity. Our research interest is focused on those compounds, which due to their physico-chemical properties and localization within the synaptic membrane might fulfill the task as neuromodulators for functional synaptic proteins. Because of this specific binding properties towards calcium and their peculiar interactions with calcium in model systems gangliosides (amphiphilic sialic acid containing glycosphingolipids) are favorite candidates for a functional involvement in synaptic transmission of information. In this study we used monolayers to investigate the molecular packing and surface potential at the air/water interface, the interaction of gangliosides with the depsipeptide valinomycin (= monovalent ion carrier), and its influenceability by calcium. Furthermore we looked at calcium effects on the single channel conductance and mean channel life-time of the monovalent ion channel gramicidin A in mixed PC/ganglioside bilayers. In pure ganglioside monolayers the addition of 0.01 mM Ca2+ induces monolayer condensation, a rise in collapse pressure (= higher film stability), a shift of phase transition (= change of conformation), and a more negative head group potential (change of electric properties). In mixed ganglioside-valinomycin monolayers the addition of Ca2+ causes phase separation and/or aggregate formation between the ganglioside and the peptide. Single channel conductance fluctuations as well as mean channel life-time were analyzed for gramicidin A incorporated into binary mixed black lipid membranes of negatively charged gangliosides (GM1, GD1a, GT1b, GMix) and neutral lecithin (DOPC) in different molar ratios. At monovalent electrolyte concentrations up to < 250 mM CsCl the single channel conductance was significantly larger in the negatively charged mixed DOPC/ganglioside membranes than in the neutral DOPC membrane. Additionally, in the presence of gangliosides the mean channel life-time is increased. The addition of calcium (0.05 mM) induced a reduction of single channel conductance of gramicidin A in DOPC- and mixed DOPC/ganglioside membranes. These physico-chemical data in connection with new electromicroscopical evidences for a precise localization of calcium, a calcium pump (Ca(2+)-ATPase), a clustered arrangement of gangliosides in synaptic terminals, and biochemical results with regard to activatory nature of exogenous gangliosides for neuronal protein phosphorylation and ATPases, support the hypothesis of a modulatory function of gangliosides in synaptic transmission.

Animals↗
PubMed1991

Evidence for the presence of a specific ganglioside GM1/valinomycin complex in mixed monolayers.

The effect of a negatively charged mono-sialoglyco-sphingolipid (GM1-ganglioside) on the molecular organization and on physiochemical properties of lipid/peptide (valinomycin) systems was investigated in monolayers at the air/water interface. At a high molar fraction of GM1, the surface pressure/area isotherms of the two-component films of the system GM1/valinomycin and the isotherm of the pure ganglioside monolayer are identical concerning the space requirement of the molecules and thereby the packing of the monolayer. Using space-filling molecular models, a simple calculation gives the theoretical amount of 4.5 ganglioside molecules associated with one molecule of the depsipeptide valinomycin. The average surface potential indicates, that valinomycin, interacting with the polar head group of GM1, becomes partly embedded within the lipid interface. For GM1/eicosanol and valinomycin/eicosanol mixtures, the agreement between theory and experimental data strongly supports the model of ideal mixing without any molecular interactions between the different components. The results suggest the formation of a ganglioside/valinomycin complex with simultaneous alteration of the surface potential and molecular structure of the single components.

Air↗
PubMed1989

Comparative monolayer investigations of surface properties of negatively charged glycosphingolipids from vertebrates (gangliosides) and invertebrates (SGL-II, lipid IV).

The surface properties of four negatively charged glycosphingolipids from vertebrates, the sialo-glycosphingolipids (= gangliosides) GM1, GD1a, GT1b and a sulfo-glycosphingolipid (= sulfatide), and of the two negatively charged glycosphingolipids from lower invertebrates, the glucurono-glycosphingolipid Lipid IV and the aminophosphono-glycosphingolipid SGL-II were investigated in monolayers at the air/water interface. The molecular peculiarities under investigation were surface pressure (pi) and surface potential (delta V) which are described for Lipid IV and SGL-II for the first time. The surface pressure/area isotherms of all glycosphingolipids were typical of a liquid-expanded monolayer and, with the exception of SGL-II, exhibited a phase transition to a liquid-condensed state at surface pressures above 20 mN/m. The surface potential/molecular area data found for gangliosides in the closely packed state at pi = 30 mN/m (GM1: delta V = -17 mV; GD1a: delta V = -35 mV; GT1b: delta V = -39 mV) showed only a slight influence of the additional number of negatively charged residues. For Lipid IV, the surface behavior was very similar to GM1 both possessing one negative group per molecule, whereas in SGL-II also the surface potential data (delta V = +173 mV) were different compared with GD1a both possessing two negative groups per molecule. The addition of Ca2+ condensed the monolayers of all glycolipids and increased the potential in the direction to more positive values, but these findings were less effective in SGL-II films. On the basis of monolayer results presented here, in biological membranes of invertebrates especially Lipid IV might play a similar role as the ganglioside GM1 in vertebrate cells.

Acidic Glycosphingolipids↗
PubMed1989

Vinpocetine pharmacokinetics in elderly subjects.

The pharmacokinetics of vinpocetine (Eusenium) were investigated in 20 elderly, healthy volunteers. Plasma levels of the drug were determined during one dose interval of either repeated intravenous infusion or oral administration. AUC, Cmax and tmax values were derived for oral application, AUC values in case of intravenous application. Oral administration of 20 mg vinpocetine resulted in 4.60 x 10(-8) mol l-1 h, 1.71 x 10(-8) mol l-1 and 2.33 h for AUC, Cmax and tmax, respectively. The appropriate values for apovincaminic acid were 1.92 x 10(-6) mol l-1 h, 6.39 x 10(-7) mol l-1 and 2.41 h. When 10 mg vinpocetine were infused for 1 h, AUC values for vinpocetine and apovincaminic acid were 3.42 x 10(-7) mol l-1 h and 1.69 x 10(-6) mol l-1 h. Absolute bioavailability of vinpocetine was 6.7%. These data were in good agreement with the literature on young and elderly subjects. Marked deviations of apovincaminic acid kinetics in elderly subjects as described earlier could not be demonstrated in this study.

Administration, Oral↗
PubMed1988

Effect of calcium and temperature on mixed lipid-valinomycin monolayers. A comparison of glycosphingolipids (ganglioside GT1b, sulphatides) and phosphatidylcholine.

The influence of calcium and temperature on pure lipid (bovine brain PC, sulphatides, ganglioside GT1b), valinomycin and mixed lipid-valinomycin monolayers at the air/water interface was studied. In mixed films, evidence was found that the two components were miscible. On the other hand, at higher surface pressures, phase separation occurs in the cases of PC and sulphatides. Measuring the area requirement and the collapse pressure the stability of both lipid and the peptide was increased in particular due to ganglioside-valinomycin interaction. The addition of 10(-5) M calcium into the subphase at 20 and 37 degrees C and surface pressures of 10 and 20 mN/m led to a condensing effect in ganglioside mixtures, with formation of aggregates as indicated also by the nearly ideal behaviour of two component monolayers.

Calcium↗
PubMed1987

Seasonal variability of sialo-glycoconjugates in the brain of the Djungarian hamster (Phodopus sungorus).

The influence of season, photoperiod and ambient temperature on the content of proteins, sialo-glycoproteins and gangliosides and on the composition of gangliosides of three different brain regions (cortex, cerebellum and basalbrain) of the Djungarian dwarf hamster (Phodopus sungorus) had been investigated. Concomittantly changes in body wt and fur colouration were recorded. Dwarf hamsters living under natural photoperiod and ambient temperature conditions ("outside") showed a distinct annual cycle in body wt (summer: about 45 g; winter: about 25 g) and fur colouration (summer: dark grey; winter: whitish). Among the three brain regions the mean concentration of proteins ranged between 120 and 155 mg protein/g wet wt. The sialo-glycoprotein content varied between 260 and 410 micrograms NeuAc/g wet wt, and that of gangliosides between 800 and 1650 micrograms NeuAc/g wet wt. Seasonal fluctuations were not found. The composition of brain gangliosides remained uninfluenced throughout the year in the cerebellum, whereas seasonal variations were observed in cortex and basalbrain. Consequently the concentration ratio of the two major mammalian ganglioside fractions GD1a vs GT1b remained almost stable in cerebellum (0.3). In contrast to this the seasonal values of cortex and basalbrain changed from 0.6 and 0.8 in winter to 0.7 and 1.1 in summer. This indicated a higher polarity of the gangliosides in these brain regions during cold adaptation. The results are discussed with regard to modulatory functions of neuronal gangliosides for the process of synaptic transmission during seasonal adaptation.

Animals↗
PubMed1987

Influence of Ca2+ and temperature on the interaction of gangliosides with valinomycin in mixed monolayers at the air/water interface.

The effects of Ca2+ and temperature on mixed ganglioside-valinomycin-monolayers at the air/water interface were studied. Surface pressure-area isotherms of the pure gangliosides (GM1, GD1a) exhibited the typical monolayer characteristics. Pressure-area isotherms of the cyclodepsipeptide, valinomycin, were determined. In mixed monolayers, positive and negative deviation from the mean molecular area indicated the two components were miscible. Especially in GD1a mixtures, the addition of 0.01 mM calcium exhibited, with low molar fractions of valinomycin, a demixing effect in the direction of the phase separation of the components.

Calcium↗