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J P Fischer

Publications and source records attributed to J P Fischer.

11 recordsLinked to original sources
PubMed1996

Ablation of neural tissue by short-pulsed lasers--a technical report.

The basis for most laser applications in neurosurgery is the conversion of laser light into heat when the incident laser beam is absorbed by the tissue. Irradiation of neural tissue with laser light therefore leads to its thermal damage. However, due to the diffusion of heat energy into the surrounding tissue, often there is thermal damage to neural tissue outside the area of the target volume. These are the characteristics of thermal laser/tissue interaction. In this paper we discuss how we used three different short-pulsed lasers to achieve non-thermal ablation of neural tissue. Three different short-pulsed lasers were used to generate ultrashort laser pulses in the picosecond to femtosecond range. The interaction of such laser pulses with tissue was predicted to be nonthermal. The short-pulsed lasers were used for the ablation of neural tissue using an in vitro calf brain model. The histopathological examination of the lesions revealed that the neural tissue had been removed very precisely without any sign of thermal damage to the surrounding tissue.

Animals↗
PubMed1992

Effect of the cholinesterase inhibiting substance galanthamine on human EEG and visual evoked potentials.

The action of galanthamine (GAL), a cholinesterase inhibiting substance, on resting EEG and on flash visual evoked potentials (VEPs) was tested in 9 healthy subjects. Alpha power was increased significantly in 4 of 8 subjects after the infusion of 10 mg, which provided a median inhibition of 47% of acetylcholinesterase in erythrocytes. Mean alpha frequency and peak alpha frequency decreased significantly in 5 of the 8 subjects by 0.22-0.98 Hz. Alpha power increase and alpha frequency decrease were not accompanied by changes in theta power. The amplitudes of the late components of the flash VEP were increased in 8 of 9 subjects receiving doses of 10-35 mg of GAL, while the early components remained unaffected. Increase of late VEP components was significantly correlated with the strength of cholinesterase inhibition. The synchronizing effect of GAL in these healthy volunteers obviously contrasts with the known desynchronizing effect of physostigmine in animal experiments.

Adult↗
PubMed1991

Galanthamine: pharmacokinetics, tissue distribution and cholinesterase inhibition in brain of mice.

Galanthamine was determined in plasma and tissue extracts of mice, after the application of 4, 6 and 8 mg/kg (i.v.), by reverse phase HPLC, with fluorescence detection. A biexponential decline of concentrations in plasma, with a terminal half-life of 43.3 min, was observed after the dose of 4 mg/kg. The volume of distribution (Vss) of 2.17 l/kg was similar to that found in other species, including man. Metabolism to the inactive diastereomer, epigalanthamine, was very limited. There was a rapid accumulation of galanthamine in tissues, which was most pronounced in the kidney (10-fold compared to plasma) and liver (5-fold). In brain, accumulation was similar to other parenchymatous organs (diaphragm, lung) and amounted to 2.10-fold. Red blood cells showed a concentration 1.34-fold greater than plasma. The accumulation of galanthamine in tissue, with the exception of liver and kidney, can be explained by passive distribution according to differences in pH, between intra- and extracellular compartments. Extraction of galanthamine from blood to brain tissue was complete, indicated by a clearance in the range of cerebral blood flow (1.05 ml min-1 g-1). The concentration-time course of galanthamine in brain tissue was parallel to that in plasma during the terminal elimination phase. Measurement of inhibition of acetylcholinesterase (AChE) in the same samples from brain revealed a maximum apparent inhibition of 43% in the homogenate of brain (1:4 w/v in phosphate buffer, 4 mg/kg, 5 min after injection).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Pharmacokinetics of galanthamine in humans and corresponding cholinesterase inhibition.

Measurements were done to determine the plasma concentrations of galanthamine and two of its metabolites, as well as the corresponding inhibition of acetylcholinesterase activity in erythrocytes after applying 5 and 10 mg galanthamine hydrobromide as a constant-rate intravenous infusion for 30 minutes and single oral doses of 10 mg in eight healthy male volunteers. The data obtained revealed first-order pharmacokinetics, complete oral bioavailability, and a mean terminal half-life of 5.68 hours (95% confidence interval, 5.17 to 6.25 hours). Renal clearance accounted for only 25% of the total plasma clearance (CL = 0.34 L.kg-1.hr-1). Only negligible quantities of the putative metabolites, epigalanthamine and galanthaminone, were detected in blood and urine. The inhibition of acetylcholinesterase activity was closely correlated with the pharmacokinetics of galanthamine, a median maximal value of 53% being achieved by applying 10 mg galanthamine intravenously. Analysis of in vitro and ex vivo concentration responses revealed no differences, indicating that no metabolites of galanthamine exert additional inhibition of acetylcholinesterase activity.

Acetylcholinesterase↗
PubMed1991

Inhibition of acetylcholinesterase activity in human brain tissue and erythrocytes by galanthamine, physostigmine and tacrine.

Galanthamine, physostigmine and 9-amino-1,2,3,4-tetrahydroacridine (tacrine) were evaluated as inhibitors of human acetylcholinesterase activity from samples of postmortem human brain, fresh brain cortex biopsies and human erythrocytes. Acetylcholinesterase activity was most effectively inhibited in all tissues by physostigmine, followed by tacrine and galanthamine. The respective inhibitor concentrations exerting a half maximal effect (IC50) on acetylcholinesterase in postmortem human brain frontal cortex were 14 nmol/l, 1.0 mumol/l and 3.2 mumol/l versus 15 nmol/l, 1.1 mumol/l and 2.8 mumol/l in the hippocampus region. In addition, the inhibition of acetylcholinesterase by galanthamine was similar in postmortem brain and brain cortical biopsies from patients submitted to brain-tumour removal, indicating that postmortem changes up to 28 h after death probably did not influence the measurement of acetylcholinesterase inhibition. While physostigmine and tacrine acted equally on acetylcholinesterase from different sources, galanthamine was 10-fold less potent in inhibiting the enzyme activity from human brain that from human erythrocytes. Comparison with issues from mice revealed that galanthamine was selectively more potent in suppressing acetylcholinesterase in human erythrocytes. The results are discussed in the light of pharmacokinetic data, and conclusions are drawn for further clinical studies.

Acetylcholinesterase↗
PubMed1990

Stereoselectivity of cholinesterase inhibition by galanthamine and tolerance in humans.

The effect of galanthamine (GAL) and its 2 major metabolites on human cholinesterases has been explored. Epigalanthamine, a diastereomer of GAL, was 130-times less potent in vitro in its effect on acetylcholinesterase (AChE) in erythrocytes than the parent compound, and it did not differ significantly from the ketone galanthaminone. In vivo, the maximal 36-55% inhibition of AChE was approached 30 min after oral administration of 10 mg GAL. The duration of the catalytic inhibition corresponded to an elimination half-life of approximately 5-7 h. GAL was well tolerated in 8/8 healthy volunteers, and 3/4 Alzheimer patients tolerated the drug up to a daily dose of 40 mg.

Administration, Oral↗
PubMed1988

The effect of molecular weight/lipophilicity on clearance of organic compounds from lungs.

The objective of this study was to test the hypothesis that lipophilicity (as measured by the octanol/water partition coefficient, P) and/or molecular weight are determining factors in the rate of clearance of organic compounds from the lung. Previous work in our laboratory has shown that organic-soluble compounds such as pyrene, benzo[a]pyrene, 1-nitropyrene, 2-aminoanthracene, phenanthridone, dibenzo[c,g]carbazole, 1,3-dichloropropene, and methyl bromide, all of which have a log P less than 6.1, clear the lung rapidly (t 1/2 less than 12 hr). In the present study, organic compounds (mainly anthraquinone dyes) having a wider range of log P's (1.95-8.65) were instilled into rat lungs and the percentage of the compound retained in the lungs at 24 hr was determined. A positive correlation between the log of the theoretical P and the percentage of the compound retained in lungs at 24 hr was found. The lipophilicity of the series of compounds studied was highly dependent on the molecular weight, so that there was also a positive correlation between the molecular weight of the compounds and the percentage of the compound retained in the lung at 24 hr. To help understand the relative importance of lipophilicity and molecular weight in determining lung retention, an additional compound with a high molecular weight but containing a polar functional group [1,5-di(2-sulfo-p-toluidino)anthraquinone] was studied. The results indicated that the lipophilicity was the more important factor in whether the material was retained in the lung. On the basis of the results of this study, organic-soluble compounds with molecular weights less than 300 Da can be expected to clear the lungs rapidly. Nonpolar, organic-soluble compounds with a molecular weight greater than 300 Da can be expected to clear the lungs more slowly.

Animals↗
PubMed1987

Differential induction of cytochrome P-450 catalyzed activities by polychlorinated biphenyls and benzo [a]pyrene in B6C3F1 mouse liver and lung.

The properties of some constitutive and inducible enzyme activities of liver and lung microsomes were determined in B6C3F1 mice pretreated by either intratracheal (i.t.) administration of benzo[a]pyrene (BaP) or polychlorinated biphenyl (PCBs) mixture (Aroclor 1254), or intraperitoneal (i.p.) administration with Aroclor 1254. After i.p. administration of Aroclor 1254, liver cytochrome P-450 content, aryl hydrocarbon hydroxylase (AHH), benzphetamine N-demethylase and nitroreductase activities were increased 2.8-, 2.0-, 2.2-, and 2.0-fold, respectively. Lung cytochrome P-450 content was also increased (1.9-fold) after i.p. administration of Aroclor 1254; AHH and nitroreductase activities, however, were not affected and benzphetamine N-demethylase activity was decreased. Aroclor 1254 administered i.t. did not affect liver cytochrome P-450 content. However, AHH and benzphetamine N-demethylase activities were decreased 1.4- and 1.2-fold, respectively, and nitroreductase activity was increased 1.6-fold. After i.t. administration of Aroclor 1254, lung cytochrome P-450 content and AHH activity were increased 1.4- and 2.2-fold, respectively. Benzphetamine N-demethylase activity was decreased 2.1-fold and nitroreductase activity was not affected. After i.t. administration of BaP, liver 7-ethoxyresorufin O-deethylase and nitroreductase activities were increased 2.2- and 1.5-fold, respectively, and benzphetamine N-demethylase activity was decreased 1.3-fold. Lung AHH and 7-ethoxyresorufin O-deethylase activities were increased 4.3- and 3.1-fold, respectively, and cytochrome P-450 content, benzphetamine N-demethylase and nitroreductase activities were decreased 1.4-, 1.2- and 1.3-fold, respectively, after BaP administration. These data indicate that different cytochrome P-450 isozymes induced in B6C3F1 mice are responsible for monooxygenase and nitroreductase activities, and that the route of administration of chemicals is important in the expression of cytochrome P-450 catalyzed activities.

Animals↗