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Biomedical subjects

J Fiedler

Publications and source records attributed to J Fiedler.

At least 55 records · Page 3Linked to original sources
PubMed1991

Cyanide sensitive and insensitive bioenergetics in a clonal neuroblastoma x glioma hybrid cell line.

The primary mechanism of cyanide (CN) intoxication is the inhibition of metabolism in the central nervous system. We determined the effects of CN on several biochemical processes in neuroblastoma x glioma hybrid NG108-15 cells, which possess numerous neuronal properties. These cells were not sensitive to a high concentration (1 mM) of NaCN, but became sensitive in the presence of the anaerobic glycolysis inhibitors sodium iodoacetate (IA) and 2-deoxyglucose (2-DG):cellular metabolic processes (e.g., DNA, RNA and protein synthesis) decreased to about 40% of control due to treatment with 0.5 mM NaCN + 0.05 mM IA and 0.1 mM NaCN + 20 mM 2-DG. ATP in cells exposed to 0.01 or 0.1 mM NaCN + 20 mM 2-DG was reduced 75% and 100% respectively within one min. Pretreatment of cells with the CN antidote cobalt (II) chloride (CoCl2) (0.06-0.18 mM) for 5 min prevented the depression of both [3H]leucine incorporation and ATP synthesis due to 1 mM NaCN + 20 mM 2-DG in a concentration-dependent manner. A proposed CN antidote alpha-ketoglutaric acid (disodium salt) also prevented the depression of cellular metabolism due to NaCN plus 2-DG. These results indicate that blocking anaerobic glycolysis makes NG108-15 cells sensitive to a low concentration of CN. Thus NG108-15 cells should be useful to study the mechanisms of neurotoxicity of CN and to test antidotes.

Adenosine Triphosphate↗
PubMed1991

Self-help quit smoking interventions: effects of self-help materials, social support instructions, and telephone counseling.

Smokers requesting self-help materials for smoking cessation (N = 2,021) were randomized to receive (a) an experimental self-quitting guide emphasizing nicotine fading and other nonaversive behavioral strategies, (b) the same self-quitting guide with a support guide for the quitter's family and friends, (c) self-quitting and support guides along with four brief counselor calls, or (d) a control guide providing motivational and quit tips and referral to locally available guides and programs. Subjects were predominantly moderate to heavy smokers with a history of multiple previous quit attempts and treatments. Control subjects achieved quit rates similar to those of smokers using the experimental quitting guide, with fewer behavioral prequitting strategies and more outside treatments. Social support guides had no effect on perceived support for quitting or on 8- and 16-month quit rates. Telephone counseling increased adherence to the quitting protocol and quit rates.

Behavior Therapy↗
PubMed1990

A study in rat brain cortex synaptic vesicles of endogenous ligands for N-methyl-D-aspartate receptors.

The presence of endogenous ligands for the N-methyl-D-aspartate receptor was looked for in highly purified rat brain cortex synaptic vesicles, the contents of which were extracted and fractionated by gel filtration on Sephadex G-10, or by three different high-voltage electrophoresis procedures. The presence of endogenous ligands was detected by their ability to compete with 50 nM L-[3H]glutamate for binding to whole rat brain N-methyl-D-aspartate receptors. The receptor preparations used were those present in purified postsynaptic densities, in which the quisqualate receptors were blocked by 10 microM quisqualate. Synaptic vesicles had a high content of N-methyl-D-aspartate receptor ligands, which on fractionation always coincided with glutamate or aspartate. A variable and very small amount of a highly acidic endogenous ligand was also found. The latter substance did not coincide in the electrophoresis with homocysteic, cysteic, quinolinic, cysteine sulphinic or homocysteine sulphinic acids, or with N-acetyl-aspartyl-glutamic acid, S-sulphocysteine or sulphoserine. We also found that a single centrifugation, in 0.25 M sucrose, 25 mM Tris-citrate, pH 7.1, of purified synaptic vesicles, at 135,000 gmax for 45 min, led to a 51% loss of endogenous glutamate, but did not change their aspartate content. Thus, in uncentrifuged vesicles the glutamate/aspartate ratio was 9.4, while in centrifuged ones the ratio was 3.9 ATP markedly enhanced L-[3H]glutamate uptake into synaptic vesicles, but did not change the binding of L-[3H]aspartate. Differences in labelled aspartate and glutamate efflux from the vesicles were also found.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1990

[Rapid glutamic acid decarboxylase test for identification of Escherichia coli].

A rapid, one-step glutamic acid decarboxylase test for the identification of Escherichia coli is described. The test gives a positive reaction (definite blue color) after 2 h to 3 h. Disturbing factors were explained. Microorganisms were cultured to Endo agar (SIFIN) supplemented with 1% meat peptone (Berlin-Chemie). For rapid liberation of the enzyme a combination of lytic agents NaCl and Triton X-100 were necessary. A total of 6,867 strains of Enterobacteriaceae of clinically isolates were parallely tested to activity of lactose, indole, citrate respectively biochemical tests with 15 reactions on the one side and activity of lactose and glutamic acid decarboxylase on the other side. 99.2% of the E. coli strains gave a positive reaction with glutamic acid decarboxylase. The rapid test selected E. coli with more reliability than the combination of the lactose, indole and citrate reactions. Expenditure of time and materials was fewer.

Bacteriological Techniques↗
PubMed1990

[Animal experimental evidence of the long-lasting efficacy of etofenamate by prolongation of the half-life after intramuscular application].

Animal Experimental Evidence of Long-lasting Liberation of Etofenamate by Half-life Prolongation after Intramuscular Application. The purpose of this investigation was to show in animal experiments that by i.m. injection of etofenamate (active substance of Rheumon i.m.) in oily solution the following effects could be obtained: a fast onset of action (gain of therapeutically relevant drug levels shortly after injection) a long-lasting efficacy (prolonged liberation from the oil depot) and better tolerability as compared to other intramuscularly applicable antiinflammatory drugs (avoidance of high plasma spikes). Etofenamate in rats is liberated with a half-life of 1.29 days from the place of application (cutaneous half-life 8.5 h). Flufenamic acid in muscles is found only in traces. After i.m. administration of etofenamate to dogs maximum plasma levels of etofenamate and flufenamic acid were reached within 2 and 4 h, resp. The mean half-lives of plasma elimination are 14 h for etofenamate and 23.2 h for flufenamic acid formed esterolytically from etofenamate (flufenamic acid oral half-life 2-4 h). Maximum plasma levels after etofenamate are only 6.5-11.8% of the maximum levels after equivalent amounts of flufenamic acid administered orally. According to these data etofenamate i.m. is a drug formulation with fast increasing plasma levels, prolonged half-life and lower maximum plasma levels as compared to orally administered preparations. The results are confirmed in animals (pharmacodynamics, toxicology and tolerability) and man (kinetics, clinical studies).

Administration, Oral↗
PubMed1990

[Renal elimination and metabolism of etofenamate in volunteers after administration of various doses].

Renal Elimination and Metabolism of Etofenamate after Intramuscular Administration of Different Doses to volunteers. Renal elimination of etofenamate (active substance of Rheumon i.m.) after i.m. injection of oily solution of etofenamate to volunteers was investigated by HPTLC and GC. After injection of 250, 500 and 1000 mg etofenamate, free and conjugated flufenamic acid (flu), 5-hydroxy- and 4'-hydroxy flufenamic acid (5-OH-flu, 4'-OH-flu) were found as main metabolites in urine. Besides that several minor metabolites were identified. The ratio of free to conjugated metabolites was 1:10 to 1:25. From the doses administered 30% were eliminated as main metabolites. Overall amounts (in mg) of the eliminated metabolites and the doses correlated with each other (r = 0.9334), whereas the percent ratio of 5-OH-flu and of 4'-OH-flu increased with dose. Half lives of renal elimination for flu, 5-OH-flu and 4'-OH-flu are largely independent of dose. The half life of flufenamic acid corresponds roughly to data from plasma levels (7-9 h), the two hydroxy derivatives are eliminated into urine with half lives from 15 to 24 h. The results show, that i.m. injection of an oily etofenamate solution follows a linear dose independent kinetic, while the amounts absorbed and renally eliminated are proportional to dose. The results correspond to plasma level studies.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1988

[Neurochemistry of the mesencephalic substantia nigra: interrelations between excitatory amino acids, N-methyl-D-aspartate type receptors and intrinsic neuronal systems].

Recent studies have demonstrated the existence of cortico-nigral fibers in the brain which may use L-glutamic or L-aspartic acid as their transmitters. Such cortico-nigral neuronal pathway seems to functionally interact with intrinsic neuronal systems in substantia nigra (SN) by first activating different subtypes of excitatory amino acid (EAA) receptors. Particularly interesting are results showing that activation of N-methyl-D-aspartate (NMDA) subtype receptor may evoke the Ca(2+)-dependent release of dopamine from dendrites of nigro-striatal neurons. In addition, NMDA and other EAA receptors may influence the functional activity of gabaergic, glycinergic and peptidergic neurons located in SN. Acidic aminoacid-containing neurons in SN may thus play a pivotal role in determining the outflow information from SN to caudal motor-related as well as rostral limbic-related areas in the brain.

Amino Acids↗
PubMed1986

Glutamate in rat brain cortex synaptic vesicles: influence of the vesicle isolation procedure.

Rat brain cortex synaptic vesicles have been isolated by 3 different procedures. The one of Hata et al. (J. Neurochem., 27 (1976) 139) gave synaptic vesicles with a high glutamate content, but also, as judged by [3H]ouabain binding and electron microscopy, with considerable contamination by plasma membrane vesicles. This did not allow a precise estimation of the glutamate content of each synaptic vesicle. The second procedure used (Life Sci., 21 (1977) 1075), in which the tissue is homogenized with an all glass homogenizer, yielded vesicles of higher purity, but with no glutamate. A slightly modified Kadota and Kadota procedure (J. Cell Biol., 58 (1973) 135) gave synaptic vesicles of a very high purity that were filtered on a Sepharose 4B column, and there, the synaptic vesicle fraction of highest purity was estimated to contain 3640 glutamate molecules in each glutamatergic vesicle. This is equivalent to an intravesicular concentration of 0.21 M, that is, at least 10 times higher than the glutamate concentration in the rat brain cortex.

Animals↗
PubMed1984

Uptake of magnesium by chromaffin granules in vitro: role of the proton electrochemical gradient.

The chromaffin granule membrane in vitro is impermeable to protons as well as to Mg2+; however, when granules are incubated in the presence of the proton ionophore carbonyl cyanide p-trifluoromethoxy-phenylhydrazone or an inhibitor of the granule membrane Mg2+-dependent ATPase, the metal ion is accumulated inside the granules. This accumulation is dependent upon the granule transmembrane potential. The simultaneous presence of the ATPase inhibitor and the proton ionophore markedly increases metal ion incorporation. Mg2+ incorporation is also promoted by nigericin in the presence of potassium or sodium ions, indicating that Mg2+ accumulation is also dependent upon the transmembrane pH gradient. Concomitant with the Mg2+ accumulation, there is a significant loss of endogenous catecholamines. It is concluded that Mg2+ accumulation is determined by the electrochemical gradient maintained across the membrane. Once the metal ion has accumulated into the granules it displaces catecholamines from their storage sites.

Adrenal Medulla↗
PubMed1981

[Gas-liquid chromatographic determination of etofenamate/ Determination, method and use in biological material (author's transl)].

Etofenamate in biological specimen can be determined by gas-liquid chromatography with etofenamate benzyl ether as internal standard. Determination in urine is done directly after extraction and concentration, whereas plasma and homogenates from organs have to be prepurified by thin-layer chromatography. Unchanged etofenamate is found in small amounts in human urine (0--4, 6--6, 6--8 h p. appl.). Inflamed rat paws after local application contain up to 75 microgram etofenamate/g in comparison to only 2 microgram flufenamic acid/g tissue. Both compounds are also found in non-inflamed paws, contents being only 3--4% as compared to the inflamed tissue. Elimination of etofenamate from the inflamed area occurs with a half-life of approx. 8.5 h. These results from gas-liquid chromatography correspond to results from t.l.c./fluorescence measurements.

Animals↗
PubMed1981

[Metabolism of etofenamate / Identification and analytic of metabolites, their pharmacological properties and species dependence of metabolism (author's transl)].

After oral application of etofenamate to animals (rat, rabbit, dog, monkey) unchanged etofenamate and numerous metabolites are found in urine. Analytical properties (thin-layer chromatographic behavior, UV- and fluorescence data) of etofenamate, 5-hydroxy-, 4'-hydroxy, 5,4'-dihydroxy-etofenamate, flufenamic acid, 5-hydroxy-, 4'-hydroxy-, 5,4'-dihydroxy-flufenamic acid are described. Derivatives of etofenamate and flufenamic acid are excreted by rabbit, dog, monkey and man, whereas flufenamic acid derivatives are excreted preferentially by rats; profound degradation takes place in dogs. Metabolism in man is more similar to monkey than to dog and rodents. Metabolic pattern after oral and cutaneous application is quite similar. The six hydroxy derivatives have no pharmacological activity--they do not contribute to the pharmacological action of the substance.

Animals↗
PubMed1980

[Analytical methods and in vitro studies with acemetacin].

1. Analytical methods (isolation, TLC, UV-spectroscopic and preferably fluorimetric determination) of [1-(p-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetoxy] acetic acid (acemetacin, TV 1322, Rantudil), its analogues, hydrolysis-products and metabolites from biological material are described. 2. Stability is also dealt with. Hydrolysis of the p-chlorobenzoyl group results in strongly fluorescing compounds and can be used in determination of acemetacin, indometacin and derivatives 3. Proof is given that in in vitro studies, such as e.g. Mizushima's protein turbidity test or the test for inhibition of prostaglandin-synthetase, only intact acemetacin (and none of its potential break-down products) is present and is active. 4. In in vitro studies, such as the inhibition of total complement and of the increase in activity of serum sulfhydryl groups, acemetacin and a series of its salts proved to be at least as effective as indometacin. 5. In comparing protein binding, acemetacin, like indometacin, is found to bind strongly to albumin. The portion of free, non-protein bound acemetacin, which thus remains available for the pharmacological action, is found to be approx. 60% higher than the corresponding portion of free indometacin.

Animals↗
PubMed1979

[Hepatological aspects of surgical interventions in the stomach].

By means of quantitative-biochemical and histomorphological methods after vagotomies changes of the liver could be proved to a smaller extent than after resections of the stomach (Billroth II). Among the bionomic operation methods the supra-selective proximal vagotomy without pylorplastics is superior to other methods under the aspect of the change of the liver.

Gastrectomy↗
PubMed1978

[The effectivity of long-term treatment of porphyria cutanea tarda from a hepatological viewpoint].

34 Patients with an ascertained porphyria cutanea tarda who underwent a long-term therapy a comprehensive internal and hepatological diagnosis was made. In these cases for the first time the estimation of the intrahepatic distribution of enzymes and its comparison with the serum enzymes were also performed. The liver histology allowed a division of our patients into three groups, in which cases the reactive hepatitides prevailed and a conspicuously large proportion of normal histological findings were present. The comparison of all data got with the literature made the conclusion possible that the phlebotomy therapy as well as the care in a special dispensary for years lead to very favourable results on liver and skin.

Bloodletting↗
PubMed1977

Inhibition of T-antigen-binding cells by idiotypic antisera.

Shared idiotypy between B- and T-cell receptors specific for the antigen L-tyrosine-p-azophenyltrimethylammonium [tyr(TMA)] was studied in an antigen-binding assay using idiotypic antisera. These idiotypic reagents were prepared by inoculation of rabbits with purified anti-tyr(TMA) antibody raised in strain 13 guinea pigs. The antisera blocked 78-83% of the antigen-binding T cells (T-ABC) and 50-55% of the antigen-binding B cells (B-ABC) from tyr(TMA)-immune strain 13 and outbred lymph node cells (LNC). An excess of normal guinea pig Ig in the ABC assay did not affect the ability of the idiotypic antisera to block T- and B-ABC. Nylon wool-passed tyr(TMA)-immune LNC were trypsin treated resulting in a 75% loss of T-ABC. The trypsin-treated population was then cultured for 16 h which resulted in a return of T-ABC to 92% of pretrypsin values. 77% of these regenerated T-ABC could be blocked with idiotypic antisera. Specificity of the idiotypic antisera was tested in L-tyrosine-p-azobenzenearsonate-immune guinea pig LNC. Neither T- nor B-ABC were blocked in this heterologous system. Further blocking experiments were performed to characterize the nature of the T-ABC receptor. A variety of anti-Ig reagents, some of which block B-ABC, do not inhibit T-ABC suggesting that variable regions on T cells are not linked to Ig Constant regions.

Animals↗