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Biomedical subjects

P J Schechter

Publications and source records attributed to P J Schechter.

At least 73 records · Page 4Linked to original sources
PubMed1980

Mapping of dyskinetic movements induced by local application of picrotoxin or (+)-gamma-acetylenic GABA on the rat motor cortex.

Unilateral application of picrotoxin or (+)-gamma-acetylenic GABA ((+)GAG) on the cortex of rats produces a characteristic dyskinetic syndrome. Using stereotaxic coordinates, the cortical localization of these abnormal movements was mapped and found to be similar to that previously described after electrical stimulation of these cortical areas: Abnormal movements of the head and forelimb were produced by picrotoxin of (+)GAG applied to sites more anteriorly and of the hindlimb more posteriorly. The degree enzyme inhibition following application of (+)GAG was used to demonstrate a very limited degree of drug diffusion. These results suggest that interferences with GABAergic function in well-defined cortical areas may play a role in dyskinetic movement disorders.

Alkynes↗
PubMed1980

L-Ornithine decarboxylase:an essential role in early mammalian embryogenesis.

The highly selective, enzyme-activated, irreversible inhibitor of L-ornithine decarboxylase, DL-alpha-difluoromethylornithine, suppresses the increase in uterine L-ornithine decarboxylase activity associated with early embryogenesis in the mouse and arrests embryonic development at that stage. Contragestational effects were confirmed in the rat and rabbit. An increase in L-ornithine decarboxylase activity that leads to a rapid increase in putrescine concentration appears to be essential during a critical period after implantation for continued mammalian embryonal growth.

Adenosylmethionine Decarboxylase↗
PubMed1980

An analysis of the cortical and striatal involvement in dyskinesia induced in rats by intracerebral injection of GABA-transaminase inhibitors and picrotoxin.

Unilateral intrastriatal injection of various substances induces a characteristic dyskinetic syndrome in rats. These substances include picrotoxin as well as a series of irreversible GABA-transaminase inhibitors. Using the degree of enzyme inhibition in various brain areas as a measure of drug distribution following intrastriatal administration of gamma-acetylenic GABA and gamma-vinyl GABA, there was found considerable retrodiffusion via the needle tract to the overlying cortex. Topical application of gamma-acetylenic GABA and gamma-vinyl GABA to the cortical surface overlying the striatum produced a high incidence of identical dyskinesias without any evidence of diffusion of drugs to the striatum. The cortically induced movements could be duplicated by picrotoxin application to a defined cortical area. These findings suggest that interference with gabaergic function in the striatum is not necessary for the production of the dyskinetic syndrome and that this syndrome may be a cortically induced phenomenon.

4-Aminobutyrate Transaminase↗
PubMed1979

Failure of oral L-histidine to influence appetite or affect zinc metabolism in man: a double-blind study.

L-Histidine, 4 g/day in gelatin capsules, was administered orally to eight normal volunteers for 2 weeks in a double-blind, balanced, crossover study with 2 weeks of placebo treatment. Body weight, serum and urinary zinc and histidine concentrations, as well as subjective ratings of appetite, taste and smell perception, and food intake were monitored. L-Histidine therapy had no significant effect on appetite, taste and smell perception, food intake, or body weight. Similarly, no effects were observed on total serum zinc, albumin-bound zinc or alpha 2-macroglobulin-bound zinc concentrations, or on urinary histidine excretion. Serum histidine concentrations increased with therapy. Urinary zinc excretion was increased significantly after 1 week, but not after 2 weeks of L-histidine therapy. It can be concluded that oral L-histidine, at the dose used, has no value as an anorectic agent.

Adult↗
PubMed1978

The effect of gamma-acetylenic GABA, an enzyme-activated irreversible inhibitor of GABA-transaminase, on dopamine pathways of the extrapyramidal and limbic systems.

gamma-Acetylenic GABA (100 mg/kg i.p.) inhibited GABA-transaminase activity and caused a several-fold increase in the concentration of GABA in rat brain. This increased GABA concentration was associated with a decreased rate of dopamine depletion following alpha-methyl-p-tyrosine treatment and a decrease in homovanillic acid in extrapyramidal and limbic structures suggesting a decrease in dopamine turnover in both pathways. In addition, gamma-acetylenic GABA injected into the ventral mesencephalic tegmentum decreased dopamine turnover in the mesolimbic forebrain. These results are consistent with a modulatory function of GABAergic neurons on extrapyramidal and limbic dopamine pathways. Inhibitory effects on dopaminergic functions of the extrapyramidal and limbic systems were also indicated by the amphetamine and apomorphine-induced ipsilateral turning after unilateral substantia nigral injections of gamma-acetylenic GABA and by the attenuation of dopamine-induced hypermotility after bilateral injections of gamma-acetylenic GABA into the nucleus accumbens.

4-Aminobutyrate Transaminase↗
PubMed1978

Automated assay of gamma-aminobutyric acid in human cerebrospinal fluid.

We describe an automated amino acid analyzer with fluorescence detection (o-phthalaldehyde) which permits sensitive and rapid determinations of gamma aminobutyric acid in human cerebrospinal fluid. Concentrations as low as 50 nmol/liter can be accurately determined in 100 mul samples at the rate of one sample per hour. Concentrations in untreated cerebrospinal fluid increase rapidly after sampling by lumbar puncture. The concentration in immediately deproteinized samples from 38 patients with intervertebral disc disorders was 220 +/- 81 nmol/liter (mean +/- SD).

Amino Acids↗
PubMed1977

Effect of elevated brain GABA concentrations on the actions of bicuculline and picrotoxin in mice.

gamma-Acetylenic GABA and gamma-vinyl GABA, two catalytic irreversible inhibitors of mammalian brain GABA transaminase that produce several-fold increases in brain GABA concentrations were tested for their effects on bicuculline and picrotoxin-induced seizures and mortality in mice. Neither inhibitor influenced the frequency of seizures or death produced by either bicuculline or picrotoxin. Both inhibitors, however, produced a dose-dependent prolongation of the time to onset of seizures and death induced by picrotoxin but by bicuculline. These results suggest differences in the antagonism by bicuculline and picrotoxin of GABA-mediated neural functions.

Aminobutyrates↗
PubMed1977

Audiogenic seizure protection by elevated brain GABA concentration in mice: effects of gamma-acetylenic gaba and gamma-vinyl GABA, two irreversible GABA-T inhibitors.

gamma-Acetylenic GABA and gamma-vinyl GABA, two catalytic irreversible inhibitors of GABA-transaminase, produce marked and sustained elevations in mouse brain GABA concentrations and protect DBA/2 mice against audiogenically induced seizures in a similar dose and time-dependent manner. The acetylenic analog also inhibits GAD activity while the vinyl compound has minimal activity against this enzyme. The increase in brain GABA concentrations induced by these compounds correlates well with attenuation of audiogenic seizure intensity (r = 0.991 and 0.962 for gamma-acetylenic and gamma-vinyl GABA respectively) and with degree of seizure protection (r = 0.974 and 0.834). Seizure intensity is reduced by 50% when brain GABA is increased to 265% and 264% of control values by the two inhibitors and seizure incidence is halved at 322% and 324%. Thus, audiogenic seizure protection in genetically susceptible mice is apparently a function of whole brain GABA concentrations.

4-Aminobutyrate Transaminase↗
PubMed1977

Effect of GABA-transminase inhibition on rectal temperature in mice.

gamma-Acetylenic GABA (amino-4-hex-5-ynoic acid) and gamma-vinyl GABA (amino-4-hex-5-enoic acid), two catalytic irreversible inhibitors of GABA-transaminase, produce marked sustained elevations in brain GABA concentrations. Associated with these biochemical changes is a decrease in the rectal temperature of mice. This hypothermia can be reversed by increasing ambient temperature. The results suggest GABA plays an important role in mammalian central thermoregulation.

4-Aminobutyrate Transaminase↗
PubMed1977

Reduced binding of added zinc in serum of patients with decompensated hepatic cirrhosis.

Binding of zinc to macromolecules when added to serum was measured by ultrafiltration. At a final ratio of 0.6 mol zinc per mol albumin, zinc dissociable by glycine was significantly greater in diluted serum from patients with decompensated alcoholic cirrhosis than in normal serum samples similarly prepared. Low serum zinc concentrations, often observed in patients with alcoholic cirrhosis, may be related in part to a reduced affinity of plasma albumin for exchangeable zinc.

Female↗