Search PubMed⌕ Search

Biomedical subjects

L C Tang

Publications and source records attributed to L C Tang.

87 records · Page 5Linked to original sources

L-3,4-dihydroxyphenylalanine-induced hypersensitivity simulating features of denervation.

The manner in which dyskinesia and intermittency of neurological control had emerged late in the therapy of Parkinsonism with L-3,4-dihydroxyphenylalanine (levodopa) had suggested to us that this drug can imprint on the brain a chemical memory of its passage. The majority of authors ascribed these events to denervation hypersensitivity caused by the nigral and other lesions of the disease. By feeding levodopa to mice, however, we induced a state that simulated denervations hypersensitivity, including hyperreaction to single injections of levodopa and increased dopamine-stimulated adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity in homogenates of caudate nuclei. These phenomena were not caused by actual denervation, because the hypersensitivity declined and disappeared some weeks after the dietary levodopa was stopped.

Adenylyl Cyclases↗

Modification of the actions of some neuroactive drugs by growth hormone.

The flat serum growth hormone (GH) patterns of untreated parkinsonian patients develop diurnal rises during treatment with levodopa. This chronic exposure to excesses of GH might lead to the eventual emergence of the "on-off" phenomenon, which would indicate a need for animal experiments. Pretreatment of mice with GH increased (1) cerebral dopa and dopamine concentrations in levodopa-treated mice, (2) cerebral accumulation of injected tritiated apomorphine and tritiated thymidine, and (3) behavioral responses to levodopa, L-m-tyrosine, apomorphine hydrochloride, and oxotremorine.

Animals↗

Cholinergic effects of molecular segments of apomorphine and dopaminergic effects of N,N-dialkylated dopamines.

The hydrochlorides of molecular segments of apomorphine [2-(3',4'-dihydroxybenzyl)-1,2,3,4-tetrahydroisoquinoline, 2-(3'4'-dihydroxybenzyl)piperidine, and 1,2,3,4-tetrahydroisoquinoline with their respective N-methyl and N-n-propyl homologs] and N,N-dialkylated dopamine compounds were synthesized and studied for (1) LD50 in intact mice; (2) stereotypy in intact mice; (3) curving of the body in unilaterally caudectomized mice; (4) rotation in 6-hydroxydopamine-lesioned rats, and (5) activation of adenylate cyclase in homogenates of mouse caudate nuclei. Instead of dopaminergic effects 1-(3',4'-dihydroxybenzyl)-2-methyl-1,2,3,4-tetrahydroisoquinoline and 2-methyl-1,2,3,4-tetrahydroisoquinoline showed cholinergic ones. These effects were blocked in atropine-pretreated animals. Of the N,N-dialkylated dopamine compounds synthesized, the N-n-propyl-N-n-butyldopamine ranked in all tests as the strongest dopamine-receptor agonist and N-methyl-N-n-propyldopamine as the weakest. In contrast, N,N-dimethyldopamine and 1-(3,4-dihydroxyphenylethyl)piperidine showed no dopaminergic effects. The effectiveness of the dopaminergic agonists depended on the length of the N-alkyl substituents suggesting interactions with hydrophobic regions of the receptor site.

Adenylyl Cyclases↗

Prolongation of the life-span in mice adapted to large amounts of L-dopa.

Various concentrations of L-dopa (levodopa, L-3,4-dihydroxyphenylalanine) were incorporated in the diets of young male Swiss albino mice, and the highest concentrations to which these mice became adapted within 3 weeks were determined. One such concentration administered indefinitely eventually induced a youthful appearance, a significantly prolonged life-span, but also corneal opacities compatible with traumatic or chemical keratitis.

Animals↗

Monoamine oxidase and cerebral uptake of dopaminergic drugs.

The brain uptake of amines that do not enter the brain or enter it poorly was promoted by noncompetitive inhibitors of monoamine oxidase, as shown by behavioral and chemical criteria. Mice pretreated with water or enzyme inhibitors other than those mentioned were placid after receiving dopamine (3,4-dihydroxyphenethylamine). Mice pretreated with monoamine oxidase inhibitors (nialamide or iproniazid) showed upon treatment with dopamine the brisk motor responses characteristic of treatment with its precursor, L-dopa (3,4-dihydroxyphenylalanine). After receiving dopamine, intact nialamide-pretreated mice showed marked increases of brain dopamine, in contrast to water-pretreated test mice or water-treated controls. In unilaterally caudectomized, nialamide-pretreated mice, dopamine induced marked lateral curving of the body toward the lesion followed by running in that direction. Noradrenaline or adrenaline induced curving in caudectomized mice, whereas intact ones remained placid.These catecholamines are bound and inactivated by monoamine oxidase. The cerebral uptakes of chemicals that are bound but not inactivated by monoamine oxidase were thereafter tested. Nialamide induced increased behavioral responses to apomorphine and to N-propyl noraporphine, increased cerebral concentrations of both, and a deep coloration of the brain from methylene blue (bound by monoamine oxidase) but not Evans blue (bound by albumin). Even large doses of nialamide, however, failed to affect the behavioral responses to oxotremorine, which has cholinergic rather than adrenergic or dopaminergic properties. Mitochondrial monoamine oxidase seems therefore to play a specific regulatory role in the transport of substances that it binds, either to inactivate or to release them.

Animals↗

Changing the actions of neuroactive drugs by changing brain protein synthesis.

Diminution of cerebral protein synthesis diminished the cerebral responses of mice to some neuroactive drugs, while an increase in synthesis increased the responses. Protein synthesis in whole brains (tested in vitro) was diminished by giving living mice different inhibitors by different routes. The inhibitors tested (chloramphenicol, cycloheximide, and puromycin) diminished the behavioral responses of the mice to levodopa without affecting either its cerebral uptake or its conversion to dopamine. A diminution of the reactions of dopaminergic receptors was suggested by the diminished responses to the dopaminergic drug, apomorphine, while participation of cholinergic ones was suggested by experiments with oxotremorine. Proof that receptors had been specifically involved was secured on homogenized caudate nuclei from chloramphenicol-treated mice, in which the dopamine-activated production of cyclic AMP was markedly diminished. A stimulator of cerebral protein synthesis, the artificial double-stranded RNA, poly(I).poly(C), increased the behavioral responses to these three drugs while it increased the dopamine-activated production of cyclic AMP. Since all these experimental increases or decreases in the responses to drugs required the lapse of only a few hours, proteins with rapid turnover rates must be critical in the activation of several kinds of cerebral receptors.

Adenosine Triphosphate↗

Melatonin and abnormal movements induced by L-dopa in mice.

Melatonin has blocked adventitious movements induced by L-dopa in intact mice. It has reversed the adventitious turning to the right, and it has induced running to the left in mice receiving L-dopa after a lesion in the right caudate nucleus.

Administration, Oral↗

Seminal plasma beta-human chorionic gonadotropin (beta-HCG): relationships with seminal characteristics and spermatozoal fertilizing capacity.

Seminal plasma beta-human chorionic gonadotropin (beta-HCG) levels were determined in 254 semen samples collected from fertile and suspected subfertile men, and their relationships with seminal characteristics and spermatozoal fertilizing capacity were evaluated. Radioimmunoassayable beta-HCG, as defined by greater than 5 mIU/ml concentration, was demonstrated in only 44.5% of all the samples studied. beta-HCG concentrations were similar in normospermic, oligospermic and azoospermic samples. There were no significant differences in beta-HCG concentration between high-motility and low-motility samples, between normal-morphology and abnormal-morphology samples, and between high-fertilizing capacity and low-fertilizing capacity samples. No significant correlations between the concentrations of beta-HCG and individual parameters of semen analysis and spermatozoal fertilizing capacity among the various groups of samples were observed. The physiological role of seminal plasma beta-HCG is presently uncertain and the relationship of its determination to male fertility requires further investigation.

Chorionic Gonadotropin↗

Spermatozoal fertilizing capacity in polyzoospermia: a preliminary study.

Men with the spermatological symptom of polyzoospermia (greater than 250 X 10(6) sperm/ml) have been reported to seldom impregnate their wives. It was the aim of this study to investigate the spermatozoal fertilizing capacity in polyzoospermia by the human sperm and zona-free hamster ova penetration bioassay. General semen characteristics and in vitro spermatozoal fertilizing capacity were studied in 12 polyzoospermic male partners of couples of infertile marriages. The results were compared with those from a control group of normospermic fertile men (n = 22). No significant differences in sperm motility, normal morphology and in vitro spermatozoal fertilizing capacity were found between the two groups. The polyzoospermic men we studied did not appear to have any defect with the spermatozoal fertilizing capacity, as assessed by the heterologous sperm--ova penetration bioassay. The apparent impairment of fertility and higher abortion rate in couples with polyzoospermic male partners, as described in the literature, may be related to chromosomal aberrations and/or other unknown functional defect of the spermatozoa.

Animals↗

Serum immunoreactive beta-endorphin in the human ovulatory cycle.

Daily serum immunoreactive beta-endorphin (IR-beta-EP) levels, in conjunction with luteinizing hormone, follicle-stimulating hormone, 17 beta-oestradiol, progesterone, and prolactin, were measured during the ovulatory cycle in five healthy Chinese women. Standardization of raw data by conversion to the statistical "Z scores" and composite plot of the five cycles showed that serum IR-beta-EP levels fluctuated during the follicular, late luteal, and menstrual phases. A preovulatory rise occurred two to three days prior to the luteinizing hormone surge, followed by a postovulatory dip for two to three days. The concentrations of IR-beta-EP were (mean +/- S.E.M.): 85.5 +/- 10.5 pg/mL (n = 36) in the follicular phase; 92.4 +/- 36.5 pg/mL (n = 5) in the ovulatory phase; 72.3 +/- 16.6 pg/mL (n = 7) in the early luteal phase; 100.0 +/- 10.7 pg/mL (n = 38) in the late luteal phase. The values in the luteal phase were the highest of any in the ovulatory cycle. The findings suggest that the fluctuation of endogenous beta-EP is under the influence of, among other factors, ovarian sex steroids. The significance of beta-EP in the regulation of gonadotropin release during normal menstrual cycles is discussed.

Adult↗