Characteristics of dopaminergic neurotoxicity produced by MPTP and methamphetamine.
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Animals↗
Biomedical subjects
A Giovanni
Publications and source records attributed to A Giovanni.
MK-801 fails to protect against the dopaminergic neuropathology produced by systemic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice or intranigral 1-methyl-4-phenylpyridinium in rats.
Previous studies from this laboratory demonstrated that (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801), an N-methyl-D-aspartate (NMDA) receptor antagonist, did not prevent neurotoxicity to dopaminergic neurons in mice produced by systemic treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). However, Turski et al. [Nature 349, 414-418 (1991)] reported that extended treatment of rats with NMDA receptor antagonists (six injections at 4-h intervals) did prevent the loss of nigral dopaminergic neurons resulting from an intranigral infusion of 1-methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of MPTP. The present studies examined if a similar extended treatment with MK-801 would protect mice from the neurotoxicity of systemically administered MPTP. Six intraperitoneal injections of MK-801 given at 4-h intervals did not protect mice against the MPTP-induced neostriatal dopamine loss measured 1 week after treatment. In other experiments, designed to replicate and expand on the results of Turski et al. (1991), the extended treatment of rats with MK-801 did not prevent MPP(+)-induced cell loss in the infused substantia nigra pars compacta or the dopamine depletion in the ipsilateral neostriatum at 7-11 days after MPP+ infusion. These results do not support the hypothesis that NMDA receptors are involved with MPTP/MPP(+)-induced neurodegeneration.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
[How to evaluate velar insufficiency?].
The evaluation of velar insufficiency is absolutely necessary in order to assess the results of surgery of the labial palatal cleft. In addition to the clinical examination which remains indispensable, the aerophonometer, applicable to adults and children as from the age of 3, enables simultaneous measurement of the flow of buccal air, the flow of nasal air, and the buccal phonogram. The comparison of the lines, the relation of the nasal air and buccal air flows, upon the emission of two standard sentences with and without nasal components, enables an objective assessment of velar functioning.
Child, Preschool↗
[A multiparameter method of computer-assisted objective vocal evaluation].
The aim of this study is to validate an aid for the evaluation of dysphonia with objective measurements. We recorded exhaled airflow, fundamental frequency and sound level pressure, for a sustained vowel "a", with 51 dysphonic subjects and 15 normal subjects. The following measurements are made on these three parameters: mean value, standard deviation and coefficient of variation. The exhaled airflow volume was also computed for a duration of 2 seconds. A principal components analysis of the measurements indicated that it is possible to recognise the classes of vocal evaluation and vocal pathology. These findings reinforce on objective aid for the vocal evaluation of dysphonia.
Diagnosis, Computer-Assisted↗
Correlation between the neostriatal content of the 1-methyl-4-phenylpyridinium species and dopaminergic neurotoxicity following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine administration to several strains of mice.
In the present study we observed pronounced differences in the capacity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce dopaminergic neurotoxicity in several strains of mice. For example, there was no MPTP-induced decrement in neostriatal dopamine content in Ace Swiss-Webster mice and a 92% decrement in Taconic Farms C57 bl mice. Several parameters which could possibly explain this differential sensitivity to MPTP were studied. These include: 1) neostriatal monoamine oxidase-B (MAO-B) activity; 2) the capacity of neostriatal synaptosomes prepared from the mouse strains to accumulate 1-methyl-4-phenylpyridinium (MPP+), the major metabolite of MPTP formed via oxidation by MAO-B; and 3) the neostriatal MPP+ content after MPTP administration to the mice. There were no significant differences in the Km values for MAO-B in the neostriatum among the strains of mice examined. Neostriatal Vmax values for MAO-B differed somewhat among the strains, with a low of 2915 +/- 172 nmol/g of tissue per hr (CD-1 mice from Charles River) and a high of 3884 +/- 203 nmol/g of tissue per hr (C57 bl mice from Taconic Farms). However, Vmax values for MAO-B in the mouse strains did not correlate significantly with the relative sensitivity of the strains to MPTP. There were no significant differences in the capacity of neostriatal synaptosomes prepared from the mouse strains to accumulate MPP+. Studies on the metabolism of MPTP after peripheral administration revealed that there was a significant (P less than .01) positive correlation between the relative sensitivity of the mouse strains to MPTP and their neostriatal MPP+ content after MPTP administration.(ABSTRACT TRUNCATED AT 250 WORDS)
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine- and 1-methyl-4-(2'-ethylphenyl)-1,2,3,6-tetrahydropyridine-induced toxicity in PC12 cells: role of monoamine oxidase A.
The toxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-methyl-4-(2'-ethylphenyl)-1,2,3,6-tetrahydropyridine (2'Et-MPTP), and their corresponding pyridinium species was studied in the rat pheochromocytoma PC12 cell line. MPTP and its analogues are known to be metabolized by monoamine oxidase (MAO) to dihydropyridinium intermediates which are further transformed, either enzymatically or spontaneously, into pyridinium species. MAO activity in PC12 cells is almost exclusively of the A form, and 2'Et-MPTP is a good substrate for both MAO-A and MAO-B. In contrast, MPTP is a poor substrate for MAO-A, but a good substrate for MAO-B. 2'Et-MPTP caused considerably more cell death than MPTP in the PC12 cells. However, 1-methyl-4-(2'-ethylphenyl)pyridinium and 1-methyl-4-phenylpyridinium, the corresponding pyridinium species formed from 2'Et-MPTP and MPTP, respectively, were equipotent as toxins. The toxic effects of the tetrahydropyridines and their corresponding pyridiniums were both concentration- and time-dependent. Measurements of the levels of the pyridinium species formed and the remaining tetrahydropyridine in the media indicated that 2'Et-MPTP was converted about five to seven times more readily into its toxic pyridinium species than was MPTP. There was, moreover, an excellent correlation between amount of pyridinium formed and cell death. There was also a parallel between the capacity of clorgyline and pargyline, irreversible MAO inhibitors, to decrease the formation of the pyridinium species and their capacity to protect against the toxic actions of the tetrahydropyridines. These data are consistent with the concept that the MAO-A-dependent formation of the pyridinium species from the tetrahydropyridine is a prerequisite for toxicity in PC12 cells.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
[Treatment of laryngotracheal stenoses in children].
Over a period of 5 years, from 1984 to 1989, 35 children were treated surgically for a laryngo-tracheal stenosis, 27 by an external approach, 8 by endoscopy with the CO2 laser. Of the children, 25 (71%) were under 5 years old at the time of treatment and 77% of the stenoses (n = 27) corresponded to a post-intubation and/or tracheotomy acquired etiology. Based on the classification of stenoses according to the extent of the impairment of the aerial lumen, the authors stress the value of conservative treatment (endoscopy) in Stage I (less than 70%, n = 8), and of treatment using the external approach in Stage II (between 70% and 90%, n = 12), in Stage III (between 90% and 99%, n = 12) and Stage IV (complete obstruction, n = 3). The technique most widely used currently is laryngo-tracheoplasty with the insertion of costal cartilage (n = 17). Analysis of the results shows that decannulation was successful in 85% of the cases. With respect to the management of stenoses in the new-born baby, the authors report on their recent experience with laryngo-trachoe-fissure in 6 cases as an alternative either to tracheotomy in difficult extubations, or to laryngo-tracheoplasty when the child's weight is particularly low.
Adolescent↗
Studies with the neurotoxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and several of its analogs.
The nigrostriatal dopaminergic neurotoxicity of MPTP was prevented in mice in a dose-dependent manner by the monoamine oxidase-B (MAO-B) inhibitor deprenyl. This finding, combined with other observations, points out the important role of MAO-B in the bioactivation of MPTP. In the present study, some comparisons between MPTP and several of its structural analogs will be presented.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
Importance of monoamine oxidase A in the bioactivation of neurotoxic analogs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is a potent dopaminergic neurotoxin that causes biochemical, pharmacological, and pathological deficits in experimental animals similar to those seen in human parkinsonian patients. All of the deficits can be prevented by treating mice with selective inhibitors of monoamine oxidase B (MAO-B), including deprenyl, prior to MPTP administration. We now report that the dopaminergic neurotoxicity of two potent MPTP analogs, namely the 2'-methyl and 2'-ethyl derivatives (2'-MeMPTP and 2'-EtMPTP), cannot be prevented by deprenyl pretreatment. However, the neurotoxicity of these two analogs can be prevented by pretreatment with a combination of deprenyl and the selective MAO-A inhibitor clorgyline at doses that are sufficient to almost completely inhibit both MAO-B and MAO-A activities. Moreover, the neurotoxicity of 2'-EtMPTP (but not of 2'-MeMPTP and MPTP) can be significantly attenuated by clorgyline alone. There was a parallel between the capacity of the MAO inhibitors to decrease the brain content of the pyridinium species after administration of the tetrahydropyridines and the capacity of the MAO inhibitors to protect against the neurotoxic action of the tetrahydropyridines. The data support the conclusion that both 2'-MeMPTP and 2'-EtMPTP are bioactivated to pyridinium species to a significant extent by MAO-A. Further, it appears that the formation of the pyridinium species plays an important role in the neurotoxic process.
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
[The voice without vocal cords].
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Humans↗
[Contribution of nuclear magnetic resonance in the neuro-otologic diagnosis of acoustic neuroma. Screening and evaluation of its extension].
Forty patients with suspected tumoral syndrome of ponto-cerebellar angle were investigated by NMR imaging. The method proved to be reliable, less invasive (lack of irritation and absence of iodized contrast) and as rapid as CT scan imaging for the diagnosis of presence and extension of an VIIIth nerve neurinoma. It also allowed avoidance of computerized gas meatography during screening for intracanal neurinomas.
Audiometry↗
[Nodular and paranodular formations].
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Adolescent↗
[Requisite selection of surgical technics in the treatment of cancer of the larynx].
Rules for functional surgery of cancer of larynx are defined by means of a detaited analysis of results of 43 cases of reconstructive anterior frontal laryngectomy, 17 cases of crico-hyoide-epiglottopexy and 32 cases of crico-hyoidopexy. The carcinologic features of this surgery are discussed, and emphasis placed on the importance of the paraglottic space and its functional conditions in the light of recent physiologic data. Surgical procedures used are outlined with, for each of them, the neoplastic localization suitable for treatment and a critical analysis of postoperative functional results. Carcinologic follow up is still insufficient for several techniques used, preventing any precise conclusions to be drawn, but the authors consider it is justifiable to perform 66% of partial as against 34% of total laryngectomies.
Humans↗