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M Verny

Publications and source records attributed to M Verny.

7 recordsLinked to original sources
PubMed1991

Abnormal Tau proteins in progressive supranuclear palsy. Similarities and differences with the neurofibrillary degeneration of the Alzheimer type.

We have previously shown that abnormal Tau species are produced during the neurofibrillary degeneration of the Alzheimer type. These abnormal Tau proteins consist of a characteristic triplet named Tau 55, Tau 64 and Tau 69 which are constantly found in Alzheimer's disease (AD) and Downs syndrome brain regions with tangles. To determine if abnormal Tau species are also produced in other neurodegenerative conditions where intraneuronal filamentous Tau aggregates are observed, we have undertaken an immuno-blot study of brain homogenates from patients with progressive supranuclear palsy (PSP), a neurological disorder characterized by the presence of tangles in subcortical and cortical brain areas. We show here that abnormal Tau species are produced in PSP but that they are different from those in AD. Indeed, although Tau 64 and 69 were present in PSP brain homogenates, possibly as the result of an abnormal phosphorylation as in AD, they were detected in smaller amounts (three times lower) than in AD. In addition Tau 55 was undetected by the immunological tools, such as the absorbed anti-PHF antisera, which specifically label the abnormal Tau proteins. Also the two-dimensional analysis revealed different isoelectric properties. Our results suggest that the production of abnormal Tau species is a very important event during all types of neurofibrillary degeneration. The differences in the pathological Tau-variant profile that were observed between PSP and AD possibly reflect different etiopathogenetic pathways and might explain the formation of different types of filamentous Tau aggregates.

Aged↗
PubMed1991

Leuko-araiosis.

Leuko-araiosis is an unspecific radiologic sign, seen with CT scan or with MRI. It can be found as well in normal elderly persons as in pathological conditions. For the sake of clarity, CT scan and MRI images have to be distinguished. CT leuko-araiosis is linked with vascular risk factors and with age. The situation is more complex for MRI leuko-araiosis (likely on account of the higher sensitivity of MRI). Some images (caps and rims), frequently seen in normal, even young, individuals, are more frequent in aging. On the contrary, abnormal images at a distance from the ventricle are more difficult to interpret. Some of them are due to pathological well defined conditions (small infarcts, Binswanger's disease, cysts, plaques). Others may be secondary to remote pathologies (such as infarcts). Others are due to little specific conditions, such as perivascular dilatations ('état criblé' due to brain vasogenic edema, or to brain atrophy whatever its cause, and more frequently seen in the elderly). Other changes, such as incomplete infarction or myelin pallor with gliosis, have been described. At last, in some cases, no clearcut pathological lesion could be found. Leuko-araiosis may be present in primary degenerative dementia of the Alzheimer type, but it is neither necessary nor sufficient to establish the diagnosis of Alzheimer's disease, and it does not seem more frequent than in elderly controls. The mechanism of leuko-araiosis in Alzheimer's disease is likely multifactorial (for example, cerebral atrophy, amyloid angiopathy, associated hypertensive arteriolosclerosis could be involved). The relationship between leuko-araiosis, myelin pallor and white matter atrophy is poorly understood, and remains to be studied.

Adult↗
PubMed1990

Constant neurofibrillary changes in the neocortex in progressive supranuclear palsy. Basic differences with Alzheimer's disease and aging.

Neocortical neurofibrillary tangles (NFT) revealed by Bodian technique and anti-tau immunolabelling were seen in 5/5 cases of progressive supranuclear palsy (PSP) aged 58-76 years. These lesions differed from Alzheimer's disease or age-related changes: (1) they were most frequent in the precentral gyrus (Brodmann's area 4) whereas associative areas are predominantly lesioned in Alzheimer's disease; (2) they affected mainly large pyramidal neurons and small cells, relatively sparing the cell population selectively involved in Alzheimer's disease; (3) they predominated in layers V and VI of area 4, whereas NFT are most dense in layers III and V in Alzheimer's disease; (4) mature senile plaques (1/5 cases) and beta-amyloid diffuse deposits (3/5 cases), which usually precede or go together with NFT in Alzheimer's disease were rare or absent (2/5) in PSP. Neuropil threads and tufts of abnormal fibres were also seen. In addition, NFT and neuropil threads were found in the hippocampus. PSP is thus another example of abnormal storage of tau developing in the neocortex in the absence of beta-amyloid deposits. It might prove a useful model for the understanding of the mechanisms of localization and spreading of tau storage in the brain.

Aged↗
PubMedDate not supplied

Biodistribution and metabolism in rats and mice of bucromarone.

The metabolism and disposition of bucromarone, labeled with 14C on the chromone group, has been investigated in C3H mice and Wistar rats. In separate experiments, animals received 4.4 mmol/kg, iv or po, [14C]bucromarone hydrochloride or succinate. More than 90% of the administered radioactivity was excreted in bile, after iv and po administration. Less than 5 min after iv injection, radioactivity concentrated in all tissues, and blood concentration became very low as compared with its initial level. After po administration, no more than 10% of the dose was incorporated in the tissues. The discrepancy between the high biliary excretion and the low tissue and blood concentration after po administration suggested that bucromarone was well absorbed through the gastrointestinal tract; but after liver uptake, drug and its metabolites were excreted in the bile, less than 10% being distributed into the extrahepatic blood. Comparison of the iv and po areas under the plasma 14C-radioactivity concentration-time curves indicated a poor bioavailability of the molecule after po administration. Analysis of the radioactivity content of bile showed that bucromarone was extensively metabolized after both administration routes. Unchanged bucromarone and three main metabolites, monodesbutylbucromarone, didesbutyl bucromarone, and 2-(3-5-dimethyl-4-hydroxybenzoyl) chromone, amounting to 85% of the bile radioactivity, were identified by HPLC and mass spectrometry. These findings are consistent with a dealkylation of the N-dibutyl group, yielding potential pharmacologically active metabolites monodesbutyl and didesbutyl bucromarone.

Administration, Oral↗
PubMedDate not supplied

Disposition and metabolism of letosteine in rats.

The metabolism and disposition of letosteine, labeled either with 14C or 35S, has been investigated in Sprague-Dawley rats. In separate experiments, rats received 20 mg/kg, iv or orally, [14C]letosteine or [35S]letosteine. Radioactivity was rapidly excreted, mainly in urine, after iv and oral administration. Recovery of radioactivity from 0-72-hr excreta averaged 95% after both routes of [14C]letosteine administration, whereas only 50% was recovered when [35S]letosteine was administered. 14CO2 accounted for about 7.3% (iv) and 5.1% (po) of the dose of [14C]letosteine. Comparison of the iv and oral areas under the plasma 14C radioactivity concentration-time curves suggested that oral absorption of letosteine was complete. Analysis of the radioactivity content of urine showed that letosteine undergoes rapid and extensive metabolism. Several metabolites were identified by TLC, HPLC, and MS. The findings are consistent with a splitting of the ester group of letosteine and subsequent cleavage of the thiazolidinyl ring, yielding cysteine, hypotaurine, taurine, and inorganic sulfate. The metabolite derived from the side chain was identified in the urine as 3-(hydroxycarbonylmethylthio)propanoic acid. It undergoes further oxidation into sulfoxide and sulfone derivatives, which are also present in the urine.

Animals↗