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Biomedical subjects

Y Michotte

Publications and source records attributed to Y Michotte.

At least 91 records · Page 5Linked to original sources
PubMed1989

Regional differences in the distribution of norepinephrine and epinephrine in human cerebral cortex: a neurochemical study using HPLC and electrochemical detection.

We performed neurochemical quantitation of the catecholamines dopamine (DA), norepinephrine (NE) and epinephrine (E) and their major metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylethylene glycol (MHPG) in 22 cortical regions of 6 postmortem human brains. Statistical analysis indicated a clear regional difference for NE and E while DA and all the metabolites under study are homogeneously distributed over the cortex. These consistent regional differences suggest the possible role of NE and E as neurotransmitters or neuromodulators in human cerebral cortex.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1989

Monoaminergic neurotransmitters in Alzheimer's disease. An HPLC study comparing presenile familial and sporadic senile cases.

Norepinephrine, epinephrine, dopamine, serotonin and their major metabolites were measured in 20 regions of the left hemisphere in 4 presenile familial cases of Alzheimer-type dementia and 4 sporadic senile cases. Both groups were compared to values in normal brains obtained in our laboratory. Quantitative determination of the monoamines was performed by HPLC with electrochemical detection. The clinical diagnosis of Alzheimer-type dementia was confirmed by histological examination of the right hemisphere and brain stem. The serotonergic system was dramatically affected in the familial cases with very low or undetectable serotonin concentrations in most cortical and subcortical areas studied and an important cell loss in the nucleus raphe dorsalis, origin of the main ascending serotonergic system. In the senile demented patients the serotonergic deficit is less important but still clearly present. The noradrenergic, adrenergic and dopaminergic systems were less affected by the disease process in senile sporadic as well as in the presenile familial type of Alzheimer's disease.

Adult↗
PubMed1989

Clinical and pharmacokinetic evaluation of controlled-release levodopa/carbidopa (CR-4) in parkinsonian patients with severe motor fluctuations: a six month follow-up study.

The results of a six month open-label study comparing the efficacy of controlled-release levodopa-carbidopa (Sinemet CR-4 200 mg/50 mg) with standard levodopa/carbidopa (250 mg/25 mg) in 17 patients with idiopathic Parkinson's disease and severe response fluctuations, are reported. Major clinical benefits included; improvement of disability, reduction of the number of 'off' periods (predominantly end-of-dose hypokinesia) and a slight increase in 'on' time. No improvement was observed in two of our patients. Mean levodopa plasma levels were comparable between the two types of formulations during optimal treatment, however systemic bioavailability was significantly higher with CR-4. Delayed onset of antiparkinsonian effect of CR-4, resulting from an increase of Tmax for levodopa, was one of the major complaints and required additional small amounts of standard levodopa in three patients.

Adult↗
PubMed1989

Basal and tolbutamide-induced plasma somatostatin in healthy subjects and in patients with diabetes and impaired glucose tolerance.

Peripheral levels of basal and tolbutamide-induced somatostatin have been measured in patients with diabetes or impaired glucose tolerance (IGT) and compared with those in normal individuals. Basal somatostatin was significantly higher in patients with Type 1 diabetes than in age-matched control subjects. This increase was most pronounced at diagnosis, and appeared to be related to metabolic control in insulin-treated patients. No increase was noted in patients with Type 2 diabetes or with IGT. Intravenous bolus injection of tolbutamide enhanced peripheral somatostatin levels in healthy volunteers in a biphasic manner. Patients with IGT also exhibited a biphasic response but the amplitude of the first phase was higher. No secretory response was detected in 27/29 Type 1 diabetic patients at diagnosis; a somatostatin response to tolbutamide became detectable again in Type 1 patients with normalization of their basal somatostatin levels but was then paradoxically related to poor blood glucose control. In Type 2 diabetes, basal somatostatin levels were similar to age-matched control subjects, but decreased upon intravenous tolbutamide administration.

Adult↗
PubMed1989

Controlled-release carbidopa/levodopa (CR) in parkinsonian patients with response fluctuations on standard levodopa treatment: clinical and pharmacokinetic observations.

The efficacy of an oral controlled-release preparation of carbidopa/levodopa (Sinemet CR 50/200 mg) was compared with conventional carbidopa/levodopa (25/250 mg) in an open-label study. Twenty patients with idiopathic Parkinson's disease and severe response fluctuations participated. At the end of 6 months of CR treatment, the major clinical benefits included improvement of disability, reduction in number of "off" periods (predominantly end-of-dose hypokinesia), and increase in percentage of "on" time. Although dosages of CR required for an optimal therapeutic response were not significantly higher compared with conventional levodopa, bioavailability significantly increased. Delayed onset of antiparkinsonian effect of CR, resulting from an increase of Tmax for levodopa, was one of the major patient complaints and required additional small amounts of standard levodopa in some patients.

Aged↗
PubMed1987

Combined ion-pair extraction and high-performance liquid chromatography for the determination of the biogenic amines and their major metabolites in single brain tissue samples.

A combined procedure based on reversed-phase liquid chromatography with electrochemical detection has been developed for the determination in the picomole range of the monoamines dopamine, norepinephrine, epinephrine and serotonin, and their major metabolites 3,4-dihydroxyphenylacetic acid, homovanillic acid, 3-methoxy-4-hydroxyphenylethylene glycol, 5-hydroxyindoleacetic acid, normetanephrine, metanephrine and 3-methoxytyramine. Sample pretreatment consists of the extraction of the neutral and acidic metabolites with ethyl acetate, followed by the extraction into heptane of the catecholamines with tetraoctylammonium bromide as counter-ion in the presence of diphenylborate. The residual supernatant is directly injected in the chromatographic system for quantification of serotonin, normetanephrine, metanephrine and 3-methoxytyramine.

Biogenic Amines↗
PubMed1987

Distribution of biogenic amines and their catabolites in brains from patients with Alzheimer's disease.

Norepinephrine, epinephrine, dopamine, serotonin and their major catabolites were measured in 17 regions of the left hemisphere of two brains obtained from two brothers with Alzheimer's disease with very early onset. The clinical diagnosis was confirmed by histological examination of the right hemispheres and brain stems. The quantitative data were compared with our values in normal brains. In the patient suffering from the less severe dementia, there was a severe reduction of the serotonin concentration in all examined neocortical areas and its concentration was even below the detection limit in the nucleus amygdalis, hippocampus, caudate nucleus, putamen, globus pallidus and substantia nigra. In the other patient, who suffered from a more pronounced dementia with myoclonus, the serotonin concentration was below the detection limit in all examined structures. In contrast with these findings, the noradrenergic, adrenergic and dopaminergic systems appeared to be relatively unaffected by the disease process. Focusing our attention on the nuclei wherein the monoamine transmitter systems originate, it appeared that neuronal losses and neurofibrillary tangles clearly predominated in the substantia grisea subependymalis, the nucleus centralis superior and the nucleus raphe dorsalis, origin of the main serotonergic system. The serotonin deficiency sheds light on possible mechanisms of myoclonus in Alzheimer's disease.

Adult↗
PubMed1987

Simultaneous determination of levodopa, carbidopa, 3-O-methyldopa and dopamine in plasma using high-performance liquid chromatography with electrochemical detection.

An analytical method is described which allows a fast, reliable and precise determination of levodopa and its metabolises 3-O-methyldopa and dopamine, as well as the peripheral aromatic amino acid decarboxylase inhibitor carbidopa, in a single 1 ml plasma sample of Parkinsonian patients. The compounds are quantitatively isolated on small Sephadex G-10 columns and determined by HPLC with electrochemical detection. Dihydroxybenzylamine or alpha-methyldopa are used as the internal standard. An example of therapeutic drug monitoring in a patient with fluctuations in motor performances is given. It is confirmed that interference with absorption of levodopa from the stomach by food can be partly responsible for these observed fluctuations.

Journal Article↗
PubMed1987

The significance of homovanillic acid and 3,4-dihydroxyphenylacetic acid concentrations in human lumbar cerebrospinal fluid.

The concentrations of the acidic dopamine (DA) catabolites homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) measured in human CSF are supposed to reflect the "turnover" of DA in the brain. The notion of "turnover" is, however, not synonymous with impulse nerve activity in the dopaminergic systems. Significant amounts of DOPAC and HVA could, indeed, be demonstrated in brain structures wherein dopaminergic innervation has not been documented. It must also be noted that DA is not only a neurotransmitter itself, but also a precursor of norepinephrine and epinephrine. Furthermore, in lumbar CSF, levels of biogenic amine catabolites partially reflect metabolism in the spinal cord and may have limited relevance to neurotransmission in the brain. To elucidate these points further, we determined the concentrations of DOPAC and HVA in 22 areas of six human brains and eight levels of six human spinal cords. The data were correlated with the concentration of DA. Quantitative determinations were done using HPLC with electrochemical detection, after solvent and ion-pair extraction. In this study, significant amounts of both DOPAC and HVA were demonstrated in brain structures not previously associated with dopaminergic innervation. The relatively lower DA concentration in these structures suggests that in these regions, the DOPAC and HVA concentrations are unrelated to dopaminergic neurotransmission. The possible role of capillary walls and glial cells in the catabolism of DA must be further evaluated. The demonstration of DOPAC and HVA in the spinal cord is another argument against the hypothesis that CSF levels of HVA and DOPAC reflect closely the activity of the dopaminergic systems in the brain.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Feasibility study concerning the use of expert systems for the development of procedures in pharmaceutical analysis.

The feasibility of using expert systems for the development of analytical procedures is investigated. A system for the computer generation of procedures to determine active drug substances in commercial formulations is proposed. It is shown that in nearly 85% of the cases investigated the present system immediately yields a correct procedure or conclusion. It is concluded that selecting methods and developing procedures with the use of expert systems is difficult but feasible.

Journal Article↗
PubMed1985

Determination of the biogenic amines and their major metabolites in single human brain tissue samples using a combined extraction procedure and high-performance liquid chromatography with electrochemical detection.

A combined extraction system for the selective and quantitative isolation of the monoamines norepinephrine, epinephrine, dopamine, serotonin (5-hydroxytryptamine) and their metabolites 3-methoxy-4-hydroxyphenylethylene glycol, 3,4-dihydroxyphenylacetic acid, 5-hydroxyindoleacetic acid, homovanillic acid and 3-methoxytyramine from one single brain tissue sample is described. The extraction system is a combination of an ethyl acetate extraction for 3-methoxy-4-hydroxyphenylethylene glycol, 3,4-dihydroxyphenylacetic acid, 5-hydroxyindoleacetic acid and homovanillic acid, and two successive ion-pair extractions. In a first step, the catecholamines are quantitatively isolated by extracting with heptane--octanol (99:1) containing 0.25% tetraoctylammonium bromide as an ion-pairing agent in the presence of 0.2% diphenylborate. In a second step, 3-methoxytyramine and 5-hydroxytryptamine are isolated from the aqueous phase with di(2-ethylhexyl)phosphoric acid as counter-ion in chloroform. Dihydroxybenzylamine, isohomovanillic acid and 5-hydroxy-N-methyltryptamine are used as the internal standards.

Biogenic Amines↗
PubMed1985

The use of capillary gas chromatography/mass spectrometry for the determination of acidic dopamine metabolites in human brain.

A capillary gas chromatographic/mass spectrometric method was developed for the determination of homovanillic acid and 3,4-dihydroxyphenylacetic acid in discrete areas of human brain known to contain only small amounts of dopamine metabolites. The electron impact mass spectra of the trimethylsilyl derivatives of homovanillic acid and 3,4-dihydroxyphenylacetic acid and their deuterated isotopic variants were used for their identification and quantification.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Possible linkage relationship between genetic markers and blood magnesium and zinc. A twin study.

In a sample of 63 like-sex dizygotic twins, red blood cell and plasma magnesium and red blood cell zinc concentrations were analyzed for linkage to each of 23 genetic systems by estimating correlation between proportion of genes identical by descent and biological resemblance for the trait. The results suggest possible linkage of red blood cell magnesium with the HLA locus and of red blood cell zinc with the GLO1 locus. However, studies applying more powerful tests are needed to confirm such conclusions.

Female↗
PubMed1984

Abnormal fatty acid turnover in the phospholipids of the red blood cell membranes of cystic fibrosis patients (in vitro study).

A study was carried out in order to investigate whether the abnormal in vitro turnover of fatty acids in the phospholipids of the red blood cell membranes of cystic fibrosis patients is intrinsic to the membrane, or whether it is induced by extrinsic serum factors. Red blood cells of cystic fibrosis patients and healthy subjects were labeled in vitro with [14C]linoleic acid, bound to albumin. The labeled cells were reincubated in autologous and homologous serum. The radioactivity present in the serum lipids and in the major phospholipid fractions of the red cell membranes was measured. Conclusions of this study are: 1) not all of the cystic fibrosis patients examined individually show an abnormal in vitro turnover of the red cell fatty acids, although they all presented abnormal fatty acid patterns for the red blood cell phospholipids, the platelet phospholipids, and the plasma lipids. 2) The in vitro abnormal fatty acid turnover occurs only in the incubations where red cells of cystic fibrosis patients are involved (in homologous and autologous serum) and not where red cells of healthy subjects are incubated in serum of cystic fibrosis patients. Consequently, the abnormal turnover is intrinsic to the red cells and is not induced by extrinsic serum factors.

Adolescent↗
PubMed1983

The adaptation of the human thyroid gland to a physiological regimen of iodide intake: evidence for a transitory inhibition of thyroid hormone secretion modulated by the intrathyroidal iodine stores.

The effects of iodide on thyroid function were so far only studied after administration of pharmacological or small continuous doses. We were interested to know how the human thyroid gland would react to a more physiological situation: small doses taken in intermittently. Ten normal male volunteers were given weekly doses of iodide: 1 mg for the first 6 weeks and 2 mg afterwards for another 6 weeks period. Intrathyroidal iodine stores were evaluated by the X-Ray-Fluorescence method. The following thyroid parameters were estimated during the 3 months period: total thyroxine, total triiodothyronine, free thyroxine, free triiodothyronine, reverse triiodothyronine, plasma inorganic iodide, thyroid stimulating hormone and thyrotropin-releasing hormone tests. The following observations were made: i) a steady increase of intrathyroidal iodine (p less than 0.01); ii) no changes in free thyroxine, free triiodothyronine, thyroid stimulating hormone, thyrotropin-releasing hormone test or plasma inorganic iodide. iii) a decrease of total thyroxine (and total triiodothyronine) with a nadir at about 3 weeks and a spontaneous rise afterwards; repetition of this phenomenon by doubling the dose of iodide. It is concluded that 1 mg or 2 mg iodide a week does not inhibit incorporation into the normal human thyroid gland and suggested that these physiological doses of iodide cause a transitory inhibition of thyroxine secretion, representing a form of autoregulation of the thyroid cell, since it was modulated by the intrathyroidal iodine stores and no evidence of pituitary mediation could be evidenced in the experimental protocol.

Adult↗
PubMed1981

The inheritance of plasma and red blood cell magnesium and zinc levels studied from twin and family data.

The variability of magnesium and zinc concentrations in plasma and erythrocytes was investigated by twin and family studies. Twins were sampled in two distinct ways and in two different West-European regions. In one of the samples, a distinction was made between twins liver together and twins living apart. Two series of families were studied, one in a homogeneous environment, the other in a more diverse environment. Samples were compared by variance analysis. The results show 1) that genetic variability is significant for red blood cell (RBC) magnesium and zinc, minor for plasma magnesium and absent for plasma zinc; 2) that the family environment affects the extent of resemblance between twins and between siblings more for plasma levels than for RBC levels of magnesium and zinc. Furthermore, the intercorrelation analysis suggests that the genetic regulation systems of RBC magnesium and zinc are different, whereas some of the environmental regulation systems of plasma magnesium and zinc are the same. Biological interpretations are brought forward and discussed.

Adolescent↗