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Biomedical subjects

Y Michotte

Publications and source records attributed to Y Michotte.

At least 73 records · Page 4Linked to original sources

Rehardening of surface softened and surface etched enamel in vitro and by intraoral exposure.

The rehardening of surface-softened and surface-etched enamel was investigated in vitro and by intraoral exposure. Surface-softened enamel was obtained by treatment with 0.1 M acetic acid buffer solution (pH = 5.5) for 3 h. Surface-etched enamel was obtained by the acid etch procedure used in clinical situations (37% phosphoric acid gel, 30 s). The enamel lesions were treated in vitro, with calcifying solutions for 8 h or were carried for 48 h in an intraoral appliance. Changes at the enamel surfaces were investigated by surface microhardness measurements. Following the treatment with calcifying solutions a significantly greater indentation length was observed in surface-etched than in surface-softened enamel. No significant difference in indentation length between both types of enamel lesions was observed following intraoral exposure. It was concluded that the initial rate of rehardening between both types of enamel lesions is comparable. At his stage remineralization occurs in microspaces created in the slightly destroyed enamel structures. The influence of the etch pits on the indentation length becomes dominating when remineralization continues. An obliteration of etch pits was observed in enamel samples treated with the calcifying solution with the highest degree of saturation. It was suggested that freshly prepared highly supersaturated calcifying solutions can be used to enhance mineral appositions in accidental etch pits.

Acetates↗

Microbore liquid chromatography with dual electrochemical detection for the determination of serotonin and 5-hydroxyindoleacetic acid in rat brain dialysates.

A microbore liquid chromatographic assay with dual electrochemical detection is described for the determination of serotonin and its metabolite 5-hydroxyindoleacetic acid in rat brain dialysates. The concentration of serotonin in these samples is usually in the low nanomolar range (fmol per 20 microliters range). To optimize separation and detection, several adaptations were made to the system with respect to the injection valve, flow-rate of the pump, connections between injector, column and detector, and cell volume of the detector. These aspects are discussed, as well as the procedure developed for optimal peak identification of serotonin and correct estimation of 5-hydroxyindoleacetic acid. The assay allows the measurement of basal serotonin release without the use of a re-uptake inhibitor added to the perfusion fluid.

Animals↗

High-performance liquid chromatography with electrochemical detection for the determination of levodopa, catecholamines and their metabolites in rat brain dialysates.

A high-performance liquid chromatographic assay with electrochemical detection is described for the simultaneous determination of levodopa, 3-O-methyldopa, dopamine, dihydroxyphenylacetic acid, homovanillic acid, 3-methoxytyramine, noradrenaline, adrenaline, 3-methoxy-4-hydroxyphenylethylene glycol and 5-hydroxyindoleacetic acid in rat brain dialysates. Samples are obtained in vivo using the microdialysis technique. Microdialysis probes are placed in the brain area to be studied and neurochemicals are collected by perfusion of the probe with modified Ringer's solution. Direct injection of the dialysates allows rapid and reliable results to be obtained.

3,4-Dihydroxyphenylacetic Acid↗

Biotransformation of L-dopa in striatum and substantia nigra of rats with a unilateral, nigrostriatal lesion: a microdialysis study.

Microdialysis was used to study the biotransformation of L-DOPA in the striatum and substantia nigra of rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the substantia nigra. The animals were pretreated with carbidopa (50 mg/kg p.o.) for 5 days. They were anaesthetized, and microdialysis probes were implanted into the intact and denervated striatum and into the intact and lesioned substantia nigra. The biotransformation of L-DOPA (5 mg/kg i.p.) in these regions was investigated. These results were compared with those obtained after administration of a much higher dose of L-DOPA (100 mg/kg i.p.). Changes in extracellular L-DOPA, 3-O-methyldopa (3-OMD), dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were determined by HPLC with electrochemical detection. Although rats with a unilateral nigrostriatal lesion did not show rotational behaviour after 5 mg/kg L-DOPA, DA levels were increased significantly both in the intact and the denervated striatum and in the intact and the lesioned substantia nigra. This increase was most pronounced in the denervated striatum. At 100 mg/kg L-DOPA, the increases in extracellular dopamine in intact and denervated striatum were about twice as high as the increases observed at the lower dose. A similar increase was observed in the intact substantia nigra. However, in the lesioned substantia nigra there was a fourfold increase. L-DOPA, at both doses, was evenly distributed between the brain areas studied and the lesion had no effect on the uptake of the drug at the blood-brain barrier.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗

Load dependency and reliability of microhardness measurements on acid-etched enamel surfaces.

The load dependency of hardness measurements was investigated on sound and demineralized enamel samples. For all samples investigated, the Knoop hardness number (KHN) varied as a function of the applied load. Higher loads enhanced indenter penetration into the test surface. The variation in KHN values observed in demineralized enamel, both surface-softened and surface-etched, was explained by a decrease in porosity as a function of depth. The reading error for indentations made on surface enamel etched with 37% phosphoric acid gel for 30 s was found to be slightly elevated compared to indentations made on a polished sound enamel surface. It was concluded that the surface microhardness technique can be used for the longitudinal investigation of etched surface enamel.

Acid Etching, Dental↗

A comparative study of the lead and cadmium content of surface enamel of Belgian and Kenyan children.

Acid etch surface enamel microbiopsies were performed on teeth from 378 children aged 6-12 years; 318 of the children lived in Belgium, an industrialized country, and 60 lived in a rural part of Kenya. In addition to lead and cadmium, calcium and phosphorus were also quantitatively determined in the etch solutions. Calcium was chosen as an internal reference for the expression of the lead and cadmium concentrations and for the assessment of the etch depth. The mean lead level in surface enamel of the Belgian children was approximately eight times higher than that of the Kenyan children. The cadmium levels were not significantly higher. An appropriate regression model taking into account differences in etch depth showed that a significant decrease of lead and cadmium with etch depth occurred and that a significant correlation between lead and cadmium in surface enamel existed for the Belgian cohort. Moreover, the same mean calcium/phosphorus ratios were obtained for the Belgian and Kenyan surface enamel samples, and were found not to play a significant role in the calibration of the lead and cadmium levels.

Belgium↗

Distribution of monoamines in human brain: evidence for neurochemical heterogeneity in subcortical as well as in cortical areas.

Norepinephrine, epinephrine, dopamine, serotonin and their major metabolites were measured by high-performance liquid chromatography with electrochemical detection in 49 regions of the human brain. The regional distribution of the different monoamines in the subcortical areas was similar to previous reports. We report here the distribution pattern of the 4 monoamines observed in the cerebral cortex. Regional differences in concentration were observed for norepinephrine, epinephrine and serotonin, with high concentrations in the frontal and parietal regions. However, no regional difference in dopamine concentrations was detected. The possible role of norepinephrine and serotonin as conventional transmitters, and of dopamine and epinephrine as neurotransmission modulators is discussed.

Aged↗

In vivo pharmacokinetics of levodopa and 3-O-methyldopa in muscle. A microdialysis study.

In the present study in vivo microdialysis sampling coupled to high-performance liquid chromatography with electrochemical detection, was used to study the pharmacokinetics of levodopa and 3-O-methyldopa in skeletal muscle in dog, after intravenous administration of levodopa. For comparison, the pharmacokinetic parameters of both compounds were simultaneously determined in plasma using blood collection. Muscle microdialysis samples and blood were continuously collected for 4 h after the administration of levodopa (25 mg/kg). Pharmacokinetic profiles of levodopa in plasma and muscle were different. The mean Tmax value of levodopa in plasma and muscle was 0.16 h and 1.0 h, respectively. The AUC0----inf for levodopa in plasma was nearly 18-fold higher in plasma than in muscle. The 3-O-methyldopa concentration increased very rapidly after the administration of levodopa, to reach a plateau after 2.5 h and 3 h in plasma and muscle, respectively. The AUC0----4 for 3-O-methyldopa was 3.6-fold higher in plasma than in muscle. The ratio levodopa/3-O-methyldopa, reflecting the metabolic rate of levodopa, was 3.5 times higher in plasma than in muscle, at the peak value of levodopa, and then rapidly declined to values lower than 1, one hour after administration of the drug. We compared our results with literature data from postmortem studies done in rat experiments. We concluded that levodopa is not accumulating in muscle as such, but is converted to 3-O-methyldopa probably before leaving the plasma compartment.

Animals↗

Clinical and pharmacokinetic comparison of oral and duodenal delivery of levodopa/carbidopa in patients with Parkinson's disease with a fluctuating response to levodopa.

The clinical effects and pharmacokinetics of orally and intraduodenally administered levodopa, in four patients with Parkinson's disease have been compared. The patients had unpredictable fluctuations in motor function and episodic unresponsiveness to single doses of levodopa. The pharmacokinetic and clinical data of these patients were compared retrospectively with those of Parkinsonian patients with fluctuations in motor performance but with preserved clinical responses to single oral doses of levodopa. There was a threshold plasma concentration of levodopa associated with the "switch on or off" effect. In addition, rapid attainment of this critical plasma concentration was associated with a quicker onset of action and a more prolonged clinical response. All the patients had delayed absorption of levodopa related to delayed and erratic gastric emptying, which contributed to the fluctuation in motor response. In contrast, the patients with fluctuating motor effects but a preserved clinical response after levodopa showed an absorption pattern comparable to that of four patients studied after duodenal delivery of levodopa. It is suggested that there is a subgroup of patients with fluctuating responses due mainly to altered peripheral pharmacokinetics of levodopa. The findings demonstrate the relevance of routine measurements of plasma levodopa in patients with Parkinson's disease in whom there are fluctuations in motor performance.

Administration, Oral↗

Continuous intravenous monitoring of levodopa and 3-O-methyldopa by microdialysis and high-performance liquid chromatography with electrochemical detection.

Microdialysis, in association with ion-pair reversed-phase high-performance liquid chromatography with electrochemical detection, was applied in vitro for the determination and quantification of levodopa and 3-O-methyldopa in blank spiked plasma and blood. The method presented gave accurate results; the calibration graphs for plasma were linear over the range of the expected values for both compounds. When using a dialysis probe with a membrane length of 1.6 cm at a 5 microliters min-1 perfusion speed, the recovery rate in plasma for levodopa was 30.1% and 68.5% for 3-O-methyldopa. However, less reproducible results were obtained for plasma levodopa levels in the range of 0.5 microliter ml-1 and lower. The microdialysis technique was subsequently successfully applied for the continuous intravenous monitoring of levodopa and 3-O-methyldopa in a levodopa-treated dogs.

Animals↗

Development and testing of bioadhesive, fluoride-containing slow-release tablets for oral use.

The bioadhesive characteristics of tablets for oral use made from modified starch, polyacrylic acid (PAA), polyethylene glycol (PEG) and sodium carboxymethylcellulose (CMC) were investigated. Adhesion force and energy were determined in-vitro and maximal adhesion time was evaluated in-vivo in human subjects. In-vitro, PAA showed the best bioadhesive properties, followed by modified maize starch and PEG with a mol. wt of 300,000-400,000 daltons. The presence of 0.1 mg of fluoride as NaF did not lead to significant differences in adhesion force and energy for the same formulation. The in-vivo bioadhesion was not strongly correlated to the in-vitro data. PAA, despite its excellent adhesion, proved to be irritating to the mucosa. PEG with a mol, wt of 200,000 daltons was subject to erosion. CMC showed good bioadhesive properties but the mechanical strength of the tablets was low. Modified maize starch tablets containing 5% (w/w) PAA and PEG with a mol. wt of 300,000 daltons proved to be the most suitable formulations for a fluoride-slow-release tablet with bioadhesive properties. In-vitro, the tablets released all of the fluoride within the 8 h period, with a high initial release. The release rate was related to the water absorption rate of the tablets. The PAA-containing formulations and the CMC formulations had the fastest release. In-vivo, fluoride levels with a minimum of 150 and a maximum of 1000 micrograms mL-1 were maintained for 8 h in the oral cavity. These fluoride levels were sustained significantly longer than those obtained with the administration of fourfold the amount of fluoride in the form of a fluoride-containing toothpaste. The release characteristics in-vivo exhibited a high variation. The use of bioadhesive polymers in oral pharmacotherapy seems promising.

Acrylates↗

Relation between lead in surface tooth enamel, blood, and saliva from children residing in the vicinity of a non-ferrous metal plant in Belgium.

Two groups of schoolchildren between seven and 12 years old residing in the vicinity of a non-ferrous industrial plant and exposed to lead (Pb) at a concentration that could cause health problems, were monitored. Concentrations of Pb in blood (blood-Pb), which were determined at regular six monthly intervals, were related to the Pb concentrations in surface tooth enamel (enamel-Pb). Acid etch biopsy samples of surface enamel were taken at the end of the five year study period in the first group (A) and after two years in the second group (B). Salivary Pb (saliva-Pb) concentrations were determined for the first study group on the same day that the enamel biopsies were performed. Calibration of the data was necessary--that is, blood-Pb concentration with respect to age and sex and enamel-Pb concentration with respect to etch depth and age. The blood-Pb concentrations declined with time. Surface enamel Pb concentrations correlated with blood-Pb concentration for the period starting with the pre-eruptive development of the incisors, related to blood-Pb concentration for a long time, and corresponded partly to the exposure at the time of pre-eruptive development and/or eruption. Through the correlation with enamel-Pb concentration, the seasonal behaviour of blood-Pb concentration became apparent. Saliva-Pb concentrations related to blood-Pb concentrations only in the short term.

Biopsy↗

In vivo use of a dual acid etch biopsy for the evaluation of lead profiles in human surface enamel.

Two successive acid etch biopsies were performed on the permanent maxillary right central incisors of two age-groups of children resident in an urban area in Belgium. Lead was determined in the biopsy solutions and the concentrations were related to etch depths which were calculated from the calcium and phosphorus concentrations in the biopsy solutions. The mean lead concentration of the first enamel biopsy layer was five times higher than in the second biopsy layer. A strong relation was observed between the two biopsies. It was shown that calibration of the lead values with respect to etch depths and Ca/P ratios was desirable and that a robust regression analysis approach was needed instead of classic least-squares regression analysis. However, the second biopsy provided more reliable lead estimates. In this study no increase in lead concentration in surface enamel could be demonstrated with age. Therefore, it was concluded that for these children the presence of lead in surface enamel had to be attributed primarily to preeruptive uptake.

Acid Etching, Dental↗

Bioequivalence of two formulations of piroxicam.

Two separate studies were performed with 12 volunteers in order to demonstrate the bioequivalence of 2 piroxicam (CAS 36322-90-4) tablet and 2 piroxicam suppository formulations after single dose administration. A validated reversed-phase HPLC method with UV-detection is described. Bioequivalence assessment was done by using the posterior probability of a mean ratio between 0.8 and 1.2, and by using the Two One-Sided Tests Procedure (i.e. the 90% confidence interval). The probability approach and the confidence interval approach were compared.

Adult↗

Metabolic activation of quercetin mutagenicity.

The mutagenicity of quercetin was reinvestigated using the Salmonella/microsome test. The mutagenicity of quercetin was enhanced by the cytosolic fraction of liver extract (S100), or by ascorbate, and even more by the complete liver supernatant (S9) in the presence of cofactors (NADP and glucose-6-phosphate). The formation of metabolites by the S9 enzymes was demonstrated by reverse-phase HPLC.

Animals↗

Development of monoaminergic neurotransmitters in fetal and postnatal rat brain: analysis by HPLC with electrochemical detection.

The monoamines dopamine, norepinephrine, epinephrine, and serotonin and their major metabolites 3,4-dihydroxyphenylacetic acid, homovanillic acid, 3-methoxy-4-hydroxyphenylethylene glycol, and 5-hydroxyindoleacetic acid were measured in the CNS of the rat during development from fetal day 18 to young adult. The catecholamines, serotonin, and their major metabolites remained low during fetal life. Concentrations measured in total brain started to increase around birth till the end of the fourth week of life after which steady-state levels were measured. Our results suggest that although monoamine systems are already morphologically well developed during late gestational life, they probably become a significant functional system only around birth and early postnatal life.

3,4-Dihydroxyphenylacetic Acid↗