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Biomedical subjects

N Colas-Linhart

Publications and source records attributed to N Colas-Linhart.

At least 37 records · Page 2Linked to original sources

Palatability of a meal influences release of beta-endorphin, and of potential regulators of food intake in healthy human subjects.

The effect of the palatability of a meal was tested on the post-prandial release of several gut hormones or neuropeptides which are known to have an effect on intake and satiety. Hormonal response was determined in plasma during the 3 h after a highly palatable and energy-rich meal or after the same meal served cold in a poorly acceptable form, as well as while fasting. The early post-prandial pancreatic polypeptide and neurotensin response was significantly higher after the highly palatable meal than after the cold one. Later responses differed only for pancreatic polypeptide. No difference was observed in cholecystokinin and neuropeptide Y levels. Post-prandial levels of beta-endorphin were elevated only after the cold meal and were associated with an elevated response of ACTH. We suggest that beta-endorphin might be secreted in response to an aversion towards the non-palatable cold meal. This could, subsequently, inhibit the cephalic phase of pancreatic polypeptide response and the early post-prandial response of neurotensin by a central anticholinergic effect. This study evidences an effect of palatability on the modulation of the digestive hormonal response after a meal.

Adult↗

Reversibility of thyroid dysfunction induced by recombinant alpha interferon in chronic hepatitis C.

OBJECTIVE: Thyroid dysfunction has been reported as a complication of interferon therapy. The aim of our study was to assess the risk factors and reversibility of thyroid disorders induced by interferon therapy. DESIGN: Prospective study. PATIENTS: A series of 68 patients with chronic hepatitis C completed a therapeutic trial of interferon alpha 2b (IFN), randomized for dose adaptation, lasting for 24 weeks. MEASUREMENTS: TSH and autoantibodies against thyroid were looked for at (-2) weeks and 24 weeks in all patients. Blood samples obtained at (-2), 12, and 24 weeks were stored for additional hormonal studies in patients who developed thyroid dysfunction. Such patients with thyroid dysfunction were followed up for at least one year. RESULTS: Only one out of 68 patients had abnormal TSH levels, and two had thyroid autoantibodies prior to interferon therapy. Eight patients (12%) developed thyroid dysfunction (five hypothyroidism and three hyperthyroidism) during treatment. In four patients (all of them with thyroid dysfunction, P < 0.001) antimicrosomal, antithyroglobulin, and/or anti-TSH receptor antibodies appeared during interferon therapy. All patients recovered normal thyroid function within 1.5 years after interferon withdrawal. No pretreatment risk factor was identified. The patients with thyroid dysfunction did not significantly differ from the others as regards the dose of interferon they received or the rate of normalization of transaminases. CONCLUSION: (i) A 12% incidence of thyroid dysfunction was observed under interferon therapy; (ii) secondary appearance under interferon therapy of elevated thyroid autoantibodies was a risk factor; (iii) the thyroid disorders induced by interferon were reversible.

Adolescent↗

Cell surface carbohydrates modulate neutrophil adherence to alveolar type II cells in vitro.

We characterized the influence of phosphorylated sugars and cell surface sialic acids on the adherence of human polymorphonuclear leukocyte (PMN) to rat alveolar type II cell (ATII cells) and human-derived A549 cell monolayers in vitro. Percent adherence of radiolabeled polymorphonuclear leukocytes was assessed after incubating cells with the carbohydrates, enzymes, or lectins to be tested. Lactose-1-phosphate (Lact1P) and maltose-1-phosphate (Malt1P) (10 mM) inhibited adherence of PMN to ATII cells and A549 cells. Maximal inhibition followed treatment of both PMN and rat ATII cells and amounted to 85 +/- 7% with Lact1P and 92 +/- 3% with Malt1P. Inhibition was concentration dependent. Incubation of PMN with mannose-6-phosphate reduced adherence to rat ATII cells and A549 cells by 36 +/- 11 and 39 +/- 8%, respectively. Maximal concentrations of sugars did not alter cellular viability. Neuraminidase-induced desialilation of ATII cells increased adherence of PMN by 36 +/- 7% to rat ATII cells and by 86 +/- 18% to A549 cells. Masking of terminal sialic acids on rat ATH cells with Limulus polyphemus agglutinin (100 micrograms/ml) increased adherence by 50 +/- 2%. These results indicate that cell surface carbohydrates are involved in the regulation of the adhesive interaction between PMN and ATII cells in vitro.

Animals↗

[Radio-isotope assays of vitamin B 12: value of the Kappa test in a multicenter evaluation].

Owing to the lack of a reference technique and of an international cobalamin (vitamin B12) standard, and the large discrepancy between laboratory norms, the authors performed a multicentric study to compare five RIA kits usually used. First, classical tests were used to evaluate the analytical performances of each kit. Results did not demonstrate any superiority of one kit over another. Secondly, B12 values were classified among three categories (low, normal and high) characterized by laboratory and then manufacturer norms. The concordance between these two "judgments" was evaluated with the Kappa coefficient. In addition, the Kappa index proved that the norms supplied by the manufacturer were better than those of laboratories. But mean Kappa coefficient established for each norm gave us an unsatisfactory result. Third, clinical informations allowed to improve the classification of the patients. New limits were defined for each technique and should be tested further, routinely in each laboratory.

Anemia↗

Lack of plasmic beta-endorphin response to a gastronomic meal in healthy humans.

In order to study the relationship between the endogenous opiate system and food intake in man, plasma concentrations of beta-endorphin were measured in ten healthy subjects. Time course of beta-endorphinemia was compared under the following conditions: basal (fasting), after an injection of pentagastrin (6 micrograms/kg), or after a gastronomic meal. No changes in plasma beta-endorphin or ACTH concentrations were observed with pentagastrin nor after the meal, despite the combination of very high sensory pleasure with intake of a very large amount of food. It is concluded that blood beta-endorphin concentration is not a sensitive index of the effects of food intake on the endogenous opioid system in man.

Adult↗

Immunoreactive beta-endorphin increases after an aspartame chocolate drink in healthy human subjects.

It has been claimed that sucrose intake induces a rise in beta-endorphins. In an attempt to discriminate between the sensorial and metabolic effects of sucrose intake in this process, the effects of two chocolate drinks were compared: one sweetened with 50 g of sucrose, the other with 80 mg of aspartame. Plasma beta-endorphin concentrations were more elevated after the aspartame drink than after sucrose or fasting, while insulin increased after drinking as much with aspartame as with sucrose. We suggest that the increase in beta-endorphin after aspartame edulcorated chocolate is related with insulin secretion in the absence of marked changes in blood glucose or with a direct effect of aspartame itself on beta-endorphin liberation.

Adolescent↗

Pharmacokinetics and biodistribution of technetium 99m labelled standard heparin and a low molecular weight heparin (enoxaparin) after intravenous injection in normal volunteers.

For a better understanding of low molecular weight heparin pharmacokinetics, 99m technetium labelled heparin and enoxaparin were injected intravenously to four normal volunteers, after approval by the Ethics Committee and preliminary animals studies. In vitro and in vivo, the labelled products proved to be stable and identical to the non-labelled drugs. Radioactivity curves in blood, organs and urines were similar for both products. Anti Xa plasma half-life was 3 times longer for enoxaparin than for heparin. Anti IIa plasma half-lives were similar. However, radioactivity persisted much longer than biological activities for both products. After chromatography, most of the radioactivity was bound to AT III, where an anti Xa activity peak was also detected. The anti Xa activity peak seen after adding AT III to plasma was much higher with heparin than with enoxaparin. In urine, biological activities, measured with AT III supplementation, were higher with enoxaparin than with heparin. These results suggest that phenomena other than biodistribution are responsible for the differences in pharmacokinetics observed between these two products. The two most likely explanations are differences in metabolism and/or a release of an endogenous factor.

Adult↗

Negative allesthesia and decreased endogenous opiate system activity in anorexia nervosa.

The combined effects of an intragastric load of glucose compared to water and of naltrexone compared to placebo were tested on preference for sucrose in six anorectic patients. While in normal subjects, glucose-induced negative allesthesia is known to disappear upon loss of weight, it persisted in anorexia nervosa (AN) despite a major weight loss; furthermore, in contrast with its effects in normoponderal subjects, naltrexone at the dose of 25 mg did not decrease the preference for sucrose nor did it enhance glucose-induced allesthesia. Basal plasma beta endorphin level determined by radioimmunoassay was higher in AN than in normal subjects (75 +/- 6.1 pmoles/l vs. 13 +/- 3.8 pmoles/l) (p less than 0.001). It is suggested that a decrease in endogenous system opiate activity might be associated with food refusal and body weight loss in anorexia nervosa.

Adolescent↗

[Cerebrospinal fluid beta-endorphin in chronic pain in man].

Concentrations of beta-endorphin in the cerebrospinal fluid were measured in 21 painless subjects and 37 patients with chronic pain. Statistical analysis of the results showed no significant difference between the two groups. This lack of correlation between beta-endorphin concentrations in the CSF and the presence of chronic pain highlights the difficulties and limitations encountered when trying to determine the role of endogenous opioid systems with this method.

Chronic Disease↗

Beta-endorphin levels after intrathecal infusion of iodinated contrast media.

Modifications in beta-endorphin levels in cerebrospinal fluid have been described following lumbar puncture and metrizamide injection. Cerebrospinal fluid (CSF) samples were obtained from 19 patients before and after lumbar myelography. Two radioimmunoassays were used. One was a commercial kit; and the other one (developed in our laboratory) used a chromatographic removal from beta-lipotrophin. No definite variation of beta-endorphin was observed after myelography, using either the commercial kit or a more sophisticated procedure. Some controls were prepared by adding metrizamide or Iopamidol in vitro to CSF samples in order to evaluate a non specific effect of these contrast media. The results obtained with these controls suggest that the discrepancy of results may be explained simply by assay artifacts due to drug interferences when using the commercial methods.

Humans↗

Microautoradiographic study of technetium-99m colloid uptake by the rat liver.

A new microautoradiographic technique was developed to study the distribution of 99mTc-labeled radiopharmaceuticals. Using a thick emulsion, it is possible to get microscopically visible tracks of internal conversion and Auger electrons. The liver uptake of microscopic particles has been thought to occur in Kupffer cells but no direct evidence has been provided for technetium colloids. Using this method, 99mTc-labeled colloids were clearly identified in Kupffer cells in the sinusoidal areas of liver. "Track" microautoradiography using a thick emulsion layer may be used on any frozen tissue sections and may provide an important tool to assess the biodistribution of 99mTc radiopharmaceuticals.

Animals↗

Technetium 99m labelled heparin: pharmacokinetics and tissue distribution in rats after vascular surgery.

Pharmacokinetics of technetium 99m (99mTc) labelled heparin was studied after I.V. infusion (70 IU/kg) in normal rats and in a group of animals just after aortic longitudinal incision and suture. Anticoagulant activity measurements and radioactivity were compared on the same plasma samples. The pharmacokinetic decay of 99mTc-heparin followed a bi-exponential pattern. Half-lives (T1, T2) were significantly shortened after surgery using both techniques. Liver accumulation of labelled heparin was decreased in "sutured" rats and a high uptake of 99mTc-heparin was found on the operated area of the aorta.

Animals↗

[Cerebrospinal fluid beta-endorphin in congenital insensitivity to pain].

Spontaneously elevated nociceptive threshold levels were markedly diminished after Naloxone injections in 4 patients with congenital insensitivity to pain. This finding suggested the hypothesis of a relation between congenital insensitivity to pain and permanent hyperfunction of an endomorphinic system. Radio-immunoassay of CSF beta-endorphin was performed in all 4 cases. The normal or only slightly elevated levels cannot explain electrophysiologic findings, but as a function of the multiplicity of endogenous opioid systems, hyperactivity of another endomorphinic system cannot be excluded. Other hypotheses may also be proposed.

Endorphins↗

[Experimental arterial microsutures. Evaluation of the risks of thrombosis using technetium 99-labeled heparin].

Following demonstration of a method of assay of circulation heparin by measurement of radioactivity after labelling with 99 m technetium, the technique was used to study effects of arterial microsuture on metabolism of heparin injected postoperatively. Results of a study involving rat aorta showed that local binding was maximum during the first half-hour and that abnormal consumption of heparin continued during the 6 hours following operation. These finding suggest that a risk of thrombosis probably persists throughout this postoperative period.

Animals↗

[Microautoradiographic method permitting the study of migration of 99m-technetium labelled leukocytes].

Cell migration studies are very important in inflammatory phenomena. Methods currently used are not quantitative and have been subject to much controversy. Homogeneity of 99mTc leukocyte labelling was verified by a microautoradiographic method (MAR), which was performed in our laboratory. This method was used in cell migration studies to verify if the migrating cells were indeed the labelled cells.

Autoradiography↗

Technetium 99m autoradiography of labelled white cells.

The cellular uptake of technetium 99m was determined on white blood cells (WBC) by autoradiography, after 'cold' tin pyrophosphate prelabelling followed by pertechnetate labelling. The autoradiographic method gave visible tracks of 99mTc internal conversion and Auger electrons. 75 +/- 5% of the treated WBC were labelled but none of the control WBC. The number and length of tracks per cell varied greatly. This was perhaps due to imaging conditions as well as to variations in cell uptake.

Autoradiography↗

99m Technetium labelled heparin: potential value as a tracer of heparin activity in pharmacokinetic and biodistribution studies.

Pharmacokinetics and biodistribution of 99m Technetium (99mTc) labelled heparin were studies to assess its value as a tracer of heparin kinetics in comparison with unlabelled heparin. In vitro, the stability and labelling efficiency (98%) of the labelled drug were excellent and elution was minimal. In vivo, after I.V. infusion of the drug, there was no difference in the same animal between anticoagulant activity measurements and radioactive countings, both displaying a plasmatic biexponential pattern (T1 = 2.9 minutes, T2 = 76 minutes). Biodistribution studies showed primarily liver, spleen and kidney accumulation, with no thyroid uptake. The advantages of this technetium labelling may therefore be used for the heparin drug in various experimental and pathological situations even in humans.

Animals↗

Five leucocyte labelling techniques: a comparative in-vitro study.

During the past years, several authors have used labelled leucocytes to detect inflammatory foci. However, before routine use in man. It is necessary to control the viability of labelled cells. Five leucocyte labelling techniques (111In-oxine, 111In-oxine without extraction, 99mTc oxine, pyrophosphate 99mTc, 51Cr) were compared using the same separation methods, conservation medium, viability assays and migration studies. Electron microscopic studies allowed the assessment of cellular damage induced by the labelling techniques as well as the calculation of the percentage of cells disrupted during preparation. Results obtained in vitro using 111In-oxine were not satisfactory and in fact appeared contradictory to those published by the authors using this technique in vivo. Even the best method, pyrophosphate 99mTc labelling, was not completely atoxic, but the functional behaviour of the leucocytes did not seem affected. While in vitro studies offer much information concerning labelled cells, they cannot predict the in vivo behaviour of these cells.

Chemotaxis, Leukocyte↗