Biomedical subjects
M Guillaume
Publications and source records attributed to M Guillaume.
[123I]Insulin metabolism in normal rats and humans: external detection by a scintillation camera.
[123I]Insulin was injected intravenously into rats and the distribution and kinetics of radioactivity were analyzed by external detection with a scintillation camera connected to a computer. When injected alone, [123I]insulin was rapidly taken up by the liver and to a smaller extent by the kidneys. After reaching a maximum at 3 to 5 minutes after injection, liver radioactivity rapidly declined and free iodide appeared in the plasma. After previous saturation of the insulin receptor compartment, [123I]insulin was concentrated by the kidneys only and the rate of appearance of free iodide was markedly decreased. The results demonstrate the potential usefulness of this noninvasive technique to visualize insulin interaction with the liver and kidneys and to study the rate of insulin degradation by each organ in vivo. Preliminary experiments in man demonstrate its feasibility and low radiotoxicity.
The evaluation of right ventricular performance using krypton-81m.
The availability of krypton-81m suitable for intravenous injection provides an easy means for assessing right ventricular function. The superimposition of the other heart chambers does not constitute a problem. The activity in the left heart is negligible and the study can be performed in the right anterior oblique position to obtain optimal separation between the right atrium and the right ventricle. Lung activity is quite high and should be corrected before computing the right ventricular ejection fraction. This correction can be accomplished by performing Tc-99m MAA perfusion scintigraphy. The measurement of the right ventricular ejection fraction appears to be reproducible with very small inter-and intraobserver variability. Good quality phase and amplitude images can be obtained with such high count rates.
Anti-inflammatory effect of LA 2851 and reference drugs on some models of inflammation. Investigation of the mechanism of action.
LA 2851 (2-4-diamino-7-methyl-pyrazolo (1,5-a) 1,3,5-triazine), a bronchodilator and antiallergic compound, in type I hypersensitivity, has been tested orally for activity against carrageenan oedema and complement dependent, reverse passive Arthus (RPA) and zymosan oedema in rats. Pharmacokinetic determinations were also realized in order to correlate plasma blood levels and pharmacological activity. LA 2851 was found active in the first test but showed a more marked effect in the immunologically mediated RPA reaction and zymosan oedema. Among reference drugs tested, theophylline showed the same pattern in contrast with non-steroidal anti-inflammatory agents. LA 2851 and theophylline, using a superfused lung preparation, were found ineffective on the synthesis of cyclooxygenase products from arachidonic acid. LA 2851 as theophylline inhibited cAMP phosphodiesterase (PDE) but this inhibition does not seem to be involved in their anti-inflammatory activity since papaverine, a potent inhibitor of PDE, was totally inactive. The activity on RPA and zymosan inflammation was achieved at the drug plasma level in the range of those required to relax the trachea. The same antagonism was obtained with the 2 drugs at a lower plasma level with LA 2851 than with theophylline for the same dose administered (25 mg/kg). LA 2851 and theophylline did not inhibit all the components of the inflammatory process since maximum inhibition did not exceed 60% up to 200 mg/kg and 100 mg/kg respectively.
Development of a reliable Hg-195m--Au-195m generator for the production of Au-195m, a short-lived nuclide for vascular imaging.
A new mercury-195m (T1/2: 41 hr) leads to gold-195m (T1/2: 30.6 sec) generator suitable for first-pass as well as steady-state radionuclide angiography studies has been developed. The distribution coefficients, Kd, for mercury (Hg-195m) and gold (Au-196), experimentally evaluated on chelating resin Chelex 100, showed this resin to be suitable as the column packing. Mercury-195m in a Trisma buffer solution at pH 7.40 was loaded on a chelating resin Chelex 100 column, together with gold carrier. Au-195m was eluted with an aqueous solution of 5% glucose in a 0.01M Trisma buffer at pH 7.70 (25 degrees C). Chemical assessment of the eluate has ensured that the eluted carrier-free gold is by no means colloidal: 80% is found in an ionic form, 20% as an uncharged species. Safe clinical use for routine diagnosis in humans is possible.
Radionuclide venography using continuous Kr-18 m infusion: preliminary note.
Continuous infusion of Kr-81m presents important advantages compared to the commonly used radionuclides for venography. High count rates can be accumulated, and a high resolution collimator can be employed to ensure good quality images. The study can be repeated immediately and multiple views can be performed until a satisfactory result is obtained. The production of radionuclide from a Rb-81--Kr-81m generator suitable for intravenous infusion is almost the same as that which is suitable for ventilation. The same generator can first be used for venography and then for ventilation imaging to complete the work-up patients suspected of having thromboembolic disease.
[Effect of long-term metformin treatment on the development of diabetes in genetically diabetic mice (DBM) (author's transl)].
Genetic diabetic obese, hyperinsulinaemic mice of the DBM (db/db) strain received long-term metformin. The drug was given orally (200 mg/kg twice a day) by gastric intubation starting from the 13th week of age to the 42 th. A continuing hypoglycemic effect was observed with a simultaneous decrease of HbA1c. The immunoreactive plasma insulin and body weight of treated homozygous mice were higher than those of homozygous controls. No significant modification of food consumption and blood lipids was noted. Pancreatic islets of homozygous controls showed, by light and electron microscopy, a characteristic hypersecreting appearance at 25 th week compared to that of heterozygous animals. Morphological dedifferentiation (canalicular changes and foreign cell colonization) followed in most cases at the 42 th week with reduction in B-cells. Pancreas of treated mice was similar to that of controls at 25 th but showed less B-cell exhaustion and islet degeneration at the 42 th week, explaining higher plasma IRI concentration.
Bronchodilator and antiallergic properties of LA 2851 (2-4-diamino-7-methyl-pyrazolo (1,5-a) 1,3,5-triazine).
LA 2851, 2-4-diamino-7-methyl-pyrazolo (1,5a) 1, 3, 5 triazine has been found to possess potent bronchodilator and inhibitor properties on experimental active and passive anaphylaxis. In vitro evaluation on guinea-pig trachea indicated that LA 2851 had relaxant properties on unstimulated and stimulated (histamine or pilocarpine) strips. Resistance and compliance measurement in anaesthetized dogs and guinea-pigs showed that the drug reversed or prevented in vivo bronchoconstriction due to histamine. The relaxant effect was not linked to beta stimulating property. LA 2851 was as active as theophylline in all tests used. LA 2851 and theophylline prevented anaphylactic shock in mice. DSCG was poorly active. IgE mediated passive cutaneous anaphylaxis in rat was dose-dependently inhibited by LA 2851 (DSCG greater than LA 2851 greater than theophylline). According to these results the compound decreased histamine release from rat mast cells induced by different secretagogues (LA 2851 greater than DSCG greater than theophylline). No tachyphylaxis (PCA) nor time preincubation dependency (mast cells) was found with LA 2851 as it has been reported for DSCG. LA 2851 by its pharmacological properties associated with a very low toxicity (2.5 to 5 times less than theophylline) provides a new potential agent for respiratory diseases.
[Medium half-life radionuclides for medical use].
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[Krypton-81 m pulmonary scintigraphy].
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DBM mice as a pharmacological model of maturity onset diabetes. Studies with metformin.
Hyperglycemic obese and hyperinsulinemic mice of DBM strain develop a diabetic syndrome which can be compared to human maturity onset diabetes. In this study 6 to 49 weeks old female mice were used. Hyperglycemia and concomitant obesity were observed at 9 weeks. Plasma immunoreactive insulin (IRI) was maximum at 15--20 weeks, then decreased progressively with broad individual variations. Metformin, administered at 200 mg/kg per os, ineffective dosage in normal mice, showed a strong hypoglycemic effect in younger mice (11--18 weeks) with a plasma IRI decrease and no blood lactate and liver glycogen alteration. Plasma metformin concentration curve showed an exponential elimination fitted to a one compartment model with a plasma half-life of 2.7 hours. Metformin-induced hypoglycemia was lower in older mice (23--29 weeks) and corroborated their lower initial plasma IRI. All these results are in accordance with those reported in man and show that DBM mice provide a suitable model for a better understanding of antidiabetic drugs effects.
The endocrine pancreas of the fetus from diabetic pregnant rat.
Diabetes was induced in female rats by streptozotocin administration prior to mating. Pregnant rats were divided into "severe diabetics" (blood glucose concentration above 300 mg/100 ml) and "mild diabetics" (blood glucose ranging from 100 to 200 mg/100 ml). When compared to control fetuses, fetuses from severely diabetic mothers showed a slight decrease of body weight on days 20.5 and 21.5. Fetal pancreatic insulin stores and plasma insulin concentrations were decreased at 19.5, 20.5 and 21.5 days. The insulin response to glucose was impaired both in vivo and in vitro. In contrast, fetuses from mildly diabetic females showed no change in body weight. Pancreatic and plasma insulin concentrations were increased at 19.5, 20.5 and 21.5 days. The response of the beta cells of term fetuses of mild diabetics to glucose stimulation was enhanced in vitro. These results are consistent with the hyperglycaemia-hyperinsulinaemia theory with regard to the fetuses from mildly diabetic rats and with an impairment of insulin biosynthesis and release in fetuses from severely diabetic females.
Distribution of various labeled thioglucoses in rodents.
Gold, silver and lead thioglucose were evaluated in rodents to determine the value of organo-metallic compounds in the study of metabolic abnormalities. Increased radioactivity concentration was noted in the hypothalamus with all compounds. Gold thioglucose concentrated in the kidneys and thymus, and 203Pb-thioglucose concentrated in the pancreas and thymus.
Vaccination tests against bovine dermatophilosis in the southern region of Chad.
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Analysis of individual preorderings to discover a typology of the individuals in a process of collective choice.
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[On the degassing at low temperature of titanium targets impregnated with hydrogen isotopes].
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The assessment of chronic venous obstructions by non invasive haemodynamic studies and imaging with Kr-81 m venography.
We study the sequelae of venous obstructions (from 15 days to several years after the thrombosis) by non invasive haemodynamic methods: Doppler velocimetry and leg plethysmography. We describe a simple physical model which permits the calculation of the leg outflow resistance from the venous occlusion plethysmography data. A radionuclide imaging of the veins is also recorded by a gammacamera during the perfusion of the limbs with Kr-81 m. This flexible technique appears suitable to analyse persistent ilio-femoro-popliteal obstructions. The results of the Doppler investigation are well related to the phlebograms. The outflow resistance of the leg depends mainly on the duration of the persistent obstruction. Recent obstructions are generally highly resistive but the level of the resistance is becoming close to normal with time (after two years).
[Pharmacokinetic study of fluoride after a single administration of Osteofluor].
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