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Biomedical subjects

B Bonnemain

Publications and source records attributed to B Bonnemain.

62 records · Page 4Linked to original sources

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France↗

Structure-activity relationship of macrocyclic and linear gadolinium chelates: investigation of transmetallation effect on the zinc-dependent metallopeptidase angiotensin-converting enzyme.

Transmetallation between commercially available solutions of gadolinium (Gd) chelates and the zinc (Zn)-dependent angiotensin-converting enzyme (ACE) was investigated. In vitro, the strongest inhibitions were observed for the linear Gd complexes, Gd diethylenetriamine pentaacetic acid (DTPA) bis-methylamide (BMA) (IC50 = .016 +/- .006 mmol/l) and Gd-DTPA (IC50 = .350 +/- .034 mmol/l). The two macrocycles Gd tetraazacyclododecane tetraacetic acid (DOTA) and Gd-HP-DO3A were similar and 400 times less active than Gd-DTPA-BMA. These effects were mainly due to the presence of free ligand for DTPA and calcium (Ca) chelate in the case of DTPA-BMA because the addition of Zn2+ in the same quantities suppresses their inhibitory effects. In vivo, these two solutions of linear Gd chelates significantly inhibited ACE activity (Gd-DTPA: (67 +/- 9% versus baseline; and Gd-DTPA-BMA: 73 +/- 2% versus baseline at the clinical dose of .1 mmol/kg), whereas no significant effect was observed for the two macrocyclic chelates Gd-DOTA and Gd-HP-DO3A. Formulating the Gd chelate solution with either an excess of free ligand or Ca chelate (to decrease Gd3+ release) in the case of linear Gd chelate may have deleterious biologic consequences.

Chelating Agents↗

Preliminary European intravenous clinical experience with a new, low osmolar, nonionic contrast medium: ioversol (Optiray).

The intravenous clinical trial program of ioversol (Optiray), a low osmolar, nonionic, monomeric contrast agent characterized by high hydrophilicity, is evaluated on the basis of results from the first clinical trials conducted in Europe as part of the development of the 300 and 350 mgI/ml formulations: 7 double-blind, comparative trials and 5 single trials were performed in a total of 743 patients, of whom 472 received ioversol and 271 a monomeric nonionic reference product. The diagnostic efficacy of ioversol was equivalent or superior to that of the reference products and tolerance was comparable to that of nonionic agents in terms of pain and heat sensations. No significant difference in adverse reactions was found and all the contrast agents studied were well tolerated by the patients.

Adult↗

Niosomes as carriers of radiopaque contrast agents for X-ray imaging.

Non-ionic surfactant vesicles (niosomes) are considered as carriers of iobitridol, a diagnostic agent used for X-ray imaging. The niosomes, with a diameter between 150 and 175 nm, are prepared using the film-hydration method followed by sonication. These vesicles were obtained with appropriate mixtures of D-alpha tocopheryl polyethylene glycol 1000 succinate, polyoxyethylene glycol 4000 stearate, sorbitan monostearate, cholesterol and dicetylphosphate. Methods allowing the increase of the rate of encapsulation and the stability of the vesicles were carried out. In addition to the study of the formulation of the vesicles, the physico-chemical and morphological properties of the vesicles have been studied.

Cholesterol↗

Biodegradable cross-linked albumin microcapsules for embolization.

The interfacial polymerization process used in the present study produced individual cross-linked albumin microcapsules, the particle size of which depended on the emulsification stirring rate. The variation in cross-linking agent concentration altered the microcapsule wall properties. As shown by SEM observations, microcapsules prepared with low acyl chloride concentrations presented rippled surfaces, while the surfaces of the microcapsules prepared with high acyl chloride concentrations were smooth. It was then suggested that the membranes of the weakly cross-linked microcapsules consisted of cross-linked and denatured albumin. Embolization experiments in the dog kidney showed that the weakly cross-linked microcapsules were biodegradable within 7 days, whereas the highly cross-linked microcapsules were degraded over more than 14 days and led to prolonged ischaemia. The results of the histological experiments carried out on a further eight dogs supported the previous findings yielded by the angiographical experiments. Moreover, they indicated that no foreign body reaction occurred. The lack of this inflammatory granuloma should be attributed to the rapid biodegradation of the microcapsules which produced reversible ischaemic lesions.

Animals↗

Effect of contrast media on whole blood filtrability. An in vitro comparative study of iohexol, iopamidol and ioxaglate on rat blood.

The effects of three contrast media, iohexol, iopamidol and ioxaglate, on rat erythrocytes were compared. Three parameters representative of the rheologic properties of blood were investigated: whole blood filtrability, red cell filtrability and morphology. Whole blood and red cell filtrabilities were both measured using an erythrometer and red cell morphology was observed with an optical microscope. Iohexol and iopamidol were found to cause a significant increase in filtrability indices and to modify the shape of red blood cells. Ioxaglate had less effect on these parameters than did the other two contrast media. The chemical structure seems to be a determining factor for red cell integrity. The study of blood rheology parameters in vitro may be useful as a model predictive of observations on human blood and of hemodynamic consequences.

Animals↗

Gadolinium as a contrast agent for NMR.

Gadolinium chloride (GdCl3) was studied as a contrast agent for nuclear magnetic resonance. This rare-earth element dramatically alters proton resonance (paramagnetic moment = 10.8 Bohr magnetons). Acute toxicity was determined by intravenous injections in mice; mean lethal dose was 100-200 mg of GdCl3 . 6 H2O/kg. Changes in T1 of plasma, kidney, liver, and brain of mice and rats were measured after intravenous injections of GdCl3 solution at a concentration of 60 mg gadolinium metal/kg. The apparatus used was a Wh 270 Brucker with a field of 63 kG. The T1 was found to be significantly decreased in plasma, kidney, and liver.

Animals↗