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Biomedical subjects

B Bonnemain

Publications and source records attributed to B Bonnemain.

At least 37 records · Page 2Linked to original sources

[Vascular contrast agents. Definition and potential applications].

Blood pool agents are characterized by a biodistribution limited to the vascular space after intravenous injection. This is different from uroangiographic agents in CT Scanner or Gd chelates in MRI which are markers for the intra and extravascular space. This unique property is potentially useful for diagnostic applications such as ischemic diseases (myocardial or cerebral perfusion defects), vascular diseases and diagnostic or follow-up of endothelial permeability disorders (diabetic patients, tumors...).

Angiography↗

Secretion in milk and transplacental transfer of two iodized oils, Lipiodol UF and Oriodol, in rabbits.

Many countries in the world are inhabited by populations suffering from iodine deficiency. These populations are affected by serious diseases directly related to iodine deficiency. Iodized oil (Lipiodol UF or Oriodol) is routinely used orally or intramuscularly to treat these populations, including pregnant women. The experiments of the present study in gravid or lactating rabbits show that there is transplacental transfer of iodine and secretion of iodine in milk after administration of iodized oil and consequently an accumulation of iodine in the thyroid glands of the mother, the fetus and the neonate. The advantages of treating pregnant women with iodized oil in the populations concerned is thus confirmed. The oral route can be substituted by the intramuscular route.

Administration, Oral↗

Toxicologic profile of iobitridol, a new nonionic low-osmolality contrast medium.

PURPOSE: The toxicologic profile of iobitridol, a new nonionic low-osomolality contrast medium, was evaluated in compliance with the current regulatory requirements in Europe, the USA and Canada. MATERIAL AND METHODS: The toxicity of iobitridol was tested following acute or repeated i.v. administration in several different species (mouse, rat, dog); single oral administration in the mouse and intracisternal injection in the rat. Furthermore, teratogenicity and mutagenicity were evaluated in the rat and rabbit. Local perivenous toxicity was assessed in the rabbit. RESULTS: The acute toxicity of iobitridol in the mouse is equivalent to that of iohexol, a reference product tested under the same conditions. Chronic administration (daily injections i.v. injection over 4 weeks) in the rat and dog did not demonstrate any particular toxicity for iobitridol. It should be noted that, unlike iohexol, iobitridol did not provoke any vacuolization of the renal tubular cells in the rat following repeated injections. Furthermore, this contrast agent did not show any teratogenic or mutagenic potential. The typical local inflammatory signs observed following perivenous injection in the rabbit were low in intensity and reversible. CONCLUSION: The toxicologic profile of iobitridol appears to be favorable and does not show any particular risk for clinical use under the usual indications of water soluble iodinated contrast agents.

Administration, Oral↗

Pharmacologic profile of iobitridol, a nonionic iodinated contrast medium.

The present article combines and summarizes the preclinic studies carried out in vitro and in vivo to determine the pharmacologic and biochemical profile of iobitridol, a new nonionic iodinated low-osmolality contrast medium (CM). The effects of this product on the main hemodynamic, bronchopulmonary, neurologic, renal, blood chemistry and electrophysiologic parameters and RBC morphology were studied in detail in comparison with CM in the same chemical category or with reference substances of the same osmolality. The in vivo studies were performed under conditions resembling clinical use. Iobitridol showed an excellent pharmacologic and biochemical profile, which was identical or superior to that of other products in its category.

Animals↗

[Magnetic resonance contract agents and perfusion imaging].

Contrast agents may be categorised as non-specific or specific agents. Non-specific agents are freely diffusible in the extracellular and extravascular compartment with the exception of the brain where only blood brain barrier lesions enables the contrast agent to pass. In the specific agent group, a new class of products has been developed, that of blood pool contrast agent, which are distributed in the total intravascular volume and are slowly cleared from the blood. Crossing the healthy capillary wall is limited and depends both on the pathological state of the endothelial permeability tissue of the organ under interest and on the characteristics of the contrast agent (size, charge, molecular shape...). The diagnostic efficacy in perfusion imaging including cerebral perfusion is modulated by the pharmacokinetic profile of the blood pool contrast agent. One way to improve the vascular residence time, consists in binding a vector such as synthetic polymer or a biological macromolecule and a lanthanide like Gd3+, Mn2+, Dy3+ or metal ions. A second way is the synthesis of ultrasmall iron oxide nanoparticles which could escape rapid recognition by the monocyte macrophage phagocytic system mainly of liver and spleen. Because of their cristalline structure and the large number of non-paired spins, five electrons for the iron metal, the nanoparticles behave as magnetic domain when an external field is applied. They consequently have a high dipolar magnetic moment, and can produce a T2 effect in vivo, resulting in a drop in the magnetic resonance signal. Possible interests and developments toward perfusion imaging are demonstrated in experimental models studies.

Animals↗

High-performance liquid chromatographic determination of iobitridol in plasma, urine and bile.

Iobitridol is a new non-ionic, low-osmolality contrast medium for urography and angiography. We have developed a method for determining iobitridol in body fluids using high-performance liquid chromatography with ultraviolet detection. The method, which is specific and reproducible, does not require an internal standard. Determinations can be carried out in body fluids against a set of standards in ethanol. The method was validated for the quantification of iobitridol in biological samples obtained during pharmacokinetic studies.

Animals↗

Iobitridol, a new nonionic low-osmolality contrast agent, and iohexol. Impact on renal histology in the rat.

RATIONALE AND OBJECTIVES: To compare the histologic effects on rat tubular cells of two nonionic contrast media with equivalent osmolalities and viscosities. METHODS: Histologic, functional (creatinine clearance), and biochemical (proteinuria and enzymuria) profiles of iohexol and iobitridol (both at 350 mg I/mL) were compared in the uninephrectomized rat. A control group (n = 14) received compared isotonic saline solution. Test substances (3 mL) were injected into the kidney at a rate of 1 mL/minute while transitory ischemia was induced by clamping the aorta above the renal artery. RESULTS: In terms of their (moderate) effects on creatinine clearance, proteinuria, and urinary N-acetyl-beta-D-glucosaminidase activity, no statistically significant difference was detected between the two low-osmolar contrast agents either 24 or 48 hours after injection. However, blinded histologic analysis of the kidneys showed significantly greater epithelial cell vacuolization in the proximal convoluted tubules of the outer cortex with iohexol (14 of 14 rats versus 3 of 14 rats for iobitridol; P < .001). The same degree of vacuolization in the inner cortex was observed for all three substances. Iobitridol also induced fewer congestive lesions in the glomerular capillaries than iohexol (4 of 14 versus 10 of 14, respectively; P < .05) and saline (5 of 6; P < .05). It is difficult to explain the lesser degree of cytoplasmic vacuolization using standard physicochemical parameters. CONCLUSION: Although iobitridol and iohexol showed similar functional and biochemical profiles when selectively injected into the single remaining kidney of rats, iobitridol induced significantly less tubular vacuolization and capillary congestion than iohexol.

Acetylglucosaminidase↗

Transplacental passage and milk excretion of iobitridol.

RATIONALE AND OBJECTIVES: Iobitridol, a new nonionic, low-osmolality urographic and angiographic contrast medium, is a marker of extracellular fluid. Excretion of iobitridol in goat's milk and transplacental passage in the gestating rabbit were evaluated compared with iohexol. METHODS: Both products were determined in biologic samples by two analytic methods: ultraviolet spectrometry (milk) and high-pressure liquid chromatography (maternal and fetal blood and amniotic fluid). RESULTS: Excretion in the milk represents 0.7% of the administered dose for iobitridol and 1.6% for iohexol. Transplacental passage is nonexistent. Iobitridol and iohexol behave in a similar manner. CONCLUSIONS: These preclinical results allow more effective prediction of the safety of iobitridol in pregnant or lactating women. However, precautions for use must be respected in the absence of specific studies in this population group.

Amniotic Fluid↗

Comparative effects of low- and high-osmolar contrast media on the renal function during early degenerative gentamicin-induced nephropathy in rats.

The nephrotoxic potentials of a high-osmolar contrast medium, diatrizoate, and of a low-osmolar contrast medium, ioxaglate, were compared during early degenerative gentamicin-induced nephropathy in the rat. Male rats (13-22/group) were uninephrectomized. Six days later, the aorta was clamped above the renal artery, and either diatrizoate or ioxaglate was administered (1 ml/min for 3 min) via an aortic puncture into the remaining kidney. Some of the rats received chronic treatment with gentamicin (50 mg/kg/day i.m., 4 days), starting 2 days before and ending 1 day after contrast medium administration. Two control groups, only one of which received gentamicin, were subjected to a 3-min renal ischemia. The creatinine clearance (CrCl) per 100 g body weight was determined before and 24 and 48 h after contrast medium injection. A second study (6 rats/group) evaluated urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion and the histologic appearance of the kidneys (blinded analysis) in the same experimental groups. Gentamicin induced a significant decrease in CrCl at baseline (0.35 +/- 0.19 vs. 0.41 +/- 0.19 ml/min; p < 0.01) and an increase in urinary NAG (128 +/- 92 vs. 39 +/- 57 mumol/h/mmol creatinine; p < 0.01). Taking into account these differences at baseline, univariate repeated-measures analysis showed that on day 1 diatrizoate caused a more marked decrease in CrCl than ioxaglate (p < 0.05), whether or not gentamicin was also administered. On day 2, the depressant effect of diatrizoate associated with gentamicin persisted (CrCl vs. day 0 = -0.19 +/- 0.10 ml/min), while that of diatrizoate alone returned to baseline (-0.05 +/- 0.24 ml/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylglucosaminidase↗

[The history of Lipiodol (1901-1994) or How a medication may evolve with the times].

The history of Lipiodol, an iodized oil perfected in 1901 by Marcel Guerbet and Laurent Lafay, offers the example of a product with multiple indications which, initially destined for therapeutic usage, was later successfully turned to radiologic applications; then, sixty years later, returned to its initial purposes. This shows that (1) very often new products find usages which their developers never suspected; (2) research can extend beyond the original synthesis and commercialization of the product; (3) at some point research on a medication becomes multidisciplinary.

Drug Therapy↗

[The discovery of Tenebryl, the first French uro-angiographic iodized hydrosoluble product].

Ténébryl was perfected in 1931 by Marcel and André Guerbet. For the company which bore their name and after the discovery of Lipiodol, this was the opportunity to explore a new area in radiology: intravenous urography. The discovery of this product is exemplary in a greater sense, since it contributed to opening the way to a new class of contrast products of which the majority today are iodized products. All the ingredients of industrial research are present here, from risk-taking to successful commercialization.

Drug Design↗

[Electrocorticographic evaluation of the neurologic tolerability of iobitridol (Xenetix), a new non-ionic contrast medium in rabbits].

Electro-corticographic tracings (two longitudinal leads, bipolar assembly) were recorded from curarized rabbits (5/group) receiving selective internal carotid artery injections of either iobitridol, a new non-ionic contrast medium, or iohexol, the high osmolar diatrizoate or hypertonic mannitol (isotonic to the non-ionic agents). A further group was submitted to the surgical preparation but was not injected. The solutions were injected at a dose of 2.5 ml during 30 seconds. The animals were anaesthetized (halothane) during the surgical period. The permeability of the blood-brain barrier was assessed by means of the extravasation of Evans'blue. Tracings were visually assessed and a semi-quantitative method for blind evaluation of fast/slow rhythms was used. This method was pharmacologically validated by the use of pentobarbital and pentylenetetrazole. Diatrizoate and iohexol induced respectively 3 and 2 paroxystic tracings during or immediately after the injection period. Iobitridol and hypertonic mannitol did not cause such effect. Paroxystic tracings in the iohexol group were not associated with extravasation of Evans'blue in the cerebral parenchyma. Blood brain barrier was disrupted in all rabbits receiving the high osmolar agent diatrizoate. Tracings of the control group were characterized by a progressive increase of fast rhythms, as those of the iobitridol and mannitol groups. On the contrary, iohexol and especially diatrizoate induced an increase in the proportion of slow waves. Taken together, these data suggest that iobitridol shows an excellent tolerability potential for clinical use.

Animals↗

Comparative study of the dialysability of iobitridol and iohexol in the rat with impaired renal function.

PURPOSE: To assess the dialysability of iobitridol, a comparative study with iohexol was conducted in the rat over 4 hours. MATERIAL AND METHODS: After ligature of the renal veins and arteries, a group of animals was submitted to continuous peritoneal dialysis, while the remainder were not. RESULTS: In the event of total renal failure, biliary excretion rose from 0.4 to 9% for iobitridol and from 2 to 16% for iohexol. In the rats submitted to peritoneal dialysis, biliary excretion decreased to 5% in the iobitridol group and to 13% in the iohexol group. Further, 18% of the test substances were eliminated in the dialysis liquid. CONCLUSIONS: As their physicochemical characteristics are very similar, the differences between the biliary excretion levels of these 2 media may be caused by a factor related to their respective molecular conformations.

Animals↗