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Biomedical subjects

C Corot

Publications and source records attributed to C Corot.

At least 37 records · Page 2Linked to original sources
PubMed1999

Interference of magnetic resonance imaging contrast agents with the serum calcium measurement technique using colorimetric reagents.

A possible interaction between either linear (Gd-DTPA-BMA and Gd-DTPA) or macrocyclic (Gd-DOTA) gadolinium complexes used as magnetic resonance imaging (MRI) contrast agents and colorimetric technique reagents for the measurement of serum calcium was evaluated on human serum pools, and its mechanism was investigated by means of UV spectrometry and electro-spray ionization mass spectrometry (ESI-MS). The highest concentration tested was 2.5 mM (corresponding to a putative strictly intravascular distribution of the compound) and the lowest dose was 0.2 mM (i.e. about two elimination half lives). Serum calcium was dosed in duplicate by conventional colorimetric techniques involving o-cresol-phthalein complexone (OCP) or methylthymol blue (MTB) as reagents. No interference was detected when mixing Gd DOTA with serum, whatever the concentration. Gd DTPA (2.5 mM) did not interfere with the colorimetric technique either. Conversely, the Gd DTPA-BMA solution induced a concentration-related variation in apparent calcium levels. In the UV experiments, solutions of 2.5 mM MRI contrast media were mixed with OCP or MTB and UV absorption spectra were recorded between 400 and 800 nm. For Gd-DOTA/OCP and Gd-DOTA/MTB, no significant variations in the absorbance were detected. However, in the presence of Gd DTPA BMA, the absorbance of OCP and MTB showed substantial and immediate variations over time. The ESI-MS studies showed a complete displacement of Gd3+ ion in the case of Gd-DTPA BMA. In the presence of OCP, we observed the disappearance of Gd-DTPA BMA and the formation of the free ligand DTPA BMA and a new complex Gd OCP with an original stoichiometry of 2/2. Such a phenomenon did not occur in the case of Gd DOTA and Gd DTPA. The decomplexation of Gd-DTPA BMA in the presence of OCP can probably be explained by the weaker thermodynamic stability of Gd-DTPA BMA compared to that of Gd-DOTA and Gd DTPA.

Bromthymol Blue↗
PubMed1999

In vitro evaluation of vascular permeability to contrast media using cultured endothelial cell monolayers.

OBJECTIVE: The efficiency of contrast agents in medical imaging depends on their distribution into vascular and interstitial compartments. The aim of this study was to compare in vitro endothelial permeability to different classes of contrast agents with various vascular persistence properties: a triiodinated nonionic monomer (ioversol), an iodinated dextran polymer (P604), and an iron oxide nanoparticle (sinerem). METHODS: Permeability studies, through collagen-coated filters with or without porcine aortic endothelial cell monolayer, were carried out by placing each filter-ring (luminal chamber) into a beaker containing a culture medium (abluminal chamber). Contrast media, diluted in the culture medium, were added to the luminal chamber. Aliquots were sampled from the abluminal chamber for contrast agent determinations. The volume cleared of the compound was calculated from the luminal side to the abluminal side. Parallel permeability tests to [3H]-H2O and Evans blue albumin were performed as references. Finally, the modulatory effect of bradykinin on endothelial permeability to albumin or to contrast agents was studied. RESULTS: The volume cleared of ioversol, P604, and sinerem through membrane filters was decreased by 19.6%, 32.1%, and 52.0%, respectively, in the presence of a cell monolayer. Bradykinin (10(-6) M) significantly increased permeability to albumin, ioversol, and sinerem. Ioversol and sinerem induced a significant decrease in permeability to albumin. CONCLUSIONS: A relation between the molecular size of the contrast agents tested and their endothelial permeability can be established with this in vitro model.

Analysis of Variance↗
PubMed1999

Thrombotic risk associated with the use of iodinated contrast media in interventional cardiology: pathophysiology and clinical aspects.

A review of the current knowledge of the anti-thrombotic properties of iodinated contrast media (CM) has been conducted. CM are classified according to their chemical structure, either ionic or non-ionic (monomeric or dimeric). Numerous in vitro and in vivo data show that, although all CM have anti-coagulant properties, ionic molecules are more potent than non-ionic and, furthermore, do not activate resting platelets, unlike non-ionic agents. These properties may lead to a decrease in thrombus formation during interventional procedures. Several clinical trials have shown that CM may play a role in the occurrence of acute thrombotic complications but also in delayed ischaemic events during interventional procedures. A recent meta-analysis showed that, compared to non-ionic monomers, ionic low-osmolar CM reduce the rate of coronary artery abrupt closure, but no significant difference was found with respect to ischaemic complications. Ionic CM lead to a lower deposit of thrombotic materials on catheters and guide-wires. To date, clinical data comparing ionic CM and non-ionic dimers are scarce, significantly heterogeneous and, unlike experimental data, they do not show differences between both classes of CM. Further studies are required to better understand the precise mechanisms of such interactions and to analyse the effect of CM when new antiplatelet agents or new procedures (stenting) are used, to comply with new clinical strategies.

Angioplasty, Balloon, Coronary↗
PubMed1998

Haemodynamic effects of macrocyclic and linear gadolinium chelates in rats: role of calcium and transmetallation.

Several studies were undertaken to compare four magnetic resonance imaging (MRI) contrast media (CM) as regards acute haemodynamic effects in rats and to investigate the mechanisms involved. (1) Normotensive rats received a rapid bolus intravenous injection of 0.5 mmol kg-1 of each CM. The effects of Gd-DOTA, Gd-HP-DO3A, Gd-DTPA and Gd-DTPA-BMA on blood pressure (BP) were compared. (2) The haemodynamic effects of Gd-DTPA (0.5 mmol kg-1) were compared to those of isovolumic and isoosmolar Zn-DTPA and glucose solutions. (3) The haemodynamic profiles of Gd-DTPA and Gd-DTPA-BMA were recorded with and without addition of ionized calcium. (4) The mechanism of Gd-HP-DO3A-induced transient rise in BP was investigated by evaluating the effects of phentolamine or diltiazem pretreatment. For (1) the greatest drop in BP occurred following Gd-DTPA (a linear chelate) injection (-18 +/- 2% vs baseline, P < 0.01). Gd-DTPA-BMA, another lineate chelate, also induced a slight but significant reduction in BP (-8 +/- 2% at 45 s, P < 0.05). Gd-DOTA, a macrocyclic CM, had virtually no haemodynamic effects. For (2) the Gd-DTPA-induced drop in BP was greater than that of the osmolality-matched glucose control and lower than that of osmolality-matched Zn-DTPA. For (3) a transmetallation phenomenon versus free ionized calcium is possible in the case of both linear CM (Gd-DTPA and Gd-DTPA-BMA) since Ca2+ significantly reduced the CM-induced decrease in BP. For (4) a transient rise in BP was observed following Gd-HP-DO3A, another macrocyclic chelate, associated with a concomitant increase in stroke volume. This effect was antagonized neither by phentolamine nor by diltiazem. The decrease in BP following injection of Gd-DTPA or Gd-DTPA-BMA may not only be osmolality-related since (a) Gd-DOTA solution, whose osmolality is greater than that of Gd-DTPA-BMA, had a lesser effect, and (b) this hypotensive effect was corrected by a addition of ionized calcium. The transient Gd-HP-DO3A-induced rise in BP is probably the consequence of a positive inotropic effect.

Animals↗
PubMed1997

Study of the complex between the contrast agent Iobitridol (Xenetix) and Elastase (PPE): a model for hydrophobic site protection in drug-protein interactions.

PURPOSE: The concept of Hydrophilic Sphere Stabilization, or Hydrophobic Shielding, has been postulated in the synthesis of biocompatible contrast agents in vascular imaging. To improve the safety of these polyiodinated agents, interactions with protein hydrophobic sites in biomacromolecules should be kept as low as possible. In order to evaluate the level of interactions with proteins, we have selected the serine proteinase Elastase, in presence of Iobitridol (Xenetix), as a model. METHODS: The complex between Iobitridol and Pancreatic Porcine Elastase was investigated by X-ray diffraction techniques, on saturated monocrystals, using the synchrotron radiation at 0.98A. RESULTS: In contrast to Iohexol, which displays several interactions including one in the active site, Iobitridol is unable to interact directly with elastase. Only one partially occupied site is found in between two molecules of the crystal packing. CONCLUSIONS: The validation of the "hydrophobic shielding" concept, which was at the origin of the design of the Iobitridol molecule, has been proven to be an essential feature in minimizing in vivo protein interactions.

Animals↗
PubMed1997

Experimental evaluation of the vascular effects and transport of an iodinated macromolecular contrast medium.

RATIONALE AND OBJECTIVES: For assessment of the tissue blood pool and overall vascularity, macromolecular contrast media have significant advantages over low molecular weight contrast agents. The authors evaluated the vascular effect and transport of a new macromolecular contrast media (MMCM), an iodinated dextran polymer of 32 kDa. METHODS: The new MMCM was obtained from dextran activated by carboxy methylation, followed by linkage with triiodinated aminophtalamid conjugates. To detect whether the tracer induces vascular leakage, MMCM (350 mg I/kg) was administered intravenously in 10 mice, or applied on the cremaster muscle of 26 mice previously injected with carbon particles; after 30 or 45 minutes, the cremaster was fixed and examined by optical microscopy. For investigation of the vascular transport 3, 5, and 15 minutes after MMCM administration, various tissue fragments were processed and examined by electron microscopy. RESULTS: In all vascular examined, MMCM does not induce plasma extravasation and the probe was detected mostly within the vascular lumen. At the ultrastructural level, a small fraction of MMCM was found in endothelial plasmalemmal vesicles (endosome-like structures) and, in time, transcytosed to the subendothelial space. No intercellular junctions were permeated by MMCM. CONCLUSIONS: The MMCM induces no vascular leakage and it is retained mainly in the plasma. Transport of MMCM is restricted to endothelial vesicles, which may explain, in part, its prolonged vascular space retention.

Angiography↗
PubMed1997

Physical, chemical and biological evaluations of CMD-A2-Gd-DOTA. A new paramagnetic dextran polymer.

PURPOSE: We investigated the synthesis and physical, chemical and biological characterisation of a carboxymethyl-dextran polymer substituted with the paramagnetic macrocyclic complex Gd-DOTA using an amino spacer. MATERIAL AND METHODS: The product was synthesised in 4 steps. Using rigorous purification conditions in each step, a polymer was obtained, i.e. CMD-A2-Gd-DOTA, whose polydispersity profile was comparable to the initial dextran (I = 1.66-Mw = 50.5 kDa). Approximately 22% of the glucose groups were replaced by Gd-DOTA and 39% were replaced by carboxyl groups. The paramagnetic efficacy of the polymer was 3 times higher than Gd-DOTA alone, which suggests that the injected doses of Gd(III) can be reduced. The vascular residence time of the polymer was measured in rats and rabbits, showing that the pharmacokinetics of the product is similar whatever the dose. Forty-five percent of the product was excreted in urine after 24 h and 1.64% was found in the liver. No acute toxicity was observed at the maximum dose injected (> 5 mmol Gd/kg) and the general biocompatibility of the product tested in vitro was comparable to that of Gd-DOTA. RESULTS AND CONCLUSION: These results show the advantages of using paramagnetic macrocyclic complexes in the synthesis of macromolecules to preserve biological stability, in contrast with linear chelates. Additional studies will be carried out to demonstrate the benefits of this type of product, particularly in functional imaging.

Animals↗
PubMed1996

In vitro comparison of the effects of contrast media on coagulation and platelet activation.

The aim of this study was to compare the in vitro effects of different classes of contrast media on both the blood coagulation system and on platelet function. Global tests (APTT, TT) and FpA and F1 + 2 generation measurements showed that ioxaglate (ionic dimer) presents the highest anticoagulant potential. The anticoagulant effects of nonionic agents were less marked, iodixanol (nonionic dimer) being significantly less anticoagulant than iohexol (nonionic monomer). Major platelet activation was observed with release of PF4, serotonin and PDGF-AB when iohexol was incubated for 1 min in whole blood. Iodixanol showed no effect over the same period, while moderate platelet activation was observed after 30 min. Under the same experimental conditions, ioxaglate had no effect on platelets even after incubation for 30 min, whereas activation was observed with 9 g/l saline control at this time. Prevention of thrombin formation and platelet activation is only achieved with ioxaglate, the ionic dimer. These findings may be clinically important in the thrombotic environment of radiological procedures and may explain the increased thrombotic risks observed with nonionic agents in interventional procedures.

Blood Coagulation↗
PubMed1996

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↗
PubMed1995

Angiography contrast agents interact with serine proteinases. The molecular structure of the model system elastase/iohexol.

Pancreatic elastase was co-crystallised with iohexol, a tri-iodo benzenic contrast agent used in angiography analyses. The X-ray analysis of the complex reveals the presence of three molecules of iohexol associated with the proteinase with low occupancy factors. Two iohexol molecules are located in and near the active site of the enzyme and provide a model for explaining the inhibition of the hemostatic system, one of the major and inconvenient side effect associated with these chemicals.

Binding Sites↗
PubMed1995

Involvement of protein solvation in the interaction between a contrast medium (iopamidol) and fibrinogen or lysozyme.

The interaction between proteins and a radiological commonly-used contrast medium (iopamidol) have been studied by calorimetry. When aqueous solutions of fibrinogen or of lysozyme (20 g/l) are mixed with an aqueous solution of iopamidol (1,3-5 benzendicardoxamid,N,N'-bis[2-hydroxy-1-(hydroxymethyl)ethyl]-5- [(2-hydroxy-1-oxopropyl)amino]-2,4,6-triiodo) in the clinical blood concentration range (26-485 mM), isothermal calorimetry reveals a weak endothermal interaction at a high concentration of iopamidol for both proteins. This endothermal effect does not appear to be due to direct protein-iopamidol association. Differential scanning calorimetry confirms the influence of iopamidol by the change in protein unfolding in the presence of contrast medium, and suggests alterations in the protein solvation as a mechanism. Dilution studies indicate that iopamidol can influence protein solvation even when water molecules are present in a molecular excess of 1000. The influence of iopamidol on the availability of water molecules and the absence of direct interaction with the protein molecules is shown by Raman spectroscopy of two amino acids in the presence of iopamidol. The spectrum of alanine is unchanged at any iopamidol concentration studied, whereas the spectrum lines due to the thiol group of cysteine are shifted in a manner consistent with altered solvation.

Calorimetry, Differential Scanning↗
PubMed1993

Effect of ioxaglate--an ionic low osmolar contrast medium--on fibrin polymerization in vitro.

Ioxaglate, an iodinated contrast agent, decreases the rates of fibrin clot formation induced by thrombin or reptilase. This effect is not related to an increase in the ionic strength of the medium since a specific control of equivalent composition does not induce such variation. The concentration of ioxaglate which led to a 50% decrease of the control clot turbidity induced by thrombin was 17.5 +/- 2 mM. Macroscopically, clots formed with ioxaglate were larger and less turbid than the isotonic control. An increase in fibrin fibre diameters and a decrease in their densities were observed. During the fibrin polymerization process, all the fibrinogen was converted into fibrin, as for both the control and ioxaglate quantitative analysis of clots and supernatants showed (1) an identical quantity of FpA in clot supernatants, (2) the same quantities of protein incorporated into clots, and (3) no trace of fibrin monomers in the clot supernatants. Furthermore, dissolution in urea of clots formed in the presence of ioxaglate occurred more rapidly than in the control. Total incorporation of fibrinogen into clots, associated with a decrease in clot turbidity, indicated the existence of a qualitative abnormality in the construction of the three-dimensional fibrin structure. Using differential scanning calorimetry, it was observed that the two domains (D and E) of fibrinogen were modified by ioxaglate, showing the absence of specificity in the interaction between ioxaglate and a particular domain.

Blood Coagulation↗