Mutagenicity assessment of two potential impurities in preparations of 5-amino-2,4,6 triiodoisophthalic acid, a key intermediate in the synthesis of the iodinated contrast agent iopamidol.

5-Aminoisophthalic acid and 5-nitroisophthalic acid (5-NIPA) are potential impurities in preparations of 5-amino-2,4,6-triiodoisophthalic acid, which is a key intermediate in the synthesis of the iodinated contrast agent iopamidol. We have studied their mutagenicity in silico (quantitative structure-activity relationships, QSAR) and by the bacterial reverse mutation assay (Ames test). First, the compounds were screened with the tools Derek Nexus™ and Leadscope®.

[CircuLite Synergy ventricular assist device: a new approach to end-stage congestive heart failure].

Background: The Synergy system, a miniature partial circulatory support device, is implanted by an off-pump, minimally invasive surgical approach. The system has been optimized to improve performance in an EU clinical trial for chronic ambulatory heart failure. This therefore offers the possibility of treating elderly chronic heart failure patients who might not usually be considered for long-term circulatory support.

B25716/1: a novel albumin-binding Gd-AAZTA MRI contrast agent with improved properties in tumor imaging.

The aim of this study is to describe the synthesis of, relaxometric characterization of, pharmacokinetic properties of, and animal imaging experiments with a new, low molecular weight gadolinium complex with high binding affinity toward serum albumin. The gadolinium(III) chelate (B25716/1) is based on the structure of the heptadentate ligand 1,4-bis(hydroxycarbonylmethyl)-6-[bis(hydroxycarbonylmethyl)]amino-6 methylperhydro-1,4-diazepine (AAZTA) covalently conjugated to an analogue of deoxycholic acid. The study was conducted as a comparison with that of an analogous complex based on the octadentate diethylenetriaminepentaacetic acid ligand B22956/1 (whose albumin binding properties were previously assessed).

Evidence for in vivo macrophage mediated tumor uptake of paramagnetic/fluorescent liposomes.

Dysprosium (Dy)-loaded liposomes act as excellent T(2)-susceptibility agents at high magnetic field strength. The R(2)-enhancement increases with the size of the liposomes and the concentration of entrapped paramagnetic metal complexes. Neuro-2a tumor cells are readily labeled when Dy-loaded liposomes, suitably functionalized with glutamine residues (Gln), are added to the culture medium as glutamine receptors are highly expressed in such proliferating tumor cells.

Lanthanide-loaded paramagnetic liposomes as switchable magnetically oriented nanovesicles.

Osmotically shrunken liposomes loaded with paramagnetic lanthanide(III) complexes orient in a static magnetic field according to the sign of their magnetic susceptibility anisotropy (Deltachi). The magnitude and sign of Deltachi are modulated by the magnetic properties of the Ln (III) ion, by the structural characteristics of the metal chelate, and by the stereochemical arrangement of the lipophilic substituents.

Determination of water permeability of paramagnetic liposomes of interest in MRI field.

The water permeability of various liposome membranes has been determined at 298K by measuring the NMR longitudinal water proton relaxation rate of vesicles encapsulating the clinically approved Gd-HPDO3A complex (HPDO3A=10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid). Two basic formulations based on DPPC (dipalmitoylphosphatidylcholine) and POPC (palmitoyl-oleylphosphatidylcholine) phospholipids were selected and investigated. Furthermore, the permeability changes caused by the membrane incorporation of amphiphiles like cholesterol and/or metal complexes of interest for designing improved liposome-based MRI contrast agents, were also investigated.

Molecular determinants in the transport of a bile acid-derived diagnostic agent in tumoral and nontumoral cell lines of human liver.

Contrast-enhanced magnetic resonance imaging (CE-MRI) is a valuable technique for the diagnosis of liver diseases. As gadocoletic acid trisodium salt (B22956/1), a new contrast agent showing high biliary excretion, may be potentially advantageous in hepatobiliary imaging, the aim of the study was to investigate the molecular mechanisms of hepatic transport of the B22956 ion in a cellular model of hepatic tumor. B22956 ion uptake was measured in tumoral (HepG2) and nontumoral (Chang liver) hepatic cell lines.

Magnetic resonance imaging of tumor cells by targeting the amino acid transport system.

An early diagnosis of cancer is crucial in the battle against this disease and the in vivo visualization of tumors at cellular level is still the most challenging goal. In order to target tumor cells, we took into account their increased metabolism and amino acid nutrients or pseudo-nutrients, which are actively transported through the cell membrane, have been chosen as vectors for new MRI contrast agents. For this reason new gadolinium complexes conjugated to agmatine, arginine, and glutamine have been synthesized and studied.

In vitro and in vivo hepatic transport of the magnetic resonance imaging contrast agent B22956/1: role of MRP proteins.

The molecular mechanisms of the hepatic transport of B22956/1, a new gadolinium complex from the class of intravascular contrast agents for MRI, which undergoes extensive biliary elimination, were studied. Biliary and urinary elimination of B22956/1 were measured in normal and in mutant MRP2 lacking rats (TR(-)); cellular trafficking of the compound was assessed in wild and MRP1 or MRP2 transfected MDCKII cells. Eight hours after IV injection of B22956/1, 90+/-8% of the dose was recovered in the bile of normal rats.

Abc protein transport of MRI contrast agents in canalicular rat liver plasma vesicles and yeast vacuoles.

The mechanism of excretion into bile of hepatospecific magnetic resonance imaging (MRI) contrast media employed labeled Gd-reagents EOB.DTPA, BOPTA, B 20790 (iopanoate-linked), and B 21690 (glycocholate-linked) for measurement in rat liver canalicular plasma membrane vesicles and yeast vacuoles. The presence of ATP gave threefold greater transport of B 20790 and B 21690 than of EOB.

Molecular mechanisms for the hepatic uptake of magnetic resonance imaging contrast agents.

The mechanisms were investigated for the hepatic transport of 4 different gadolinium complexes used as contrast agents for magnetic resonance imaging (MRI). In basolateral rat hepatocyte plasma membrane vesicles, Gd-DTPA uptake was indistinguishable from non-specific binding to vesicles; Gd-BOPTA and Gd-EOB-DTPA entered plasma membrane vesicles following a linear, concentration-dependent mechanism up to 1.5 mM of substrate.

[Laparoscopic cholecystectomy in patients previously treated with heart transplantation. A clinical case].

A 46-years old patient who had already undergone cardiac transplantation was scheduled for laparoscopic cholecystectomy following a diagnosis of cholelithiasis. In this particular case we were not faced with any problems even in presence of a denervated heart. Since the patient was immnosuppressed, we had to look for the best compromise between the need of monitoring closely the most important vital parameters and contemporarily reducing invasivity as much as possible.

[Clinical usefulness of transesophageal echocardiography in heart surgery complications].

The role of monoplane transesophageal echocardiography (TEE) in rapid decision making process was investigated in 115 critically ill patients (pts) with early postoperative complications after cardio-thoracic surgery (hypotension, central venous pressure and/or wedge pressure elevation, electrocardiographic S-T segment elevation). Systolic and diastolic function of left ventricle, left ventricular wall motion abnormalities, right ventricular function, valves or prosthetic valves function, left ventricular outflow tract and morphologic changes were evaluated. Echocardiographic diagnoses were classified as: useful, incomplete, not diagnostic, misleading, unexpected.

A prospective study of the clinical benefits of prostacyclin in 554 cardiopulmonary bypass procedures.

Abnormal bleeding after cardiopulmonary bypass (CPB) may result from incomplete neutralization of heparin, increased fibrinolytic activity, consumption of coagulation factors, or from a reduction in the number of circulating platelets together with impairment of platelet function. Although researchers have reason to believe that hemostasis after CPB could be improved with prostacyclin (PGI(2)), a potent inhibitor of platelet aggregation, the drug's clear-cut benefits in this respect have not yet been confirmed. After conducting an initial study concerning the fate of platelets during CPB, in which we determined that PGI(2) had a protective effect, we investigated the effects of PGI(2) infusion during CPB on postoperative blood loss in 554 open-heart surgery patients, 200 of whom underwent valve replacement, 200 of whom had coronary artery bypass grafting (CABG), and 154 of whom underwent repeat valve replacement or CABG.

[Abnormal electrocardiographic changes induced by hypocalcemia secondary to extracorporeal circulation].

We report hereby the case of a 20-year-old woman, whose electrocardiogram showed unusual repolarization abnormalities 36 hours after open heart surgery. They were due to pure hypocalcemia (7,1 mg/100 ml) secondary to extracorporeal circulation, were sudden in onset, transient, variable within a few minutes, and immediately suppressed by intravenous calcium chloride. Some of the changes were similar to those already reported in literature (lengthening of QT and ST segments, changes in T wave voltage but not duration) whereas other were quite unusual i.