Influence of different calcic antagonists on the Caco-2 cell monolayer integrity or "TEER, a measurement of toxicity?".

The purpose of this work was to investigate the interest of the TEER measurement, a quite simple measure, as an evaluation of toxicity, in function of time and level of drug in the experimental medium, for different anticalcic agents. The extend of the increase and decrease of TEER, was evaluated by measuring the TEERmax and calculating the TEER50 respectively. Three groups of compounds could be therefore considered. The first, characterized by a quite short period of TEER increase, followed by an extremely rapid decrease (high values of TEER50), included perhexiline and prenylamine. The most toxic compounds, the second one, characterized by the smallest variations of TEER, included verapamil and diltiazem. This group was related with the less toxic compounds, the third group, represented by bepridil, characterized by dependant-dose TEERmax and TEER50. Therefore, the TEER measurement appeared as a quite simple approach of comparative toxicity of anticalcic agents.

Transepithelial transport of bepridil in the human intestinal cell line, Caco-2, using a "dynamic model".

The purpose of the study was to go further into the transepithetial transport of bepridil, an anticalcic agent, through monolayer cells Caco-2, using a "dynamic model" including a transfer of inserts with Caco-2 cells into new wells, free of drug, at regular intervals, in order to simulate the blood flux. The state of cells was evaluated by measuring the transepithelial electrical resistance and the transport of bepridil was followed using a gas chromatography/mass spectrometry determination. This study exhibits the importance of the basolateral renewal both on the transport of bepridil and the maintenance of cells in a satisfactory state. Two elimination phases from the cell compartment seem to occur, with basolateral half lives respectively of 12.2 and 25.6 hours, probably linked with two kinds of cellular binding sites. This dynamic model permits the reflection and simulation of the slowness of the in vivo absorption of bepridil in the small intestine.

Isotopic effect study of propofol deuteration on the metabolism, activity, and toxicity of the anesthetic.

The use of isotopic substitution to delay the oxidative metabolism of the anesthetic propofol 1 was studied. The aromatic hydrogens of propofol 1 were replaced by deuterium to produce the mono- and trideuterated derivatives 4 and 5. In vitro metabolic studies on human hepatic microsomes showed no isotopic effect in the para hydroxylation of propofol, and 1, 4, and 5 display similar hypnotic activity and toxicity in mice.

Heterocyclization of functionalized vinylic derivatives of imidazo.

Heterocyclization of functionalized vinylic derivatives of imidazo[1,2-a]pyridines was explored experimentally and theoretically using semiempirical AM1 and ab initio methods. A range of functionalized vinylic derivatives (azido, amino, and carbodiimide groups) were prepared for conversion into pyrroloazaindoles 19-22, imidazo[1,x]-, (x = 5, 6, 7, 8), [2,6]-, and [2,7]naphthyridines 28-30, 35-38 by thermal reaction. In the case of vinylic groups in the 5 position, peri annulation also was observed. The experimental and theoretical data are compared and discussed.

[Esophageal bezoar resulting from nasogastric enteral feeding in an intensive care unit]. / Bézoard oesophagien survenu chez des patients recevant une alimentation entérale en réanimation.

We report two cases of oesophageal bezoar in patients given enteral nutrition by nasogastric tubing in an intensive care unit. These two complications occurred during the year following the replacement of our standard enteral feed by a new preparation enriched in proteins. In both patients, the bezoar could be endoscopically removed. The enteral feeding solution is likely to be responsible for the development of this complication because no other factor known to favour this complication such as concomitant administration of sulfacrate or anti-acid agents was given to the patients; and the bezoar developed shortly after the new enteral feeding solution was used, a hypothesis supported by several similar case reports in the medical literature.

Motion of phospholipidic vesicles along an inclined plane: sliding and rolling.

The migration of giant phospholipidic vesicles along an inclined plane in a quiescent fluid was observed as a function of the mass and the radius R of the vesicles, and as a function of the angle of inclination of the plane. Vesicles were swollen, and did not adhere to the substrate surface. It was observed from a side-view chamber that they have quasispherical shapes. The vesicles mainly slide along the plane, but also roll. The ratio omegaR/v of rotational to translational velocities is of the order of 0.15 for vesicles of radius ranging from 10 to 30 microm. Values of this ratio, and variations of v versus R, are well described by Goldman et al.'s model developed for the motion of rigid spheres close to a wall [Chem. Eng. Sci. 22, 637 (1967)]. In this framework, the thickness of the fluid film between the vesicle and the substrate derived from fitting experimental data was found to be equal to 48 nm.

High-performance liquid chromatographic determination of phenylephrine and tropicamide in human aqueous humor.

A high-performance liquid chromatographic method for the simultaneous determination of phenylephrine and tropicamide in human aqueous humor was developed. After centrifugation, an aliquot of the supernatant was injected onto the column and the eluent was monitored at 280 nm then 254 nm after 5 min. Separation was performed on a CN column with 0.01 M Pic B8 (octane sulfonic acid)-acetonitrile (65:35, v/v) as mobile phase. The standard curves were linear in the detection range. The precision of the method (expressed by relative standard deviation) and the accuracy (mean error in per cent) were <5% for both intra- and interassays.

Transepithelial transport of bepridil in the human intestinal cell line, Caco-2, using two media, DMEMc and HBSS.

The purpose of this work was to study transepithelial transport of bepridil, an anticalcic agent, through monolayer cells Caco-2, using two experimental media with different chemical components. For experimentation, the measure of the transepithelial electrical resistance (TEER) allowed us to evaluate the state of cells; and the quantities of bepridil have been quantified using a gas chromatography/mass spectrometry system. First, when using the medium alone, without bepridil, Caco-2 cell integrity is, at least, maintained for 8 h using both media. However, for 24-h studies, only the DMEMc medium, rich in essential nutriments, allowed cell integrity to be maintained. Then, with bepridil in HBSS medium, the TEER measurement showed a dose-dependent toxic effect of bepridil, whereas in the DMEMc medium, the toxic effect was only found for the highest dose (12 microg). This difference is probably related to the high binding of bepridil to proteins of the DMEMc medium, therefore minimising the concentration of the free compound. The kinetics of bepridil result from two phenomena: first, an immediate passage of a slight part of bepridil through the cell barrier and second, a high retention of most of the bepridil dose in the cell level. The transfer of bepridil from the apical to the basolateral compartment appears quantitatively and kinetically different using DMEMc or HBSS medium. The retention of the compound in the 'filter with Caco-2 cells' compartment is higher in DMEMc medium (60% at 3 microg) than in HBSS medium (46% at 3 microg), and bepridil entering the basolateral compartment is delayed in the DMEMc medium. This study exhibits the importance of the selected medium on results and interpretation of data and the predominance of DMEMc to study the transport of lipophilic compounds highly retained in cells.

[Transfusion-associated HIV contamination between January 1980 and September 1985]. / Contamination transfusionnelle par le VIH de janvier 1980 à septembre 1985.

This study reports the results of a retrospective survey of transfusion-related HIV-contamination in patients who were admitted in our neurosurgery department, between the 1st January 1980 and the 30th September 1985. In our area of France, the risk of HIV-contamination is low. During this 5-year-period the blood donors were not tested for HIV. Six hundred twenty-one patients were identified from the operating room registers. The administered blood components were always noted in these registers for each patient. Among these 621 patients, 233 died rapidly. Three hundred eighty files were taken out from the central archives' department. Eight files could not be found. These 380 files were examined for the patient's address, or the family's one, or the regular doctor's name and address. A letter was sent to the latter in order to inform him about the patient's transfusion. The doctor had to ask the patient to order a HIV-test. A recall letter was sent 8 months later as required. The patients who did not have a regular doctor were contacted directly by phone or letter, or indirectly through their family. Thirteen months after the beginning of this survey it was established that 334 patients died (53.5%) and only 151 patients were found and tested. One of them was HIV-positive. As this patient suffered from a hemophilia B, he had been medically followed and his positive serology was known since 1988. It was impossible to get any answer from 136 other patients who represent 22% of all patients and 47% of still alive patients or supposed to be so.(ABSTRACT TRUNCATED AT 250 WORDS)

Identification of several human urinary metabolites of 6-benzoyl benzoxazolinone by gas chromatography/mass spectrometry.

The biotransformation of 6-benzoyl benzoxazolinone (6-BB), a non-narcotic peripheral analgesic, was studied in eight healthy volunteers after oral administration of a single dose of 1 g. Urinary metabolites were extracted either with ethyl acetate at different pH values or by percolating at pH 5 through Amberlite XAD 2 ion-exchange resin. Eluates were concentrated under vacuum, purified by thin-layer chromatography and analysed by gas chromatography/mass spectrometry or direct insertion probe mass spectrometry. Metabolites were identified with reference to the mass spectra of various synthesized compounds assumed to be metabolites of 6-BB, as N-methylated or monohydroxylated compounds. Another metabolic pathway was cleavage of the benzoxazolinone heterocycle giving 2-amino-5-benzoyl phenol after hydrolysis and decarboxylation. N-methyl, N-acetyl and hydroxylated metabolites having an amino-5-benzoyl phenol structure were also found.

[Deglutition disorders caused by an injury to the foramen lacerum posterior]. / Troubles de la déglutition secondaires à une lésion traumatique du trou déchiré postérieur.

Dysphagia due to a traumatic lesion of the foramen lacerum posterior is relatively rare. Two cases are described in which swallowing troubles were perceived when the post-traumatic coma improved; these were ascribed to a traumatic lesion of the foramen lacerum posterior injuring the cranial nerves. Treatment involves preventing inhalation and nasogastric feeding whilst starting active and early rehabilitation of swallowing. Recovery is possible in most cases without surgery.