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Biomedical subjects

J C Olivier

Publications and source records attributed to J C Olivier.

At least 19 recordsLinked to original sources

In situ nasal absorption of midazolam in rats.

Intranasal (i.n.) midazolam (MDZ) administrations may be used successfully for preoperative sedation, especially in young patients. However, clinicians have to use the commercial parenteral formulation, the low pH of which (3.3), necessary to solubilize MDZ (pK(a) 6.1), is probably responsible for the signs of local irritation frequently reported. As a starting point to design a formulation suitable for the nasal route, MDZ nasal absorption was investigated in rats. The effects of the MDZ solution concentration (10--100 microg/ml), osmolality (from less than 10 mOsm/kg up to 450 mOsm/kg) and pH (3.3--7.4) were studied using an in situ perfusion technique. MDZ was determined by reversed-phase HPLC in the circulating solution and results were expressed in clearance terms. MDZ absorption was independent of its concentration. The pH of the solutions was the key-parameter and only a pH above 4 allowed significant absorption. These results were consistent with a passive diffusion absorption of MDZ and partly followed the pH partition theory. In conclusion, satisfactory MDZ absorption should be expected with a formulation at a pH suitable for the nasal route in human (5.5--6.5).

Absorption↗

Niosomes and polymeric chitosan based vesicles bearing transferrin and glucose ligands for drug targeting.

PURPOSE: To prepare polymeric vesicles and niosomes bearing glucose or transferrin ligands for drug targeting. METHODS: A glucose-palmitoyl glycol chitosan (PGC) conjugate was synthesised and glucose-PGC polymeric vesicles prepared by sonication of glucose-PGC/cholesterol. N-palmitoylglucosamine (NPG) was synthesised and NPG niosomes also prepared by sonication of NPG/ sorbitan monostearate/ cholesterol/ cholesteryl poly-24-oxyethylene ether. These 2 glucose vesicles were incubated with colloidal concanavalin A gold (Con-A gold), washed and visualised by transmission electron microscopy (TEM). Transferrin was also conjugated to the surface of PGC vesicles and the uptake of these vesicles investigated in the A431 cell line (over expressing the transferrin receptor) by fluorescent activated cell sorter analysis. RESULTS: TEM imaging confirmed the presence of glucose units on the surface of PGC polymeric vesicles and NPG niosomes. Transferrin was coupled to PGC vesicles at a level of 0.60+/-0.18 g of transferrin per g polymer. The proportion of FITC-dextran positive A431 cells was 42% (FITC-dextran solution), 74% (plain vesicles) and 90% (transferrin vesicles). CONCLUSIONS: Glucose and transferrin bearing chitosan based vesicles and glucose niosomes have been prepared. Glucose bearing vesicles bind Con-A to their surface. Chitosan based vesicles are taken up by A431 cells and transferrin enhances this uptake.

Carcinoma, Squamous Cell↗

Indirect evidence that drug brain targeting using polysorbate 80-coated polybutylcyanoacrylate nanoparticles is related to toxicity.

PURPOSE: To investigate the mechanism underlying the entry of the analgesic peptide dalargin into brain using biodegradable polybutylcyanoacrylate (PBCA) nanoparticles (NP) overcoated with polysorbate 80. METHODS: The investigations were carried out with PBCA NP and with non biodegradable polystyrene (PS) NP (200 nm diameter). Dalargin adsorption was assessed by HPLC. Its entry into the CNS in mice was evaluated using the tail-flick procedure. Locomotor activity measurements were performed to compare NP toxicities. BBB permeabilization by PBCA NP was studied in vitro using a coculture of bovine brain capillary endothelial cells and rat astrocytes. RESULTS: Dalargin loading was 11.7 microg/mg on PBCA NP and 16.5 microg/ mg on PS NP. Adding polysorbate 80 to NP led to a complete desorption. Nevertheless, dalargin associated with PBCA NP and polysorbate 80 induced a potent and prolonged analgesia, which could not be obtained using PS NP in place of PBCA NP. Locomotor activity dramatically decreased in mice dosed with PBCA NP, but not with PS NP. PBCA NP also caused occasional mortality. In vitro, PBCA NP (10 microg/ml) induced a permeabilization of the BBB model. CONCLUSIONS: A non specific permeabilization of the BBB, probably related to the toxicity of the carrier, may account for the CNS penetration of dalargin associated with PBCA NP and polysorbate 80.

Analgesics↗

Capillary electrophoresis monitoring of the competitive adsorption of albumin onto the orosomucoid-coated polyisobutylcyanoacrylate nanoparticles.

The simultaneous and rapid quantitation of a glycoprotein, human orosomucoid, and a protein, human serum albumin (HSA), by micellar electrokinetic capillary electrophoresis was developed and optimized (pH and sodium dodecyl sulfate concentration) in order to study the competitive adsorption of HSA onto orosomucoid-coated nanoparticles of polyisobutylcyanoacrylate. This method provided satisfactory repeatability and the response was linear for concentrations of orosomucoid and HSA ranging from 0.025 to 0.500 mg/mL (r > 0.994 for both proteins). To study the competitive adsorption of HSA, the amounts of free orosomucoid and free HSA were determined in the supernatant obtained after centrifugation of the orosomucoid-coated nanoparticle suspension incubated with HSA. Furthermore, the quantities of both orosomucoid and HSA absorbed onto nanoparticles were also determined after desorption of these molecules from the nanoparticle surface, using sodium dodecyl sulfate. No analytical interference was observed with this surfactant. The results showed that HSA did not at all absorb onto the orosomucoid-coated nanoparticles and, thus, that this protein did not displace the layer of absorbed orosomucoid from the nanoparticle surface.

Adsorption↗

Impedance transfer: acoustic impedance of the annular ligament and stapedial tendon reconstruction in otosclerosis surgery.

The resistance rebuilt around the lower tip of the piston must be the same as that created by the annular ligament of the stapes footplate. Otherwise, the threshold at which an acoustic or barotrauma is able to damage the membranes and hair cells of the inner ear will be lowered. The elasticity reestablished around the lower tip of the piston plays a part in the quality and quantity of hearing for the low frequencies up to 3 kHz. To protect the ear against acoustic traumas, an attempt to rebuild the stapedial reflex is proposed.

Acoustic Impedance Tests↗

Survival and evolution of vein grafts in otosclerosis surgery: structural and ultrastructural evidence.

The annular ligament of the stapes footplate measures 0.2 mm2 and contains elastic fibers that restrict perilymphatic movement to a molecular level. This resistance of the annular ligament prevents excessive movement of labyrinthine fluids that are potentially hazardous to the membranous and cellular structures of the inner ear. However, if the resistance of the annular ligament is overcome, then inner ear damage can occur. The vein graft, as used in our technique for otosclerosis surgery, occupies a space of 0.2 mm2 between the edge of the stapedotomy hole and the piston and has nearly the same compliance and resistance as the annular ligament of the stapes footplate. The vein graft becomes integrated with the middle-ear mucosa. It develops a rich and active blood supply and the smooth muscle cells and elastic fibers remain, although the latter show some modification of ultrastructural pattern. The graft becomes overlaid by the middle-ear epithelium. Even samples of vein graft that have been present for many years retain surviving elastic fibers, including those that have become fibrotic. In time, the number of elastic fibers increases as a result of the activity of fibroblasts, which build a poorly colored collagen.

Adult↗

Stapedotomy: the JB Causse technique.

The Jean-Bernard Causse technique of stapedotomy, derived from Jean René Causse "Teflon-interposition" technique, offers an optimum reconstitution of the function of the annular ligament of the stapes footplate. The quantity and quality of hearing depend significantly, among other things, on the function of the stapes footplate annular ligament. Its impedance keeps the perilymph motion within a physiological acoustic amplitude quantum level unless the movements are so excessive as in barotrauma and acoustic trauma which would have overworked even the annular ligament of a normal footplate. This surgical technique permits snorkling, scuba-diving, airplane landing, eustachian tube dysfunction after surgery as in a normal individual who did not undergo otosclerosis surgery. A comparative study on the postoperative hearing based on 3,000 out of 14,000 cases done by J C Bausse technique, 127 cases with small fenestra technique and 267 cases of complete platinectomy showed too large stapedotomy gives poor high tones and too small stapedotomy poor low tones. Five year follow-up on the hearing loss indicated that total platinoctomy has 1.7 times more alteration of 4 kHz frequency in comparison to the technique reconstituting the annular ligament. Yearly audiogram to check the evolution of cochlear otospongiosis may lead the surgeon to prescribe sodium fluoride if the mid-frequencies are deteriorating and vascular drugs if the high pitch frequencies are deteriorating.

Ear Diseases↗

[Brain stem auditory evoked potentials. Risk of error in infants under 6 months].

Auditory tests employing brain stem evoked potentials may reveal deafness with a normal tympanogram in very young infants which improves after several months. A possible etiological factor is persistence in the middle ear of partial mesenchymatous remnants which have already freed the drum but persist in certain regions of the tympanic cavity.

Acoustic Impedance Tests↗

[Directivity a qualitative function of hearing aids (author's transl)].

"Directivity" is the name applied by the authors to the overall audioprosthetic phenomena which they have demonstrated in their research into the correction of deficient hearing, using hearing aids equipped with directional microphones. They propose a double blind test in order to attempt to demonstrate objectively the reasons which experimentally and in the Laboratory decide the choice of a hearing aid with a directional microphone or an omni-directional microphone. Amongst other things, the test makes it possible to confirm whether the improvement in intelligibility in a recreated noisy atmosphere is linked or not to the possibilities of directional detection offered by aids equipped with a directional microphone.

Adult↗