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Biomedical subjects

J C Cazin

Publications and source records attributed to J C Cazin.

72 records · Page 4Linked to original sources
PubMed1980

[Changes in the cholesterol levels of high density lipoproteins following the intravenous administration of triton WR 1339 to rats (author's transl)].

The aim of the present study was to determine, in the rat, changes in the plasma lipids and lipoprotein levels after single or iterative administration of triton WR 1339 in order to elicit the inverse relation between triglyceride and high density lipoprotein levels in man and animal. 24 hours after the acute intravenous injection of triton WR 1339 increases of cholesterol and glyceride were observed while HDL decreased. These effects are potentiated by iterative intravenous administration of triton. According to Nikkila these variations could be explained by the fact that a part of HDL proceeds from the catabulism of lipoproteins rich in glycerides. At the time of the recovery of epuration process, the HDL regeneration from VLDL that are abondant in the plasma should represent the changes observed. The effects found after iterative intravenous administration of triton, confirm that infusion of the detergent induces in the blood a decrease of the catabolism of lipoproteins rich in triglycerides and at the same time the disappearing of blood HDL.

Animals↗
PubMed1980

Antioedematous properties of benzoxazolinone-beta-amino-ketones.

Four chemically related benzoxazolinone-beta-amino-ketones act in vitro on the guinea pig ileum as histamine, serotonin, bradykinin and prostaglandin antagonists. These compounds decrease the rat carrageenan-induced paw oedema mediated by the above-mentioned mediators. With the aim of bringing out the acting mechanisms of that inhibition we studied their ability to inhibit various models of oedema induced either by the release or the injection of the involved mediators. It seems that there is a good enough correlation between the former results obtained in vitro and the present results.

Animals↗
PubMedDate not supplied

A routine HPLC method for monitoring midazolam in serum.

A routine high-performance liquid chromatographic method for measuring midazolam in human serum has been developed. The sample preparation procedure consisted of simple liquid-liquid extraction with dichloromethane, followed by evaporation under nitrogen. The mobile phase used was a mixture of acetonitrile at 0.02 M and sodium acetate at pH 3.0 (80:20, v/v) and a flow-rate of 1.2 mL/min. The separation was performed on two cyanopropyl columns (150 x 4.6 mm). The detection was by UV absorption at 240 nm. A linear range from 10 to 1,000 ng/mL and a quantification limit of 7.4 ng/mL of serum was reached. The mean intra-assay and inter-assay reproducibility from serum sample spiked with 100 ng/mL were 4.1 and 4.7%, respectively. The recoveries from serum sample spiked with 50, 100, 500 ng/mL were 85.46, 85.38 and 85.57%, respectively. This method was developed to allow pharmacokinetics study of midazolam in young patients in short surgical interventions.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

On-line HPLC-electrospray ionization mass spectrometry: a pharmacological tool for identifying and studying the stability of Gd3+ complexes used as magnetic resonance imaging contrast agents.

The identification of MRI contrast agents (CAg) as gadolinium complexes often used at very low concentrations in Pharmacology was carried out by ESI-MS or HPLC-ESI-MS. Firstly, Omniscan, Dotarem and Magnevist were tested. In these compounds, the Gd3+ ion must be solidly chelated by linear or macrocyclic ligands because of the severe toxicity of the free Gd3+. Spectra were obtained at low voltage, preserving the non-covalent binding integrity of the complexes, and at various higher voltages showing the progressive destruction of the complexes. Secondly, a direct reaction of these drugs with the oxidative human neutrophil production, induced in vitro by Phorbol 12-myristate 13-acetate enhancing the respiratory burst, was investigated. This was done to mimic what happens in the case of inflammatory diseases, or infection, or when people are likely to develop anaphylactoid reactions, as the i.v. injection of CAg causes contact between the complexes and neutrophils in the blood. Analysis by HPLC-ESI-MS coupling did not show any direct reaction between Gd complexes and the chemical compounds in the neutrophil oxidative metabolism, even if uncertainty remains as regards meglumine salt. HPLC-ESI-MS is a good way of visualizing characteristic, Gd isotopic distribution and of following its associations in biological samples.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Determination of cyclohexamone after derivatization with 2,4-dinitrophenyl hydrazine in intravenous solutions stored in PVC bags by high performance liquid chromatography.

A high performance liquid chromatographic procedure is described for the determination of cyclohexanone leached in intravenous solutions from the poly(vinyl chloride) bags. After derivatization with 2,4-dinitrophenylhydrazine and extraction with pentane, the cyclohexanone derivative was analysed on a C18 BDS Hypersil column using mobile phase mixture of acetonitrile:water (55:45). Ultra-violet detection was performed at 368 nm. The limit of quantification was 30 ng/mL and the assay was linear from 0.05 to 50 micrograms/mL. The recovery was better than 95%. The proposed method is satisfactory in its accuracy and precision with particularly relative standard deviations (RSD) for intra-assay and inter-assay of below 10%. This method has been successfully used for the determination of cyclohexanone in aqueous solutions such as sodium chloride (0.9%) and glucose (5%) stored in PVC containers. The values obtained varied between 2.04 and 44.9 micrograms/mL according to solutions and volume.

Chromatography, High Pressure Liquid↗
PubMedDate not supplied

Solid phase extraction and high performance liquid chromatographic determination of dobutamine in plasma of dialysed patients.

An isocratic reversed-phase high performance liquid chromatographic method has been developed for th e determination of dobutamine in the plasma of dialysed patients. A solid phase extraction method with a Sep-Pak C18 cartridge was used to isolate the drug and isoxsuprine (internal standard) from plasma. The separation was carried out on an ODS-Hypersil column with 0.1 M phosphate buffer:acetonitrile:methanol (72:20:8 v/v/v) as the mobile phase. The recovery of dobutamine added to plasma by the extraction procedure was 87 +/- 2.3% (mean +/- SD). The accuracy and reproducibility of the method were within acceptable limits over the concentration range 0-1000 ng/mL. Quantification was by fluorescence detection at 275 nm excitation and 310 nm emission wavelengths with a detection limit of 5 ng/mL for dobutamine. This procedure was applied to ascertain the pharmacokinetics of dobutamine infusion in nine patients with cardiogenic shock and end-stage renal disease undergoing haemodialysis.

Chemical Phenomena↗
PubMedDate not supplied

Pharmacokinetics of midazolam: comparison of sublingual and intravenous routes in rabbit.

In France, the legal routes used to administer midazolam to a patient are intravenously and intramuscularly. For anaesthetists, these routes are not well adapted to paediatric use; they lead to pain at injection site and stress on children. The sublingual route should be a good compromise between stress and quick efficiency. We have developed a sublingual tablet of midazolam. The aim of the present investigation is to compare the pharmacokinetic parameters of midazolam tablets administered by the sublingual and intravenous routes in 6 rabbits to determine the bioequivalence between these routes. We have estimated the 1-hydroxy-midazolam serum level by difference between RRA and HPLC values. By the sublingual route, midazolam absorption is substantial and fast. The statistical analysis, on data obtained with HPLC dosage, shows no significant difference between pharmacokinetic parameter values calculated after intravenous and sublingual administration (0.5 mg). The absolute bioavailability was close to 100%. With RRA dosage, however, AUCs were greater than those obtained by HPLC dosage (174%). 1-hydroxy-midazolam seems to have a great importance in BZD activity. To estimate the bioequivalence between intravenous and sublingual midazolam administration, it is necessary to take into account the active metabolites.

Administration, Sublingual↗
PubMedDate not supplied

In vitro effects of spiramycin and dirithromycin on IL1 beta production by human LPS-stimulated mononuclear cells.

Polymorphonuclear neutrophils are the predominant cells in acute inflammatory lesions and their functions and recruitment are regulated by cytokines, including IL1, TNF and IL8. Antibiotic modulation of inflammatory effects has stimulated investigations of antibiotics for their potential activity as immunomodulators over their primary bactericidal or bacteriostatic activities. This study reports the influence of macrolides, spiramycin and dirithromycin on IL1 beta production. Mononuclear cells, isolated from healthy human volunteers, were preincubated with macrolides (0.1 to 500 micrograms/ml) and stimulated by Escherichia coli lipopolysaccharide. Then, IL1 beta production was detected by western blotting analysis. At therapeutic concentrations, dirithromycin and spiramycin seemed to enhance IL1 beta production by LPS-stimulated cells, with +37 per cent and +28 per cent at 1 microgram/ml respectively. At supratherapeutic concentrations, these drugs seemed to inhibit IL1 beta production through protein kinase C inhibition, with inhibitory concentrations 50 per cent of 378 micrograms/ml for dirithromycin and 234 micrograms/ml for spiramycin. So, macrolides may modulate the host defence system through their influence on cytokine production.

Anti-Bacterial Agents↗
PubMedDate not supplied

Compatibility study of 5-fluorouracil with PVC bags after repackaging into two types of infusion admixtures.

The stability and compatibility of 5-fluorouracil (5-FU) in admixtures for continuous intravenous infusion using PVC bags and administration sets were studied. 5-fluorouracil was reconstituted and diluted to 1.8 mg/ml for infusion in polyvinyl chloride and glass containers, and to 1 mg/ml to 16 mg/ml for storage in polyvinyl chloride bags containing 5 per cent dextrose or 0.9 per cent sodium chloride injections. Admixtures were stored at +4 degrees C and with protection from light, for 7 days. Analyses were performed by HPLC. No significant drug loss was observed during simulated infusions using PVC infusion bags and administration sets vs glass bottles and administration sets, over an infusion period used in hospitals (24 h). The solution stored at +4 degrees C with protection from light in PVC bags showed that at 1 mg/ml to 16 mg/ml, 5-fluorouracil was stable at least for 7 days in 0.9 per cent sodium chloride and 5 per cent dextrose.

Antimetabolites, Antineoplastic↗
PubMedDate not supplied

Indomethacin distribution in acute pharmacological response among rats.

A detailed examination of quantitative relationships of pharmacological action with plasma and tissue concentrations of indomethacin has been undertaken in the rat, after single oral administration of two sustained release preparations. In this study, drug was assayed by high performance liquid chromatography, whereas antiinflammatory response was assessed through the carrageenin-induced edema test. Significant linear correlations (p less than 0.001) were found between logarithmically transformed percent inhibition of edema and logarithmically transformed plasma, as well as tissue levels of indomethacin. However, the lack of significance for partial correlation regarding tissue concentration, contrary to plasma concentration, suggests that pharmacological response is more closely related to the latter, indicating that antidematous effect is mediated via the circulating drug rather than a local action in target tissues. This assumption is further discussed from the equivalence point of view. The relevance of this type of study in the case of topical administration of indomethacin is addressed as well. Taking into account the predictive value of the rat paw edema test for clinical efficacy, relationships similar to those observed are to be expected in man. The high correlation existing between plasma concentration of indomethacin and its pharmacological effect justifies the development and use of sustained release preparations in order to improve the outcome of treatment with this nonsteroidal antiinflammatory drug.

Animals↗
PubMedDate not supplied

Amisulpride evaluation by radioreceptor assay comparison with HPLC procedure after single administration in the rabbit.

A radioreceptor assay (RRA) was developed to determine plasma levels of amisulpride. In in vitro binding conditions, the RRA technique was sensitive (11.6 nmol/l) and reliable, with a high degree of precision. The reproducibility of the method through statistical coefficients was < 7%. This method was applied to a pilot pharmacokinetic study in rabbits following single i.v. administration of amisulpride at 10 mg/kg. The results obtained were compared with those obtained by high performance liquid chromatography method (HPLC) in order to assess the validity of this new RRA technique.

Amisulpride↗
PubMedDate not supplied

Decrease of hypochlorous acid and hydroxyl radical generated by stimulated human neutrophils: comparison in vitro of some thiol-containing drugs.

Among reactive oxygen species generated by human neutrophils during inflammatory disorders, hypochlorous acid and hydroxyl radical are especially involved in many diseases such as arteriosclerosis or emphysema. It was shown in vitro that two thiol-containing drugs, mesna and N-acetylcysteine, have antioxidant properties towards these oxidants. The 50% inhibitory concentrations (IC50s) of mesna and N-acetylcysteine for hypochlorous acid production by stimulated neutrophils were 29 and 30 mcM, respectively, and for hydroxyl radical production, IC50s were 520 and 480 mcM, respectively. With this in vitro demonstrated effectiveness, both mesna and N-acetylcysteine have been considered as therapeutic antioxidants to decrease tissue damage inflicted by an excess of activated neutrophils by scavenging hypochlorous acid and hydroxyl radical.

Acetylcysteine↗