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Biomedical subjects

M Luyckx

Publications and source records attributed to M Luyckx.

At least 19 recordsLinked to original sources
PubMed1995

Scavenging of reactive oxygen species by letosteine, a molecule with two blocked-SH groups. Comparison with free-SH drugs.

Acute production of reactive oxygen species by polymorphonuclear neutrophils during the respiratory burst may induce tissue injuries. In this in vitro study, it was demonstrated that letosteine, a mucolytic agent containing two blocked thiol groups, had antioxidant activity, but only when it was first submitted to alkaline hydrolysis. In a cell-free system, hydrogen peroxide, hypochlorous acid and hydroxyl radical concentrations were reduced by half by letosteine concentrations of 200, 15 and 350 mumol/l, respectively. The mechanism of letosteine action may be related to the -SH group liberated in vitro by hydrolysis, which seemed to react by scavenging the reactive oxygen species in the same way as acetylcysteine and MESNA, free-thiol drugs known for their antioxidant properties. So, letosteine, a compound with blocked -SH groups which in vivo can metabolically become free, may have a therapeutic application in preventing oxidative tissue injury damage induced by the respiratory burst.

Acetylcysteine↗
PubMed1995

High-performance liquid chromatographic method for the determination of budesonide in bronchoalveolar lavage of asthmatic patients.

A simple, sensitive and selective method for the determination of budesonide in bronchoalveolar lavage (BAL) using high-performance liquid chromatography (HPLC) with UV detection was developed. BAL samples were extracted twice with methylene chloride, the extracts were centrifuged and the organic layer separated and dried under nitrogen. The samples were reconstituted in the mobile phase and 80 microliters were injected on to a Spherisorb ODS column with UV absorbance detection at 250 nm. The mobile phase was methanol-aqueous buffer (69:31, v/v). Inter-assay coefficients of variation were measured at 7.81 and 500 ng/ml with ranges of 0.89-7.31%. Average recoveries were 97% or greater. This method was successfully implemented for the analysis of BAL from asthmatics, in order to establish the amount of budesonide available to the lung and to investigate the efficacy of inhaler systems. Patients (n = 9) inhaled four puffs of 200 micrograms of budesonide and BAL was performed 10 min after the last inhalation. Only four BAL out of the nine presented detectable amounts of budesonide. The concentrations in BAL in these four patients were 13.44-84.18 ng/ml, corresponding to total amounts of 0.847-7.997 micrograms.

Administration, Inhalation↗
PubMed1995

Stability, compatibility and plasticizer extraction of miconazole injection added to infusion solutions and stored in PVC containers.

The stability of miconazole in various diluents and polyvinyl chloride (PVC) containers was determined and the release of diethylhexyl phthalate (DEHP) from PVC bags into intravenous infusions of miconazole was measured. An injection formulation (80 ml) containing a 1% solution of miconazole with 11.5% of Cremophor EL was added to 250-ml PVC infusion bags containing 5% glucose injection or 0.9% sodium chloride injection, to give an initial nominal miconazole concentration of 2.42 mg ml-1, the mean concentration commonly used in clinical practice. Samples were assayed by stability-indicating high-performance liquid chromatography (HPLC) and the clarity was determined visually. Experiments were conducted to determine whether the stability and compatibility of miconazole would be compromised, and whether DEHP would be leached from PVC bags and PVC administration sets during storage and simulated infusion. There was no substantial loss of miconazole over 2 h simulated infusion irrespective of the diluent, and over 24 h storage irrespective of temperature (2-6 degrees C and 22-26 degrees C). All the solutions initially appeared slightly hazy. Leaching of DEHP was also detected during simulated delivery using PVC bags and PVC administration sets. There was a substantial difference between the amounts of DEHP released from PVC bags and from administration sets, and also between the amounts released in solutions stored in PVC bags at 2-6 degrees C and 22-26 degrees C over 24 h. At the dilution studied, miconazole was visually and chemically stable for up to 24 h. The storage of miconazole solutions in PVC bags seems to be limited by the leaching of DEHP rather than by degradation. To minimize patient exposure to DEHP, miconazole solutions should be infused immediately after their preparation in PVC bags.

Antifungal Agents↗
PubMed1994

Stability and compatibility studies of cephamandole nafate with PVC infusion bags.

A rapid isocratic technique was developed for the analysis of cephamandole nafate and cephamandole in parenteral solutions using high-performance liquid chromatography (HPLC) with UV detection and C18 column. The availability and compatibility of drugs from solutions infused via plastic infusion bags through plastic administration sets have been examined. No significant drugs loss was observed during simulated infusions (n = 4) for 1 h using PVC infusion bags and administration sets. No significant difference was found between infusion solutions (5% glucose or 0.9% NaCl). The stability of drugs was also studied in solution in PVC bags after storage at room temperature and at 4 degrees C without protection from light. The results show the stability of cephamandole nafate during 24 h at room temperature and 7 days storage at 4 degrees C to be satisfactory, irrespective of the infusion solution (5% glucose or 0.9% NaCl). However, an almost immediate and total transformation of cephamandole nafate to cephamandole in 5% glucose has been observed, whereas in 0.9% NaCl both forms were found in similar proportions.

Calibration↗
PubMed1994

Stability and compatibility of cisplatin and carboplatin with PVC infusion bags.

The availability and compatibility of drugs from solutions infused via PVC infusion bags through PVC administration sets have been examined. No significant drug loss was observed during simulated infusions using PVC infusion bags and administration sets over time periods used in hospitals (cisplatin, 2 h; carboplatin, 1 h). The stability of carboplatin was studied in 5% dextrose. In 0.9% NaCl, we observed that carboplatin could be converted to cisplatin in the presence of chloride ions. With cisplatin, no significant difference was found between infusion solutions (5% dextrose or 0.9% NaCl). The stability of cisplatin (5% dextrose or 0.9% NaCl) and carboplatin (5% dextrose) was also studied in PVC bags after storage in the dark at room temperature. The results show that the drugs were stable over the 9-day storage period studied.

Biocompatible Materials↗
PubMed1994

Protective role of glutathione on alpha 1 proteinase inhibitor inactivation by the myeloperoxidase system. Hypothetic study for therapeutic strategy in the management of smokers' emphysema.

In smoking subjects with obvious emphysema, the interaction between neutrophil-derived MPO and H2O2 produced by alveolar inflammatory cells (alveolar macrophages (AM) and polymorphonuclear neutrophils (PMN)) has the ability to spontaneously inactivate, in vitro, the alpha 1 proteinase inhibitor (alpha 1PI). This inactivation can induce a desequilibrium of the protease-antiprotease balance in the lungs. In this study, we investigated the ability of glutathione to protect alpha 1PI. In a cellular model of alpha 1PI inactivation mimicking the effects of alveolar inflammatory cells present in the lower respiratory tract of smoking patients with emphysema, we demonstrated that glutathione can protect alpha 1PI against the oxidative inactivation by these activated cells. This protection has been computed in a cellular experimentation (AM and MPO-system) with a 50% inhibitory concentration of 62 microM. Moreover, glutathione has an important inhibitory effect directly on H2O2 released by PMA-stimulated AM (IC50 = 30 microM) or PMA stimulated PMN (IC50 = 70 microM). The mechanism, which governs glutathione may be a result of a scavenging effect on H2O2 as demonstrated in a free cellular experiment. With this in vitro demonstrated effectiveness, glutathione as a therapeutic antioxidant, via the aerosol, has been proposed, in order to prevent tissue damage, inflicted by an excess of activated phagocytic cells, in some lung diseases such as smoking patients with emphysema.

Glutathione↗
PubMed1994

A rapid density gradient technique for separating polymorphonuclear granulocytes.

A gradient separation technique followed by isotonic ammonium chloride haemolysis was compared with two methods for the isolation of polymorphonuclear neutrophils from blood. This technique provided a high yield, excellent purity without lymphocyte and erythrocyte contamination, and made it possible to isolate more than 50 x 10(6) human neutrophils from 15 ml of blood. The polymorphonuclear neutrophils isolated in this way were capable of generating a large amount of reactive oxygen species. This technique for the separation of polymorphonuclear neutrophils is an effective method for in vitro studies.

Cell Separation↗
PubMed1994

Pro-oxidant properties of methotrexate: evaluation and prevention by an anti-oxidant drug.

Polymorphonuclear neutrophils (PMNs) have the ability to liberate large amounts of reactive oxygen species like hydrogen peroxide. This free radicals release may have beneficial effect in chemotherapy but may also lead to cytotoxicity in case of prolongated inflammatory reaction. This in vitro study demonstrates that methotrexate (MTX), an anticancer drug, increases the amount of hydrogen peroxide released by stimulated PMNs in a dose-dependent manner with a maximum increase of 43.7% (i.e. 22 microM of hydrogen peroxide) for 500 microM of MTX. The mechanism which govern MTX reaction seems to be a result of an intracellular pro-oxidant mechanism by intervention on the oxidative metabolism of PMNs rather than a cell-free chemical interaction. Moreover, an association of MTX with mesna, an anti-oxidant drug, allowed to suppress the excess of hydrogen peroxide production. This association might be used in anticancer therapy, during oxidative burst, particularly when MTX is used in high concentrations, in order to limit toxic effects induced by free radicals.

Antioxidants↗
PubMed1994

Stability and compatibility studies of cefaloridine, cefuroxime and ceftazidime with PVC infusion bags.

A rapid isocratic technique was developed for the analysis of three cephalosporins: cefaloridine, cefuroxime and ceftazidime in parenteral solutions using high-performance liquid chromatography (HPLC) with UV detection and C18 column. The availability and compatibility of drugs from solutions infused via plastic infusion bags through plastic administration sets have been examined. No significant drugs loss was observed during the simulated infusions (n = 4) for 1 h using PVC infusion bags and administration sets. No significant difference was found between infusion solutions (5% glucose or 0.9% NaCl). The stability of drugs was also studied in solution in PVC bags after storage at room temperature and at +4 degrees C without protection from light. The results show the stability of drugs during 24 h at room temperature and 7 d storage at +4 degrees C to be satisfactory, irrespective of the infusion solution (5% glucose or 0.9% NaCl).

Ceftazidime↗
PubMed1993

Comparison of in vitro effects of two thiol-containing drugs on human neutrophils hydrogen peroxide production.

During inflammatory disorders, potentially destructive reactive oxygen species, especially hydrogen peroxide, are produced by activated phagocytic cells. It was demonstrated in vitro that mesna and N-acetylcysteine (NAC), mucolytic thiols, have antioxidant properties. An estimation was made of the 50% inhibitory concentration (IC50) of mesna and NAC for PMA-induced H2O2 production by human neutrophils, the results being 70 mcM and 77 mcM, respectively. The mechanism which governs mesna and NAC reactions results from a scavenging effect of H2O2: the calculated IC50s of this effect were 30 mcM and 42 mcM, respectively, in free cellular experimentation. The results suggest that mesna and NAC might be used as antioxidants in aerosols to prevent tissue damage inflicted by this reactive oxygen species, especially in the lungs.

Acetylcysteine↗
PubMed1992

Stability and compatibility of four anthracyclines: doxorubicin, epirubicin, daunorubicin and pirarubicin with PVC infusion bags.

A rapid isocratic technique was developed for the analysis of four anthracyclines (doxorubicin, epirubicin, daunorubicin and pirarubicin) in parenteral solutions using high pressure liquid chromatography (HPLC) with fluorescence detection and a C18 Hypersil ODS column. The availability and compatibility of these drugs from solutions infused via PVC infusion bags through PVC administration sets have been examined. No significant drug loss was observed during simulated infusions (n = 4) for 24 h using PVC infusion bags and administration sets. No significant difference was found between infusion solutions (5% glucose or 0.9% NaCl), except for pirarubicin. The reconstitution of pirarubicin in 0.9% NaCl was impossible, because we observed a precipitation of the compound in solution. The stability of the drugs was also studied in solution, in PVC bags after storage at 4 degrees C with protection from light. The results show the stability of doxorubicin, epirubicin and daunorubicin during 7 days of storage to be satisfactory, irrespective of the infusion solution (5% glucose or 0.9% NaCl). In the case of pirarubicin, the stability of the drug was satisfactory during 5 days of storage in 5% glucose, but beyond, we observed a degradation of the compound with formation of doxorubicin in the infusion solution.

Antibiotics, Antineoplastic↗
PubMed1991

Rapid determination by high performance liquid chromatography of di-2-ethylhexyl phthalate in plasma stored in plastic bags.

A rapid sensitive technique was developed for the analysis of di-2-ethylhexyl phthalate (DEHP) in plasma stored in plastic bags by using high performance liquid chromatography (HPLC) with UV detection and a Hypersil ODS column. The compound was easily and efficiently extracted with a mixture of sodium hydroxide and acetonitrile, which allowed the deproteinization of plasma samples. The recovery was greater than 95% and the intra- and inter-assay coefficients of variation were better than 6.5%. The results obtained showed that the amount of DEHP accumulated in plasma varied according to different parameters and depended on the storage conditions (time, temperature and shaking) and also on the lipid content of the stored plasma and the sterilization process of the PVC bags.

Blood Specimen Collection↗
PubMed1991

3-Thienyl- and 3-furylaminobutyric acids. Synthesis and binding GABAB receptor studies.

Baclofen (beta-(p-chlorophenyl)-GABA) is a selective agonist for the bicuculline-insensitive GABAB receptor. The search for new compounds that bind to the GABAB receptor is very important to clarify structural requirements. We report herein the synthesis and the binding studies of variously substituted 3-thienyl- and 3-furylaminobutyric acids. 4-Amino-3-(5-methyl-2-thienyl)butyric acid (5d) and 4-amino-3-(5-chloro-2-thienyl)butyric acid (5h) are potent and specific ligands for GABAB receptor. The IC50 values for the displacement of (R)-(-)-[3H]baclofen are 1.34 and 0.61 microM for 5d and 5h, respectively, as compared to 0.33 microM for baclofen.

Animals↗
PubMed1991

Pharmacokinetics of epirubicin after intravenous administration: experimental and clinical aspects.

A method is described for the extraction and determination of epirubicin and its main metabolites epirubicinol and glucuronides in plasma, using high performance liquid chromatography (HPLC) with fluorescence detection. The extraction was performed with column Sep-Pak C18, which allowed a quantitative recovery of compounds. This method was used first in studies performed in five rabbits after intravenous administration of 3 mg/kg epirubicin, and later in a cancer patient, who received 50 mg/m2 epirubicin in rapid intravenous infusion. Although not statistically significant, kinetics of epirubicin were fitted in both cases to a tri-exponential model. Common metabolites were detected in rabbits and human, particularly the glucuronides. However, kinetics of epirubicin glucuronides and epirubicinol glucuronides were very different. Production and elimination were very fast in rabbit at very low levels and were undetectable two hours after administration, while in human, elimination was slower and greater amounts were detected 1-2 h after administration. The rabbit seemed to be an interesting animal species for pharmacokinetic studies because of easy blood sampling, detection of small amounts of glucuronides and because of a good fit to tri-exponential kinetics model.

Animals↗
PubMed1990

Rapid quantitative determination of epirubicin and its metabolites in plasma using high performance liquid chromatography and fluorescence detection.

A rapid sensitive and selective isocratic technique was developed for the analysis of plasma epirubicin and three of its known fluorescent metabolites epirubicinol, 4'-O-beta-D-glucuronyl-4'-epidoxorubicin and 4'-O-beta-D-glucuronyl 1,3-dihydro-4'-epidoxorubicin, with daunorubicin as an internal standard, by using high performance liquid chromatography (HPLC) with fluorescence detection and a 'Hypersil ODS' column. The drugs were easily and efficiently extracted with a Sep-Pak C18 cartridge and the mean recoveries were greater than 85%. Intraassay and Interassay coefficients of variation (plasma samples) were better than 8.25%. An example of pharmacokinetic study obtained in a cancer patient after intravenous injection of epirubicine is described.

Chromatography, High Pressure Liquid↗
PubMed1987

Synthesis and pharmacological evaluation of gamma-aminobutyric acid analogues. New ligand for GABAB sites.

Baclofen (beta-p-chlorophenyl-GABA) is the only selective agonist for the bicuculline-insensitive GABAB receptor. We report the synthesis of new GABA analogues and baclofen analogues. In vitro, two compounds, 4-amino-3-benzo[b]furan-2-ylbutanoic acid (9g) and 4-amino-3-(5-methoxybenzo[b]furan-2-yl)butanoic acid (9h), showed an affinity for the GABAB receptor. The results obtained with racemic compounds of benzofuran structure, new for this series, and the surprising inactivity of compound 3a (4-amino-3-(4-hydroxyphenyl)butanoic acid) permit the proposal of an hypothesis for the structure-activity relationships with regard to GABAB receptor.

Animals↗