Biomedical subjects

M Cazin

Publications and source records attributed to M Cazin.

At least 55 records · Page 3Linked to original sources

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

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↗

PubMed1990

Effects of anaerobiosis upon morphology and energy metabolism of alveolar macrophages cultured in gas phase.

Metabolic and morphological effects of anoxia were studied in alveolar macrophages obtained by lung lavage from guinea-pigs by means of an original method of cell culture allowing direct contact with air without interposition of liquid medium. After selection by glass adherence, alveolar cells were layered on a porous membrane applied to the surface of a reservoir filled with nutrient medium. Alveolar macrophages were then cultured in gas phase under either aerobic or anaerobic conditions for 24, 48 and 72 h. Cellular adenosine triphosphate (ATP) content, an indicator of cell vitality, significantly decreased by 68 and 88% after 48 and 72 h of exposure to anaerobic environment, respectively. Significant increases in lactate production (68% at 24 h) and in glucose uptake (125% at 24 h), evidence of marked glycolytic activity, occurred before these falls in intracellular ATP and parallel decreases in culture medium pyruvate level (76 and 85% at 48 and 72 h, respectively). The shift of energy metabolism resulted in cell death after 72 h, as noted by morphological degeneration and decreased cellular ATP content. Twenty-four hour re-exposure to normoxic atmosphere showed that recovery was possible when duration of anaerobiosis did not exceed 48 h. This reversibility in anoxic cell injury has been related to plasma membrane integrity. The results of these studies indicate that alveolar macrophage resistance to anaerobiosis is limited as ATP content falls and morphological degeneration occurs after 48 h. This novel approach of anaerobic effects at the cell level should be adaptable to investigations of activity and, in particular, the mechanisms of metabolic activity of antianoxic drugs.

Adenosine Triphosphate↗

PubMed1989

Pharmacological activity, blood and tissue levels of indomethacin after single oral administration of two long-acting forms in the rat.

The duration of pharmacological action in the rat (carrageenin edema inhibition) of a long-acting indomethacin form (Dolcidium PL) was compared to that of a reference long-acting indomethacin form after a single oral dose (3 mg/kg) considered as the ED50 value and compatible with clinical use. Kinetic comparison of both forms was achieved in the blood and at the level of the inflammatory site. There was an identical bioavailability, but the rate of indomethacin release from the test preparation was significantly slower than that of the reference form. Greater pharmacological potency and significantly longer duration of action were also demonstrated for the former, indicating that this novel formulation exhibited better sustained release characteristics than the reference form, and thus exerted an optimal pharmacological effect (over 24 hr). Since there is a high degree of correlation of clinical efficacy with potency in the rat foot edema test, better effectiveness of Dolcidium PL should be expected in man. The reduction in peak plasma level of indomethacin should improve its tolerability as well.

Administration, Oral↗

PubMed1988

Use of alveolar macrophages in antianoxic drug studies.

Alveolar macrophages are able to adapt their energy metabolism to very difficult survival conditions. Gaseous phase culture is adaptable to alveolar macrophages because it reproduces in vitro conditions very similar to in vivo conditions. It is easy to modify the incubation gas composition for hypoxia and anaerobiosis. Metabolic changes and cell injury were evaluated in three studies carried out after 24 hr of gaseous phase culture in normoxia and in anaerobiosis with a possible treatment with 0.01 microgram/ml vincamine: 1) ATP content assay by bioluminescence, the witness of cell vitality which decreases significantly in anaerobiosis; 2) Lactate assay which shows the metabolism derivation towards the anaerobic pathways; and 3) Tritiated deoxyglucose (DOG) incorporation, which shows glucose requirements after hypoxic incubation, maintaining or recovering a certain level of energetic activity. This incorporation greatly increases after anaerobic culture. Vincamine has no activity in normoxia. The three parameters are not significantly different from control, but in anaerobiosis, vincamine reveals an interesting protective effect. ATP content decreases under treatment and DOG incorporation increases. This demonstrates that vincamine is able to maintain cell metabolic activity for a longer period of time after the beginning of hypoxic trial. Cells can better use their energy storage and the metabolic pathways which enable them to restore themselves, thanks to vincamine treatment. It has been shown that cell membrane integrity was preserved by tests using cytochalasin B. DOG was not incorporated by cells treated with cytochalasin B after 24 hr of anaerobic culture and normally incorporated by control cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1987

A study of the effect of decimal and centesimal dilutions of arsenic on the retention and mobilization of arsenic in the rat.

Having developed a pharmacokinetic method for studying the fate of orally administered arsenious anhydride by a radioactive tracer method, the influence of Hahnemannian dilutions of arsenicum album on the elimination and retention of this toxin in the rat was then investigated. The effects of centesimal (cH) and decimal (dH) dilutions were studied. All the dilutions studied were found to be active. The strongest effects were observed after the administration of dilutions corresponding to a concentration of 10(-14) (14dH and 7cH). Overall, the decimal dilutions augmented the elimination of arsenic more than the centesimals. The observed results were submitted to mathematical analysis. A mathematical model, which confirms that Hahnemannian dilutions have biological effects which are a direct function of the degree of dilution, was developed.

Administration, Oral↗

PubMed1986

Chemical and pharmacological studies of 2-(amino-methyl)acrylophenones.

The structure-activity relationships of nine products of the acrylophenone family have been studied. In a previous report 2-(4-methyl-1-piperazinylmethyl)acrylophenone was shown to be an antimicrotubular drug. The effects of these drugs on the bovine brain tubulin polymerization were determined by a turbidimetric assay. The median inhibitory concentrations (ID50) ranged from 1.5 X 10(-5) to 5 X 10(-5) mol/l. Their action on the inhibition of 3H-colchicine binding to tubulin was determined by DEAE (diethylaminoethyl)cellulose filter assay. These compounds are weak inhibitors of colchicine binding. Pharmacological studies of these drugs revealed a strong inhibition of the human ADP-induced platelet aggregation. Moreover, they markedly decreased the serum cholesterol, triglycerides and phospholipids levels of rats after injection of Triton WR 1339 (4-(1,1,3,3-tetramethylbutyl)phenol polymer with formaldehyde and oxirane). They inhibited Candida albicans, Penicillium notatum and Aspergillus versicolor growth. Thus, these nine compounds possess interesting pharmacological properties which are very likely to be related to the acrylic moiety of the molecules.

Acrylates↗

PubMed1985

Effect of diabetogenic action of streptozotocin on rat serum lipoproteins.

After studying the diabetogenic action of streptozotocin in rats on adipose tissue cellularity, the authors attempted to demonstrate the influence of streptozotocin on cholesterol and phospholipid composition of the different serum lipoproteins. Intravenous injection of that antibiotic induced in rats a diabetes which appears at the latest on about the third day and finally remains at a fixed value at about the second week. All very low density lipoproteins (VLDL) are increased, which is not surprising since diabetes induces a hypertriglyceridemia and VLDL are triglyceride carriers. On the other hand, high density lipoproteins (HDL) are decreased, so that we can ask the question: Is HDL decrease due to diabetes or as a result of hypertriglyceridemia?

Animals↗