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Biomedical subjects

A Lugnier

Publications and source records attributed to A Lugnier.

At least 19 recordsLinked to original sources

Inhalation of toluene diisocyanate affects cytochrome P450 2B1 expression in rat lung.

In the lung the expression of xenobiotic-metabolizing enzymes such as cytochromes P450 (CYP) and glutathione S-transferases (GST) may be affected by inhaled pollutants. Toluene diisocyanate (TDI) is a highly volatile chemical compound known to induce a wide array of diseases in workers exposed to vapors or sprays, including respiratory allergy and asthma. We investigated the effect of inhaled TDI on expression of CYP 1A1, 2B1, 2E1, and 3A1 and of alpha-, mu-, and pi-GST in rat lung. Animals were exposed to targeted concentrations of 0.01, 0.1, or 1 ppm TDI vapors or to cleaned filtered air for 8 h. Expression of CYP and GST was analyzed 18 24 h after the end of exposure using western blotting, northern blotting, and immunohistochemistry. Constitutive levels of CYP 2B1 and 3A1 proteins were found in lung tissue from control rats, whereas CYP 1A1 and 2E1 proteins were not detectable. Animal exposure to TDI vapors neither modified CYP 3A1 protein expression, nor led to any detectable expression of CYP 1A1 or 2E1. In contrast, exposure to 1 ppm TDI induced a 40% reduction in CYP 2B1 protein levels. This decrease was associated with a 33% decrease in CYP 2B1 mRNA levels. Additionally, CYP 2B1 immunolabeling localized to ciliated epithelial cells, Clara cells, and type II alveolar cells in the lung tissue of control rats was markedly decreased in animals exposed to 1 ppm TDI. Constitutive levels of alpha-, mu-, and pi-GST proteins were found in lung tissue from control rats. Exposure to TDI had no effect on lung expression of either of the GST. In conclusion, this study clearly shows a selective decrease in CYP 2B1 expression by TDI vapors in rat lung. The contribution of CYP 2B1 to metabolize further xenobiotics is therefore altered.

Administration, Inhalation↗

Effect of toluene diisocyanate and its corresponding amines on viability and growth of human lung fibroblasts in culture.

Toluene diisocyanate (TDI) is a highly volatile chemical known to cause occupational asthma in exposed workers. TDI-induced asthma is associated with airway epithelium injury and repair, and subepithelial fibrosis. We investigated the effect of TDI and its hydrolysis products, the 2,4- and 2,6-toluenediamines (TDA), on viability and growth of human lung fibroblasts (HLFs) in culture, using a tetrazolium-based cell viability assay. The effects of increasing concentrations of each of these chemicals were evaluated on quiescent cells seeded at two densities (2500 and 5000 cells/well) and treated for 24 or 48 h. TDI (10(-4)-10(-5) mol/L, as a mixture of 80% 2,4-TDI and 20% 2,6-TDI) exhibited a partial but significant cytotoxic effect (10-24%, p<0.05) on HLFs. This effect was observed at both cell densities, and was time- and concentration-dependent. 2,4-TDA, at lower concentrations (10(-8)-10(-6) mol/L) applied for 48 h, also partially reduced HLF viability (10-15%, p<0.05), whereas it tended to trigger cell growth at concentrations higher than 10(-5) mol/L. 2,6-TDA exhibited both a cytotoxic and a proliferative effect on HLFs that depended on concentration, time of exposure and cell culture density. Significant cytotoxicity was only observed after 24 h of treatment with 10(-7)-10(-6) mol/L 2,6-TDA, and reached greater intensity in cells cultured at the highest density. In contrast, 2,6-TDA stimulated HLF growth only after 48 h of incubation at 10(-4) mol/L on cells cultured at the lowest density. Taken together, our results showed that TDI and 2,4-TDA somewhat decreased HLF viability, whereas 2,6-TDA appeared to exhibit both a cytotoxic and a growth stimulatory effect on these cells. TDI and 2,4-TDA are thus suggested to contribute to airway epithelium damage associated with TDI-induced asthma, whereas 2,6-TDA might either trigger epithelial damage or induce cell proliferation that could contribute to epithelium repair or subepithelial fibrosis.

Asthma↗

Induction of nitric oxide synthase by chlorinated pesticides (p,p'-DDT, chlordane, endosulfan) in rat liver.

The aim of this study is to investigate the effect of certain polychlorinated pesticides on the induction of rat liver Ca(2+)-independent nitric oxide synthase (NOS) and compare it with the effect of bacterial lipopolysaccharide. Our results show that endosulfan and p, p'-DDT treatment significantly increases the NOS activity while no significant induction by any route of administration was observed in the case of chlordane. Our results show therefore that a wide variety of chlorinated pesticides, which are considered as hepatic tumor promotors, can stimulate the expression of NO synthase in vivo.

Animals↗

Study of mercury content in edible mushrooms.

The influence of time and temperature of mineralisation of mushrooms was studied for mercury determination by cold vapor atomic absorption. Optimal conditions for a complete mercury recuperation were obtained using a mixture of nitric and sulphuric acid (6 ml HNO3, 4 ml H2SO4) in presence of KMnO4 (3 ml of a 0.44 M solution) at 95 degrees C for 4 h, with 1 g wet sample. The detection limit of method was 3.2 ng/g. These conditions have shown high reproductibility and accuracy.

Basidiomycota↗

Rapid method for analysis of chloroacetanilide and chloronitrophenoxyaniline herbicides by gas chromatography.

The herbicides Alachlor and Alclonifen are recently used in France for pre-emergent weed control in corn, essentially in association. For this reason, an improved method has been developed by gas chromatography for simultaneously characterising and quantifying the two herbicides. The best conditions were obtained by using a gas chromatograph equipped with an ion trap detector, and a 30 m x 0.25 mm DB-1701 fused silica capillary column. Retention times of Alachlor and Aclonifen were 12.8 and 23.2 min respectively. The limit of detection was of 2.0 ppb for each herbicide.

Acetamides↗

Determination of total mercury in estuary, lake and river sediments.

In order to improve the quality of the results in sediment analysis, the Community Bureau of Reference (BCR) of the European Communities has developed 3 sediment reference materials (CRM) from estuarine, lake and river origins. Certification of mercury content in these materials was achieved by 3 methods (cold vapor atomic absorption spectrometry, plasma emission spectrometry, neutron activation analysis with radiochemical separation). The values finally certified in the CRM estuarine, lake and river sediments are 1.77 +/- 0.06, 0.67 +/- 0.02, 1.03 +/- 0.13 mg/kg respectively.

Geologic Sediments↗

Toxicological findings after fatal amitriptyline self-poisoning.

A case of fatal self-poisoning with amitriptyline is reported. Both the drug and its metabolite nortriptyline were quantified in several post-mortem tissues and fluids, including vitreous humor. Results are discussed in the light of the existing literature.

Adult↗

Toxicological findings after fatal dextromoramide injection.

A death involving dextromoramide injection is presented. The drug was analyzed in whole blood, bile, stomach contents, kidney, brain and liver. The whole blood concentration was 1526 ng/ml. The results are compared with the existing literature.

Adult↗

Subnanogram GC/NPD method for the determination of sparteine in biological fluids.

A gas chromatographic method is presented for identification and quantification of sparteine in biological fluids using cyclizine as an internal standard. No derivation is necessary and after a single alkaline extraction, GC analysis of sparteine is achieved in less than 8 min. A subnanogram limit of detection is allowed by the use of a nitrogen phosphorous detector (NPD). This method is simple, reproducible, selective, and applicable in both clinical and pharmacokinetic studies.

Chromatography, Gas↗

[Determination of dextromethorphan and its major metabolite dextrorphan by gas chromatography].

A gas chromatography assay has been developed for the determination of dextromethorphan and dextrorphan in human fluids. Drugs are extracted with chloroform-isopropanol-n-heptane (50/17/33, v/v) form alkalinized samples using cyclizine as an internal standard, analysed using a 3 p. cent OV-17 column, and detected by selective nitrogen detection. The lower detection limits are 0.4 and 0.7 micrograms/l for dextromethorphan and dextrorphan, respectively.

Chromatography, Gas↗

Prolonged sedation with propofol in ICU patients: recovery and blood concentration changes during periodic interruptions in infusion.

Propofol (mean dose 2.85 mg kg-1 h-1) was administered for 4 days by continuous i.v. infusion for sedation in 14 agitated and restless ICU patients. This provided rapid control of the level of sedation. When the infusion was discontinued, adequate recovery with response to commands was obtained in most patients by 10 min. Recovery times and the decrease in blood propofol concentration were similar after 24, 48, 72 and 96 h of infusion. Cumulative effects, tachyphylaxis, or other untoward effects were not observed.

Adult↗

Acute voluntary intoxication by ricin.

1 A 21-year-old student ingested thirty ricin seeds in a suicidal attempt, some of which were masticated. Three hours later he developed severe diarrhoea with vomiting and abdominal cramps, followed by extracellular dehydration and circulatory collapse. 2 Biological changes included haemoconcentration. He recovered following symptomatic treatment by infusion of saline and glucose solutions. 3 Ricin was quantified by a radioimmunologic method using Iodine 125, and showed that only a small part of the ricin contained in the seeds was absorbed.

Adult↗