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M Lhermitte

Publications and source records attributed to M Lhermitte.

At least 37 records · Page 2Linked to original sources
PubMed2001

In-vitro analysis of the contribution of CYP2D6.35 to ultra-rapid metabolism.

From 10 to 30% of CYP2D6 ultra-rapid metabolizers of Caucasian origin harbor alleles with duplicated or amplified functional CYP2D6 genes. Recently, the CYP2D6*35 allele has been reported to be more frequent in ultra-rapid metabolizing subjects than in extensive metabolizers, suggesting a possible role of this variant in CYP2D6 duplication-negative ultra-rapid metabolizing subjects. In this study, we examined the functional consequences of the Val11Met, Arg296Cys and Ser486Thr amino acid substitutions associated with the CYP2D6*35 on the expression and catalytic activity of the variant enzyme, heterologously expressed in yeast. Our results indicate that the functional activity and level of expression of recombinant CYP2D6.35 are comparable with those of the wild-type enzyme, thus precluding the hypothesis that the high level of enzyme activity in CYP2D6 duplication-negative ultra-rapid metabolizing subjects is a consequence of the expression of a more catalytically effective CYP2D6.35 enzyme.

Alleles↗
PubMed2000

Valproic acid intoxication identified by 1H and 1H-(13)C correlated NMR spectroscopy of urine samples.

Analysis of biological fluids by proton and carbon nuclear magnetic resonance spectroscopy (1H and 13C NMR) is a promising tool in clinical biology. We used this method for rapid toxicological screening in the case of two suicide attempts. For each case, a urine sample was analysed at 300 MHz by 1D and 2D sequences (TOCSY and HMBC) in a short experimental time. Quantification was performed by peak integration on the 1D 1H NMR spectrum. For the two patients, results showed the same resonances of the major metabolite, valproyl-O-glucuronide at concentrations of 121 and 44 mmol/l.

Adolescent↗
PubMed2000

Increase in endogenous brain superoxide dismutase as a potential mechanism of lipopolysaccharide-induced brain ischemic tolerance.

A low dose (0.5 mg/kg) of lipopolysaccharide (LPS), administered 72 hours before 60-minute middle cerebral artery occlusion, induced a delayed neuroprotection proven by the significant decrease (-35%) of brain infarct volume in comparison with control, whereas infarct volumes remained unchanged in rats treated 12, 24, or 168 hours before ischemia. This delayed neuroprotective effect of LPS was induced only with low doses (0.25 to 1 mg/kg), whereas this effect disappeared with a higher dose (2 mg/kg). The delayed neuroprotection of LPS was induced in the cortical part of the infarcted zone, not in the subcortical part. The beneficial effect of LPS on consequences of middle cerebral artery occlusion was suppressed by dexamethasone (3 mg/kg) and indomethacin (3 mg/ kg) administered 1 hour before LPS, whereas both drugs had no direct effect on infarct volume by themselves, suggesting that activation of inflammatory pathway is involved in the development of LPS-induced brain ischemic tolerance. Preadministration of cycloheximide, an inhibitor of protein synthesis, also blocked LPS-induced brain ischemic tolerance suggesting that a protein synthesis is also necessary as a mediating mechanism. Superoxide dismutase (SOD) could be one of the synthesized proteins because lipopolysaccharide increased SOD brain activity 72 hours, but not 12 hours, after its administration, which paralleled the development of brain ischemic tolerance. In contrast, catalase brain activity remained unchanged after LPS administration. The LPS-induced delayed increase in SOD brain content was suppressed by a previous administration of indomethacin. These data suggest that the delayed neuroprotective effect of low doses of LPS is mediated by an increased synthesis of brain SOD that could be triggered by activation of inflammatory pathway.

Adaptation, Physiological↗
PubMed1999

Colchicine poisoning: report of a fatal case with body fluid and post-mortem tissue analysis by high-performance liquid chromatography.

A case involving a suicide by the ingestion of colchicine tablets is presented. Liquid chromatography has been used to measure the drug level in blood and in post-mortem tissues of the patient (a 42-year-old man). Plasma concentration 24 h after ingestion was 4.5 ng/mL. On autopsy, the kidney showed the highest concentration (396 ng/g). High concentrations were also found in the liver (347 ng/g) and heart (334 ng/g). Low concentrations were detected in the lung (58 ng/g), muscle (10 ng/g) and brain (5 ng/g).

Adult↗
PubMed1999

[Analysis of two cases of valproic acid intoxication by 1H NMR spectroscopy and gas chromatography/mass spectrometry].

Analysis of urine samples from two poisoned patients was performed using proton nuclear magnetic resonance (1H NMR) spectroscopy and a classical GC/MS protocol. Valproic acid as its glucuronide was identified and quantified in the 1H NMR spectra recorded directly from 0.5 mL of the collected samples. Moreover, a significant lactic aciduria could be observed. Comparison with the GC/MS findings suggests that 1H NMR spectroscopy can be clinically useful.

Acidosis, Lactic↗
PubMed1999

[Hepatonephritis and massive ingestion of buprenorphine].

We present a case of a severe hepatitis associated with acute renal failure and anuria consequently to the ingestion of 112 mg of buprenorphine, 48 hours before. The normalisation of hepatic and renal functions is associated with discontinuation of buprenorphine administration and hemodialysis treatment. Buprenorphine seems to be directly responsible for this hepatonephritis as indicated by the high plasmatic levels of buprenorphine (224 ng/ml) and norbuprenorphine (30 ng/ml) never described until now. Buprenorphine toxicity could be due to the inappropriate ingestion mode (oral instead of sublingual) and could be increased by previous acetaminophen intake.

Acute Kidney Injury↗
PubMed1999

[Identification and quantitative determination of chlorinated++ solvents after solid phase microextraction. Applications in hospital toxicology].

A simple method for the research and the identification of chlorinated solvents in biological fluids and tissues is described. The solvents are extracted using headspace solidphase microextraction and detected or measured by gas chromatography with electron capture detector. Three accidental poisonings are reported: one with carbon tetrachloride, one with trichlorethylene and the last one is a double intoxication with tetrachloroethylene and trichlorethylene.

Chromatography, Gas↗
PubMed1999

[Identification and quantification of exogenous metabolites in biological liquids with new development in NMR spectroscopy in one and two dimensions].

By comparison of urine 1H NMR spectrum from a healthy person with those from poisoned patient, we have displayed one or several signals related to intoxication. In complement, various 1H and 13C NMR sequences in 1 and 2 dimensions (J-resolved, TOCSY, HMBC) were used to identify xenobiotic metabolites and quantify them in urine from patients poisoned with salicylate acetyl, chloroquine, valproïc acid, ethylene glycol and pesticides. NMR techniques provide a rapid determination on a small sample volume without pretreatment.

Adolescent↗
PubMed1998

Poisoning with methanol and ethylene glycol:1H NMR spectroscopy as an effective clinical tool for diagnosis and quantification.

Analysis of serum and urine samples from three patients in a metabolic acidotic state was performed using biochemical methods and proton nuclear magnetic resonance (1H NMR). Methanol and ethylene glycol were identified by their singlet peaks in the 1H NMR spectra recorded directly from 0.5 ml of the collected samples. Quantification of these compounds was obtained simultaneously with that of their metabolites, formate and glycolate respectively and of lactate and ethanol, the latter being used as an antidote. The NMR results were found to be very similar to the biochemical findings. The results presented here suggest that 1H NMR can be clinically useful since it quickly provides information on the onset of metabolic acidosis and on the biotransformation of xenobiotics.

Acidosis↗
PubMed1998

Genotypic and phenotypic analysis of the polymorphic thiopurine S-methyltransferase gene (TPMT) in a European population.

1. Characterization of allelic variants of the TPMT gene (TPMT) responsible for changes in TPMT activity, and elucidation of the mechanism by which these alleles act, are required because of the clinical importance of this polymorphism for patients receiving thiopurine drugs. 2. We defined the mutational and allelic spectrum of TPMT in a group of 191 Europeans. Using PCR-SSCP, we screened for mutation the entire coding sequence, the exon-intron boundaries, the promoter region and the 3'-flanking region of the gene. Six mutations were detected throughout the ten exons and seven TPMT alleles were characterized. Four of them, TPMT*2, *3A, *3C and *7, harbouring the known mutations, G238C, G460A, A719G or T681G, were nonfunctional and accounted for 0.5, 5.7, 0.8 and 0.3% of the allele totality, respectively. 3. Within the promoter region, six alleles corresponding to a variable number of tandem repeats (VNTR), were identified. VNTR*V4 and *V5a which harbour four or five repeats of a 17-18 bp unit, were the most frequent (55% and 34%, respectively). The other VNTR alleles, having from five to eight repeats, were rarer. 4. The TPMT phenotype was correctly predicted by genotyping for 87% of individuals. A clear negative correlation between the total number of repeats from both alleles and the TPMT activity level was observed, indicating that VNTRs contribute to interindividual variations of TPMT activity. Therefore, additional analysis of the promoter region of TPMT can improve the phenotype prediction rate by genotyping.

Alleles↗
PubMed1998

Prevalence of drugs of abuse in urine of drivers involved in road accidents in France: a collaborative study.

The collaborative, anonymous, case-control study was intended to determine the prevalence of opiates, cocaine metabolites, cannabinoids and amphetamines in the urine of drivers injured in road accidents and to compare these values with those of non-accident subjects ("patients") in France. Recruitment was performed nationwide in the emergency departments of five hospitals and comprised 296 "drivers" aged 18 to 35 and 278 non-traumatic "patients" in the same age range. Females represented 28.4% of "drivers" and 44.2% of "patients." Screening for drugs in urine was performed by fluorescence polarization immunoassays in each center. Each positive result was verified using gas chromatography-mass spectrometry (GC-MS), in a single laboratory. Statistical analysis comprised single-step logistic regression and simultaneously took account of confounding factors and the final differences in prevalence values between the two populations or different subgroups. Cannabinoids were found in 13.9% of drivers (16.0% of males and 8.3% of females, p < 0.05) and 7.5% of patients (12.3% of males, 1.6% of females, p < 0.0001); only in females was this prevalence higher in injured drivers than in patients (p < 0.05). Opiates were present in 10.5% of drivers' and 10.4% of patients' urine samples (NS), and were more frequent in urine samples positive for cannabinoids, in drivers (p < 0.01) as well as in patients (p < 0.001). The prevalence of cocaine metabolites in drivers and patients was 1.0 and 1.1% and that of amphetamines 1.4 and 2.5%, respectively. No causal relationship between drugs and accidents should be inferred from this retrospective study. Nevertheless, the high prevalence of cannabis and opiate (licit or illicit) use in young people, whether injured drivers or patients, has potential implications for road traffic safety in France. Cocaine and amphetamines did not appear to be a major problem, unlike the experience in other countries.

Accidents, Traffic↗
PubMed1997

1H-NMR analysis of trimethylamine in urine for the diagnosis of fish-odour syndrome.

This paper reports the use of proton NMR spectroscopy for the analysis of trimethylamine in the urine of a patient with trimethylaminuria. Analysis of this compound was also performed for other members of his family. Qualitative and quantitative determination of trimethylamine and trimethylamine-N-oxide was simultaneously performed on untreated urine within a few minutes. The application of the method is discussed.

Amine Oxidase (Copper-Containing)↗
PubMed1997

Diagnosis of a case of acute chloroquine poisoning using 1H NMR spectroscopy: characterisation of drug metabolites in urine.

Analysis of biological fluids by proton nuclear magnetic resonance spectroscopy (1H NMR) is a promising tool in clinical biology. We have used this method for a rapid toxicological screening in the case of a suicide attempt. A urine sample was analysed at 300 and 600 MHz by 1D and 2D sequences (J-resolved and TOCSY) in a short experimental time. Quantification was realized by peak integration of the 1D spectrum. The results showed the presence of chloroquine and its major metabolite monodesethylchloroquine at concentrations of 462 and 140 mg/L, respectively. Ethanol was also detected in the spectrum. It can be concluded that 1H NMR provides many advantages as a tool for clinical diagnosis in a case of acute intoxication.

Acute Disease↗
PubMed1997

1H NMR investigation of toxic effects of lindane and paraquat on Hep 3B and Hep G2 human hepatoma cell lines.

Lindane and paraquat induce biochemical changes in the liver. In order to specify their molecular impact at the cellular level, a 300 MHz 1H NMR investigation of hepatoma cell lines Hep 3B and Hep G2 responses was performed. Cells were exposed over 24 h to 50 mg/L lindane (0.178 mM) or to 100 mg/L (0.389 mM) paraquat concentrations. The main observation following exposure to lindane was a decrease in betaine methyl groups (3.26 ppm) which could be related to the steatosis reported by some authors. Specifically, in Hep G2 cells with this pesticide, the glycine peak (3.56 ppm) was lowered, thus confirming that the glycine synthesis pathway involving methionine, choline, and betaine was disturbed by lindane. Moreover, in this hepatoma cell line, the p-chlorobenzoate ion could be detected as a doublet at 7.55 ppm. In Hep 3B cells, paraquat increased betaine and methionine levels, suggesting disturbance in glycine biosynthesis. Possibilities of cellular uptake were considered, and the presence of this herbicide in cells was revealed by spectrophotometric and NMR measurements after chlorhydric hydrolysis, suggesting interaction with cellular components. The impact of paraquat on Hep G2 cells appeared to be located on mitochondrial function, as indicated by the observed decrease in succinate and pyruvate levels.

Adenosine Triphosphate↗
PubMed1997

Structures of sulfated oligosaccharides isolated from the respiratory mucins of a non-secretor (O, Le(a + b -)) patient suffering from chronic bronchitis.

Mucin glycopeptides were prepared from the respiratory mucus of a non-secretor, chronic bronchitic patient with blood group O, Le(a + b-). Oligosaccharides were released by alkaline borohydride treatment and purified by anion-exchange chromatography, size-exclusion chromatography and high performance anion-exchange chromatography. Structural studies employed 400-MHz 1H-NMR spectroscopy and matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS). Nine monosulfated oligosaccharides ranging in size from tetra- to hexasaccharide, were fully characterized in this study. The sulfate group occurs either on the C-3 of a terminal galactose residue or on the C-6 of a N-acetylglucosamine residue. In keeping with the non-secretor status of the patient, no structure with an (alpha 1-2)-linked fucose residue was found. Five of the structures had fucose present in (alpha 1-3)-linkage in the X determinant, while only one oligosaccharide (compound 7b) was seen with fucose (alpha 1-4)-linked in the Le(a) determinant. Eight structures isolated from the mucins of the non-secretor patient had not been found previously in the respiratory mucins; they are listed below.

ABO Blood-Group System↗