Biomedical subjects

C Giroud

Publications and source records attributed to C Giroud.

At least 19 recordsLinked to original sources

PubMed2002

JET quasistationary internal-transport-barrier operation with active control of the pressure profile.

Quasistationary operation has been achieved on the Joint European Torus tokamak in internal-transport-barrier (ITB) scenarios, with the discharge time limited only by plant constraints. Full current drive was obtained over all the high performance phase by using lower hybrid current drive. For the first time feedback control on the total pressure and on the electron temperature profile was implemented by using, respectively, the neutral beams and the ion-cyclotron waves. Although impurity accumulation could be a problem in steady state ITBs, these experiments bring some elements to answer to it.

Journal Article↗

PubMed2002

Discharges in the JET tokamak where the safety factor profile is identified as the critical factor for triggering internal transport barriers.

Joint European Torus discharges which demonstrate the critical role the safety factor profile, q, can play in the formation of internal transport barriers (ITB) are examined. In these discharges, the target parameters, including the E x B flows, were kept virtually the same, except for the q profile. In a discharge with a nonmonotonic q, an ITB was triggered whereas a discharge with monotone q made no such transition. Thus, there is strong evidence that the q profile was the critical factor for the triggering of an ITB. Possible interpretations of this finding are discussed.

Journal Article↗

PubMed2001

Hypothermia and undressing associated with non-fatal bromazepam intoxication.

A 42-year-old woman with a history of depression was found unconscious, lying near her car in an early autumn morning. The lower part of her body was undressed and there were multiple purple spots and excoriations on the body suggesting at first a sexual assault. On admission to the intensive care unit, she presented a hypothermia with a central temperature of 28.4 degrees C. The biological samples obtained at the hospital were analysed. Blood concentration of bromazepam was 7.7 mg/l, which is above the highest level reported till now in a case of fatal intoxication.

Adult↗

PubMed2001

Delta(9)-THC, 11-OH-Delta(9)-THC and Delta(9)-THCCOOH plasma or serum to whole blood concentrations distribution ratios in blood samples taken from living and dead people.

The recreational use and abuse of Cannabis is continuously increasing in Switzerland. Cannabinoids are very often detected alone or in combination with other drugs in biological samples taken from drivers suspected of driving under the influence of drugs. Moreover, they are also frequently found in blood specimens from people involved in various medico-legal events, e.g. muggings, murders, rapes and working accidents as well. In order to assess the influence of Cannabis exposure on man behavior and performances, it is often needed to estimate the time of Cannabis use. For that purpose two mathematical models have been set up by Huestis and coworkers. These models are based on cannabinoids concentrations in plasma. Because plasma samples are rarely available for forensic determinations in our laboratory, it could be useful to assess the time-laps since Cannabis use through these models from whole blood values. One prerequisite to the use of these models from whole blood values is the knowledge of the plasma to whole blood concentrations distribution ratios of cannabinoids. In this respect, the Delta(9)-THC, 11-OH-Delta(9)-THC and Delta(9)-THCCOOH concentrations were measured in plasma and whole blood taken from eight volunteers who smoke Cannabis on a regular basis. Cannabinoids levels were also determined in "serum" and whole blood samples taken from six corpses. The values of the plasma to whole blood distribution ratios were found to be very similar and their individual coefficient of variation relatively low suggesting that plasma levels could be calculated from whole blood concentrations taken into account a multiplying factor of 1.6. The data obtained postmortem suggest that the distribution of cannabinoids between whole blood and "serum" is scattered over a larger range of values than those determined from living people and that more cannabinoids (mean value of the serum/whole blood concentrations ratios=2.4) can be recovered from the "serum" fraction. The successful use of the mathematical models of Huestis and coworkers may, therefore, rely in part upon the selection of the appropriate blood sample, i.e. plasma. When plasma is not available, whole blood values could be considered with some caution taken into account a multiplying factor of 1.6 to calculate plasma concentrations from blood values. In the case of blood samples taken after death, the use of these models to assess the time of Cannabis use is not recommended.

Dronabinol↗

PubMed2001

Molecular characterisation of mitochondrial and cytosolic trypanothione-dependent tryparedoxin peroxidases in Trypanosoma brucei.

In trypanosomatids, removal of hydrogen peroxide and other aryl and alkyl peroxides is achieved by the NADPH-dependent trypanothione peroxidase system, whose components are trypanothione reductase (TRYR), trypanothione, tryparedoxin (TRYX) and tryparedoxin peroxidase (TRYP). Here, we report the cloning of a multi-copy tryparedoxin peroxidase gene (TRYP1) from Trypanosoma brucei brucei encoding a protein with two catalytic VCP motifs similar to the cytosolic TRYP from Crithidia fasciculata. In addition, we characterise a novel single copy gene encoding a second tryparedoxin peroxidase (TRYP2). TRYP2 shows 51% similarity to TRYP1, possesses a putative mitochondrial import sequence at its N-terminus and has a variant IPC motif replacing the second VCP motif implicated in catalysis in other 2-Cys peroxiredoxins. TRYP1 and TRYP2 were expressed in Escherichia coli, and the purified recombinant proteins shown to utilise hydrogen peroxide in the presence of NADPH, trypanothione, TRYR and TRYX from T. brucei, similar to the C. fasciculata cytoplasmic system. Western blots showed that TRYX, TRYP1 and TRYP2 are expressed in both bloodstream and procyclic forms of the life cycle. To determine the precise localisation of TRYX, TRYP1 and TRYP2 in the parasite, polyclonal antibodies to purified recombinant TRYX and TRYP1 and monoclonal antibody to TRYP2 were generated in mice. In-situ immunofluorescence and immunoelectron microscopy revealed a colocalisation of TRYX and TRYP1 in the cytosol, whereas TRYP2 was principally localised in the mitochondrion.

Amino Acid Sequence↗

PubMed2001

[Cannabis and automobile driving].

Cannabis use has increased considerably during the last 15 years. One of the major problems dealing with cannabis use is driving under the influence of drugs. With the exception of ethyl alcohol, the majority of the epidemiological studies have shown that cannabis is the most frequently detected substance in people suspected of driving under the influence of drugs. Experimental studies are therefore needed to assess cannabis effects on driving capability. Many studies indicate that cannabis impairs psychomotor performance. This impairment becomes obvious when high doses of cannabis are taken, when ethyl alcohol or other drugs are simultaneously ingested, or when sustained attention is needed. Moreover, cannabis effects are qualitatively different from those observed after ethyl alcohol consumption. In forensic practice, cannabis impairment of driving performance must be related to cannabinoids blood concentrations. To facilitate the interpretation of cannabinoids blood levels, several models were set up recently. These models must be further improved in order to fit in with all circumstances of cannabis use.

Accidents, Traffic↗

PubMed2001

Observation of zero current density in the core of jet discharges with lower hybrid heating and current drive.

Simultaneous current ramping and application of lower hybrid heating and current drive (LHCD) have produced a region with zero current density within measurement errors in the core ( r/a< or =0.2) of JET tokamak optimized shear discharges. The reduction of core current density is consistent with a simple physical explanation and numerical simulations of radial current diffusion including the effects of LHCD. However, the core current density is clamped at zero, indicating the existence of a physical mechanism which prevents it from becoming negative.

Journal Article↗

PubMed2000

Salvia divinorum: an hallucinogenic mint which might become a new recreational drug in Switzerland.

Salvia divinorum Epling & Jativa is an hallucinogenic mint traditionally used for curing and divination by the Mazatec Indians of Oaxaca, Mexico. Young people from Mexican cities were reported to smoke dried leaves of S. divinorum as a marijuana substitute. Recently, two S. divinorum specimens were seized in a large-scale illicit in-door and out-door hemp plantation. Salvinorin A also called divinorin A, a trans-neoclerodane diterpene, was identified in several organic solvent extracts by gas chromatography-mass spectrometry. The botanical identity of the plant was confirmed by comparing it to an authentic herbarium specimen. More plants were then discovered in Swiss horticulturists greenhouses. All these data taken together suggest that many attempts exist in Switzerland to use S. divinorum as a recreational drug. This phenomenon may be enhanced because neither the magic mint, nor its active compound are banned substances listed in the Swiss narcotic law.

Diterpenes↗

PubMed2000

Effects of ultraviolet light on free and peptide-bound pyridinoline and deoxypyridinoline cross-links. Protective effect of acid pH against photolytic degradation.

Little is known about the photodegradation of pyridinoline (Pyd) and deoxypyridinoline (Dpd), which are two mature cross-links stabilizing collagen within extracellular matrix. In this study, highly purified free Pyd and Dpd cross-links have been degraded by irradiation with ultraviolet light and we have shown that photolysis varies with the pH value. Assessment of photolysis in basic (pH 9) and neutral (pH 7) solutions by high-performance liquid chromatography as well as by UV absorbance measurement indicates that both cross-links are degraded after a 24 h UV exposure, while in acidic solution (pH 3) only Dpd is photolysed, suggesting that acid pH provides major protection against Pyd photolysis. Photodegradation products have been studied by amino-acid and mass spectral analysis. Both methods confirm the lack of Pyd degradation in acid pH. Furthermore, amino-acid analysis allows us to identify hydroxylysine and lysine as a result of Pyd and Dpd photolysis, respectively, indicating that the mechanism of photodegradation involves the cleavage of the pyridinium ring on each side of the quaternary nitrogen. Finally, we have also studied the photolysis of different molecular species of type I collagen peptides, obtained by digestion with collagenase of demineralized turkey bone. Our results indicate that even when they are part of the structure of collagen peptide, Pyd and Dpd can be photolysed. However, we have shown that the larger the peptide is, the smaller are the effects of UV irradiation.

Amino Acids↗

PubMed1999

Fatal flecainide intoxication.

A fatal case attributed to flecainide acetate (Tambocor), a class Ic antiarrythmic drug, is presented. Flecainide was detected by GC/MS in gastric contents, blood and liver as well. The urine analysis revealed the presence of its dealkylated metabolite. Body fluids and tissue concentrations determined by GC/ECD were 7.7 mg/kg in femoral blood, 0.26 mg/kg in bile, 18 mg/kg in liver, 0.17 mg/kg in cerebrospinal fluid, 0.22 mg/kg in brain cortex and 28.9 mg/kg in urine. The total amount of flecainide in gastric contents was about 43 mg. Even taking into account the postmortem redistribution of flecainide, its blood level still remains in the toxic range.

Aged↗

PubMed1999

Fatal overdose of tramadol and alprazolam.

A 30-year-old woman, with history of depression, was found dead after the ingestion of an unknown quantity of Xanax (alprazolam), Tramal (tramadol) and alcohol. At the autopsy only a slight decomposition and a diffuse visceral congestion were noticed. Biological samples obtained at autopsy were analysed to detect the presence of alprazolam, tramadol and alcohol. Blood concentrations of alprazolam, alcohol and tramadol were 0.21 mg/l, 1.29 g/kg and 38.3 mg/l, respectively.

Adult↗

PubMed1999

Method for quantification of morphine and its 3- and 6- glucuronides, codeine, codeine glucuronide and 6-monoacetylmorphine in human blood by liquid chromatography-electrospray mass spectrometry for routine analysis in forensic toxicology.

Simultaneous determination of opiates and their glucuronides in body fluids has a great practical interest in the forensic assessment of heroin intoxication. A selective and sensitive method for quantification of morphine and its 3- and 6-glucuronides, codeine, codeine glucuronide and 6-monoacetylmorphine (6-MAM) based on liquid chromatography-electrospray ionisation mass spectrometry is described. The drugs were analysed in human autopsy whole blood after solid-phase extraction on a C8 cartridge. The separation was performed on an ODS column in acetonitrile (analysis time 15 min). For the quantitative analysis, deuterated analogues of each compound were used as internal standards. Selected-ion monitoring was applied where the molecular ion was chosen for quantification. The limits of quantification were 0.5 ng/ml for morphine and 6-MAM and 1 ng/ml for the 6-glucuronide of morphine, codeine-6-glucuronide and codeine and 5 ng/ml for the 3-glucuronide of morphine.

Calibration↗

PubMed1999

[Brief history of recent hemp cultivation in Switzerland and subsequent medico-legal problems resulting from hemp cultivation].

In March 1995, a decision about cultivation of cannabis was issued by the Swiss Federal Offices of Public Health, Police and Agriculture in order to satisfy the growing interest of farmers and other people in hemp farming. It pointed out that 1)... each hemp plant contains THC and must be therefore considered a drug, 2)... no permission is required for those who grow hemp without the intention to produce drugs ... meaning that the choice of the plant variety was not restricted to those which are characterized by a low THC concentration and grown in a few countries belonging to the European Union. Claiming that natural hemp must contain significant amounts of THC and thanks to the Swiss legislation, areas dedicated to hemp cultivation develop considerably. Most hemp plants which are submitted to our laboratories by the police for THC quantification belong to the drug-type. Nowadays, a great deal of goods (food and beverages, cosmetics, drugs) made of hemp are marketed in Switzerland. Strong suspicions exist however that several of these products could be used as a screen for the illegal market of cannabis. For instance, despite financial support from the state, fiber hemp cultivation remains unsuccessful. No advantage with regard to seed productivity, edible seed and essential oils qualities and yields have been found for drug hemp over fiber hemp by agricultural research stations up to now. Several clues about the possible illicit use of hemp goods rich in THC, especially hemp tea made of flower tops and "therapeutic" pillows filled with cannabis exist. Recently, two Federal edits were issued in order to restrict the selling of hemp seedlings and of hemp foods and beverages to those containing only low amounts of THC. However, the marketing of hemp plants used for decorating remains free partly explaining the recent success of these "beautiful" plants. Broadly speaking, the Swiss and European legislations about hemp have approached mutually during the last years.

Agriculture↗

PubMed1999

Affinity chromatography using trypanocidal arsenical drugs identifies a specific interaction between glycerol-3-phosphate dehydrogenase from Trypanosoma brucei and Cymelarsan.

A 36-kDa protein was isolated by affinity chromatography using Cymelarsan, an arsenical drug currently used in African trypanosomiasis treatment, as ligand. This protein was identified as glycerol-3-phosphate dehydrogenase. Trypanosomal glycerol-3-phosphate was bound covalently, whereas its counterpart from rabbit muscle bound by ionic interaction. Arsenical drugs inhibit the enzyme in a dose-dependent manner. Oxidation of cysteine residues protects against inactivation without significantly diminishing enzymic activity. Drug concentrations giving 50% inhibition of the dehydrogenase activity were determined for the enzyme from both Trypanosoma brucei and rabbit and indicate a higher sensitivity of the trypanosomal enzyme to arsenical drugs and thiol reagents. MS was used to identify residues of glycerol-3-phosphate dehydrogenase bound by Cymelarsan; they are not conserved in the mammalian enzyme.

Animals↗

PubMed1999

Method for the isolation and purification of pyridinoline and deoxypyridinoline crosslinks from bone by liquid chromatographic techniques.

Significant progress has been made in recent years in the development of new bone resorption markers, based principally on the urinary excretion of pyridinoline (Pyd) and deoxypyridinoline (Dpd) crosslinks. For their measurement, in spite of the recent development of immunoassays, HPLC remains the method of reference. However, the lack of an appropriate internal standard requires large amounts of pure crosslinks for external standardisation. Herein, we describe an efficient method for the isolation of both crosslinks from bone of adult turkey by isocratic semi-preparative HPLC. Demineralized bone is hydrolysed in hydrochloric acid, 9 M. A first liquid extraction step in butanol allowed to eliminate less polar compounds. The aqueous phase was concentrated and separated by gel filtration on Biogel P2 and eluted by acetic acid solution (10%). Fractions containing pyridinoline were pooled, concentrated, and purified on a CF1 cellulose column. Pyd and Dpd crosslinks were then separated isocratically by HPLC on a C18 reversed phase column (Vydac 218 TP 1010, 250x10 mm) and eluted with HFBA as the ion-pairing agent. Retention times of Pyd and DPD were 23.6 and 28.7 min, respectively. Both crosslinks prepared by HPLC were then transformed as hydrochloride to cellulose phosphate and desalted on Sephadex G-10 columns. These two further steps yielded highly purified compounds (the purity was greater than 98% evaluated by aminoacid analysis). In conclusion, the efficiency of this method allows to obtain rapidly Pyd and Dpd without interfering compounds as proven by spectral studies (NMR and mass spectroscopy).

Amino Acids↗

PubMed1999

Exit association-mediated suicide: toxicologic and forensic aspects.

The Swiss German chapter of the Exit Association provides conditional assistance to individuals wishing to end their own lives. The Exit Association advocates death with dignity and fights for the right to freely choose the timing of one's own death. According to the Swiss criminal code (articles 114 and 115), altruistic assistance to suicide is not punishable. Active euthanasia is punished by imprisonment. An individual commits active euthanasia if he or she is driven by honorable motives (e.g., pity) and causes the death of another person wishing to die who seriously and insistently requests such action. Based on our information, the preparation for suicide and its completion relies on a well-defined protocol. First, the candidate's eligibility for Exit Association assistance is verified. The candidate then writes a farewell declaration that explicitly confirms the will to terminate his or her own life. A written report describes the events during the suicide procedure. Depending on the circumstances, the investigative judge requests a forensic autopsy and toxicologic analyses. The results of the forensic investigations conducted in the cases presented here are in agreement with the scenario described in the reports of the Exit Association, namely, suicide by massive ingestion of pentobarbital.

Aged↗

PubMed1999

Interferon-beta inhibits activated leukocyte migration through human brain microvascular endothelial cell monolayer.

Perivascular leukocyte infiltration into the central nervous system is characteristic of multiple sclerosis (MS) pathology. Interferon-beta (IFN-beta) has shown efficacy in the treatment of patients with MS, but the relevant mechanisms remain incompletely understood. In this study the effects of IFN-beta on leukocyte transendothelial migration were investigated using cells relevant to MS pathogenesis, namely human brain microvascular endothelial cells (HB-MVEC). Activated, but not resting leukocytes exhibited a high transendothelial migration capacity. HB-MVEC prestimulated with tumor necrosis factor (TNF) and IFN-gamma significantly promoted leukocyte transendothelial migration. IFN-beta inhibited the activated leukocyte transendothelial migration on TNF/IFN-gamma-activated HB-MVEC in a dose-dependent manner. A matrix metalloproteinase (MMP) inhibitor and monoclonal antibodies to lymphocyte function antigen-1 (LFA-1) or intercellular adhesion molecule-1 (ICAM-1), but not to very late antigen-4 or to vascular cell adhesion molecule-1 significantly inhibited the transendothelial migration of stimulated leukocytes, suggesting that this phenomenon involves the LFA-1/ICAM-1 interaction and MMP. However IFN-beta did not interfere with the binding of leukocytes to HB-MVEC unless IFN-beta was preincubated with leukocytes or added to HB-MVEC at the time of stimulation. Furthermore IFN-beta did not modulate the expression of adhesion molecules on either stimulated leukocytes or activated HB-MVEC, but partially reduced TNF and interleukin-1 production from stimulated leukocytes during coculture with HB-MVEC. Interestingly, in the presence of IFN-beta, a significant down-regulation of MMP-9 release from stimulated leukocytes was found, especially for the activated form of MMP-9. These results indicate that inhibition of leukocyte transendothelial migration is an important mechanism accounting for the beneficial effects of IFN-beta in the treatment MS patients.

Brain↗

PubMed1998

Both TNF receptors are required for direct TNF-mediated cytotoxicity in microvascular endothelial cells.

The conditions under which tumor necrosis factor-alpha (TNF) induces apoptosis in primary microvascular endothelial cells (MVEC) were investigated. In the absence of sensitizing agents, TNF induced apoptosis after 3 days of incubation in confluent MVEC. In contrast, upon addition of the transcriptional inhibitor actinomycin D (Act. D), confluence was no longer required and apoptosis occurred already after 16 h. To assess the role of either TNF receptor (TNFR) type in apoptosis, MVEC isolated from mice genetically deficient in TNFR1 (Tnfr1o mice) or TNFR2 (Tnfr2o mice) were incubated with TNF in the presence or absence of Act. D. Under sensitized conditions, Tnfr2o MVEC were lysed like controls, whereas Tnfr1o MVEC were completely resistant, indicating an exclusive role for TNFR1. In contrast, in the absence of Act. D, confluent monolayers of wild-type cells were lysed by TNF, but both Tnfr1o and Tnfr2o MVEC were resistant to TNF-mediated toxicity, indicating a requirement for both TNFR types. Overexpression of the anti-apoptotic protein bcl-xL in MVEC led to a protection against the direct, but not the sensitized cytotoxicity of TNF. In conclusion, in pathophysiologically relevant conditions, both TNFR appear to be required for TNF-induced apoptosis in MVEC.

Animals↗