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Bertrand Ludes - One of the best experts on this subject based on the ideXlab platform.

  • Clozapine Dose-Concentration relationships in plasma, hair and sweat specimens of schizophrenic patients.
    Forensic science international, 2000
    Co-Authors: Vincent Cirimele, Pascal Kintz, Olivier Gosselin, Bertrand Ludes
    Abstract:

    The aim of the present study was to establish an analytical method for the determination of clozapine in sweat and to determine whether the clozapine level in hair and sweat were correlated to the daily Dose of clozapine delivered to patients. Twenty-six subjects treated with clozapine at 200-700 mg/day for refractory psychosis were included in the study. Clozapine was determined in plasma by liquid chromatography coupled to a diode array detection system, after extraction with an organic solvent at pH 9.5. Clozapine was extracted from hair and sweat patches specimens by incubation in methanol overnight at 40 degrees C. The residues were analyzed by gas chromatography coupled to mass spectrometry in the electronic impact mode of detection. It was possible to determine clozapine in Concentrations ranging from 30 to 1016 ng/ml in plasma (n = 22), from 0.17 to 34.24 ng/mg in hair (n = 23) and from 49 to 5609 ng/patch in sweat (n = 20). Preliminary results suggest a lack of correlation between daily regimen of clozapine and plasma levels of the drug. Therefore, a better Dose-Concentration relationship was observed in our study between daily Dose and hair Concentration (r = 0.542, P < 7%) or between daily Dose and sweat Concentration (r = 0.589, P < 6%), but with wide variations for patients at the same posology. However, the idea of using quantitative drug measurements in hair or sweat to ascertain whether a patient has taken his treatment exactly as prescribed will remain inapplicable.

  • Clozapine Dose–Concentration relationships in plasma, hair and sweat specimens of schizophrenic patients
    Forensic Science International, 2000
    Co-Authors: Vincent Cirimele, Pascal Kintz, Olivier Gosselin, Bertrand Ludes
    Abstract:

    Abstract The aim of the present study was to establish an analytical method for the determination of clozapine in sweat and to determine whether the clozapine level in hair and sweat were correlated to the daily Dose of clozapine delivered to patients. Twenty-six subjects treated with clozapine at 200–700 mg/day for refractory psychosis were included in the study. Clozapine was determined in plasma by liquid chromatography coupled to a diode array detection system, after extraction with an organic solvent at pH 9.5. Clozapine was extracted from hair and sweat patches specimens by incubation in methanol overnight at 40°C. The residues were analyzed by gas chromatography coupled to mass spectrometry in the electronic impact mode of detection. It was possible to determine clozapine in Concentrations ranging from 30 to 1016 ng/ml in plasma ( n =22), from 0.17 to 34.24 ng/mg in hair ( n =23) and from 49 to 5609 ng/patch in sweat ( n =20). Preliminary results suggest a lack of correlation between daily regimen of clozapine and plasma levels of the drug. Therefore, a better Dose–Concentration relationship was observed in our study between daily Dose and hair Concentration ( r =0.542, P r =0.589, P

  • Dose-Concentration relationships in hair from subjects in a controlled heroin-maintenance program.
    Journal of analytical toxicology, 1998
    Co-Authors: Pascal Kintz, Petra Bundeli, Rudolf Brenneisen, Bertrand Ludes
    Abstract:

    Hair specimens were collected from the vertex area of 20 subjects taking part in a heroin-maintenance program. Subjects were administered, under controlled conditions, heroin hydrochloride in 2 or 3 Doses/day intravenously. Heroin Doses ranged from 30 to 800 mg/day, and were self-administered. In all cases, a 4-cm segment from the proximal zone (root) was analyzed, which corresponded to about 100 days of hair growth. During that period, total heroin administered ranged from 14,100 to 71,540 mg. All special features of hair such as coloring, bleaching, etc. were noted. Each sample was washed twice with dichloromethane (5 mL, 2 min) and, after drying, cut into small pieces of approximately 1 mm. A 30-35-mg aliquot was incubated overnight at 45 degrees C in 1 mL methanol in the presence of 200 ng of heroin-d9, 6-acetylmorphine-d3, and morphine-d3. The methanolic extract was then evaporated to dryness, and the residue was derivatized by silylation (BSTFA + 1% TMCS). Drugs were analyzed by gas chromatography-mass spectrometry in electron impact mode. Limits of quantitation were set to 0.1 ng/mg. Concentrations ranged from 0 to 4.53, 0.38 to 10.11, and 0.71 to 5.20 ng/mg for heroin, 6-acetylmorphine, and morphine, respectively. 6-Acetylmorphine was the major analyte present in hair in all but five cases. Heroin was present in the highest Concentration in three cases, and morphine was the major metabolite in two cases, probably because of hydrolysis. Subjects tested positive for heroin in all but two cases. No correlation between the Doses of administered heroin and the Concentrations of total opiates in hair was observed (r = 0.346). However, when considering a single analyte, it was observed that the correlation coefficient seemed to be linked to its plasma half-life. A weak correlation coefficient corresponds to a drug with a short plasma half-life, and the correlation coefficient increases when plasma half-life increases, as r = 0.12, 0.25, and 0.64 for heroin, 6-acetylmorphine, and morphine, respectively. These results suggest that using quantitative drug measurements in hair to determine the amount of drug ingested will remain inapplicable until more is known about the factors that may influence the incorporation of drugs into hair and a way to reduce the observed variability.

Sukchan Lee - One of the best experts on this subject based on the ideXlab platform.

  • High Dose Concentration administration of ascorbic acid inhibits tumor growth in BALB/C mice implanted with sarcoma 180 cancer cells via the restriction of angiogenesis.
    Journal of translational medicine, 2009
    Co-Authors: Chang-hwan Yeom, Gunsup Lee, Jin-hee Park, Seyeon Park, Hye Ree Lee, Young Seon Hong, Joo-sung Yang, Sukchan Lee
    Abstract:

    To test the carcinostatic effects of ascorbic acid, we challenged the mice of seven experimental groups with 1.7 × 10-4 mol high Dose Concentration ascorbic acid after intraperitoneal administrating them with sarcoma S-180 cells. The survival rate was increased by 20% in the group that received high Dose Concentration ascorbic acid, compared to the control. The highest survival rate was observed in the group in which 1.7 × 10-4 mol ascorbic acid had been continuously injected before and after the induction of cancer cells, rather than just after the induction of cancer cells. The expression of three angiogenesis-related genes was inhibited by 0.3 times in bFGF, 7 times in VEGF and 4 times in MMP2 of the groups with higher survival rates. Biopsy Results, gene expression studies, and wound healing analysis in vivo and in vitro suggested that the carcinostatic effect induced by high Dose Concentration ascorbic acid occurred through inhibition of angiogenesis.

  • high Dose Concentration administration of ascorbic acid inhibits tumor growth in balb c mice implanted with sarcoma 180 cancer cells via the restriction of angiogenesis
    Journal of Translational Medicine, 2009
    Co-Authors: Chang-hwan Yeom, Gunsup Lee, Jin-hee Park, Seyeon Park, Hye Ree Lee, Young Seon Hong, Joo-sung Yang, Sukchan Lee
    Abstract:

    To test the carcinostatic effects of ascorbic acid, we challenged the mice of seven experimental groups with 1.7 × 10-4 mol high Dose Concentration ascorbic acid after intraperitoneal administrating them with sarcoma S-180 cells. The survival rate was increased by 20% in the group that received high Dose Concentration ascorbic acid, compared to the control. The highest survival rate was observed in the group in which 1.7 × 10-4 mol ascorbic acid had been continuously injected before and after the induction of cancer cells, rather than just after the induction of cancer cells. The expression of three angiogenesis-related genes was inhibited by 0.3 times in bFGF, 7 times in VEGF and 4 times in MMP2 of the groups with higher survival rates. Biopsy Results, gene expression studies, and wound healing analysis in vivo and in vitro suggested that the carcinostatic effect induced by high Dose Concentration ascorbic acid occurred through inhibition of angiogenesis.

Chang-hwan Yeom - One of the best experts on this subject based on the ideXlab platform.

  • High Dose Concentration administration of ascorbic acid inhibits tumor growth in BALB/C mice implanted with sarcoma 180 cancer cells via the restriction of angiogenesis.
    Journal of translational medicine, 2009
    Co-Authors: Chang-hwan Yeom, Gunsup Lee, Jin-hee Park, Seyeon Park, Hye Ree Lee, Young Seon Hong, Joo-sung Yang, Sukchan Lee
    Abstract:

    To test the carcinostatic effects of ascorbic acid, we challenged the mice of seven experimental groups with 1.7 × 10-4 mol high Dose Concentration ascorbic acid after intraperitoneal administrating them with sarcoma S-180 cells. The survival rate was increased by 20% in the group that received high Dose Concentration ascorbic acid, compared to the control. The highest survival rate was observed in the group in which 1.7 × 10-4 mol ascorbic acid had been continuously injected before and after the induction of cancer cells, rather than just after the induction of cancer cells. The expression of three angiogenesis-related genes was inhibited by 0.3 times in bFGF, 7 times in VEGF and 4 times in MMP2 of the groups with higher survival rates. Biopsy Results, gene expression studies, and wound healing analysis in vivo and in vitro suggested that the carcinostatic effect induced by high Dose Concentration ascorbic acid occurred through inhibition of angiogenesis.

  • high Dose Concentration administration of ascorbic acid inhibits tumor growth in balb c mice implanted with sarcoma 180 cancer cells via the restriction of angiogenesis
    Journal of Translational Medicine, 2009
    Co-Authors: Chang-hwan Yeom, Gunsup Lee, Jin-hee Park, Seyeon Park, Hye Ree Lee, Young Seon Hong, Joo-sung Yang, Sukchan Lee
    Abstract:

    To test the carcinostatic effects of ascorbic acid, we challenged the mice of seven experimental groups with 1.7 × 10-4 mol high Dose Concentration ascorbic acid after intraperitoneal administrating them with sarcoma S-180 cells. The survival rate was increased by 20% in the group that received high Dose Concentration ascorbic acid, compared to the control. The highest survival rate was observed in the group in which 1.7 × 10-4 mol ascorbic acid had been continuously injected before and after the induction of cancer cells, rather than just after the induction of cancer cells. The expression of three angiogenesis-related genes was inhibited by 0.3 times in bFGF, 7 times in VEGF and 4 times in MMP2 of the groups with higher survival rates. Biopsy Results, gene expression studies, and wound healing analysis in vivo and in vitro suggested that the carcinostatic effect induced by high Dose Concentration ascorbic acid occurred through inhibition of angiogenesis.

Vincent Cirimele - One of the best experts on this subject based on the ideXlab platform.

  • Clozapine Dose-Concentration relationships in plasma, hair and sweat specimens of schizophrenic patients.
    Forensic science international, 2000
    Co-Authors: Vincent Cirimele, Pascal Kintz, Olivier Gosselin, Bertrand Ludes
    Abstract:

    The aim of the present study was to establish an analytical method for the determination of clozapine in sweat and to determine whether the clozapine level in hair and sweat were correlated to the daily Dose of clozapine delivered to patients. Twenty-six subjects treated with clozapine at 200-700 mg/day for refractory psychosis were included in the study. Clozapine was determined in plasma by liquid chromatography coupled to a diode array detection system, after extraction with an organic solvent at pH 9.5. Clozapine was extracted from hair and sweat patches specimens by incubation in methanol overnight at 40 degrees C. The residues were analyzed by gas chromatography coupled to mass spectrometry in the electronic impact mode of detection. It was possible to determine clozapine in Concentrations ranging from 30 to 1016 ng/ml in plasma (n = 22), from 0.17 to 34.24 ng/mg in hair (n = 23) and from 49 to 5609 ng/patch in sweat (n = 20). Preliminary results suggest a lack of correlation between daily regimen of clozapine and plasma levels of the drug. Therefore, a better Dose-Concentration relationship was observed in our study between daily Dose and hair Concentration (r = 0.542, P < 7%) or between daily Dose and sweat Concentration (r = 0.589, P < 6%), but with wide variations for patients at the same posology. However, the idea of using quantitative drug measurements in hair or sweat to ascertain whether a patient has taken his treatment exactly as prescribed will remain inapplicable.

  • Clozapine Dose–Concentration relationships in plasma, hair and sweat specimens of schizophrenic patients
    Forensic Science International, 2000
    Co-Authors: Vincent Cirimele, Pascal Kintz, Olivier Gosselin, Bertrand Ludes
    Abstract:

    Abstract The aim of the present study was to establish an analytical method for the determination of clozapine in sweat and to determine whether the clozapine level in hair and sweat were correlated to the daily Dose of clozapine delivered to patients. Twenty-six subjects treated with clozapine at 200–700 mg/day for refractory psychosis were included in the study. Clozapine was determined in plasma by liquid chromatography coupled to a diode array detection system, after extraction with an organic solvent at pH 9.5. Clozapine was extracted from hair and sweat patches specimens by incubation in methanol overnight at 40°C. The residues were analyzed by gas chromatography coupled to mass spectrometry in the electronic impact mode of detection. It was possible to determine clozapine in Concentrations ranging from 30 to 1016 ng/ml in plasma ( n =22), from 0.17 to 34.24 ng/mg in hair ( n =23) and from 49 to 5609 ng/patch in sweat ( n =20). Preliminary results suggest a lack of correlation between daily regimen of clozapine and plasma levels of the drug. Therefore, a better Dose–Concentration relationship was observed in our study between daily Dose and hair Concentration ( r =0.542, P r =0.589, P

Pascal Kintz - One of the best experts on this subject based on the ideXlab platform.

  • Clozapine Dose-Concentration relationships in plasma, hair and sweat specimens of schizophrenic patients.
    Forensic science international, 2000
    Co-Authors: Vincent Cirimele, Pascal Kintz, Olivier Gosselin, Bertrand Ludes
    Abstract:

    The aim of the present study was to establish an analytical method for the determination of clozapine in sweat and to determine whether the clozapine level in hair and sweat were correlated to the daily Dose of clozapine delivered to patients. Twenty-six subjects treated with clozapine at 200-700 mg/day for refractory psychosis were included in the study. Clozapine was determined in plasma by liquid chromatography coupled to a diode array detection system, after extraction with an organic solvent at pH 9.5. Clozapine was extracted from hair and sweat patches specimens by incubation in methanol overnight at 40 degrees C. The residues were analyzed by gas chromatography coupled to mass spectrometry in the electronic impact mode of detection. It was possible to determine clozapine in Concentrations ranging from 30 to 1016 ng/ml in plasma (n = 22), from 0.17 to 34.24 ng/mg in hair (n = 23) and from 49 to 5609 ng/patch in sweat (n = 20). Preliminary results suggest a lack of correlation between daily regimen of clozapine and plasma levels of the drug. Therefore, a better Dose-Concentration relationship was observed in our study between daily Dose and hair Concentration (r = 0.542, P < 7%) or between daily Dose and sweat Concentration (r = 0.589, P < 6%), but with wide variations for patients at the same posology. However, the idea of using quantitative drug measurements in hair or sweat to ascertain whether a patient has taken his treatment exactly as prescribed will remain inapplicable.

  • Clozapine Dose–Concentration relationships in plasma, hair and sweat specimens of schizophrenic patients
    Forensic Science International, 2000
    Co-Authors: Vincent Cirimele, Pascal Kintz, Olivier Gosselin, Bertrand Ludes
    Abstract:

    Abstract The aim of the present study was to establish an analytical method for the determination of clozapine in sweat and to determine whether the clozapine level in hair and sweat were correlated to the daily Dose of clozapine delivered to patients. Twenty-six subjects treated with clozapine at 200–700 mg/day for refractory psychosis were included in the study. Clozapine was determined in plasma by liquid chromatography coupled to a diode array detection system, after extraction with an organic solvent at pH 9.5. Clozapine was extracted from hair and sweat patches specimens by incubation in methanol overnight at 40°C. The residues were analyzed by gas chromatography coupled to mass spectrometry in the electronic impact mode of detection. It was possible to determine clozapine in Concentrations ranging from 30 to 1016 ng/ml in plasma ( n =22), from 0.17 to 34.24 ng/mg in hair ( n =23) and from 49 to 5609 ng/patch in sweat ( n =20). Preliminary results suggest a lack of correlation between daily regimen of clozapine and plasma levels of the drug. Therefore, a better Dose–Concentration relationship was observed in our study between daily Dose and hair Concentration ( r =0.542, P r =0.589, P

  • Dose-Concentration relationships in hair from subjects in a controlled heroin-maintenance program.
    Journal of analytical toxicology, 1998
    Co-Authors: Pascal Kintz, Petra Bundeli, Rudolf Brenneisen, Bertrand Ludes
    Abstract:

    Hair specimens were collected from the vertex area of 20 subjects taking part in a heroin-maintenance program. Subjects were administered, under controlled conditions, heroin hydrochloride in 2 or 3 Doses/day intravenously. Heroin Doses ranged from 30 to 800 mg/day, and were self-administered. In all cases, a 4-cm segment from the proximal zone (root) was analyzed, which corresponded to about 100 days of hair growth. During that period, total heroin administered ranged from 14,100 to 71,540 mg. All special features of hair such as coloring, bleaching, etc. were noted. Each sample was washed twice with dichloromethane (5 mL, 2 min) and, after drying, cut into small pieces of approximately 1 mm. A 30-35-mg aliquot was incubated overnight at 45 degrees C in 1 mL methanol in the presence of 200 ng of heroin-d9, 6-acetylmorphine-d3, and morphine-d3. The methanolic extract was then evaporated to dryness, and the residue was derivatized by silylation (BSTFA + 1% TMCS). Drugs were analyzed by gas chromatography-mass spectrometry in electron impact mode. Limits of quantitation were set to 0.1 ng/mg. Concentrations ranged from 0 to 4.53, 0.38 to 10.11, and 0.71 to 5.20 ng/mg for heroin, 6-acetylmorphine, and morphine, respectively. 6-Acetylmorphine was the major analyte present in hair in all but five cases. Heroin was present in the highest Concentration in three cases, and morphine was the major metabolite in two cases, probably because of hydrolysis. Subjects tested positive for heroin in all but two cases. No correlation between the Doses of administered heroin and the Concentrations of total opiates in hair was observed (r = 0.346). However, when considering a single analyte, it was observed that the correlation coefficient seemed to be linked to its plasma half-life. A weak correlation coefficient corresponds to a drug with a short plasma half-life, and the correlation coefficient increases when plasma half-life increases, as r = 0.12, 0.25, and 0.64 for heroin, 6-acetylmorphine, and morphine, respectively. These results suggest that using quantitative drug measurements in hair to determine the amount of drug ingested will remain inapplicable until more is known about the factors that may influence the incorporation of drugs into hair and a way to reduce the observed variability.