Hafid Belhadj-tahar - Academia.edu (original) (raw)
Papers by Hafid Belhadj-tahar
![Research paper thumbnail of Radiolabeling of [ 18 F]-fluoroethylnormemantine and initial in vivo evaluation of this innovative PET tracer for imaging the PCP sites of NMDA receptors](https://attachments.academia-assets.com/38386822/thumbnails/1.jpg)
](The N-methyl-D-aspartate receptor (NMDAr) is an ionotropic receptor that mediates excitatory tran... more The N-methyl-D-aspartate receptor (NMDAr) is an ionotropic receptor that mediates excitatory transmission. NMDAr overexcitation is thought to be involved in neurological and neuropsychiatric disorders such as Alzheimer disease and schizophrenia. We synthesized [ 18 F]-fluoroethylnormemantine ([ 18 F]-FNM), a memantine derivative that binds to phencyclidine (PCP) sites within the NMDA channel pore. These sites are primarily accessible when the channel is in the active and open state. Methods: Radiosynthesis was carried out using the Raytest® SynChrom R&D fluorination module. Affinity of this new compound was determined by competition assay. We ran a kinetic study in rats and computed a time-activity curve based on a volume-of-interest analysis, using CARIMAS® software. We performed an ex vivo autoradiography, exposing frozen rat brain sections to a phosphorscreen. Adjacent sections were used to detect NMDAr by immunohistochemistry with an anti-NR1 antibody. As a control of the specificity of our compound for NMDAr, we used a rat anesthetized with ketamine. Correlation analysis was performed with ImageJ software between signal of autoradiography and immunostaining. Results: Fluorination yield was 10.5% (end of synthesis), with a mean activity of 3145 MBq and a specific activity above 355 GBq/μmol. Affinity assessment allowed us to determine [ 19 F]-FNM IC50 at 6.1 10 −6 M. [ 18 F]-FMN concentration gradually increased in the brain, stabilizing at 40 minutes post injection. The brain-to-blood ratio was 6, and 0.4% of the injected dose was found in the brain. Combined ex vivo autoradiography and immunohistochemical staining demonstrated colocalization of NMDAr and [ 18 F]-FNM (r = 0.622, p b 0.0001). The highest intensity was found in the cortex and cerebellum, and the lowest in white matter. A low and homogeneous signal corresponding to unspecific binding was observed when PCP sites were blocked with ketamine. Conclusions: [ 18 F]-FNM appears to be a promising tracer for imaging NMDAr activity for undertaking preclinical studies in perspective of clinical detection of neurological or neuropsychological disorders
Annales de Toxicologie Analytique, 2013
Objectives: A liquid/liquid extraction technique on solid support of Δ 9 -tetradydrocannabinol (T... more Objectives: A liquid/liquid extraction technique on solid support of Δ 9 -tetradydrocannabinol (THC), 11-hydroxy-Δ 9 -tetradydrocannabinol (11-OH-THC) and 11-nor-Δ 9 -tetradydrocannabinol-9-carboxylic acid (THC-COOH) in plasma was developed in order to be assayed by high-performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS). Methods: The samples were extracted by liquid/liquid extraction over solid support of an extraction cartridge. The extracts were thereafter dried down and injected into the HPLC-MS/MS system set with a positive electrospray mode using a Waters XTerra MS C18 3.5-μm 2.1 × 150 mm column. Results: The extraction recovery levels were 66%, 70% and 71% for THC, and 75%, 93% and 101% for 11-OH-THC at concentrations of 2.5, 5 and 10 ng/mL, respectively. They were 86% and 78% for THC-COOH at concentrations of 5 and 10 ng/mL. The limits of detection (LOD) were 0.09, 0.08 and 0.91 ng/mL for THC, 11-OH-THC and THC-COOH, respectively. The limits of quantification (LOQ) were 0.16, 0.15 and 3.24 ng/mL for THC, 11-OH-THC and THC-COOH, respectively. The inter-series incertitude CV determined for concentrations of 1, 2.5 and 10 ng/mL were 12.1%, 12.0% and 6.4% for THC, 14.5%, 11.1% and 7.2% for 11-OH-THC, and 14.9%, 26.2% and 11.3% for THC-COOH. Conclusion: The novel extraction method for THC, 11-OH-THC and THC-COOH developed in this work is rapid, sensitive and specific. It may be a valuable tool for predictive toxicology, high-throughput metabolism and pharmacokinetic studies of cannabinoids.
Canadian Society of Forensic Science Journal, 2008
ABSTRACT Based on initial clinical observations, the global population was divided into four grou... more ABSTRACT Based on initial clinical observations, the global population was divided into four groups: those without the presence of lividity and rigidity (GI); those with the presence of lividity and rigidity (GII); those with signs of putrefaction (GIII); and the group that included the bodies kept in the funeral home at low temperature (GIV). There was no significant difference in the troponin levels between group GI (short postmortem delay) and GII (intermediate postmortem delay). A significant increase in this marker was observed in GIII (presence of putrefaction) compared with GI + GII (absence of putrefaction). For short and intermediate delays, storage in the funeral home did not modify the kinetic release of troponin. On the other hand, an increase in the level of Ic-Tn was positively correlated with the duration of cardiac massage. Since the troponin level rises during putrefaction, an exclusion limit was determined to be 11 mg/l, above which the results were deemed uninterpretable. Under these conditions, the predictive capacity of Troponin Ic for cardiac death is optimal at 0.8 mg/l with sensitivity and specificity estimated at 86 percent and 100 percent, respectively. Application of this marker requires knowledge of the circumstances of death and anamnestic elements, as well as observations and examinations of the body. Under these conditions, cardiac troponin apparently is a helpful element to use in determining suspicious deaths, particularly sudden deaths. The authors analyzed the Ic-Tn concentrations at the time of 32 body removals conducted from 2005 to 2006 in northern suburbs of Paris. 2 tables, 1 figure, and 26 references
Introduction: The setting up of Mediterranean collaboration in forensic research is dependent on ... more Introduction: The setting up of Mediterranean collaboration in forensic research is dependent on inter-organisational collaboration and on governmental policy for scientific initiatives. The recent improvements in transportation and communication technologies have made it easier to organize long-distance collaboration research activities. However to get over physical distance between collaborating researchers requires good coordination and the presence of an efficient intermediary. Thanks to the interface of AFPreMed, French (IRCGN, Claude Bernard Laboratory) and Algerian researcher teams (CHU of Tizi-Ouzou) have recently initiated a forensic toxicological collaboration. In this abstract we report an example of Mediterranean collaborative investigations concerning the first case of fatal human poisoning by vanadium. Case report: At 10h30 p.m., a 24-year-old woman was admitted to the emergency department of the university hospital of Tizi-Ouzou (Algeria), for diffuse abdominal pain, ...
Forensic Medicine and Anatomy Research, 2013
In this prospective study, we evaluated the use of PCT when collecting the body which was carried... more In this prospective study, we evaluated the use of PCT when collecting the body which was carried out. The chosen cut-off was set at 10 ng/mL because at this level, the PCT was associated to a multiorgan failure attributable to a septic shock. For 90 cases, two groups were stratified by their final diagnosis: 33 of for non violent deaths and 57 of violent deaths. There was no significant elevation of procalcitonin rate (PCT) in the group of violent deaths. We noted 6 elevations of PCT rate above 10 ng/mL for non violent deaths (15.4%) and in 3 cases there was an evidence for an infectious context (recent antiinfectious treatments, chemotherapy in progress).
Journal of Hepatology, 2008
changes in fibrosis scores were +0.36 (95% CI 0.07−0.64) and +0.32 (95% CI −0.39−1.03) in the E1 ... more changes in fibrosis scores were +0.36 (95% CI 0.07−0.64) and +0.32 (95% CI −0.39−1.03) in the E1 and placebo group, respectively (p = 0.87), while changes in inflammation scores were +0.81 (0.33−1.29) and +1.28 (0.22−2.34; p = 0.36). Multiple regression indicated the following factors as significantly associated with fibrosis progression: BMI at baseline (BMI < 25 predicted to progress +0.59 more than BMI > 25), previous IFN treatment (IFN-experienced patients progress more than IFN-naive patients), and Ishak fibrosis stage at baseline (low fibrosis progress +0.80 more than high fibrosis). No association was seen between histological evolution from baseline and age, gender, HCV E1 Ab status and ALT at baseline, or ribavirin history.
Acta Clinica Belgica, 2006
In situ microdialysis allows monitoring of metabolic cellular processes at the tissue level in vi... more In situ microdialysis allows monitoring of metabolic cellular processes at the tissue level in vivo. In the assessment of physiopathologic alterations seen in lipodystrophy, monitoring of glycerol release is pivotal. Indeed, it allows to quantify the pharmacological responsiveness of subcutaneous adipose tissue in humans. Until now, the small volume of microdialysate collected (5-15 microL/sample) restricted the assessment of glycerol level to the use of the radio-enzymatic method or the reference spectrophotometric microanalysis technique. The aim of this study was to adapt the method of glycerol measurement by iminequinone spectrophotometry colorimetric assay (520 nm) using the following reagent: 0.5 IU Glycerokinase, 1.23 IU glycerophosphate oxidase, 0.98 IU peroxidase, 4.6 mM Mg, 5.4 mM 4-chlorophenol, 0.25 mM 4-aminoantipyrine and 1.4 mM ATP. The assay was setup to run on Olympus AU 2700 automate (15 pL sample volume). The sensitivity of the method was improved by adding a 0.2 mmol triglyceride (TG) solution and 1.5 IU lipase to samples, reducing the limit of free glycerol quantification to 0.020 mmol/L. The analytical repeatability was 2.0% and the reproducibility was 7.9%. The present method thus demonstrated the feasibility of pharmacodynamic exploration of local cutaneous responsiveness in vivo in clinical trials.
Nuclear Medicine and Biology, 1994
Bisphosphonates (BPs) are characterized by a PϪCϪP backbone structure and two phosphonic acid gro... more Bisphosphonates (BPs) are characterized by a PϪCϪP backbone structure and two phosphonic acid groups bonded to the same carbon, and are established as osteoclast-mediated bone resorption inhibitors. The nature of the groups attached to the central carbon atom are responsible in determining the potency of bisphosphonates as anti-resorption drugs. However, it is not yet clear the exact relationship between their molecular structure and pharmacologic activities. In this study, molecular geometries of pamidronate, alendronate and neridronate, differing only in the length of the aliphatic chains, were predicted by molecular mechanics and their interactions with hydroxyapatite, the main bone mineral component, were examined. We report the synthesis and radiochemical characterization of 153 Sm complexes with pamidronate, alendronate and neridronate. Hydroxyapatite binding and biodistribution studies of these complexes have shown a good correlation with the theoretical molecular modeling interaction studies. So, it is possible to conclude that computational chemistry techniques are a good approach to evaluate specific interactions and may play a relevant role in determining the relative ability of BPs to mineral bone, and open new perspectives to the design of new BPs with increased pharmacological activity. These techniques could be extended to BPs as ligands to carrier radioactive metals, aiming for new bone therapeutic radiopharmaceuticals.
Nuclear Medicine and Biology, 1996
We have synthesized and characterized seven ligands derived from 2-aminocyclopentene-ldithiocarbo... more We have synthesized and characterized seven ligands derived from 2-aminocyclopentene-ldithiocarboxylic acid with different donor sets ( SN2-, SNO'-, SNN2-, SNN03-and SNNN3-) and different substituents on the sulfur moieties -SR (with R = H, CH, or C,H,O(CH,)CH).
European Neuropsychopharmacology, 2014
Forensic Medicine and Anatomy Research, 2015
ABSTRACT The aim of the present work was to investigate the exposure to the medical and industria... more ABSTRACT The aim of the present work was to investigate the exposure to the medical and industrial toxic chemicals. The research was carried out on hair, nail and blood samples in a panel of 40 healthy volunteers aged 7 to 77 with an average of 45 ± 19 years (18 women (45%) and 22 men (55%)). All of these individuals had not received medication for at least 1 year, including antibiotics and psychotropic. This study was realized from July 2013 to March 2014 in Beijing, China. The method for an accurate and reliable screening of medical and an industrial toxic chemical was based on detection and assay by ultra-high performance liquid chromatography with UV detection type of diode arrays. Also more than 10,000 toxic molecules commonly found in western industrial countries were screened by coupling gas chromatography and mass spectrometry. The main results indicate that the molecules analyzed are mainly antibiotic (Gentamycine and Tobramycine), antidepressant (Amitriptylin and its metabolites), narcotic (MDMA and Clonitazene), ingredient in cosmetics (Benzenediol and Benzoic acid), insecticide (Carbamate derivative), ketamine, chlorhexidine and phthalate derivatives. There are no detailed documented baseline data of the analysis of medical and Industrial toxic pollutants in hair, nail and blood samples in Beijing; however, this study should be completed on samples from other provinces of China. This study is the first of its kind. Therefore, further studies should be conducted in other cities and provinces of China to be compared with each other.
Sulfonylureas are herbicides ( ) which will find increased use due to their wide-spectrum effects... more Sulfonylureas are herbicides ( ) which will find increased use due to their wide-spectrum effects on weeds and their low toxic effects on mammals (1). The effects of sulfonylureas on plants, micro-algae and bacteria are due to the inhibition of acetolactate synthase (ALS) involved in the synthesis of acetolactic and butyric acids, which are the precursors of the branched-chain amino acids: isoleucine, leucine and valine (2). Indeed, ALS catalyzes the condensation of pyruvate with acetaldehyde by means of amine hydroxy-ethyl-thiamine diphosphatase. The final amino acid results from the transfer of the glutamate amino group to the a-ketonic acid through transaminase .
Nuclear Instruments & Methods in Physics Research Section A-accelerators Spectrometers Detectors and Associated Equipment, 2007
S-EOE-MAG3-β-alanine-CCK4 vector (S-EOE-MAG3-β-alanine: S-(1-ethoxyethyl) mercaptoacetyltriglycyl... more S-EOE-MAG3-β-alanine-CCK4 vector (S-EOE-MAG3-β-alanine: S-(1-ethoxyethyl) mercaptoacetyltriglycyl -β-alanine and CCK4: Trp-Met-Asp-Phe-NH2) was obtained by successive condensations of activated amino acids on resin with high chemical purity. This biovector was complexed at high dilution scale with 99mTc as well as at ponderable level with 185/187Re and 99Tc. In particular, this biovector was efficiently labelled with 99mTc (yield>95%) in one step under pH 7–8
Annales de Toxicologie Analytique, 2013
Objectives: A liquid/liquid extraction technique on solid support of Δ 9 -tetradydrocannabinol (T... more Objectives: A liquid/liquid extraction technique on solid support of Δ 9 -tetradydrocannabinol (THC), 11-hydroxy-Δ 9 -tetradydrocannabinol (11-OH-THC) and 11-nor-Δ 9 -tetradydrocannabinol-9-carboxylic acid (THC-COOH) in plasma was developed in order to be assayed by high-performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS). Methods: The samples were extracted by liquid/liquid extraction over solid support of an extraction cartridge. The extracts were thereafter dried down and injected into the HPLC-MS/MS system set with a positive electrospray mode using a Waters XTerra MS C18 3.5-μm 2.1 × 150 mm column. Results: The extraction recovery levels were 66%, 70% and 71% for THC, and 75%, 93% and 101% for 11-OH-THC at concentrations of 2.5, 5 and 10 ng/mL, respectively. They were 86% and 78% for THC-COOH at concentrations of 5 and 10 ng/mL. The limits of detection (LOD) were 0.09, 0.08 and 0.91 ng/mL for THC, 11-OH-THC and THC-COOH, respectively. The limits of quantification (LOQ) were 0.16, 0.15 and 3.24 ng/mL for THC, 11-OH-THC and THC-COOH, respectively. The inter-series incertitude CV determined for concentrations of 1, 2.5 and 10 ng/mL were 12.1%, 12.0% and 6.4% for THC, 14.5%, 11.1% and 7.2% for 11-OH-THC, and 14.9%, 26.2% and 11.3% for THC-COOH. Conclusion: The novel extraction method for THC, 11-OH-THC and THC-COOH developed in this work is rapid, sensitive and specific. It may be a valuable tool for predictive toxicology, high-throughput metabolism and pharmacokinetic studies of cannabinoids.
Addictive Disorders & Their Treatment, 2014
Infection and Drug Resistance, 2008
The aim of this biomedical trial was to clarify the physiological role of procalcitonin (PCT) in ... more The aim of this biomedical trial was to clarify the physiological role of procalcitonin (PCT) in renal parenchyma apoptosis and fi brosis caused by acute childhood pyelonephritis. This prospective study enrolled 183 children. All children were treated with bi-therapy according to the French consensus on acute pyelonephritis treatment dated November 16, 1990: intravascular administration of ceftriaxone 50 mg/kg/day and netromicine 7 mg/kg/day during the fi rst 48 hours, followed by specifi c antibiotherapy suited to antibiogram. On admission, PCT, C-reactive protein, and phospholipase A2 were quantifi ed in serum. Scintigraphy monitoring with 99m Tc-DMSA was performed on day 4 and 9 months later, in the presence of persistent abnormalities. On day 4, 78% presented renal parenchyma alterations and 30% renal fi brosis 9 months after admission. Paradoxically, PCT level was signifi cantly lower in the presence of renal fi brosis due to cell apoptosis (4.19 vs 7.59 µgL -1 ). A signifi cant increase in PCT indicated favorable progress (recovery 7.55 vs aggravation 3.34) and no difference between recovery and improvement. This result suggests the protective effect of PCT against apoptosis by nitric oxide down-regulation.
Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 2007
S-EOE-MAG3-β-alanine-CCK4 vector (S-EOE-MAG3-β-alanine: S-(1-ethoxyethyl) mercaptoacetyltriglycyl... more S-EOE-MAG3-β-alanine-CCK4 vector (S-EOE-MAG3-β-alanine: S-(1-ethoxyethyl) mercaptoacetyltriglycyl -β-alanine and CCK4: Trp-Met-Asp-Phe-NH2) was obtained by successive condensations of activated amino acids on resin with high chemical purity. This biovector was complexed at high dilution scale with 99mTc as well as at ponderable level with 185/187Re and 99Tc. In particular, this biovector was efficiently labelled with 99mTc (yield&amp;amp;amp;amp;gt;95%) in one step under pH 7–8
Nuclear Medicine and Biology, 2015
The N-methyl-d-aspartate receptor (NMDAr) is an ionotropic receptor that mediates excitatory tran... more The N-methyl-d-aspartate receptor (NMDAr) is an ionotropic receptor that mediates excitatory transmission. NMDAr overexcitation is thought to be involved in neurological and neuropsychiatric disorders such as Alzheimer disease and schizophrenia. We synthesized [(18)F]-fluoroethylnormemantine ([(18)F]-FNM), a memantine derivative that binds to phencyclidine (PCP) sites within the NMDA channel pore. These sites are primarily accessible when the channel is in the active and open state. Radiosynthesis was carried out using the Raytest® SynChrom R&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;D fluorination module. Affinity of this new compound was determined by competition assay. We ran a kinetic study in rats and computed a time-activity curve based on a volume-of-interest analysis, using CARIMAS® software. We performed an ex vivo autoradiography, exposing frozen rat brain sections to a phosphorscreen. Adjacent sections were used to detect NMDAr by immunohistochemistry with an anti-NR1 antibody. As a control of the specificity of our compound for NMDAr, we used a rat anesthetized with ketamine. Correlation analysis was performed with ImageJ software between signal of autoradiography and immunostaining. Fluorination yield was 10.5% (end of synthesis), with a mean activity of 3145MBq and a specific activity above 355GBq/μmol. Affinity assessment allowed us to determine [(19)F]-FNM IC50 at 6.1 10(-6)M. [(18)F]-FMN concentration gradually increased in the brain, stabilizing at 40minutes post injection. The brain-to-blood ratio was 6, and 0.4% of the injected dose was found in the brain. Combined ex vivo autoradiography and immunohistochemical staining demonstrated colocalization of NMDAr and [(18)F]-FNM (r=0.622, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001). The highest intensity was found in the cortex and cerebellum, and the lowest in white matter. A low and homogeneous signal corresponding to unspecific binding was observed when PCP sites were blocked with ketamine. [(18)F]-FNM appears to be a promising tracer for imaging NMDAr activity for undertaking preclinical studies in perspective of clinical detection of neurological or neuropsychological disorders.
The N-methyl-D-aspartate receptor (NMDAr) is an ionotropic receptor that mediates excitatory tran... more The N-methyl-D-aspartate receptor (NMDAr) is an ionotropic receptor that mediates excitatory transmission. NMDAr overexcitation is thought to be involved in neurological and neuropsychiatric disorders such as Alzheimer disease and schizophrenia. We synthesized [ 18 F]-fluoroethylnormemantine ([ 18 F]-FNM), a memantine derivative that binds to phencyclidine (PCP) sites within the NMDA channel pore. These sites are primarily accessible when the channel is in the active and open state. Methods: Radiosynthesis was carried out using the Raytest® SynChrom R&D fluorination module. Affinity of this new compound was determined by competition assay. We ran a kinetic study in rats and computed a time-activity curve based on a volume-of-interest analysis, using CARIMAS® software. We performed an ex vivo autoradiography, exposing frozen rat brain sections to a phosphorscreen. Adjacent sections were used to detect NMDAr by immunohistochemistry with an anti-NR1 antibody. As a control of the specificity of our compound for NMDAr, we used a rat anesthetized with ketamine. Correlation analysis was performed with ImageJ software between signal of autoradiography and immunostaining. Results: Fluorination yield was 10.5% (end of synthesis), with a mean activity of 3145 MBq and a specific activity above 355 GBq/μmol. Affinity assessment allowed us to determine [ 19 F]-FNM IC50 at 6.1 10 −6 M. [ 18 F]-FMN concentration gradually increased in the brain, stabilizing at 40 minutes post injection. The brain-to-blood ratio was 6, and 0.4% of the injected dose was found in the brain. Combined ex vivo autoradiography and immunohistochemical staining demonstrated colocalization of NMDAr and [ 18 F]-FNM (r = 0.622, p b 0.0001). The highest intensity was found in the cortex and cerebellum, and the lowest in white matter. A low and homogeneous signal corresponding to unspecific binding was observed when PCP sites were blocked with ketamine. Conclusions: [ 18 F]-FNM appears to be a promising tracer for imaging NMDAr activity for undertaking preclinical studies in perspective of clinical detection of neurological or neuropsychological disorders
Annales de Toxicologie Analytique, 2013
Objectives: A liquid/liquid extraction technique on solid support of Δ 9 -tetradydrocannabinol (T... more Objectives: A liquid/liquid extraction technique on solid support of Δ 9 -tetradydrocannabinol (THC), 11-hydroxy-Δ 9 -tetradydrocannabinol (11-OH-THC) and 11-nor-Δ 9 -tetradydrocannabinol-9-carboxylic acid (THC-COOH) in plasma was developed in order to be assayed by high-performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS). Methods: The samples were extracted by liquid/liquid extraction over solid support of an extraction cartridge. The extracts were thereafter dried down and injected into the HPLC-MS/MS system set with a positive electrospray mode using a Waters XTerra MS C18 3.5-μm 2.1 × 150 mm column. Results: The extraction recovery levels were 66%, 70% and 71% for THC, and 75%, 93% and 101% for 11-OH-THC at concentrations of 2.5, 5 and 10 ng/mL, respectively. They were 86% and 78% for THC-COOH at concentrations of 5 and 10 ng/mL. The limits of detection (LOD) were 0.09, 0.08 and 0.91 ng/mL for THC, 11-OH-THC and THC-COOH, respectively. The limits of quantification (LOQ) were 0.16, 0.15 and 3.24 ng/mL for THC, 11-OH-THC and THC-COOH, respectively. The inter-series incertitude CV determined for concentrations of 1, 2.5 and 10 ng/mL were 12.1%, 12.0% and 6.4% for THC, 14.5%, 11.1% and 7.2% for 11-OH-THC, and 14.9%, 26.2% and 11.3% for THC-COOH. Conclusion: The novel extraction method for THC, 11-OH-THC and THC-COOH developed in this work is rapid, sensitive and specific. It may be a valuable tool for predictive toxicology, high-throughput metabolism and pharmacokinetic studies of cannabinoids.
Canadian Society of Forensic Science Journal, 2008
ABSTRACT Based on initial clinical observations, the global population was divided into four grou... more ABSTRACT Based on initial clinical observations, the global population was divided into four groups: those without the presence of lividity and rigidity (GI); those with the presence of lividity and rigidity (GII); those with signs of putrefaction (GIII); and the group that included the bodies kept in the funeral home at low temperature (GIV). There was no significant difference in the troponin levels between group GI (short postmortem delay) and GII (intermediate postmortem delay). A significant increase in this marker was observed in GIII (presence of putrefaction) compared with GI + GII (absence of putrefaction). For short and intermediate delays, storage in the funeral home did not modify the kinetic release of troponin. On the other hand, an increase in the level of Ic-Tn was positively correlated with the duration of cardiac massage. Since the troponin level rises during putrefaction, an exclusion limit was determined to be 11 mg/l, above which the results were deemed uninterpretable. Under these conditions, the predictive capacity of Troponin Ic for cardiac death is optimal at 0.8 mg/l with sensitivity and specificity estimated at 86 percent and 100 percent, respectively. Application of this marker requires knowledge of the circumstances of death and anamnestic elements, as well as observations and examinations of the body. Under these conditions, cardiac troponin apparently is a helpful element to use in determining suspicious deaths, particularly sudden deaths. The authors analyzed the Ic-Tn concentrations at the time of 32 body removals conducted from 2005 to 2006 in northern suburbs of Paris. 2 tables, 1 figure, and 26 references
Introduction: The setting up of Mediterranean collaboration in forensic research is dependent on ... more Introduction: The setting up of Mediterranean collaboration in forensic research is dependent on inter-organisational collaboration and on governmental policy for scientific initiatives. The recent improvements in transportation and communication technologies have made it easier to organize long-distance collaboration research activities. However to get over physical distance between collaborating researchers requires good coordination and the presence of an efficient intermediary. Thanks to the interface of AFPreMed, French (IRCGN, Claude Bernard Laboratory) and Algerian researcher teams (CHU of Tizi-Ouzou) have recently initiated a forensic toxicological collaboration. In this abstract we report an example of Mediterranean collaborative investigations concerning the first case of fatal human poisoning by vanadium. Case report: At 10h30 p.m., a 24-year-old woman was admitted to the emergency department of the university hospital of Tizi-Ouzou (Algeria), for diffuse abdominal pain, ...
Forensic Medicine and Anatomy Research, 2013
In this prospective study, we evaluated the use of PCT when collecting the body which was carried... more In this prospective study, we evaluated the use of PCT when collecting the body which was carried out. The chosen cut-off was set at 10 ng/mL because at this level, the PCT was associated to a multiorgan failure attributable to a septic shock. For 90 cases, two groups were stratified by their final diagnosis: 33 of for non violent deaths and 57 of violent deaths. There was no significant elevation of procalcitonin rate (PCT) in the group of violent deaths. We noted 6 elevations of PCT rate above 10 ng/mL for non violent deaths (15.4%) and in 3 cases there was an evidence for an infectious context (recent antiinfectious treatments, chemotherapy in progress).
Journal of Hepatology, 2008
changes in fibrosis scores were +0.36 (95% CI 0.07−0.64) and +0.32 (95% CI −0.39−1.03) in the E1 ... more changes in fibrosis scores were +0.36 (95% CI 0.07−0.64) and +0.32 (95% CI −0.39−1.03) in the E1 and placebo group, respectively (p = 0.87), while changes in inflammation scores were +0.81 (0.33−1.29) and +1.28 (0.22−2.34; p = 0.36). Multiple regression indicated the following factors as significantly associated with fibrosis progression: BMI at baseline (BMI < 25 predicted to progress +0.59 more than BMI > 25), previous IFN treatment (IFN-experienced patients progress more than IFN-naive patients), and Ishak fibrosis stage at baseline (low fibrosis progress +0.80 more than high fibrosis). No association was seen between histological evolution from baseline and age, gender, HCV E1 Ab status and ALT at baseline, or ribavirin history.
Acta Clinica Belgica, 2006
In situ microdialysis allows monitoring of metabolic cellular processes at the tissue level in vi... more In situ microdialysis allows monitoring of metabolic cellular processes at the tissue level in vivo. In the assessment of physiopathologic alterations seen in lipodystrophy, monitoring of glycerol release is pivotal. Indeed, it allows to quantify the pharmacological responsiveness of subcutaneous adipose tissue in humans. Until now, the small volume of microdialysate collected (5-15 microL/sample) restricted the assessment of glycerol level to the use of the radio-enzymatic method or the reference spectrophotometric microanalysis technique. The aim of this study was to adapt the method of glycerol measurement by iminequinone spectrophotometry colorimetric assay (520 nm) using the following reagent: 0.5 IU Glycerokinase, 1.23 IU glycerophosphate oxidase, 0.98 IU peroxidase, 4.6 mM Mg, 5.4 mM 4-chlorophenol, 0.25 mM 4-aminoantipyrine and 1.4 mM ATP. The assay was setup to run on Olympus AU 2700 automate (15 pL sample volume). The sensitivity of the method was improved by adding a 0.2 mmol triglyceride (TG) solution and 1.5 IU lipase to samples, reducing the limit of free glycerol quantification to 0.020 mmol/L. The analytical repeatability was 2.0% and the reproducibility was 7.9%. The present method thus demonstrated the feasibility of pharmacodynamic exploration of local cutaneous responsiveness in vivo in clinical trials.
Nuclear Medicine and Biology, 1994
Bisphosphonates (BPs) are characterized by a PϪCϪP backbone structure and two phosphonic acid gro... more Bisphosphonates (BPs) are characterized by a PϪCϪP backbone structure and two phosphonic acid groups bonded to the same carbon, and are established as osteoclast-mediated bone resorption inhibitors. The nature of the groups attached to the central carbon atom are responsible in determining the potency of bisphosphonates as anti-resorption drugs. However, it is not yet clear the exact relationship between their molecular structure and pharmacologic activities. In this study, molecular geometries of pamidronate, alendronate and neridronate, differing only in the length of the aliphatic chains, were predicted by molecular mechanics and their interactions with hydroxyapatite, the main bone mineral component, were examined. We report the synthesis and radiochemical characterization of 153 Sm complexes with pamidronate, alendronate and neridronate. Hydroxyapatite binding and biodistribution studies of these complexes have shown a good correlation with the theoretical molecular modeling interaction studies. So, it is possible to conclude that computational chemistry techniques are a good approach to evaluate specific interactions and may play a relevant role in determining the relative ability of BPs to mineral bone, and open new perspectives to the design of new BPs with increased pharmacological activity. These techniques could be extended to BPs as ligands to carrier radioactive metals, aiming for new bone therapeutic radiopharmaceuticals.
Nuclear Medicine and Biology, 1996
We have synthesized and characterized seven ligands derived from 2-aminocyclopentene-ldithiocarbo... more We have synthesized and characterized seven ligands derived from 2-aminocyclopentene-ldithiocarboxylic acid with different donor sets ( SN2-, SNO'-, SNN2-, SNN03-and SNNN3-) and different substituents on the sulfur moieties -SR (with R = H, CH, or C,H,O(CH,)CH).
European Neuropsychopharmacology, 2014
Forensic Medicine and Anatomy Research, 2015
ABSTRACT The aim of the present work was to investigate the exposure to the medical and industria... more ABSTRACT The aim of the present work was to investigate the exposure to the medical and industrial toxic chemicals. The research was carried out on hair, nail and blood samples in a panel of 40 healthy volunteers aged 7 to 77 with an average of 45 ± 19 years (18 women (45%) and 22 men (55%)). All of these individuals had not received medication for at least 1 year, including antibiotics and psychotropic. This study was realized from July 2013 to March 2014 in Beijing, China. The method for an accurate and reliable screening of medical and an industrial toxic chemical was based on detection and assay by ultra-high performance liquid chromatography with UV detection type of diode arrays. Also more than 10,000 toxic molecules commonly found in western industrial countries were screened by coupling gas chromatography and mass spectrometry. The main results indicate that the molecules analyzed are mainly antibiotic (Gentamycine and Tobramycine), antidepressant (Amitriptylin and its metabolites), narcotic (MDMA and Clonitazene), ingredient in cosmetics (Benzenediol and Benzoic acid), insecticide (Carbamate derivative), ketamine, chlorhexidine and phthalate derivatives. There are no detailed documented baseline data of the analysis of medical and Industrial toxic pollutants in hair, nail and blood samples in Beijing; however, this study should be completed on samples from other provinces of China. This study is the first of its kind. Therefore, further studies should be conducted in other cities and provinces of China to be compared with each other.
Sulfonylureas are herbicides ( ) which will find increased use due to their wide-spectrum effects... more Sulfonylureas are herbicides ( ) which will find increased use due to their wide-spectrum effects on weeds and their low toxic effects on mammals (1). The effects of sulfonylureas on plants, micro-algae and bacteria are due to the inhibition of acetolactate synthase (ALS) involved in the synthesis of acetolactic and butyric acids, which are the precursors of the branched-chain amino acids: isoleucine, leucine and valine (2). Indeed, ALS catalyzes the condensation of pyruvate with acetaldehyde by means of amine hydroxy-ethyl-thiamine diphosphatase. The final amino acid results from the transfer of the glutamate amino group to the a-ketonic acid through transaminase .
Nuclear Instruments & Methods in Physics Research Section A-accelerators Spectrometers Detectors and Associated Equipment, 2007
S-EOE-MAG3-β-alanine-CCK4 vector (S-EOE-MAG3-β-alanine: S-(1-ethoxyethyl) mercaptoacetyltriglycyl... more S-EOE-MAG3-β-alanine-CCK4 vector (S-EOE-MAG3-β-alanine: S-(1-ethoxyethyl) mercaptoacetyltriglycyl -β-alanine and CCK4: Trp-Met-Asp-Phe-NH2) was obtained by successive condensations of activated amino acids on resin with high chemical purity. This biovector was complexed at high dilution scale with 99mTc as well as at ponderable level with 185/187Re and 99Tc. In particular, this biovector was efficiently labelled with 99mTc (yield>95%) in one step under pH 7–8
Annales de Toxicologie Analytique, 2013
Objectives: A liquid/liquid extraction technique on solid support of Δ 9 -tetradydrocannabinol (T... more Objectives: A liquid/liquid extraction technique on solid support of Δ 9 -tetradydrocannabinol (THC), 11-hydroxy-Δ 9 -tetradydrocannabinol (11-OH-THC) and 11-nor-Δ 9 -tetradydrocannabinol-9-carboxylic acid (THC-COOH) in plasma was developed in order to be assayed by high-performance liquid chromatography and tandem mass spectrometry (HPLC-MS/MS). Methods: The samples were extracted by liquid/liquid extraction over solid support of an extraction cartridge. The extracts were thereafter dried down and injected into the HPLC-MS/MS system set with a positive electrospray mode using a Waters XTerra MS C18 3.5-μm 2.1 × 150 mm column. Results: The extraction recovery levels were 66%, 70% and 71% for THC, and 75%, 93% and 101% for 11-OH-THC at concentrations of 2.5, 5 and 10 ng/mL, respectively. They were 86% and 78% for THC-COOH at concentrations of 5 and 10 ng/mL. The limits of detection (LOD) were 0.09, 0.08 and 0.91 ng/mL for THC, 11-OH-THC and THC-COOH, respectively. The limits of quantification (LOQ) were 0.16, 0.15 and 3.24 ng/mL for THC, 11-OH-THC and THC-COOH, respectively. The inter-series incertitude CV determined for concentrations of 1, 2.5 and 10 ng/mL were 12.1%, 12.0% and 6.4% for THC, 14.5%, 11.1% and 7.2% for 11-OH-THC, and 14.9%, 26.2% and 11.3% for THC-COOH. Conclusion: The novel extraction method for THC, 11-OH-THC and THC-COOH developed in this work is rapid, sensitive and specific. It may be a valuable tool for predictive toxicology, high-throughput metabolism and pharmacokinetic studies of cannabinoids.
Addictive Disorders & Their Treatment, 2014
Infection and Drug Resistance, 2008
The aim of this biomedical trial was to clarify the physiological role of procalcitonin (PCT) in ... more The aim of this biomedical trial was to clarify the physiological role of procalcitonin (PCT) in renal parenchyma apoptosis and fi brosis caused by acute childhood pyelonephritis. This prospective study enrolled 183 children. All children were treated with bi-therapy according to the French consensus on acute pyelonephritis treatment dated November 16, 1990: intravascular administration of ceftriaxone 50 mg/kg/day and netromicine 7 mg/kg/day during the fi rst 48 hours, followed by specifi c antibiotherapy suited to antibiogram. On admission, PCT, C-reactive protein, and phospholipase A2 were quantifi ed in serum. Scintigraphy monitoring with 99m Tc-DMSA was performed on day 4 and 9 months later, in the presence of persistent abnormalities. On day 4, 78% presented renal parenchyma alterations and 30% renal fi brosis 9 months after admission. Paradoxically, PCT level was signifi cantly lower in the presence of renal fi brosis due to cell apoptosis (4.19 vs 7.59 µgL -1 ). A signifi cant increase in PCT indicated favorable progress (recovery 7.55 vs aggravation 3.34) and no difference between recovery and improvement. This result suggests the protective effect of PCT against apoptosis by nitric oxide down-regulation.
Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment, 2007
S-EOE-MAG3-β-alanine-CCK4 vector (S-EOE-MAG3-β-alanine: S-(1-ethoxyethyl) mercaptoacetyltriglycyl... more S-EOE-MAG3-β-alanine-CCK4 vector (S-EOE-MAG3-β-alanine: S-(1-ethoxyethyl) mercaptoacetyltriglycyl -β-alanine and CCK4: Trp-Met-Asp-Phe-NH2) was obtained by successive condensations of activated amino acids on resin with high chemical purity. This biovector was complexed at high dilution scale with 99mTc as well as at ponderable level with 185/187Re and 99Tc. In particular, this biovector was efficiently labelled with 99mTc (yield&amp;amp;amp;amp;gt;95%) in one step under pH 7–8
Nuclear Medicine and Biology, 2015
The N-methyl-d-aspartate receptor (NMDAr) is an ionotropic receptor that mediates excitatory tran... more The N-methyl-d-aspartate receptor (NMDAr) is an ionotropic receptor that mediates excitatory transmission. NMDAr overexcitation is thought to be involved in neurological and neuropsychiatric disorders such as Alzheimer disease and schizophrenia. We synthesized [(18)F]-fluoroethylnormemantine ([(18)F]-FNM), a memantine derivative that binds to phencyclidine (PCP) sites within the NMDA channel pore. These sites are primarily accessible when the channel is in the active and open state. Radiosynthesis was carried out using the Raytest® SynChrom R&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;D fluorination module. Affinity of this new compound was determined by competition assay. We ran a kinetic study in rats and computed a time-activity curve based on a volume-of-interest analysis, using CARIMAS® software. We performed an ex vivo autoradiography, exposing frozen rat brain sections to a phosphorscreen. Adjacent sections were used to detect NMDAr by immunohistochemistry with an anti-NR1 antibody. As a control of the specificity of our compound for NMDAr, we used a rat anesthetized with ketamine. Correlation analysis was performed with ImageJ software between signal of autoradiography and immunostaining. Fluorination yield was 10.5% (end of synthesis), with a mean activity of 3145MBq and a specific activity above 355GBq/μmol. Affinity assessment allowed us to determine [(19)F]-FNM IC50 at 6.1 10(-6)M. [(18)F]-FMN concentration gradually increased in the brain, stabilizing at 40minutes post injection. The brain-to-blood ratio was 6, and 0.4% of the injected dose was found in the brain. Combined ex vivo autoradiography and immunohistochemical staining demonstrated colocalization of NMDAr and [(18)F]-FNM (r=0.622, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.0001). The highest intensity was found in the cortex and cerebellum, and the lowest in white matter. A low and homogeneous signal corresponding to unspecific binding was observed when PCP sites were blocked with ketamine. [(18)F]-FNM appears to be a promising tracer for imaging NMDAr activity for undertaking preclinical studies in perspective of clinical detection of neurological or neuropsychological disorders.