Hafid Belhadj-Tahar

Procalcitonin implication in renal cell apoptosis induced by acute pyelonephritis in children

The aim of this biomedical trial was to clarify the physiological role of procalcitonin (PCT) in renal parenchyma apoptosis and fibrosis 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: intra-vascular administration of ceftriaxone 50 mg/kg/day and netromicine 7 mg/kg/day during the first 48 hours, followed by specific antibiotherapy suited to antibiogram. On admission, PCT, C-reactive protein, and phospholipase A2 were quantified in serum. Scintigraphy monitoring with 99mTc-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 fibrosis 9 months after admission. Paradoxically, PCT level was significantly lower in the presence of renal fibrosis due to cell apoptosis (4.19 vs 7.59 μgL−1). A significant 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.

Technetium labeling of bi, tri and tetradentate ligands derived from 2-aminocyclopentene-1-dithiocarboxylic acid: Characterization and biodistribution of their oxo and nitrido 99mtechnetium complexes

We have synthesized and characterized seven ligands derived from 2-aminocyclopentene-1-dithiocarboxylic acid with different donor sets (SN2-, SNO2-, SNN2-, SNNO3- and SNNN3-) and different substituents on the sulfur moieties-SR (with R = H, CH3 or C2H5O(CH3)CH). With five of these ligands technetium nitrido complexes have been obtained with high yields (over 95%) using rather harsh conditions (pH = 1, temperature > or = 80 degrees C), whereas for technetium oxo complexes similar high yields were only obtained with two ligands but with mild conditions (pH = 7-8, temperature approximately equal to 50 degrees C). Changing an OH group for an NH2 has a drastic effect upon labeling yields. The possibility of complexing ligands as either oxo (TcO)3+ or nitrido (TcN)2+ derivatives increases the number of available labeled agents with different overall change and consequently with different biological behavior.

Case Report of Cathinone-Like Designer Drug Intoxication Psychosis and Addiction With Serum Identification

The use of designer drugs commonly marketed as “Bath Salts” or “Energy” has dramatically risen in recent years. Fatalities and cases of aggressive behavior, even cannibalism have been recently reported in the media. However, these cases have been poorly documented. In this paper, we report a case of repetitive and similar acute psychotic episodes induced by Energy 3 intake. Comparative Analyses of Energy 3 sample and patient’s serum by gas chromatography-mass spectrometry detected the presence of 2 synthetic cathinone derivatives: methylenedioxypyrovalerone and pentylone. Finally, this patient’s clinical picture is characterized by the insidious development of dependence to this product. The absence of patient’s personal addiction history, the late onset of this dependence, and its high intensity, suggest a high addiction potential of these substances.

Synthesis, characterization and biodistribution of new 99mTc oxo and nitrido complexes with Bi- and tetradendate unsaturated NS and N2S2 Schiff bases derived from 2-aminocyclopentene-1-dithiocarboxylic acid as potential heart imaging agents

The synthesis, characterization and 99mTc labelling of unsaturated diamino dithiol ligands with methyl dithiocarboxylate functions: 2-aminocyclopentene-1-dithiocarboxylic methyl ester (H2L1), N,N-ethylene bis(methyl 2-aminocyclopentene-1-dithiocarboxylate) (H2L2) and N,N-propylene bis (methyl 2-aminocyclopentene-1-dithiocarboxylate) (H2L3) are described. Cationic oxo (Tc = O) and neutral nitrido (Tc = N) complexes were obtained. Biodistribution studies in rat showed a good heart uptake of 99mTcN-L2 (2% ID at 5 min) with a high heart-to-blood ratio (5.8 at 5 min), but this complex also exhibited high lung and liver uptake.

Radiolabeling of [18F]-fluoroethylnormemantine and initial in vivo evaluation of this innovative PET tracer for imaging the PCP sites of NMDA receptors.

INTRODUCTIONnThe 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.nnnMETHODSnRadiosynthesis 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.nnnRESULTSnFluorination 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<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.nnnCONCLUSIONSn[(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.

New Potential In Situ Anticancer Agent Derived from [188Re]rhenium Nitro-Imidazole Ligand Loaded 5th Generation Poly-L-Lysine Dendrimer for Treatment of Transplanted Human Liver Carcinoma in Nude Mice

Hepatocellular carcinoma (HCC) is the most common primary liver tumor and one of the fifth most common tumors worldwide. In this article we report the results of in vivo studies of potential anticancer agent [188Re] rhenium-ImDendrim derived from [188Re]rhenium-nitro-imidazole-methyl -1,2,3-triazol-methyl-di-(2-pycolyl)amine as radioactive ligand loaded 5th generation poly-L-lysine denrimer (172,3 kDa, 20 nM). Methods: 5.0 × 10âx81¶ cells were subcutaneously injected into mice. Once tumor established, 4 mice lots were treated with a single dose of the test item (37, 74, 92.5 and 111 MBq of [188Re]rhenium-ImDendrim, respectively) compared to control lots (free [188Re]rhenium and non-radioactive ImDendrim). By the end of the study in six weeks post-test compound administration, the tumors were collected for histological analysis. Results: The treatment was well tolerated. In fact, [188Re]rhenium-ImDendrim shows high significant anti-tumor property in this experimental cancer model even with the lowest dose of 37 MBq compared to control groups. These results were further confirmed by histological analysis. Large tumor mass only observed in tumors sections from mice in the control groups, were disappeared in favour of collagen tissue in treated groups. In conclusion, this novel potential radiopharmaceutical agent has giving promising experimental results by showing an anti-tumoral activity in this experimental of liver cancer model in mice under the tested conditions.

L'intérêt en Médecine Légale de la Troponine Ic Devant Une Mort Suspecte

RÉSUMÉ Nous évaluons dans cet article lintérêt de la troponine Ic lors de la levée du corps dans le but dorienter les circonstances de décès suspect. Dans ce contexte, 32 analyses de la troponine Ic ont été effectuées dans le cadre de la levée du corps dans la banlieue nord Parisienne (France) entre 2005 et 2006. Après lexamen clinique initial, la population globale a été subdivisée en 4 groupes: un premier groupe (GI) sans présence de lividité et rigidité, un deuxième groupe (GII) avec présence de lividité et rigidité, un troisième groupe (GIII) avec présence de signes de putréfaction et un quatrième groupe (GIV) dont les corps ont été conservés au funérarium à basse température. Il ny a pas de différence significative entre le taux de troponine Ic concernant les groupes (GI) sans présence de lividité et rigidité et (GII) avec présence de lividité et de rigidité. Par contre il y a une augmentation significative du taux de troponine en présence de la putréfaction comparée à labsence de décomposition (GIII>50μg/L versus GI+GII= 13,5μg/L avec p<0,001). En labsence de putréfaction, la conservation des corps au funérarium ne semble pas modifier la cinétique de relargage de la troponine Ic. Par contre, il y a une augmentation significative de ce biomarqueur en relation avec la durée et lintensité du massage cardiaque. Afin de saffranchir du phénomène de putréfaction qui contribue à laugmentation du taux de la troponine Ic, nous avons estimé statistiquement le seuil dexclusion de ce marqueur à 11μg/L au-delà duquel toute valeur a été exclue et donc ininterprétable. Dans ces conditions la capacité prédictive de la troponine Ic vis à vis dun décès dorigine cardiaque est optimale pour 0,8μg/L avec une sensibilité et une spécificité estimée respectivement à 86% et 100%. Cependant la pertinence dapplication de ce biomarqueur requière la connaissance des circonstances et des éléments anamnestiques ainsi que lobservation et lexamen du corps. Moyennant ces précautions, la troponine Ic est à considérer comme une aide précieuse dans lorientation du diagnostic de mort suspecte et en particulier la mort subite.

Synthesis and biodistribution of new oxo and nitrido 99mTc complexes with asymmetrical potentially dianionic or trianionic tetradentate SNNO ligands derived from methyl-2-aminocyclopentene-1-dithiocarboxylic acid.

In this work, 10 new asymmetrical tetradentate SNNO ligands were prepared by reaction of the amine function of methyl 2-[(beta-aminoethyl)amino]cyclopentene-1-dithiocarboxylate with various bifunctional substituents bearing hydroxyl/ketone and hydroxyl/aldehyde functional groups and with diethyl oxalate. 99mTc labeling efficiency was optimized by adjusting temperature and pH conditions. Seven nitrido and two oxo 99mTc complexes were isolated. Six of them proved to be stable near physiological conditions. Biodistribution studies in the rat showed a significant heart uptake for four of them and strong kidney and liver uptake for the other two.