Understanding the Global Problem of Drug Addiction is a Challenge for IDARS Scientists

IDARS is an acronym for the International Drug Abuse Research Society. Apart from our scientific and educational purposes, we communicate information to the general and scientific community about substance abuse and addiction science and treatment potential. Members of IDARS are research scientists and clinicians from around the world, with scheduled meetings across the globe. IDARS is developing a vibrant and exciting international mechanism not only for scientific interactions in the domain of addiction between countries but also ultimately as a resource for informing public policy across nations. Nonetheless, a lot more research needs to be done to better understand the neurobiological basis of drug addiction – A challenge for IDARS scientists

Long-Term Protective Effects of Methamphetamine Preconditioning Against Single-Day Methamphetamine Toxic Challenges

Methamphetamine (METH) use is associated with neurotoxic effects which include decreased levels of dopamine (DA), serotonin (5-HT) and their metabolites in the brain. We have shown that escalating METH dosing can protect against METH induced neurotoxicity in rats sacrificed within 24 hours after a toxic METH challenge. The purpose of the current study was to investigate if the protective effects of METH persisted for a long period of time. We also tested if a second challenge with a toxic dose of METH would cause further damage to monoaminergic terminals. Saline-pretreated rats showed significant METH-induced decreases in striatal DA and 5-HT levels in rats sacrificed 2 weeks after the challenge. Rats that received two METH challenges showed no further decreases in striatal DA or 5-HT levels in comparison to the single METH challenge. In contrast, METH-pretreated rats showed significant protection against METH-induced striatal DA and 5-HT depletion. In addition, the METH challenge causes substantial decreases in cortical 5-HT levels which were not further potentiated by a second drug challenge. METH preconditioning provided almost complete protection against METH –induced 5-HT depletion. These results are consistent with the idea that METH pretreatment renders the brain refractory to METH-induced degeneration of brain monoaminergic systems

Biomarkers of oxidative stress: methods and measures of oxidative DNA damage (COMET assay) and telomere shortening

Oxidative stress is fast becoming the nutritional and medical buzzword for the twenty-first century. The theoretical importance of oxidative stress in diabetes is highlighted by its potential double impact on metabolic dysfunction on one hand and the vascular system on the other hand. The new concept of oxidative stress, being an important trigger in the onset and progression of diabetes and its complications, emphasizes the need for measurement of markers of oxidation to assess the degree of oxidative stress. While we have been routinely measuring biomarkers in our molecular epidemiology projects, here we discuss the utility of two assays, (a) DNA damage assessment by COMET measurement and (b) telomere length measurement. As DNA damage is efficiently repaired by cellular enzymes, its measurement gives a snapshot view of the level of oxidative stress. The protocol allows for measurement of oxidative DNA damage (FPG-sensitive DNA strand breaks). Telomere length measured by Southern blotting technique allows one to estimate the chronic burden of oxidative stress at the molecular level and is now considered as biomarker of biological aging

Neurotensin receptors in human meningiomas.

We have investigated the presence of neurotensin receptors in human meningiomas by in vitro binding autoradiography. Ten of the 12 meningiomas tested displayed specific [3H]neurotensin binding. All meningothelial (n = 3) and transitional (n = 5) meningiomas were positive, whereas only 2 of the 4 fibroblastic meningiomas showed measurable concentrations of neurotensin binding sites. Within the tumors, [3H]neurotensin binding was preferentially observed in syncytial areas. Saturation experiments showed that the maximal binding capacity (Bmax) greatly varied among tumors, ranging from low values to more than 290 fmol/mg of protein. All positive tumors had neurotensin binding sites with a dissociation constant (kd) within the nanomolar range and a pharmacological specificity for [3H]neurotensin similar to neurotensin receptors

Gestion des crises lors du dépassement des seuils de traitabilité des filières biologiques : cas de l'ammonium à Choisy-le-Roi

Les usines du Syndicat des Eaux d'Ile-de-France tendent à reproduire en les accélérant les cycles biologiques les plus importants de l'auto épuration. Les gains qui résultent de cette application sont évidents : la suppression de la chloration de l'eau brute a permis la réduction à son niveau le plus bas de la production de composés organochlorés sapides et dangereux ; l'utilisation étagée de l'ozone et le couplage avec la filtration sur charbon actif granulé ont abaissé la valeur du paramètre carbone organique et notamment de la fraction assimilable ultérieurement dans le réseau ce qui conduit à une grande stabilité du résiduel bactériostatique : le seuil de saveur a été très significativement réduit. En revanche la biologie s'accomode mal de variations brutales de la qualité de l'eau brute et les seuils de traitabilité sont variables en fonction de paramètres multiples. Concernant la nitrification, sa mise en place à Choisy a été à l'origine d'une évolution profonde des modalités de l'exploitation. Pour éviter un retour à la chloration finale génératrice de saveurs, le fonctionnement de la filière doit être suivi de très près. Un système expert et un réseau d'alerte rendent possible l'anticipation de toute décision telle que le ralentissement de la vitesse de filtration et l'utilisation des secours. Un effort particulier doit être mené en parallèle pour contrôler en permanence la qualité de la ressource et l'utilisation optimale des dispositifs d'épuration

Isolation and characterisation of sugarcane rhizobacteria and their effect on nematodes

International audienceA survey showed that species of Burkholderia were frequently associated with the roots of sugarcane. Based on amplified ribosomal DNA restriction analysis the isolates of these bacteria belonged to Burkholderia groups A,B,C,F and G. Data collected from field trials revealed a succession of species during the growth of the crop. Strains belonging to the B. cepacia complex were dominant during the early stages of growth but, in time, were replaced by isolates of the B. tropicalis and B. caribensis groups. In a series of in vitro bioassays it was found that a large proportion of the Burkholderia isolates tested paralysed juveniles of a root-knot nematode, Meloidogyne sp

Unilateral MPTP-induced parkinsonism in monkeys. A quantitative autoradiographic study of dopamine D1 and D2 receptors and re-uptake sites.

The cynomolgus monkeys received a unilateral intracarotid injection of the neurotoxin N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in order to induce a chronic model of hemi-parkinsonism. The procedure was well tolerated by the animals. Unilateral injection of MPTP caused rigidity and bradykinesia of the contralateral limbs, but the animals were able to eat and drink without levodopa therapy. During spontaneous motor activity, animals rotated toward the lesioned side whereas systemic apomorphine injection stimulated circling toward the normal non-lesioned side. Twelve weeks after MPTP injection, we found a marked reduction in striatal and nigral [3H]-mazindol binding on the MPTP-injected side which is indicative of a loss in both dopaminergic nerve terminals and cell bodies. The unilateral dopaminergic denervation was associated with an ipsilateral increase in striatal and a reduction in nigral [3H]-spiperone-labelled D2 dopamine receptors; these changes are consistent with the known localization of the D2 receptors on striatal dopaminergic nerve terminals and on nigral dopaminergic cell bodies. In contrast, no changes in [3H]-SCH 23390-labelled D1 dopamine receptors were observed at the level of either the striatum or the substantia nigra. This study describes a well tolerated procedure which induces a clinical and morphological hemi-parkinsonian syndrome. This animal model may be useful in the studies of new antiparkinsonian drugs, for testing the functional efficacy of brain tissue implants and in the understanding of the physiopathogenesis of levodopa-induced dyskinesias

Sham transplantation protects against 6-hydroxydopamine-induced dopaminergic toxicity in rats: behavioral and morphological evidence.

Administration of the neurotoxin 6-hydroxydopamine (6-OHDA) to rat brain causes biochemical and neuroanatomical changes to the nigrostriatal dopaminergic pathway similar to those observed in Parkinson's disease (PD). Although the cause of PD is unknown, it has been hypothesized that the neurodegenerative changes seen in PD might result from exposure to a neurotoxin. Therefore, strategies for limiting neurotoxin-induced dopaminergic damages, like those caused by 6-OHDA, may be of both clinical and basic interest. Accordingly, we tested the ability of both fetal neural (striatum) and fetal non-neural (liver) tissue implants to protect the rat striatum against the toxic effects of a subsequent intrastriatal injection of 6-OHDA. Non-grafted rats (lesion only) showed amphetamine-induced rotational behavior and a decrease in striatal [3H]mazindol-labeled dopamine uptake sites after 6-OHDA injection. In contrast, the animals grafted with striatum or liver showed no behavioral or biochemical changes. Interestingly, sham-transplanted control animals were also protected against the 6-OHDA-induced toxicity. These results suggest that the resistance of the dopaminergic system against 6-OHDA neurotoxicity observed in grafted and sham-transplanted animals is likely to be related to the surgical procedure itself. This observation points to a possible role for surgery-related events in the clinical improvement described in PD patients who underwent intracerebral transplantation