Neoadjuvant chemoradiation and pancreaticoduodenectomy for initially locally advanced head pancreatic adenocarcinoma

International audienceThe most accepted treatment for locally advanced pancreatic adenocarcinoma (LAPA) is chemoradiotherapy (CRT). We sought to determine the benefit of pancreaticoduodenectomy (PD) in patients with LAPA initially treated by neoadjuvant CRT

Binding properties of 3-[125I]iodophencyclidine, a new radioligand for N-methyl-D-aspartate-gated ionic channels.

International audienceThe binding properties of the 125I-labeled phencyclidine derivative N-[1-(3-[125I]iodophenyl)cyclohexyl]piperidine (3-[125I]iodo-PCP), a new ligand of the N-methyl-D-aspartate (NMDA)-gated ionic channel, were investigated. Association and dissociation kinetic curves of 3-[125I]iodo-PCP with rat brain homogenates were well described by two components. About 32% of the binding was of fast association and fast dissociation, and the remaining binding was of slow association and slow dissociation. Saturation curves of 3-[125I]iodo-PCP also were well described using two binding sites: one of a high affinity (KDH = 15.8 +/- 2.3 nM) and the other of a low affinity (KDL = 250 +/- 40 nM). 3-Iodo-PCP inhibited the binding of 3-[125I]iodo-PCP with inhibition curves that were well fitted by a two-site model. The binding constants (KiH, BmaxH; KiL, BmaxL) so obtained were close to those obtained in saturation experiments. Ligands of NMDA-gated ionic channels also inhibited the binding of 3-[125I]iodo-PCP with two constants, KiH and KiL. There was a very good correlation (r = 0.987) between the affinities of these ligands to bind to NMDA-gated ionic channels and their potencies to inhibit the binding of 3-[125I]iodo-PCP with a high affinity. Moreover, the regional distribution of the high-affinity binding of 3-[125I]-iodo-PCP paralleled that of tritiated N-[1-(2-thienyl)cyclohexyl]piperidine ([3H]TCP). In contrast to that of [3H] TCP, the binding of 3-[125I]iodo-PCP to well-washed rat brain membranes was fast and insensitive to glutamate and glycine.(ABSTRACT TRUNCATED AT 250 WORDS

Restoring GABA tone rescues hippocampal long-term depression impaired after maternal immune stress

International audienceRat maternal immune challenge with lipopolysaccharide (LPS) led to an early disturbance of glutamatergic synaptic plasticity in the hippocampus of male offspring (Lanté et al., 2007, 2008). This was evidenced by a premature loss of the ability to exhibit long-term depression (LTD) (Escobar et al., 2011), which occurred between the second and the third postnatal weeks instead of after the first postnatal month. We hypothesized this would be related to GABAergic system deficiency.Sprague Dawley rats received either 500 μg kg−1 LPS or 2 ml kg−1 isotonic saline ip on gestational day 19. Male offspring's hippocampus was studied between postnatal days 12–25. GABAergic interneuron density was determined by stereology. GABAergic transmission and the effect of tiagabine on glutamatergic synaptic plasticity were assessed with patch clamp and extracellular recordings respectively.Prenatal LPS triggered a clear deficit of GABAergic interneurons predominant in the CA3 area of the hippocampus, associated with presynaptic GABAergic transmission deficiency, as shown by reduced evoked inhibitory post synaptic currents and by a reduction of the frequency of miniature post synaptic currents. Of note, GABAA and GABAB receptors and GABA transporters appeared mainly unaffected.Increasing ambient GABA by impairing GABA re-uptake with tiagabine did not interact with the occurrence of LTD in normal animals in this developmental window, but rescued the impaired synaptic plasticity observed in LPS-challenged rats.Deficiency in tonic actions of GABA seems to be central to the dysregulation of synaptic plasticity observed after immune prenatal challenge. Modulating GABAergic tone may be a valuable therapeutic strategy for the cognitive impairment associated with this condition