Search results for "PAM"
showing 10 items of 1768 documents
Modeling interactions between Human Equilibrative Nucleoside Transporter-1 and other factors involved in the response to gemcitabine treatment to pre…
2014
Background Pancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive malignancy, characterized by largely unsatisfactory responses to the currently available therapeutic strategies. In this study we evaluated the expression of genes involved in gemcitabine uptake in a selected cohort of patients with PDAC, with well-defined clinical-pathological features. Methods mRNA levels of hENT1, CHOP, MRP1 and DCK were evaluated by means of qRT-PCR in matched pairs of tumor and adjacent normal tissue samples collected from PDAC patients treated with gemcitabine after surgical tumor resection. To detect possible interaction between gene expression levels and to identify subgroups of patients a…
Inhibitory purinergic transmission in mouse caecum: Role for P2Y1 receptors as prejunctional modulators of ATP release
2007
Using conventional microelectrode recording techniques, we investigated, in the circular muscle of the mouse caecum, the neurotransmitter(s) involved in the neurally-evoked inhibitory junction potentials (IJPs) and the existence of possible prejunctional mechanisms controlling neurotransmitter release. Electrical field stimulation with single pulses elicited IJPs, consisting only of a "fast" hyperpolarization, while using train stimuli (30-50 Hz) the initial fast hyperpolarization was followed by a slower hyperpolarization. The fast and the slow component were selectively antagonized by apamin, a blocker of calcium-activated potassium channels, and N(omega)-nitro-l-arginine methyl ester (l-…
Mechanisms underlying hyperpolarization evoked by P2Y receptor activation in mouse distal colon
2006
In murine colonic circular muscle, ATP mediates fast component of the nerve-evoked inhibitory junction potentials, via activation of P2Y receptors and opening of apamin-sensitive Ca2+-dependent K+ channels. We investigated, using microelectrode recordings, the intracellular events following P2Y-receptor activation by electrical field stimulation or by adenosine 5'-O-2-thiodiphosphate (ADPbetaS), ATP stable analogue. The fast-inhibitory junction potential amplitude was reduced by thapsigargin or ciclopiazonic acid (CPA), sarcoplasmic reticulum Ca2+-ATPase inhibitors, by ryanodine, which inhibits Ca2+ release from ryanodine-sensitive stores, and by 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (S…
Effects of 7-OH-DPAT and U 99194 on the behavioral response to hot plate test, in rats
2005
Aim of present study was to investigate in male Wistar rats, whether behavioral response to hot plate test application could be influenced by systemic administration of 7-OH-DPAT, a dopaminergic (DA) D3 versus D2 receptor agonist, or U 99194, a DA D3 versus D2 receptor antagonist. Each trial lasted no more than 10 s and the whole experimental session lasted 120 min. Animal behavior was recorded by means of a digital videocamera and later, frame by frame examined using a professional videorecorder. Latency of each behavioral pattern, characterizing the response, was analysed, showing significant changes only with U 99194. A multivariate cluster analysis indicated the presence of three main b…
The effects of diazepam on the behavioral structure of the rat's response to pain in the hot-plate test: Anxiolysis vs. pain modulation
2011
The aim of the present study was to evaluate, by means of quantitative and multivariate analyses, the effects of diazepam on the behavioral structure of the rat's response to pain in the hot-plate test as well as whether such changes are associated with drug-induced effects on anxiety and/or nociception. To this purpose, ten groups of male Wistar rats were intraperitoneally injected with saline, diazepam (0.25, 0.5 and 2 mg/kg), FG-7142 (1, 4 and 8 mg/kg) or morphine (3, 6 and 12 mg/kg). The mean number and mean latency to first appearance were calculated for each behavioral component. In addition, multivariate cluster and adjusted residual analyses based on the elaboration of transition ma…
Effects of Substantia Nigra pars compacta lesion on the behavioral sequencing in the 6-OHDA model of Parkinson’s disease
2019
The basal ganglia circuitry plays a crucial role in the sequential organization of behavior. Here we studied the behavioral structure of the animals after 21 days of 6-OHDA-induced lesion of the dopaminergic nigrostriatal system. Frequencies and durations of individual components of the behavioral repertoire were calculated; moreover, whether a temporal organization of the activity was present, it was investigated by using T-pattern analysis, a multivariate approach able to detect the real-time sequential organization of behavior. Six sham-depleted and six rats with unilateral 6−OHDA-lesion of the Substantia Nigra pars compacta were used. As to quantitative evaluations, the comparison betwe…
Impact of recommendations on the initial therapy of Parkinson’s disease: A population-based study in France
2011
International audience; Levodopa induces long-term motor complications in Parkinson's disease (PD). Therapeutic strategies that prevent motor complications are needed. Our aim was to evaluate the impact of recommendations of a French consensus conference published in 2000 on initial PD therapy. We identified 308 PD patients as part of a population-based study performed within the Mutualité Sociale Agricole in five French districts (2007). Neurologists confirmed PD diagnosis. We compared initial therapy in 102 patients treated before 12/31/2000 to that of 206 patients treated afterwards. Initial treatment was in agreement with the recommendations if dopamine agonists were used in patients <6…
Simultaneous controlled iontophoretic delivery of pramipexole and rasagiline in vitro and in vivo: Transdermal polypharmacy to treat Parkinson's dise…
2018
[EN] Effective treatment of Parkinson's disease (PD) involves administration of therapeutic agents with complementary mechanisms of action in order to replenish, sustain or substitute endogenous dopamine. The objective of this study was to investigate anodal co-iontophoresis of pramipexole (PRAM; dopamine agonist) and rasagiline (RAS; MAO-B inhibitor) in vitro and in vivo. Passive permeation of PRAM and RAS (20 mM each) across porcine skin after 6 h was 15.7 +/- 1.9 and 16.0 +/- 2.9 mu g/cm(2), respectively. Co-iontophoresis at 0.15, 0.3 and 0.5 mA/cm(2) resulted in statistically significant increases in delivery of PRAM and RAS; at 0.5 mA/cm(2), cumulative permeation of PRAM and RAS was 61…
Imaging of Orthotopic Glioblastoma Xenografts in Mice Using a Clinical CT Scanner: Comparison with Micro-CT and Histology
2016
Purpose There is an increasing need for small animal in vivo imaging in murine orthotopic glioma models. Because dedicated small animal scanners are not available ubiquitously, the applicability of a clinical CT scanner for visualization and measurement of intracerebrally growing glioma xenografts in living mice was validated. Materials and Methods 2.5x106 U87MG cells were orthotopically implanted in NOD/SCID/ᵞc-/- mice (n = 9). Mice underwent contrast-enhanced (300 μl Iomeprol i.v.) imaging using a micro-CT (80 kV, 75 μAs, 360° rotation, 1,000 projections, scan time 33 s, resolution 40 x 40 x 53 μm) and a clinical CT scanner (4-row multislice detector; 120 kV, 150 mAs, slice thickness 0.5 …
Sox-2 Positive Neural Progenitors in the Primate Striatum Undergo Dynamic Changes after Dopamine Denervation.
2013
The existence of endogenous neural progenitors in the nigrostriatal system could represent a powerful tool for restorative therapies in Parkinson's disease. Sox-2 is a transcription factor expressed in pluripotent and adult stem cells, including neural progenitors. In the adult brain Sox-2 is expressed in the neurogenic niches. There is also widespread expression of Sox-2 in other brain regions, although the neurogenic potential outside the niches is uncertain. Here, we analyzed the presence of Sox-2(+) cells in the adult primate (Macaca fascicularis) brain in naïve animals (N = 3) and in animals exposed to systemic administration of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine to render th…