Introduction La membrane plasmique de l’adipocyte est très fragile et vulnérable à la pression mécanique. Cette caractéristique est principalement due à sa largeur et son unique vacuole gorgée de ...lipides exerçant une pression constante de l’intérieur de la cellule. Ainsi, l’adipocyte mature éclate au bout de 24 à 48 heures en condition de culture classique. Par conséquent, la plupart des études sur les adipocytes sont réalisées sur des préadipocytes différenciés in vitro ou des lignées cellulaires 3T3-L1. Néanmoins, le métabolisme et les fonctions biologiques étudiés dans ces modèles sont significativement différents de ceux observés chez des adipocytes matures de tissu humain fraîchement recueilli. Cette différence représente un obstacle majeur pour les évaluations précliniques. Matériels et méthodes Après prélèvement du tissu adipeux humain frais, les adipocytes matures sont séparés des autres types cellulaires via digestion par la collagénase. Une fois isolés, les adipocytes sont encapsulés dans un gel peptidique les maintenant en culture jusqu’à 7 jours au moins. Pour maintenir la survie et les fonctions biologiques des adipocytes, AdipoPhYt a élaboré un procédé d’encapsulation breveté. Observations Ce modèle permet d’évaluer l’efficacité de différents composés des industries pharmaceutique, cosmétique et nutrition sur des processus métaboliques du tissu adipeux comme la lipolyse, la lipogenèse, la résistance à l’insuline, l’inflammation, la fibrose, etc. Conclusion Des études de validation ont permis de montrer que ce modèle permet de préserver la survie et le profil de sécrétion des adipocytes. La pertinence biologique de ce modèle permet de mener des études de longue durée sur les processus métaboliques des adipocytes matures. De plus, ce modèle est adapté aux études de criblage grâce à sa miniaturisation en plaque de 96 puits. Enfin, le procédé d’encapsulation, très flexible, est utilisable pour d’autres types cellulaires et ouvre des perspectives de développement de modèles de co-culture biomimétiques.
The history of ketamine and phencyclidine from their development as potential clinical anaesthetics through drugs of abuse and animal models of schizophrenia to potential rapidly acting ...antidepressants is reviewed. The discovery in 1983 of the NMDA receptor antagonist property of ketamine and phencyclidine was a key step to understanding their pharmacology, including their psychotomimetic effects in man. This review describes the historical context and the course of that discovery and its expansion into other hallucinatory drugs. The relevance of these findings to modern hypotheses of schizophrenia and the implications for drug discovery are reviewed. The findings of the rapidly acting antidepressant effects of ketamine in man are discussed in relation to other glutamatergic mechanisms.
Highlights • Empathy and sympathy converge at the early stage of the mirroring processing. • Mirror system and executive functions are co-activated in empathy but not sympathy. • Right prefrontal ...cortex monitors the shift from mirroring to mentalizing processes. • Three distinct periods characterize the neural time course of empathy at 60–630 ms.
The colonic mucus barrier is commonly described as a continuous double layer covering the epithelium, separating the microbiota from the intestinal tissue. This model is currently considered valid ...throughout the colon. The colon is characterised by regional anatomo-functional specificities such as presence and consistency of contents and location. In this study, we characterised the organisation of the colonic mucus barrier in proximal and distal colon of rodents by histological and FISH staining, taking into account aforementioned specificities. By using longitudinal sections and imaging extensive areas of tissue with and without colonic contents, we have obtained a spatiotemporal overview of mucus organisation in the colon. We describe for the first time that the colonic mucus layer covers the faeces instead of the epithelium in the distal colon. This faecal mucus layer confines the microbiota to the faeces and prevents it from remaining in empty distal colon. In the proximal colon, the mucus did not form a separating layer between bacteria and epithelium. We conclude that the organisation of colonic mucus is reliant on the presence of the colonic content, and the location within the colon. Our findings reopen the discussion on the nature of the colonic mucus barrier.
Functional networks are comprised of neuronal ensembles bound through synchronization across multiple intrinsic oscillatory frequencies. Various coupled interactions between brain oscillators have ...been described (e.g., phase-amplitude coupling), but with little evidence that these interactions actually influence perceptual sensitivity. Here, electroencephalographic (EEG) recordings were made during a sustained-attention task to demonstrate that cross-frequency coupling has significant consequences for perceptual outcomes (i.e., whether participants detect a near-threshold visual target). The data reveal that phase-detection relationships at higher frequencies are dependent on the phase of lower frequencies, such that higher frequencies alternate between periods when their phase is either strongly or weakly predictive of visual-target detection. Moreover, the specific higher frequencies and scalp topographies linked to visual-target detection also alternate as a function of lower-frequency phase. Cross-frequency coupling between lower (i.e., delta and theta) and higher frequencies (e.g., low- and high-beta) thus results in dramatic fluctuations of visual-target detection.
► Cross-frequency coupling shapes visual perception. ► The phase of lower frequencies determines the influence of higher frequencies. ► The frequencies and scalp topographies linked with detection are not static. ► Oscillations at multiple frequencies are linked to visual-target detection.
We consider the unbounded settling dynamics of a circular disk of diameter
$d$
and finite thickness
$h$
evolving with a vertical speed
$U$
in a linearly stratified fluid of kinematic viscosity
...$\unicodeSTIX{x1D708}$
and diffusivity
$\unicodeSTIX{x1D705}$
of the stratifying agent, at moderate Reynolds numbers (
$Re=Ud/\unicodeSTIX{x1D708}$
). The influence of the disk geometry (diameter
$d$
and aspect ratio
$\unicodeSTIX{x1D712}=d/h$
) and of the stratified environment (buoyancy frequency
$N$
, viscosity and diffusivity) are experimentally and numerically investigated. Three regimes for the settling dynamics have been identified for a disk reaching its gravitational equilibrium level. The disk first falls broadside-on, experiencing an enhanced drag force that can be linked to the stratification. A second regime corresponds to a change of stability for the disk orientation, from broadside-on to edgewise settling. This occurs when the non-dimensional velocity
$U/\sqrt{\unicodeSTIX{x1D708}N}$
becomes smaller than some threshold value. Uncertainties in identifying the threshold value is discussed in terms of disk quality. It differs from the same problem in a homogeneous fluid which is associated with a fixed orientation (at its initial value) in the Stokes regime and a broadside-on settling orientation at low, but finite Reynolds numbers. Finally, the third regime corresponds to the disk returning to its broadside orientation after stopping at its neutrally buoyant level.
Background and Purpose
Phytocannabinoids in Cannabis sativa have diverse pharmacological targets extending beyond cannabinoid receptors and several exert notable anticonvulsant effects. For the first ...time, we investigated the anticonvulsant profile of the phytocannabinoid cannabidivarin (CBDV) in vitro and in in vivo seizure models.
Experimental Approach
The effect of CBDV (1–100 μM) on epileptiform local field potentials (LFPs) induced in rat hippocampal brain slices by 4‐aminopyridine (4‐AP) application or Mg2+‐free conditions was assessed by in vitro multi‐electrode array recordings. Additionally, the anticonvulsant profile of CBDV (50–200 mg·kg−1) in vivo was investigated in four rodent seizure models: maximal electroshock (mES) and audiogenic seizures in mice, and pentylenetetrazole (PTZ) and pilocarpine‐induced seizures in rats. The effects of CBDV in combination with commonly used antiepileptic drugs on rat seizures were investigated. Finally, the motor side effect profile of CBDV was investigated using static beam and grip strength assays.
Key Results
CBDV significantly attenuated status epilepticus‐like epileptiform LFPs induced by 4‐AP and Mg2+‐free conditions. CBDV had significant anticonvulsant effects on the mES (≥100 mg·kg−1), audiogenic (≥50 mg·kg−1) and PTZ‐induced seizures (≥100 mg·kg−1). CBDV (200 mg·kg−1) alone had no effect against pilocarpine‐induced seizures, but significantly attenuated these seizures when administered with valproate or phenobarbital at this dose. CBDV had no effect on motor function.
Conclusions and Implications
These results indicate that CBDV is an effective anticonvulsant in a broad range of seizure models. Also it did not significantly affect normal motor function and, therefore, merits further investigation as a novel anti‐epileptic in chronic epilepsy models.
Linked Articles
This article is part of a themed section on Cannabinoids. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.167.issue‐8
Since the initial report by Lehn et al. in 1979, ruthenium tris(bipyridine) (Ru(bpy)32+) and its numerous derivatives were applied as photosensitizers (PSs) in a large panel of photocatalytic ...conditions while the bis(terpyridine) analogues were disregarded because of their low quantum yields and short excited-state lifetimes. In this study, we prepared a new terpyridine ligand, 4′-(4-bromophenyl)-4,4‴:4″,4‴′-dipyridinyl- 2,2′:6′,2″-terpyridine (Bipytpy) and used it to prepare the heteroleptic complex Ru(Tolyltpy)(Bipytpy)(PF6)2 (1; Tolyltpy = 4′-tolyl-2,2′:6′,2′-terpyridine). Complex 1 exhibits enhanced photophysical properties with a higher quantum yield (7.4 × 10–4) and a longer excited-state lifetime (3.8 ns) compared to those of Ru(Tolyltpy)2(PF6)2 (3 × 10–5 and 0.74 ns, respectively). These enhanced photophysical characteristics and the potential for PS–catalyst interaction through the peripheral pyridines led us to apply the complex for visible-light-driven hydrogen evolution. The photocatalytic system based on 1 as the PS, triethanolamine as a sacrificial donor, and cobaloxime as a catalyst exhibits sustained activity over more than 10 days under blue-light irradiation (light-emitting diode centered at 450 nm). A maximum turnover number of 764 was obtained after 12 days.
Plasmablastic lymphoma (PBL), initially described in 1997 in the oral cavity of HIV positive patients, is now recognized as a distinct aggressive and rare entity of diffuse large B-cells lymphoma by ...the World Health Organization (WHO) classification. Since the original description, others cases have been reported. However, these are largely derived from case reports or small series limiting any definitive conclusions on clinical characteristics and outcome.
The clinical, biological, pathological features and outcome of a cohort including 135 patients with PBL, from LYSA centers in France and Belgium, were reported and analyzed.
The median age was 58 years, with a male predominance. The cohort was divided into 56 HIV-positive patients, 17 post-transplant patients and 62 HIV-negative/non-transplanted patients. Within HIV-negative/non-transplanted, a relative immunosuppression was found in most cases (systemic inflammatory disease, history of cancer, increased age associated with weakened immune system). We have also described a new subtype, PBL arising in a chronic localized inflammatory site, without any sign of immunosuppression. At presentation, 19% of patients showed oral involvement. Immunophenotype showed CD138 positivity in 88% of cases and CD20 negativity in 90% of cases. Chemotherapy was administered to 80% of patients, with a complete response (CR) rate of 55%. The median overall survival (OS) was 32 months. In univariate analysis, HIV positive status showed better OS when compared with HIV negative status. In multivariate analysis, International Prognostic Index score, chemotherapy and CR were associated with survival benefit.
This cohort, the largest reported to date, increases the spectrum of knowledge on PBL, rarely described. However, specific guidelines to clarify treatment are lacking, and may improve the poor prognosis of this rare disease.
PDF
