Dendritic cells (DCs) are well known as professional antigen-presenting cells (APC) able to initiate specific T-cell responses to pathogens in lymph nodes (LN) draining the site of infection. ...However, the respective contribution of migratory and LN-resident DCs in this process remains unclear. As DC subsets represent important targets for vaccination strategies, more precise knowledge of DC subsets able to present vaccine antigens to T cells efficiently is required. To investigate the capacities of DCs migrating in the lymph (L-DCs) to initiate a specific T-cell response, we used physiologically generated DCs collected from a pseudoafferent lymphatic cannulation model in sheep. The CD1b.sup.+ L-DCs were assessed for presenting antigens from the vaccine attenuated strain of Salmonella enterica serovar Abortusovis. CD1b.sup.+ L-DCs were able to phagocytose, process and to present efficiently Salmonella antigens to effector/memory T cells in vitro. They were shown to be efficient APC for the priming of allogeneic naive T cells associated with inducing both IFN-gamma and IL-4 responses. They were also efficient in presenting Salmonella antigens to autologous naive T cells associated with inducing both IFN-gamma and IL-10 responses. The capacities of L-DCs to process and present Salmonella antigens to T cells were investigated in vivo after conjunctival inoculation of Salmonella. The CD1b.sup.+ L-DCs collected after inoculation were able to induce the proliferative response of CD4.sup.+ T cells suggesting the in vivo capture of Salmonella antigens by the CD1b.sup.+ L-DCs, and their potential to present them directly to CD4.sup.+ T cells. In this study, CD1b.sup.+ L-DCs present potential characteristics of APC to initiate by themselves T cell priming in the LN. They could be used as target cells for driving immune activation in vaccinal strategies.
Purpose:
Partial volume effects (PVEs) are consequences of the limited spatial resolution in emission tomography leading to underestimation of uptake in tissues of size similar to the point spread ...function (PSF) of the scanner as well as activity spillover between adjacent structures. Among PVE correction methodologies, a voxel-wise mutual multiresolution analysis (MMA) was recently introduced. MMA is based on the extraction and transformation of high resolution details from an anatomical image (MR/CT) and their subsequent incorporation into a low-resolution PET image using wavelet decompositions. Although this method allows creating PVE corrected images, it is based on a 2D global correlation model, which may introduce artifacts in regions where no significant correlation exists between anatomical and functional details.
Methods:
A new model was designed to overcome these two issues (2D only and global correlation) using a 3D wavelet decomposition process combined with a local analysis. The algorithm was evaluated on synthetic, simulated and patient images, and its performance was compared to the original approach as well as the geometric transfer matrix (GTM) method.
Results:
Quantitative performance was similar to the 2D global model and GTM in correlated cases. In cases where mismatches between anatomical and functional information were present, the new model outperformed the 2D global approach, avoiding artifacts and significantly improving quality of the corrected images and their quantitative accuracy.
Conclusions:
A new 3D local model was proposed for a voxel-wise PVE correction based on the original mutual multiresolution analysis approach. Its evaluation demonstrated an improved and more robust qualitative and quantitative accuracy compared to the original MMA methodology, particularly in the absence of full correlation between anatomical and functional information.
Issue Title: Theme issue on Urinary Bladder Prostaglandin E^sub 2^ (PGE^sub 2^) is well known to modulate urinary bladder functions, but it is also thought to be involved in the pathophysiology of ...lower urinary tract dysfunctions, since high levels of PGE^sub 2^ have been found in overactive bladder (OAB) patients. beta-Adrenoceptors are major players in detrusor muscle relaxation, and the selective beta^sub 3^-adrenoceptor (AR) agonist mirabegron was recently approved for the treatment of overactive bladder (OAB). beta-Adrenoceptor modulation of PGE^sub 2^ excitatory effects on bladder detrusor muscle was investigated by i.v. mirabegron after intravesical PGE^sub 2^ infusion in conscious rats. Non-voiding activity (NVA) was assessed under isovolumetric conditions. In addition, mirabegron and isoprenaline (0.01-10 muM) were studied on PGE^sub 2^-increased micro-contractile activity during isometric tension recordings of intact isolated bladder muscle strips. Our investigations showed that PGE^sub 2^ dramatically increased NVA in vivo and spontaneous micro-contractions in vitro. In vivo administration of mirabegron (0.1, 0.3 and 3 mg/kg) reduced PGE^sub 2^-augmented NVA in dose-dependent manner, while the PGE^sub 2^-increased micro-contractions in isolated bladder strips were poorly inhibited. Isoprenaline inhibited PGE^sub 2^-augmented micro-contractions in a concentration-dependent manner and had a higher potency compared to mirabegron. The apparent pKB of 7.25 for metoprolol at the isoprenaline concentration-response curve for PGE^sub 2^-augmented micro-contractions suggests a beta^sub 1^-AR-mediated.
Abstract Introduction11 CMADAM is a radioligand suitable for PET studies of the serotonin transporter (SERT). Metabolite analysis in human and non-human plasma samples using HPLC separation has shown ...that 11 CMADAM was rapidly metabolized. A possible metabolic pathway is the S-oxidation which could lead to SOMADAM and SO2 MADAM. In vitro evaluation of these two potential metabolites has shown that SOMADAM exhibited a good affinity for SERT and a good selectivity for SERT over NET and DAT. Methods Comparative PET imaging studies in non-human primate brain with 11 CMADAM and 11 CSOMADAM were carried out, and plasma samples were analyzed using reverse phase HPLC. We have explored the metabolism of 11 CMADAM in rat brain with a view to understand its possible interference for brain imaging with PET. Results PET imaging studies in non-human primate brain using 11 CSOMADAM indicated that this tracer does not bind with high amounts to brain regions known to be rich in SERT. The fraction of 11 CSOMADAM in non-human primate plasma was approximately 5% at 4 min and 1% at 15 min after 11 CMADAM injection. HPLC analysis of brain sample after 11 CMADAM injection to rats demonstrated that 11 CSOMADAM was not detected in the brain. Conclusions11 CSOMADAM is not superior over 11 CMADAM as a SERT PET radioligand. Nevertheless, 11 CSOMADAM has been identified as a minor labeled metabolite of 11 CMADAM measured in monkey plasma. 11 CSOMADAM was not detected in rat brain.
Sodium butyrate (SB) is used as an acidifier in animal feed. We hypothesized that supplemental SB impacts gastric morphology and function, depending on the period of SB provision. The effect of SB on ...the oxyntic and pyloric mucosa was studied in 4 groups of 8 pigs, each supplemented with SB either during the suckling period (d 4-28 of age), after weaning (d 29 to 39-40 of age) or both, or never. We assessed the number of parietal cells immunostained for H+/K+-ATPase, gastric endocrine cells immunostained for chromogranin A and somatostatin (SST) in the oxyntic mucosa, and gastrin-secreting cells in the pyloric mucosa. Gastric muscularis and mucosa thickness were measured. Expressions of the H+/K+-ATPase and SST type 2 receptor (SSTR2) genes in the oxyntic mucosa and of the gastrin gene in the pyloric mucosa were evaluated by real-time RT-PCR. SB increased the number of parietal cells per gland regardless of the period of administration (P < 0.05). SB addition after, but not before, weaning increased the number of enteroendocrine and SST-positive cells (P < 0.01) and tended to increase gastrin mRNA (P = 0.09). There was an interaction between the 2 periods of SB treatment for the expression of H/K-ATPase and SSTR2 genes (P < 0.05). Butyrate intake after weaning increased gastric mucosa thickness (P < 0.05) but not muscularis. SB used orally at a low dose affected gastric morphology and function, presumably in relationship with its action on mucosal maturation and differentiation.
Ochlerotatus (Finlaya) japonicus japonicus is a potential vector of arboviruses such as Japanese encephalitis virus and West Nile virus. The latter already is present in France. We report the species ...for the 1st time in metropolitan France and in Europe. Two larvae were collected in July and October 2000 in used tires in a village in northwestern France. Collections were made in a stack of recycled tires from a company that imports from the USA and Japan. The lack of other mutes of introduction for the species confirms tires as a means of worldwide spread. Larval stages found in the area indicate that the species is reproducing locally.
In this report, we describe the synthesis of a novel library of $\alpha$7 nAChR ligands based on the modulationof the quinuclidine, quinazoline and tropane moieties. Spirane derivatives were newly ...synthesized understereo specific 1,3 dipolar cylcoadditions. Only amide derivatives bonded efficiently to the receptor withKi measured between 14 and 133 nM. The best fluorinated candidate was selected and radiolabeled. Thepotent $^{18}$F4 PET tracer was evaluated in rats and its brain accumulation quantified.
In order to improve fluoro-de-triazenation methodology, the fluorination reaction on 3,3-diethyl-1-(4-substituted aryl)triazenes using boron trifluoride under conventional and microwave heating in ...different organic solvents and in the absence of protic acid (no unwanted Ar-A byproduct formation) were studied. Display omitted
► Fluorination of 3,3-diethyl-1-(4-substituted aryl)triazenes. ► Fluoro-de-triazenation methodology using boron trifluoride under conventional and microwave heating in different organic solvents. ► Absence of protic acid, thus avoiding the competitive formation of the unwanted compound Ar-A.
Fluoro-de-triazenation of 3,3-diethyl-1-aryltriazenes can be achieved by conventional or under microwave heating in carbon tetrachloride, in the presence of boron trifluoride diethyl etherate without any protic acid to avoid corresponding unwanted byproduct formation.
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