Anaerobic degradation of papermill sludge in a two-phase digester containing rumen microorganisms and colonized polyurethane foam

Summary The use of reticulated polyurethane foam as a support material for the immobilization of methanogenic associations and its application to the anaerobic treatment of fine particulate solid wastes was investigated. The colonization of polyurethane support particles in a continuous upflow reactor fed on a mixture of acetate, propionate and butyrate, was both rapid and dense. The combination of rumen microorganisms and colonized support particles in a two-phase digester resulted in an efficient anaerobic decomposition of papermill sludge.     

Development of SPECT imaging agents for the norepinephrine transporters: [123I]INER

A series of reboxetine analogs was synthesized and evaluated for in vitro binding as racemic mixtures. The best candidate (INER) was synthesized as the optically pure (S,S) enantiomer, labeled with iodine-123 and its in vivo binding determined by SPECT imaging in baboons. The in vivo specificity, selectivity, and kinetics of [123I]INER make it a promising agent for imaging NET in vivo by noninvasive SPECT imaging.     

Potent mGluR5 antagonists: pyridyl and thiazolyl-ethynyl-3,5-disubstituted-phenyl series

We report the synthesis of four series of 3,5-disubstituted-phenyl ligands targeting the metabotropic glutamate receptor subtype 5: (2-methylthiazol-4-yl)ethynyl (1a-j,), (6-methylpyridin-2-yl)ethynyl (2a-j), (5-methylpyridin-2-yl)ethynyl (3a-j,), and (pyridin-2-yl)ethynyl (4a-j,). The compounds were evaluated for antagonism of glutamate-mediated mobilization of internal calcium in an mGluR5 in vitro assay. All compounds were found to be full antagonists and exhibited low nanomolar to subnanomolar activity.     

Functionalization at position 3 of the phenyl ring of the potent mGluR5 noncompetitive antagonists MPEP

We described the synthesis and biological evaluation of MPEP analogs functionalized at the position 3 of the phenyl ring. The results point out the limitation in the choice of a functional group at this position; the only substituents leading to retention of activity are NO(2) (IC(50)=13 nM) and CN (IC(50)=8 nM).     

Airway cellularity, lipid laden macrophages and microbiology of gastric juice and airways in children with reflux oesophagitis

Background and methods

Human metapneumovirus (hMPV) is a recently discovered respiratory virus associated with bronchiolitis, pneumonia, croup and exacerbations of asthma. Since respiratory viruses are frequently detected in patients with acute exacerbations of COPD (AE-COPD) it was our aim to investigate the frequency of hMPV detection in a prospective cohort of hospitalized patients with AE-COPD compared to patients with stable COPD and to smokers without by means of quantitative real-time RT-PCR.

Results

We analysed nasal lavage and induced sputum of 130 patients with AE-COPD, 65 patients with stable COPD and 34 smokers without COPD. HMPV was detected in 3/130 (2.3%) AE-COPD patients with a mean of 6.5 × 10⁵ viral copies/ml in nasal lavage and 1.88 × 10⁵ viral copies/ml in induced sputum. It was not found in patients with stable COPD or smokers without COPD.

Conclusion

HMPV is only found in a very small number of patients with AE-COPD. However it should be considered as a further possible viral trigger of AE-COPD because asymptomatic carriage is unlikely.     

Synthesis of 5- and 6-substituted 2-(4-dimethylaminophenyl)-1,3-benzoxazoles and their in vitro and in vivo evaluation as imaging agents for amyloid plaque

A series of novel 5- and 6-substituted 2-(4-dimethylaminophenyl)-1,3-benzoxazoles was synthesized and their potential as imaging probes for Alzheimer’s Disease (AD)-related amyloid plaque was evaluated in vitro and in vivo. In vitro binding affinities for Aβ1–40 peptide of several of these compounds were in the low-nanomolar range . The lowest K_i of 9.3 nM was found for N-(2-(4-(dimethylamino)phenyl)-1,3-benzoxazol-5-yl)-4-iodobenzamide (1e). Its ¹²³I-radiolabeled form ([¹²³I]1e) was subsequently prepared by iododestannylation of the corresponding tributylstannyl precursor and evaluated in vivo in a baboon model using SPECT imaging. Contrary to our expectations, 1e did not cross the blood–brain barrier (BBB) to any significant extent.     

Imagerie moléculaire du transporteur vésiculaire de l’acétylcholine (VACh) par le [123I]-5-iodobenzovézamicol dans la démence de type Alzheimer (DTA)

Alzheimer's disease (AD) is characterized by a premature decline of cholinergic neurons. The 5-IBVM is an analogue of the vesamicol that binds to the presynaptic vesicular acetylcholine transporter (VAChT). The exploration of this target should be useful to make an early diagnosis of AD. Our first aim was to propose a method of non invasive VAChT quantification according to 5-IBVM kinetic. 5-IBVM was injected to four AD patients (age = 77 ± 3.9 years and MMSE = 24.5 ± 1.02) were included in this methodological study. The single-photon emission computed tomography (SPECT) images were obtained at five, 20, 35 and 50 minutes, at then at three, five and 22 hours after intravenous injection of 5-IBVM (185MBq). The time activity curves were obtained after SPECT images coregistration on a MRI masque. Specific volume of interest (SPE = SPEcific) were manually drawn on striatum, pons, thalamus and para-hippocampic gyrus including hippocampus; reference volumes of interest (REF = REFerence) were drawn on frontal and occipital cerebral cortex. On the basis of uptake kinetic, two modelisation approaches were considered: transient equilibrium model for reversible ligand (binding potential (BP) = (SPE ? REF)/REF) and Patlak graphical analysis for irreversible tracers (slope given by K_i/DV_ref where K_i is the influx contant and DV_ref is the distribution volume of the reference region). We observed an inflection or a stady state of the activity curves in the different regions studied between 250 and 1400 minutes, what seems to confirm that the tracer is little reversible. BP values obtained at 21 hours with occipital areas as reference and K_i/DV_ref values were respectively 4.62 ± 0.42 and 0.07 ± 0.01. The SPE classification according to BP and K_i/DV_ref values were similar to the classification according to the compartmental analysis (Kuhl 1994).The transient equilibrium model with late acquisition seems the more suitable because IBVM kinetic and practical simplicity of performing in clinical routine.     

Olfactory contribution to Fos expression during mating in inexperienced male hamsters

Male hamsters are very dependent on chemosensory cues for normal mating behavior. We have previously reported that central, vomeronasal pathways are intensely and selectively activated during mating or pheromonal stimulation. The contribution of main olfactory sensory input to the patterns of c-fos activation was investigated in this study. Sexually inexperienced male hamsters were either made anosmic by intranasal infusion of zinc sulfate or remained intact. Fos protein immunoreactivity was analyzed in main olfactory and vomeronasal pathways of the zinc sulfate-treated, anosmic animals after mating with receptive females for 45 min, and compared with Fos patterns seen in intact mating animals, some of which have been described in a previous publication. The zinc sulfate-treated anosmic males described here all mated when given access to receptive females. Whether mated or unstimulated, anosmic males had little or no Fos expression in main olfactory pathways; significantly less even than in unstimulated intact animals. Mating did not increase Fos expression in main olfactory pathways of intact animals over that of unstimulated intact controls. However, Fos expression in central vomeronasal pathways was significantly higher in mating anosmic males, as in intact males, compared with appropriate non-mating controls. Fos expression was significantly different between intact and zinc sulfate-treated anosmic mating males in only one area studied. The rostral anterior medial amygdala, known to receive a small olfactory terminal field, had significantly lower Fos expression in zinc sulfate-treated anosmic males that mated when compared with intact-mating animals. Thus, functional main olfactory input to the rostral vomeronasal amygdala can be demonstrated but does not appear to be critical for mating behavior in previously inexperienced male hamsters with intact vomeronasal organs. Other main olfactory input appears to have a negligible contribution to Fos-patterns in such animals.