Whole-body biodistribution, radiation dosimetry estimates for the PET norepinephrine transporter probe (S,S)-[18F]FMeNER-D2 in non-human primates.

Background: (S,S)-[F]FMeNER-D2 is a recently developed norepinephrine transporter ligand which is a potentially useful radiotracer for mapping the brain and heart norepinephrine transporter in vivo using positron emission tomography. In this work, we quantified the biodistribution over time and radiation exposure to multiple organs with (S,S)-[F]FMeNER-D2.

Methods: Whole-body images were acquired for 21 time points in two cynomolgus monkeys for approximately 270 min after injection of radioligand.

Solar photocatalytic oxidation of pretreated wastewaters: laboratory scale generation of design data for technical-scale double-skin sheet reactors.

Batchwise heterogeneous photocatalytic oxidation of model wastewater (solutions of the azo dye "Acid Orange 7" in tap water) has been performed in a laboratory-scale stirred vessel reactor with non-submerged UV-A lamps using titanium dioxide "P25" as photocatalyst. Comparison to results of solar pilot-scale Plexiglass double-skin sheet reactor (DSSR) experiments indicates that the lab-scale method may predict area demand for technical-scale DSSR design. Characteristic UV-A fluences leading to TOC or COD reduction to e(-1) of the initial concentrations were determined in lab-scale stirred vessel experiments for treated effluents of seven different industrial branches, secondary municipal effluent and biologically treated greywater.

Two C-methyl derivatives of [11C]WAY-100635--effects of an amido alpha-methyl group on metabolism and brain 5-HT1A receptor radioligand behavior in monkey.

Purpose: [carbonyl-11C]N-(2-(1-(4-(2-methoxyphenyl)-piperazinyl)ethyl)-N-pyridinyl)cyclohexanecarboxamide ([carbonyl-11C]WAY-100635) is an effective radioligand for imaging brain 5-HT1A receptors with positron emission tomography (PET). However, this radioligand has some drawbacks for deriving relative regional receptor densities, including rapid metabolism, which acts against accurate definition of an arterial input function for compartmental modeling, and very low nonspecific binding in brain, which detracts from the accuracy of modeling by a simplified reference tissue (cerebellum) approach. Here, in a search for a radioligand that overcomes these limitations, we investigated the effects of introducing a single methyl group at either of the carbon atoms alpha to the amide bond in [11C]WAY-100635.

Synthesis, in vivo and in vitro biological activity of novel azaline B analogs.

Several azaline B analogs (2-10) were synthesized and evaluated for their ability to antagonize GnRH in vitro and for duration of action in inhibiting luteinizing hormone secretion in a castrated male rat assay in vivo. Analogs, 8 (IC(50) = 1.85 nM), and 9 (IC(50) = 1.

A preliminary PET evaluation of the new dopamine D2 receptor agonist [11C]MNPA in cynomolgus monkey.

This study describes the preliminary positron emission tomography (PET) evaluation of a dopamine D(2)-like receptor agonist, (R)-2-(11)CH(3)O-N-n-propylnorapomorphine ([(11)C]MNPA), as a potential new radioligand for in vivo imaging of the high-affinity state of the dopamine D(2) receptor (D(2)R). MNPA is a selective D(2)-like receptor agonist with a high affinity (K(i)=0.17 nM).

Effects of vinpocetine on the redistribution of cerebral blood flow and glucose metabolism in chronic ischemic stroke patients: a PET study.

The pharmacological effects of the neuroprotective drug vinpocetine, administered intravenously in a 14-day long treatment regime, on the cerebral blood flow and cerebral glucose metabolism in chronic ischemic stroke patients (n=13) were studied with positron emission tomography in a double-blind design. The regional and global cerebral metabolic rates of glucose (CMRglc) and cerebral blood flow (CBF) as well as vital physiological parameters, clinical performance scales, and transcranial Doppler parameters were measured before and after the treatment period in patient groups treated with daily intravenous infusion with or without vinpocetine. While the global CMRglc values did not change markedly as a result of the infusion treatment with (n=6) or without (n=7) vinpocetine, the global CBF increased and regional CMRglc and CBF values showed marked changes in several brain structures in both cases, with more accentuated changes when the infusion contained vinpocetine.

[11C]vinpocetine: a prospective peripheral benzodiazepine receptor ligand for primate PET studies.

Vinpocetine, a synthetic derivative of the Vinca minor alkaloid vincamine, is a widely used drug in neurological practice. We tested the hypothesis that vinpocetine binds to peripheral benzodiazepine binding sites (PBBS) and is therefore a potential ligand of PBBS. Positron emission tomography (PET) measurements in two cynomolgous monkeys showed that pretreatment with vinpocetine markedly reduced the brain uptake of [11C]PK11195, a known PBBS radioligand.

Preparation of highly specific radioactivity [18F]flumazenil and its evaluation in cynomolgus monkey by positron emission tomography.

A straightforward method for the preparation of no-carrier-added (n.c.a.

Feature uncertainty: a novel test to probe prefrontal dysfunction in unaffected siblings of schizophrenia patients.

Previous studies indicated that neuropsychological impairments are potential endophenotypes of schizophrenia. However, the sensitivity of these procedures is not sufficient and their brain substrates are poorly defined. The aim of this study was to measure the behavioral performance of siblings of schizophrenia patients and controls on a novel feature uncertainty (FU) task that selectively activates dorsal anterior cingulate cortex relative to orientation (OR) and spatial frequency (SF) discrimination.

N-oxide analogs of WAY-100635: new high affinity 5-HT(1A) receptor antagonists.

WAY-100635 [N-(2-(1-(4-(2-methoxyphenyl)piperazinyl)ethyl))-N-(2-pyridinyl)cyclohexanecarboxamide] 1 and its O-desmethyl derivative DWAY 2 are well-known high affinity 5-HT(1A) receptor antagonists, which when labeled with carbon-11 (beta+; t(1/2) = 20.4 min) in the carbonyl group are effective radioligands for imaging brain 5-HT(1A) receptors with positron emission tomography (PET). In a search for new 5-HT(1A) antagonists with different pharmacokinetic and metabolic properties, the pyridinyl N-oxide moiety was incorporated into analogs of 1 and 2.

Magnesium in animal nutrition.

Magnesium (Mg) supplementation remarkably improves the digestibility of feed. In cows and sows, it has improved the reproduction and shortened the service period. In broilers it increased weight gain, and it has increased egg production of laying hens.

Freeze concentration for enrichment of nutrients in yellow water from no-mix toilets.

Separately collected urine ("yellow water") can be utilized as fertilizer. In order to decrease storage volumes and energy consumption for yellow water transport to fields, enrichment of nutrients in yellow water has to be considered. Laboratory-scale batch freeze concentration of yellow water has been tested in ice-front freezing apparatus: a stirred vessel and a falling film freeze concentrator (coolant temperatures: -6 to -16 degrees C).

Multicenter phase II study of the oral MEK inhibitor, CI-1040, in patients with advanced non-small-cell lung, breast, colon, and pancreatic cancer.

Purpose: This multicenter, open-label, phase II study was undertaken to assess the antitumor activity and safety of the oral mitogen-activated extracellular signal regulated kinase kinase (MEK) inhibitor, CI-1040, in breast cancer, colon cancer, non-small-cell lung cancer (NSCLC), and pancreatic cancer.

Patients And Methods: Patients with advanced colorectal, NSCLC, breast, or pancreatic cancer received oral CI-1040 continuously at 800 mg bid. All patients had measurable disease at baseline, a performance status of 2 or less, and adequate bone marrow, liver, and renal function.

AlphaA-Conotoxin OIVA defines a new alphaA-conotoxin subfamily of nicotinic acetylcholine receptor inhibitors.

The venoms of cone snails are rich in multiply disulfide-crosslinked peptides, the conotoxins. Conotoxins are grouped into families on the basis of shared cysteine patterns and homologous molecular targets. For example, both the kappaA- and alphaA-conotoxin families share the same Class IV Cys pattern (-CC-C-C-C-C-), but differ in their molecular targets.

KappaM-conotoxin RIIIK, structural and functional novelty in a K+ channel antagonist.

Venomous organisms have evolved a variety of structurally diverse peptide neurotoxins that target ion channels. Despite the lack of any obvious structural homology, unrelated toxins that interact with voltage-activated K(+) channels share a dyad motif composed of a lysine and a hydrophobic amino acid residue, usually a phenylalanine or a tyrosine. kappaM-Conotoxin RIIIK (kappaM-RIIIK), recently characterized from the cone snail Conus radiatus, blocks Shaker and TSha1 K(+) channels.

Joint explorative analysis of neuroreceptor subsystems in the human brain: application to receptor-transporter correlation using PET data.

Positron emission tomography (PET) has proved to be a highly successful technique in the qualitative and quantitative exploration of the human brain's neurotransmitter-receptor systems. In recent years, the number of PET radioligands, targeted to different neuroreceptor systems of the human brain, has increased considerably. This development paves the way for a simultaneous analysis of different receptor systems and subsystems in the same individual.

Positron emission tomographic evaluation of the putative dopamine-D3 receptor ligand, [11C]RGH-1756 in the monkey brain.

The dopamine-D3 receptor is of special interest due to its postulated role in the pathophysiology and treatment of schizophrenia and Parkinson's Disease. Increasing evidences support the assumption that the D3 receptors are occupied to a high degree by dopamine at physiological conditions. Research on the functional role of the D3 receptors in brain has however been hampered by the lack of D3 selective ligands.

Segregation of two endocannabinoid-hydrolyzing enzymes into pre- and postsynaptic compartments in the rat hippocampus, cerebellum and amygdala.

Fatty acid amide hydrolase (FAAH) and monoglyceride lipase (MGL) catalyse the hydrolysis of the endocannabinoids anandamide and 2-arachidonoyl glycerol. We investigated their ultrastructural distribution in brain areas where the localization and effects of cannabinoid receptor activation are known. In the hippocampus, FAAH was present in somata and dendrites of principal cells, but not in interneurons.

Immunocytochemically defined interneuron populations in the hippocampus of mouse strains used in transgenic technology.

Transgenic mice are overtaking the role of model animals in neuroscience. They are used in developmental, anatomical, and physiological as well as experimental neurology. However, most results on the organization of the nervous system derive from the rat.

PET evaluation of novel radiofluorinated reboxetine analogs as norepinephrine transporter probes in the monkey brain.

(S,S)-2-(alpha-(2-Fluoromethoxyphenoxy)benzyl)morpholine ((S,S)-FMeNER) was found to be a selective high-affinity ligand for the norepinephrine transporter (NET). (S,S)-FMeNER) was labeled with fluorine-18 (t1/2 = 109.8 min) by O-fluoromethylation of desfluoromethoxy-(S,S)-FMeNER with [18F]bromofluoromethane.

Smelling human sex hormone-like compounds affects face gender judgment of men.

Although strong cross-sensory interactions between visual, tactile and auditory modalities have already been shown, we know little about how chemosensory information affects processing in other sensory modalities. We studied whether smelling gender-specific odorous sex hormone-like steroids: 5-alpha-androgenst-16-en-3-one (androgen) or oestra-1, 3, 5 (10), 16-tetraen-3-ol (estrogen) can bias face gender discrimination. We found that, as a result of inhalation of androgen, men perceive faces to be more masculine as compared to when they are exposed to estrogen.

Limbic reductions of 5-HT1A receptor binding in human temporal lobe epilepsy.

Objective: To test the hypothesis that in mesial temporal lobe epilepsy (MTLE) there is involvement outside of mesial structures and that this involvement affects serotonin systems, thus suggesting a mechanism for affective symptoms in this population.

Methods: Serotonin 5-HT1A receptor binding was studied with PET and [Carbonyl-11C]WAY-100 635 in 14 patients (6 with left-, 8 with right-sided mesial temporal lobe focus) and 14 controls. The 5-HT1A receptor binding potential was calculated for hippocampus, amygdala, orbitofrontal, insular, lateral temporal, and anterior cingulate cortex, in raphe nuclei, and in two regions presumably uninvolved in the epileptogenic process (parietal, and dorsolateral frontal neocortex).