Ubiquitous atmospheric production of organic acids mediated by cloud droplets.

Atmospheric acidity is increasingly determined by carbon dioxide and organic acids1-3. Among the latter, formic acid facilitates the nucleation of cloud droplets4 and contributes to the acidity of clouds and rainwater1,5. At present, chemistry-climate models greatly underestimate the atmospheric burden of formic acid, because key processes related to its sources and sinks remain poorly understood2,6-9. Here we present atmospheric chamber experiments that show that formaldehyde is efficiently converted to gaseous formic acid via a multiphase pathway that involves its hydrated form, methanediol. In warm cloud droplets, methanediol undergoes fast outgassing but slow dehydration. Using a chemistry-climate model, we estimate that the gas-phase oxidation of methanediol produces up to four times more formic acid than all other known chemical sources combined. Our findings reconcile model predictions and measurements of formic acid abundance. The additional formic acid burden increases atmospheric acidity by reducing the pH of clouds and rainwater by up to 0.3. The diol mechanism presented here probably applies to other aldehydes and may help to explain the high atmospheric levels of other organic acids that affect aerosol growth and cloud evolution.

Evaluation of the antifungal effect of plant extracts on oral Candida spp. - a critical methodological analysis of the last decade.

INTRODUCTION: In 2022, the World Health Organization published a report encouraging researchers to focus on Candida spp. to strengthen the global response to fungal oral infections and antifungal resistance. In the context of innovative research, it seems pertinent to investigate the antifungal potential of natural extracts of plants and the methodology involved in the recent reports. The aim of this systematic review is to identify the current state of in vitro research on the evaluation of the ability of plant extracts to inhibit Candida spp. MATERIAL AND METHODS: A bibliographic search has been developed to on a 10-year period to identify which plant extracts have an antifungal effect on the Candida spp. found in the oral cavity. RESULTS: A total of 20 papers were reviewed and fulfilled all the selection criteria and were included in the full data analysis. DISCUSSION: Plants have been tested in a wide range of states - whole extracts, extraction of particular components such as flavonoids or polyphenols, or even using the plant to synthesize nanoparticles. Of forty-five plants tested, five of them did not show any effect against Candida spp., which weren't part of the same family. There is a wide range of plant that exhibit antifungal proprieties. CONCLUSION: Many plants have been tested in a wide range of states - whole extracts, extraction of components such as flavonoids or polyphenols, or even using the plant to synthetize nanoparticles. The combination of plants, the addition of plants to a traditional antifungal and the interference with adhesion provided by some plants seem to be promising strategies. Nonetheless, on contrary to drugs, there is a critical lack of standardization on methodologies and protocols, which makes it difficult to compare data and, consequently, to conclude, beyond doubts, about the most promising plants to fight Candida spp. oral infections.

Our changing atmosphere: evidence based on long-term infrared solar observations at the Jungfraujoch since 1950.

The Institute of Astrophysics of the University of Liège has been present at the High Altitude Research Station Jungfraujoch, Switzerland, since the late 1940s, to perform spectrometric solar observations under dry and weakly polluted high-mountain conditions. Several solar atlases of photometric quality, extending altogether from the near-ultra-violet to the middle-infrared, were produced between 1956 and 1994, first with grating spectrometers then with Fourier transform instruments. During the early 1970s, scientific concerns emerged about atmospheric composition changes likely to set in as a consequence of the growing usage of nitrogen-containing agricultural fertilisers and the industrial production of chlorine-bearing compounds such as the chlorofluorocarbons and hydro-chlorofluorocarbons. Resulting releases to the atmosphere with ensuing photolysis in the stratosphere and catalytic depletion of the protective ozone layer prompted a worldwide consortium of chemical manufacturing companies to solicit the Liège group to help in clarifying these concerns by undertaking specific observations with its existing Jungfraujoch instrumentation. The following pages evoke the main steps that led from quasi full sun-oriented studies to priority investigations of the Earth's atmosphere, in support of both the Montreal and the Kyoto Protocols.

BARCOS, an automation and remote control system for atmospheric observations with a Bruker interferometer.

In order to make long-term monitoring of the atmospheric composition using commercial Bruker Fourier transform spectrometers more cost effective, a system called BARCOS has been developed. The system enables one to perform the operation of the spectrometric atmospheric observations in a remotely controlled or autonomous way, without human presence at the measuring site. Several observation geometries are foreseen, including solar and lunar absorption spectrometry. BARCOS is built using existing commercial hardware and software components, including the Bruker software for the operation of the spectrometer (OPUS) and runs in a personal computer (Microsoft) environment. It includes a small meteorological station. It is a flexible system, allowing manual interventions at any time. To run BARCOS effectively, the only prerequisite is that internet access is available at the site of operation. This article describes the BARCOS system hardware and software configurations.

The Orbiting Carbon Observatory (OCO-2) tracks 2-3 peta-gram increase in carbon release to the atmosphere during the 2014-2016 El Niño.

The powerful El Niño event of 2015-2016 - the third most intense since the 1950s - has exerted a large impact on the Earth's natural climate system. The column-averaged CO2 dry-air mole fraction (XCO2) observations from satellites and ground-based networks are analyzed together with in situ observations for the period of September 2014 to October 2016. From the differences between satellite (OCO-2) observations and simulations using an atmospheric chemistry-transport model, we estimate that, relative to the mean annual fluxes for 2014, the most recent El Niño has contributed to an excess CO2 emission from the Earth's surface (land + ocean) to the atmosphere in the range of 2.4 ± 0.2 PgC (1 Pg = 1015 g) over the period of July 2015 to June 2016. The excess CO2 flux is resulted primarily from reduction in vegetation uptake due to drought, and to a lesser degree from increased biomass burning. It is about the half of the CO2 flux anomaly (range: 4.4-6.7 PgC) estimated for the 1997/1998 El Niño. The annual total sink is estimated to be 3.9 ± 0.2 PgC for the assumed fossil fuel emission of 10.1 PgC. The major uncertainty in attribution arise from error in anthropogenic emission trends, satellite data and atmospheric transport.

Cholinergic neurotransmission studied in vivo using positron emission tomography or single photon emission computerized tomography.

During the past decade, considerable efforts have been made in the development of radiopharmaceuticals for the in vivo study of the cholinergic neurotransmission using positron emission tomography or single photon emission computerized tomography. The main cholinergic radioligands, labelled with positron- or gamma-photon-emitting radionuclides, are reviewed with respect to use as in vivo markers of either acetylcholinesterase, vesicular acetylcholine transporter, brain and heart muscarinic receptors, or cholinergic nicotinic receptors. The main results obtained in the in vivo study of the physiology, pharmacology or pathology of the different steps of the cholinergic neurotransmission using single photon emission computerized tomography and positron emission tomography are discussed.

Regional specific binding of [11C]RO 15 1788 to central type benzodiazepine receptors in human brain: quantitative evaluation by PET.

The central type benzodiazepine receptors were studied in 17 healthy human subjects with 11C-RO 15 1788 and positron emission tomography (PET). The brain regional distribution of the tracer in eight control studies performed after injection of trace doses of 11C-RO 15 1788 was consistent with that of benzodiazepine receptors. Saturation studies with co-injected cold RO 15 1788 in the remaining subjects showed a dose-dependent decrease of brain radiotracer until full inhibition of specific binding was achieved with doses above 0.1 mg/kg (four studies). Based on the results, a simple method to estimate the specifically bound 11C-RO 15 1788 regionally in a single PET study is proposed, using the data from the full-saturation studies as a stable estimate of the nondisplaceable radioligand concentration. Using this method, it was found that quasiequilibrium between the estimated specifically bound and nondisplaceable components was achieved at times equal to or longer than 20 min after tracer administration. The validity of this method was partly supported by further results, showing a good agreement between the regional specific binding so calculated and postmortem data of receptor density.

Effects of unilateral lesion of the nucleus basalis of Meynert on brain glucose utilization in callosotomized baboons: a PET study.

Prior work has demonstrated that unilateral lesions of the nucleus basalis of Meynert (NbM) in baboons induce a marked reduction in glucose utilization of the ipsilateral cerebral cortex, linearly proportional to the depression in cortical choline acetyltransferase (ChAT) activity achieved. Unexpectedly, there was also marked hypometabolism of the contralateral cerebral cortex, and glucose utilization recovered gradually on both sides despite persistent deficit in cortical ChAT activity. To investigate the role of the corpus callosum (CC) in this bilateral metabolic effect and subsequent recovery, three baboons were subjected to unilateral electrolytic NbM lesion greater than 3 months following section of the anterior CC. Brain glucose utilization was sequentially studied by positron emission tomography; ChAT activity was measured and histological sections obtained after death. In these animals, the NbM lesion also induced significant metabolic depression over the ipsilateral cortex, proportional to the reduction in ChAT activity. Corpus callosotomy did not prevent the contralateral metabolic effects, suggesting that the latter do not normally operate through the CC. However, there was no significant recovery of glucose utilization, suggesting that, following unilateral NbM lesion, the CC normally mediates, at least in part, the recovery of cortical glucose utilization.

Modeling analysis of [11C]flumazenil kinetics studied by PET: application to a critical study of the equilibrium approaches.

The multi-injection modeling approach was used for the in vivo quantitation of benzodiazepine receptors in baboon brain using positron emission tomography (PET) and [11C]flumazenil (RO 15-1788) as a specific ligand. The model included three compartments (plasma, free, and bound ligand) and five parameters (including the benzodiazepine receptor concentration). The plasma concentration after correction for the metabolites was used as the input function. The experimental protocol consisted of four injections of labeled and/or unlabeled ligand. This protocol allows the evaluation, from a single experiment, of the five model parameters in various regions of interest. For example, in the temporal cortex, the concentration of receptor sites available for binding (B'max) and the equilibrium dissociation constant (Kd) were estimated to be 70 +/- 15 pmol/ml and 15.8 +/- 2.2 nM, respectively. The validity of the equilibrium approach, which is the most often used quantitation method, has been studied from simulated data calculated using these model parameters. The equilibrium approaches consist of reproducing in PET studies the experimental conditions that permit the use of the usual in vitro methods such as Scatchard analysis. These approaches are often open to criticism because of the difficulty of defining the notion of equilibrium in in vivo studies. However, it appears that the basic relation of Scatchard analysis is valid over a broader range of conditions than those normally used, such as the requirement of a constant bound/free ratio. Simulations showed that the values of the receptor concentration (B'max) and the equilibrium dissociation constant (Kd) found using Scatchard analysis are always underestimated. These simulations also suggest an explanation concerning the dependency of B'max and Kd on the time point employed for the Scatchard analysis, a phenomenon found by several authors. To conclude, we propose new protocols that allow the estimation of the B'max and Kd parameters using a Scatchard analysis but based on a protocol including only one or two injections. These protocols being entirely noninvasive, it thus becomes possible to investigate possible changes in receptor density and/or affinity in patients.

Kinetic analysis of central [76Br]bromolisuride binding to dopamine D2 receptors studied by PET.

The in vivo kinetic analysis of dopamine D2 receptors was obtained in baboon brain using positron emission tomography (PET) and [76Br]bromolisuride [( 76Br]BLIS) as radioligand. An injection of a trace amount of [76Br]BLIS was followed 3 h later by an injection of a mixture of [76Br]BLIS and BLIS in the same syringe (coinjection experiment). A third injection performed at 6 h was either an excess of unlabeled ligand (displacement experiment) or a second coinjection. This protocol allowed us to evaluate in the striatum of each animal and after a single experiment the quantity of available receptors (B'max) and the kinetic parameters including the association and dissociation rate constants (k + 1VR and k-1, respectively, where VR is the volume of reaction). The cerebellum data were fitted using a model without specific binding. All the parameters were estimated using nonlinear mathematical models of the ligand-receptor interactions including or not including nonspecific binding. The plasma time-concentration curve was used as an input function after correction for the metabolites. An estimate of standard errors was obtained for each PET study and for each identified parameter using the covariance matrix. The average values of B'max and KdVR were 73 +/- 11 pmol/ml tissue and 1.9 +/- 0.9 pmol/ml, respectively. The nonspecific binding was identifiable in the experiment where the last injection corresponded to a second coinjection. We found that approximately 6% of the striatal binding was nonspecific after a tracer injection of [76Br]BLIS. The nonspecific binding appeared to be reversible in the striatum but irreversible in the cerebellum.

Mössbauer spectroscopy and perturbed angular correlation studies of the rare-and alkaline-earth bone uptake.

Emission Mössbauer spectra and Perturbed Angular Correlation measurements have been performed on samples of mineral bone powder labelled with 161Tb3+ or 133Ba2+ ions after either in vitro absorption or uptake by metabolic pathway. The study of these hyperfine spectra, compared with those carried out when 161Tb or 133Ba are situated in either hydroxyde lattice or phosphate one, shows that the uptake modes of rare-and alkaline-earth ions on the bone matrix are different. The rare earth ion seems to be absorbed on the surface bone in an environment of hydroxyl groups similar to the structure of a rare earth hydroxyde. The alkaline earth ion bone uptake appears more complicated and would make according to the following process : at first, surface absorption on the hydroxylapatite in a hydroxyde environment and then cationic exchange with the calcium phosphate groups into bone crystals.

Pentylenetetrazol-induced seizure is not mediated by benzodiazepine receptors in vivo.

The selective benzodiazepine antagonist RO 15-1788, labelled with carbon 11 [11C] RO 15-1788, as a specific marker, together with positron emission tomography, allows the in vivo study of benzodiazepine receptors in primates. In addition, when coupled with recordings of electroencephalographic activity, this method offers the feasibility of studying the correlation between occupancy of benzodiazepine receptors and the convulsant action of drugs acting at the benzodiazepine-GABA receptor complex in vivo. The present study showed that convulsant doses of pentylenetetrazol (PTZ) could affect the binding of [11C] RO 15-1788 in vivo in two ways, depending on the doses tested: at concentrations of 20 and 30 mg/kg, pentylenetetrazol increased the binding of [11C] RO 15-1788 whereas larger concentrations displaced the binding of [11C] RO 15-1788. The direct correlation between the occupancy of respective benzodiazepine receptors, afforded by increasing convulsant doses of pentylenetetrazol, revealed that competitive interaction with benzodiazepine receptors was not necessary for pentylenetetrazol to induce the appearance of seizures in vivo.

Chronic MPTP treatment reproduces in baboons the differential vulnerability of mesencephalic dopaminergic neurons observed in Parkinson's disease.

Chronic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to baboons was shown previously to result in a motor syndrome and a pattern of striatal dopaminergic fibre loss similar to those observed in idiopathic Parkinson's disease. In the present study, tyrosine hydroxylase-immunoreactive neurons were quantified in the mesencephalon of control (n = 4) and chronically MPTP-treated (n = 3) baboons. MPTP induced a significant reduction in neuronal cell density in the substantia nigra (63.8% reduction) and the ventral tegmental area (53.1%). Within the substantia nigra, obvious mediolateral and dorsoventral gradients of neuronal cell loss were observed. First, the pars lateralis was more affected than the lateral divisions of the pars compacta (89.6% vs 73.8% cell loss), which in turn were more depleted than the medial divisions (60.1% reduction). Second, the ventral regions of the pars compacta were more degenerated than the dorsal parts (82.4 vs 51.5% decrease). This regional pattern is strikingly similar to that observed in Parkinson's disease and indicates that two subpopulations of dopaminergic neurons are distinguishable on the basis of their differential vulnerability to MPTP. Finally, the present study confirms that chronic mitochondrial complex I inhibition using MPTP in primates is sufficient to reproduce the typical dopaminergic cell loss and striatal fibre depletion observed in Parkinson's disease.

Riluzole protects from motor deficits and striatal degeneration produced by systemic 3-nitropropionic acid intoxication in rats.

The putative neuroprotective effect of riluzole was investigated in a rat model of progressive striatal neurodegeneration induced by prolonged treatment (three weeks, intraperitoneal) with 3-nitropropionic acid, an irreversible inhibitor of succinate dehydrogenase. Quantitative analysis of motor behaviour indicated a significant protective effect (60%) of riluzole (8 mg/kg/day) on 3-nitropropionic acid-induced motor deficits as assessed using two independent motor tests. Furthermore, quantitative analysis of 3-nitropropionic acid-induced lesions indicated a significant 84% decrease in the volume of striatal damage produced by 3-nitropropionic acid, the neuroprotective effect apparently being more pronounced in the posterior striatum and pallidum. In addition, it was checked that this neuroprotective effect of riluzole against systemic 3-nitropropionic acid did not result from a decreased bioavailability of the neurotoxin or a direct action of riluzole on 3-nitropropionic acid-induced inhibition of succinate dehydrogenase. We found that riluzole significantly decreased by 48% the size of striatal lesions produced by stereotaxic intrastriatal injection of malonate, a reversible succinate dehydrogenase inhibitor. Furthermore, the inhibition of cortical and striatal succinate dehydrogenase activity induced by systemic 3-nitropropionic acid was left unchanged by riluzole administration. The present results, consistent with a beneficial effect of riluzole in amyotrophic lateral sclerosis, suggest that this compound may be useful in the treatment of chronic neurodegenerative diseases.

Quantifiable bradykinesia, gait abnormalities and Huntington's disease-like striatal lesions in rats chronically treated with 3-nitropropionic acid.

Impairment in energy metabolism is thought to be involved in the aetiology of Huntington's disease. In line with this hypothesis, chronic systemic administration of the mitochondrial toxin 3-nitropropionic acid to rats and monkeys produces selective striatal lesions similar to Huntington's disease. The present study examined whether rats treated with varying regimen of 3-nitropropionic acid could present motor abnormalities reminiscent of Huntington's disease symptomatology, correlated with Huntington's disease specific striatal symptomatology. Subacute 3-nitropropionic acid treatment (15 mg/kg per day intraperitoneally for 10 days) produced dramatic motor symptoms associated with extensive neuronal loss and gliosis in the lateral striatum as well as severe hippocampal degeneration in 50% of the cases. In contrast, chronic 3-nitropropionic acid treatment (10 mg/kg per day subcutaneously for one month) led to more subtle excitotoxic-like lesions, selective for the dorsolateral striatum and more closely resembling Huntington's disease striatal pathology. Animals with these Huntington's disease-like lesions showed spontaneous motor symptoms including mild dystonia, bradykinesia and gait abnormalities, which were barely detectable on visual inspection but could be readily identified and quantified by computerized video analysis. In these chronic animals, the degree of striatal neuronal loss was significantly correlated with the severity of spontaneous motor abnormalities, as is the case in Huntington's disease. The present study demonstrates that chronic low-dose 3-nitropropionic acid treatment in rats results in a valuable model of both the histological features and motor deficits which occur in Huntington's disease. Despite the interanimal variability in terms of response to 3-nitropropionic acid treatment, this rat model may be particularly useful for evaluating the functional benefits of new therapeutic strategies for Huntington's disease, particularly those aiming to reduce the severity of motor symptoms.

Stable parkinsonian syndrome and uneven loss of striatal dopamine fibres following chronic MPTP administration in baboons.

The progressive degeneration of dopamine neurons observed in idiopathic Parkinson's disease was mimicked by injecting low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to baboons, on a chronic basis. Five Papio papio baboons were treated on two different regimens (chronic intravenous administration at weekly intervals for 20-21 months or, daily MPTP treatment for five days followed five to six months later by chronic weekly injections for 5-21.5 months). All animals were assessed for motor symptoms during and after neurotoxic treatment. Both regimens invariably resulted in the appearance of a progressive and irreversible syndrome characterized by action and resting tremor, cogwheel rigidity, postural impairments, hypokinesia and bradykinesia. In some animals, symptoms of resting tremor and rigidity initially restricted to one side of the body became bilateral within a few months of treatment. Subtle abnormalities that may be found in idiopathic Parkinson's disease such as alterations of the blink reflex response were also noted. Neuropathological examination of caudate nucleus, putamen, substantia nigra and ventral tegmental area in brain sections stained for tyrosine hydroxylase showed a typical uneven striatal dopamine fibre loss and a neuronal depletion in the dopaminergic mesencephalic cell groups that reproduce those observed in idiopathic Parkinson's disease. Immunocytochemical observations and behavioural data show that chronic rather than acute MPTP injection regimens can replicate most of the neuropathological and the clinical features typical of idiopathic Parkinson's disease, possibly by increasing the ability of this neurotoxin to target specific subpopulations of mesencephalic dopaminergic neurons.

[11C]methionine pancreatic scanning with positron emission computed tomography.

By the use of [11C]methionine and positron computed tomography (PCT), images of the pancreas were obtained in 32 patients. The injection of between 10 and 20 mCi of this product enables four to six transverse sections to be obtained. Seventeen of the patients studied had no exocrine pancreatic disease, and in all these cases the pancreas was clearly visible. In four cases of pancreatic carcinoma and one of retroperitoneal tumor, there were abnormalities visible. In five cases of chronic pancreatitis, no pancreatic uptake was observed. In a sixth case, concentration was visible, but only in the head of the pancreas. One case of acute pancreatitis, which showed no concentration during the acute phase, returned to normal after recovery. When visible, the pancreas was easily located and distinguishable from the intestinal image, except in two cases that were uninterpretable for technical reasons. No false positive or negative was observed, but a differential diagnosis between cancer and pancreatitis was impossible.

A primate model of Huntington's disease: functional neural transplantation and CT-guided stereotactic procedures.

In this article, we show that 1) computed tomographic (CT)-guided stereotactic infusion of an excitotoxin into the striatum of a nonhuman primate provides a useful neuropathologic and behavioral model for Huntington's disease. 2) High-resolution positron emission tomography (PET) can be used to image the decreased glucose utilization and the preservation of dopaminergic terminals in the lesioned striatum by using 2-fluoro-deoxy-D-glucose (2FDG) and N-(C-11)-methyl-2-beta-carbomethoxy-3-beta-phenyl tropane (CPT) as tracers. 3) Transplantation of cross-species striatal fetal tissue into the lesioned caudate-putamen reduces many of the abnormal motor movements and behavioral changes seen in the Huntington's disease primate model. 4) Graft rejection results in the return of the abnormal signs of the pregrafted state. These results indicate that treatment of the neuronal deficit in Huntington's disease can involve intervention at the local neuronal circuit level. CT-guided stereotactic implantation of cells that might protect or replace this defective circuitry may eventually provide an effective treatment for Huntington's disease.

In vivo bidirectional modulatory effect of benzodiazepine receptor ligands on GABAergic transmission evaluated by positron emission tomography in non-human primates.

The central type benzodiazepine receptor (BDZr), an allosteric modulatory site of the GABAA receptor-anion channel, has been shown in vitro to respond to drugs with positive efficacy (agonists), zero efficacy (competitive antagonists) and drugs with negative efficacy (inverse agonists). However, this general concept of the function of BDZr drugs has rarely been assessed in intact living brain. We report here in on a non-invasive in vivo assessment of the intrinsic efficacies of BDZr drugs in the brain of non-human primates. We have performed an in vivo simultaneous determination of fractional BDZr occupancy and the resulting pharmacological efficacies of the full agonist diazepam, the partial agonist bretazenil, the antagonist flumazenil (Ro15-1788), the partial inverse agonist Ro15-4513 and the full inverse agonist methyl beta-carboline-3-carboxylate (beta-CCM). Positron emission tomography (PET) was used to estimate fractional BDZr occupancy measured as the in vivo displacement in the brain of the positron emitter radioligand, [11C]flumazenil. Simultaneously, the proconvulsant or anticonvulsant efficacies of the BDZr drugs were measured as their abilities to facilitate or counteract the central effects of an infusion of pentylenetetrazol, a non-competitive GABA antagonist acting on the picrotoxin site of the receptor complex. This was measured using electroencephalographic recording (EEG). Our results show that, in vivo, the fractional receptor occupancy by a given drug is perfectly correlated with its resulting graded pharmacological effects, as predicted from the competitive drug receptor interaction theory. Furthermore, the slope of the relationship between fractional receptor occupancies and the resulting pharmacological effects (an index of intrinsic efficacy) strictly depends on the BDZr ligand considered. Diazepam displayed a strong positive intrinsic efficacy, and, in contrast, beta-CCM a marked negative one. Between these two extremes, the partially active drugs bretazenil and Ro15-4513, which required a large fractional receptor occupancy to produce significant anti- or proconvulsant effects, respectively, displayed only a weak intrinsic efficacy. Flumazenil did not produce any significant pharmacological effect. We observed that the in vivo intrinsic efficacies of diazepam, flumazenil and beta-CCM correlate with their intrinsic efficacies as measured by their modulatory effects on the GABA-dependent membrane chloride conductance in vitro. Thus, the intrinsic efficacies measured using PET and EEG are likely to reflect the different in vivo abilities of BDZr drugs to induce or stabilize the GABAA-benzodiazepine chloride channel in a given conformation.(ABSTRACT TRUNCATED AT 400 WORDS)

[76Br]bromolisuride: a new tool for quantitative in vivo imaging of D-2 dopamine receptors.

Bromolisuride, an ergoline derivative, was labeled with the positron emitter radionuclide, bromine 76. In vitro and in vivo binding and competition studies in rats demonstrated a high affinity (KD = 0.3 nM) and a high specificity of this new radioligand for D-2 dopamine receptors. PET kinetic studies in baboons showed an accumulation of [76Br]bromolisuride in the striatum which reached a maximum 30 min post-injection and which could be displaced by haloperidol. All these results indicated that this new ligand is certainly suitable for the non-invasive in vivo quantitative imaging of D-2 dopamine receptor sites in human brain.